Дисертації з теми "Treatment of human diseases and conditions"
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Roodhouse, Amanda. "Modeling human leg arteries: a comparison of conditions and diseases." Thesis, Wichita State University, 2011. http://hdl.handle.net/10057/5029.
Повний текст джерелаThesis (M.S.)--Wichita State University, College of Engineering, Dept. of Mechanical Engineering.
Mondal, Utpal Kumar. "CARBONIC ANHYDRASE MODULATORS FOR DETECTION AND TREATMENT OF HUMAN DISEASES." Diss., Temple University Libraries, 2019. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/543241.
Повний текст джерелаPh.D.
Carbonic anhydrases (CAs, EC 4.2.1.1) are a class of metalloenzymes that catalyze the hydration of CO2 under physiologic conditions and are involved in many physiological and pathological processes. Modulation of CA activity, particularly CA inhibition is exploited pharmacologically for the treatment of many diseases such as cancer, glaucoma, edemas, mountain sickness. CA activation has been less frequently investigated till recently. Genetic deficiencies of several CA isozymes are reported in the literature and reflect the important role of carbonic anhydrases in human physiology and homeostasis. Activation of CA isozymes in brain have been correlated recently with spatial learning and memory. Based on these premises, activators of CA isozymes have the potential to alleviate mild dementias and to act as potential nootropic agents. In chapter 3, continuing our long-term interests towards the development of potent and selective CAAs, we carried out X-ray crystallographic studies with a small series of pyridinium histamine derivatives, previously developed as CAAs by our group. This study revealed important insights into the binding of this class of activators into the active site of CA II isozyme. A potent pyridinium histamine CAA 25i was successfully crystallized with CA II isozyme and was found to bind into the hydrophobic region of the active site, with two binding conformations being observed. This is one of the very few X-ray crystal structures of a CAA available. Based on the findings of this X-ray crystallographic study and building on our previously developed ethylene bis-imidazole CAAs, we advanced a novel series of lipophilic bis-imidazoles. Enzymatic assays carried out on purified human CA isozymes revealed several low nanomolar potent activators against various brain-relevant CA isozymes. Bis-imidazole 30e was found to be a nanomolar potent activator for CA IV, CA VA and CA IX. Due to their conjugated structure, these CAAs were also fluorescent and therefore were fully characterized in terms of photophysical properties, with several representatives proving to display very good fluorophores. The very good activation profile against several different CA isozymes, along with excellent fluorescence properties recommend these compounds as great molecular tools for elucidation of role of CA isozymes in brain physiology, as well as towards improvement of memory and learning. Focusing on inhibition of CA isozymes, it must be stressed that over the last decade a clear connection had been established between the expression of CA IX and CA XII and cancer. Since cancer is the second most common cause of death in the world, we explored the possibility to kill cancer cells via inhibition of different CA isozymes present in cancer cells. The membrane bound carbonic anhydrase IX (CA IX) isozyme represents a particularly interesting anticancer target as it is significantly overexpressed in many solid tumors as compared to normal tissues. In malign tissues this CA isozyme was found to play important role in pH homeostasis and promotes tumor cell survival, progression and metastasis. Thus, CA IX represents a potential biomarker and an appealing therapeutic target for the detection and treatment of cancer. CA IX can be targeted either through the development of small or large molecular weight, potent, and selective inhibitors or through the development of CA IX targeted drug delivery systems for selective delivery of potent chemotherapeutic agents. Building on these premises, in this dissertation, we also revealed our continuing efforts towards the development of potent and selective CA IX inhibitors along with their translation into the development of CA IX targeted drug delivery systems. In chapter 4, we designed a series of small molecular weight (MW) ureido 1,3,4-thiadiazole sulfonamide derivatives employing the “tail approach”, through the decoration of established sulfonamide CA inhibitor warheads with different tail moieties via ureido linker. The generated CAIs were tested against tumor associated CA IX and CA XII isozymes and off-target cytosolic isozymes CA I and CA II, and were revealed to be moderate to highly selective and nanomolar, even sub-nanomolar, potent CA IX inhibitors. Several potent pan-inhibitors were also identified in this section. We assessed these CAIs for their in vitro cell killing ability using MDA-MB 231 breast cancer cell line expressing CA IX and CA XII. The most efficient CAI proved to be ureido-1,3,4-thiadiazole-2-sulfonamide 69, which showed subnanomolar potency against purified human CA IX and CA XII isozymes, with good selectivity against CA I and CA II, and consistent, statistically significant cancer cell killing. In Chapter 5, continuing our efforts towards the development of potent and selective CA IX inhibitors, we designed, synthesized, characterized and evaluated a new series of PEGylated 1,3,4-thiadiazole-2-sulfonamide CAIs, bearing different PEG backbone length. We increased the PEG size from 1K to 20K, in order to better understand the impact of the PEG linker length on the in vitro cell killing ability against CA IX expressing cancer cell lines and also against a CA IX negative cell line. In vitro cell viability assays revealed the optimum PEG linker length for this type of bifunctional bis-sulfonamide CAIs in killing the tumor cells. The most efficient PEGylated CAI was found to bis-sulfonamide DTP1K 91, which showed consistent and significant cancer cell killing at concentrations of 10−100 μM across different CA IX and CA XII expressing cancer cell lines. DTP1K 91 did not affect the cell viability of CA IX negative NCI-H23 tumor cells, thus revealing a CA IX mediated cell killing for these inhibitors. In chapter 6, we decided to further explore the possibility of using CA IX as a targeting epitome for the development of a gold nanoparticle-based drug delivery system. We translated the oligoEG- and PEGylated CAI conjugates into efficient targeting ligands for gold nanoparticle decoration along with chemotherapeutic agent doxorubicin (Dox), in a novel multi-ligand gold nanoplatform designed to selectively release the drug intracellularly, in order to enhance the selective tumor drug uptake and tumor killing. We were successful in developing compatible CAI- and Dox- ligands for efficient dual functionalization of gold nanoparticles. Our optimized, CA IX targeted gold nanoplatform was found to be very efficient towards killing HT-29 tumor cells especially under hypoxic conditions, reducing the hypoxia-induced chemoresistance, thus confirmed the potentiating role of CA IX as a targeting epitome.
Temple University--Theses
Masokwane, Patrick Maburu Dintle. "Prevalence of non-AIDS defining conditions and their associations with virologic treatment failure among adult patients on anti-retroviral treatment in Botswana." University of the Western Cape, 2016. http://hdl.handle.net/11394/5247.
Повний текст джерелаBackground: The recognition of HIV/AIDS as a chronic life-long condition globally in recent years has demanded a different perception and an alignment to its association with other chronic diseases. Both HIV and other chronic non-communicable diseases are significant causes of morbidity and mortality. Their combined DALY contributions for Botswana would be significant if research and strategies in controlling these conditions are not put in place. Natural aging and specific HIV-related accelerated aging of patients who are on antiretroviral treatment means that age-related diseases will adversely affect this population. Princess Marina Hospital Infectious Diseases Care Clinic has been in operation since 2002. The clinic has initiated over 16 000 patients on anti-retroviral treatment (ART) since 2002. The current study estimated the prevalence of non-AIDS defining conditions (NADCs) in the attendees of the clinic in 2013. The majority of patients that attended the clinic had been on treatment for over three years with some patients more than ten years. These ART experienced patients were more likely to be susceptible to chronic non-communicable diseases, including non-AIDS defining conditions. The nomenclature used in classification of NADCs in the current study was appropriate for resource-limited settings; because the study setting offered HIV treatment under resources constraints. Aim: The current study characterised non-AIDS defining conditions, and determined their associations with virologic treatment failure in a cohort of patients that were enrolled at Princess Marina Hospital antiretroviral clinic in Gaborone, Botswana. Methods: A retrospective cross sectional study of records of patients who attended the Princess Marina Infectious Diseases Care Clinic in 2013. Stratified random sampling of a total of 228 patients’ records was achieved from a total population of 5,781 records. Data was transcribed into a Microsoft Excel Spreadsheet and then exported to Epi-Info statistical software for analysis. Results: Eighty (35%) cases of NADCs were reported/diagnosed in the study sample; with 27% (n=62) of the patients having at least one condition, 6.7% (n=17) two conditions, and 0.4% (n=1) three conditions. The top prevalent conditions were hypertension (n= 40), hyperlipidaemia (n=7) and lipodystrophy (n=7). The prevalence of NADCs on the various categories of patients compared with the total sample population was as follows: active patients (prevalence ratio= 0.70), transferred out patients (prevalence ratio = 1.24), patients who died (prevalence ratio=2.04) and patients who were lost to follow-up (prevalence ratio =2.86). The prevalence of NADCs was significantly associated with increasing age (p<0.001); having social problems (p=0.028); having been on treatment for over three years (p=0.007); an outcome of death (p = 0.03) and being lost to follow-up (p=0.007). The study showed that being controlled on second line or salvage regimen (p=0.014) and the presence of adherence problems in the past was associated with virologic failure (p=0.008). There was no association of presence of NADCs to virologic failure. Conclusions: There was significant morbidity of non-AIDS defining conditions in the Princess Marina Infectious Diseases Care Clinic shown by a prevalence of NADCs in the clinic of 35% in 2013.The significant associations of the presence of NADCs and virologic failure with outcomes of death and loss to follow-up illustrate the adverse effects that NADCs are having, and calls for strategies to address multi-morbidities in HIV patients on antiretroviral treatment.
Langenhan, Jana [Verfasser]. "Development of specific immunoadsorbers for the treatment of human pemphigus diseases / Jana Langenhan." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2012. http://d-nb.info/1026457408/34.
Повний текст джерелаTalegaonkar, Sonia S. "The Role of Human MSC Derived Exosomes in the Treatment of Periodontal Diseases." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/4969.
Повний текст джерелаSimon, Remil B. S., Darshan M. D. Shah, Peter B. S. Blosser, Demetrio M. D. Macariola, and Jeffrey M. D. Carlsen. "Treatment of CMV Vitritis in a Preterm Newborn." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/165.
Повний текст джерелаLai, Wing-hon Kevin, and 黎永漢. "Generation of vasculogenic progenitor cells from human induced pluripotent stem cells for the treatment of cardiovascular diseases." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/197112.
Повний текст джерелаpublished_or_final_version
Medicine
Doctoral
Doctor of Philosophy
Khalid, Mahwish Rani, and Mahwish Rani Khalid. "Line1: Implications in the Etiology of Human Diseases, Clinical Utilities, and Pharmacological Target for Disease Treatment." Thesis, The University of Arizona, 2017. http://hdl.handle.net/10150/626716.
Повний текст джерелаLi, Xiang, and 李想. "Effects of human mesenchymal stem cells on cigarette smoke-induced lung damage." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B49618209.
Повний текст джерелаpublished_or_final_version
Medicine
Master
Master of Philosophy
Chacko, Anu. "Comparison of human and animal Chlamydia pneumoniae responses to interferon gamma and penicillin treatment." Thesis, Queensland University of Technology, 2015. https://eprints.qut.edu.au/85438/1/Anu_Chacko_Thesis.pdf.
Повний текст джерелаMahmood, Dler Faieeq Darweesh. "Thioredoxin-1 (Trx1) : a new target in the treatment of cardiovascular diseases." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2014. http://tel.archives-ouvertes.fr/tel-01069096.
Повний текст джерелаRocha, Mariana Frota Cúcio De Moraes. "A novel assay to measure mitochondrial dysfunction in human skeletal muscle : implications for the diagnosis and treatment of mitochondrial diseases." Thesis, University of Newcastle upon Tyne, 2016. http://hdl.handle.net/10443/3255.
Повний текст джерелаSianangama, Pharaoh Collins. "Effects of human chorionic gonadotropin administration at various times following breeding on corpus luteum number, diameter, progesterone profiles and pregnancy rates in dairy cattle." Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/28745.
Повний текст джерелаLand and Food Systems, Faculty of
Graduate
Chan, Wan-yi, and 陳韻怡. "Influenza A virus infection of human respiratory epithelium: tissue tropism and innate immuneresponses." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B41633696.
Повний текст джерелаStevenson, Cheryl. "Nutrient intake, gastrointestinal microbiota and the effect of Lactobacillus plantarum 299V in irritable bowel syndrome patients." Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/96018.
Повний текст джерелаENGLISH ABSTRACT: Background: Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder. GI symptoms and impaired quality of life affect between 10-20% of all adults, corresponding to about 25-50% of all patients who visit a gastroenterologist’s clinic. In recent years, several novel mechanisms of IBS that likely relate to previously established theories have been identified. Inflammation, postinfectious low-grade inflammation, immunological and genetic predisposition along with altered microbiota are critical in IBS development, while several dietary factors may also play a role in this syndrome. However, none of these factors accounts for the full repertoire of IBS symptoms, and the pathophysiology of this condition is not fully understood. The overarching aim of this study was to investigate the nutrient intakes, GI microbiota and the effect of Lactobacillus plantarum (L.plantarum) 299v in IBS patients. Sub-aims: 1) Update healthcare professionals on current probiotic information and provide an overview of probiotic treatment approaches, with special emphasis on IBS, 2) conduct a well designed randomised, double blind, placebo-controlled trial (RCT) with L. plantarum 299v as part of an intervention and establish whether a course of probiotics may alleviate undesirable symptoms of IBS and improve quality of life, 3) assess nutrient intake in patients with irritable bowel syndrome (IBS) compared to dietary recommendations, 4) validate and assess the reproducibility of food records and 5) identify possible nutrient risk components for establishing GI microbiota involved in IBS and as part of an intervention, determine whether a course of probiotics may alter stool microbiota. Results: 1) A review article published by the author provides an overview of current probiotic treatment options to health care professionals and indicates certain probiotics are a promising therapeutic treatment option for management of IBS symtpoms, 2) the effects of the single strain probiotic, L. plantarum 299v, supplementation was evaluated in a RCT. Compared to placebo, the probiotic supplementation showed no significant reduction in GI symptom severity scores, particularly abdominal pain relief. Quality of life was also not improved in the treatment versus control group. Both the treatment and placebo groups improved significantly over the trial period, indicating a large placebo effect, 3) nutrient intakes of the IBS patients compared to current dietary reference recommendations indicates that this group of patients are at risk for nutrient inadequacies in key macro and micronutrients, 4) the validity and reliability of the dietary data showed good reliability but poor validity as measured by plasma fatty acids and 5) the GI microbiota composition in the phenotypically different diarrhoea-predominant IBS (D-IBS) vs. constipation-predominant IBS (C-IBS) showed that D-IBS patients had significantly lower counts of Lactobacillus plantarum compared to C-IBS patients. The probiotic had no significant effects on the GI microbiota as measured by quantitative polymerase chain reaction (qPCR). It was found that nutrient intakes had a significant impact on the microbiota. Lower fibre intakes were associated with higher Bacteroides spp., lower Bifidobacteria bifidum and Lactobacillus plantarum counts in both IBS groups. Conclusion: Taken together, L.plantarum 299v did not alleviate the GI symptoms of IBS, nor was it associated with significant changes in the GI microbiota. IBS patients may be at risk of key nutrient inadequacies. The influence of nutrient intakes on the GI microbiota provides an attractive explanation as a potential pathophysiological factor for IBS.
AFRIKAANSE OPSOMMING: Agtergrond: Prikkelbare derm-sindroom (PDS) is ‘n algemene gastro-intestinale (GI) stoornis. GI simptome affekteer die lewenskwaliteit van 10-20% van alle volwassenes. Dit stem ooreen met ongeveer 25-50% van alle pasiënte wat ‘n gastroënteroloog konsulteer. Verskeie oorspronklike meganismes vir die ontwikkeling van PDS is onlangs identifiseer. Inflammasie, post-infektiewe lae-graadse inflammasie, immunologiese en genetiese vatbaarheid tesame met veranderde mikrobiota is krities vir die ontwikkeling van PDS. Sekere dieetfaktore mag ook bydraend wees tot hierdie sindroom. Geen van hierdie faktore is egter verantwoordelik vir die volle spektrum van PDS simptome nie en die patofisiologie van die toestand word ook nog nie ten volle verstaan nie. Die oorkoepelende doel van hierdie studie is om nutriëntinname, GI mikrobiota en die uitwerking van L.plantarum 299v in PDS pasiënte bepaal. Sub-doelwitte: 1) Om gesondheidswerkers in te lig aangaande die nuutste inligting oor probiotika en om ‘n oorsig van probiotika behandelingsopsies te verskaf, met spesiale klem op PDS, 2) om ‘n goed beplande ewekansige, dubbel-blinde, plasebo-beheerde kliniese studie met L.plantarum 299v as deel van die intervensie uit te voer om sodoende te bepaal of ‘n kursus probiotika ongewensde simptome van PDS kan verbeter en lewenskwaliteit sodoende verhoog, 3) om nutriëntinname in pasiënte met PDS te bepaal vergeleke met dieet aanbevelings, 4) om die geldigheid en herhaalbaarheid van voedselrekords te bepaal en 5) om moontlike nutriënt risikokomponente vir die ontwikkeling van GI mikrobiota betrokke in PDS te identifiseer en om as deel van ‘n intervensie te bepaal of ‘n kursus probiotika stoelgang mikrobiota patrone verander. Resultate: 1) ‘n Oorsigartikel gepubliseer deur die kandidaat dui probiotika aan as ‘n belowende terapeutiese opsie in die behandeling van PDS simptome, 2) die effek van ‘n enkelstam probiotikum, L.plantarum 299v, is evalueer deur ‘n ewekansige, dubbel-blinde, plasebo-beheerde kliniese studie. Vergeleke met die plasebo, het probiotiese aanvulling geen betekenisvolle vermindering in die GI simptome in PDS pasiënte tot gevolg gehad nie. Lewenskwaliteit het ook nie verbeter in die behandelde versus die kontrole groep nie. Beide die behandelde en plasebo groepe het aansienlik verbeter oor die studietydperk, wat ‘n groot plasebo effek aandui, 3) nutriëntinname van die PDS groep vergeleke met huidige dieetaanbevelings, dui daarop dat hierdie groep pasiënte ‘n risiko het vir die ontwikkeling van kern nutriënttekorte (makro- en mikronutriënte), 4) die geldigheid en betroubaarheid van die dieetdata dui op goeie betroubaarheid, maar swak geldigheid soos bepaal deur plasma vetsure en 5) die dermkanaal mikrobiotiese samestelling in die verskillende fenotipes, diarree-oorheersende PDS (D-PDS) vs. konstipasie-oorheersende PDS (K-PDS) dui daarop dat D-PDS pasiënte aansienlike minder Lactobacillus plantarum gehad het vergeleke met K-PDS pasiënte. Die probiotikum het geen beduidende uitwerking op die oorheersende mikrobiota gehad nie, soos gemeet deur kwantitatiewe polimerase kettingreaksie (kPKR). Daar is gevind dat dieet ‘n beduidende impak op die mikrobiota gehad het. Daar is ‘n verband tussen laer vesel inname en hoёr Bacteroides spp. en laer Bifidobacteria bididum en Lactobacillus plantarum tellings gevind in beide PDS groepe. Gevolgtrekking: Die L.plantarum 299v enkelstam probiotikum het nie die gastrointestinale simptome van PDS pasiënte verlig nie en daar is ook geen beduidende veranderinge in die mikrobiota gevind nie. PDS pasiënte mag ‘n verhoogde risiko toon vir kern nutriënttekorte. Die invloed van nutriëntinname op GI mikrobiota verskaf ‘n belowende verduideliking as ‘n potensiële patofisiologiese faktor in PDS.
Briggs, Virginia G. "Injection Treatment for Lower Back Pain in Older Adults with Lumbar Spinal Stenosis: A Dissertation." eScholarship@UMMS, 2009. https://escholarship.umassmed.edu/gsbs_diss/439.
Повний текст джерелаSharifi, Bella. "The Development of Novel Apurinic/Aprymidinic Endonuclease/Redox-factor 1 Inhibitors for the Treatment of Human Melanoma." Chapman University Digital Commons, 2019. https://digitalcommons.chapman.edu/pharmaceutical_sciences_theses/7.
Повний текст джерелаLignell, Anders. "In vitro Pharmacodynamics of Antifungal Agents in the Treatment of Candida Infections." Doctoral thesis, Uppsala universitet, Infektionssjukdomar, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-133781.
Повний текст джерелаBurke, Arista. "Expression of the chimeric SAF gene from Human Papillomavirus in the methylotrophic yeasts Pichia pastoris and Hansenula polymorpha." Thesis, Stellenbosch : Stellenbosch University, 2011. http://hdl.handle.net/10019.1/6908.
Повний текст джерелаENGLISH ABSTRACT: The link between infection with Human Papillomavirus (HPV) and the development of cervical cancer has been established by several epidemiology studies. Cervical cancer is the second most common cancer among women and it occurs at a rate of 22.8 cases per 100 000 women in South Africa. Approximately 86% of newly reported cases of cervical cancer occur in developing countries where limited access to medical facilities hampers efforts to prevent and screen for HPV infection. Two commercial virus-like particle (VLP) vaccines consisting of HPV major structural protein L1, which protect against the most common high-risk HPV-types, are currently available. The high cost and type specificity of these commercially available vaccines have necessitated the development of a low cost, broad-spectrum HPV vaccine. Inclusion of the minor structural protein L2 has been shown to induce broadly cross-neutralizing antibodies and therefore a chimera was constructed that contains an epitope of L2 inserted within the L1 sequence. This construct, renamed SAF, was shown to be highly immunogenic and thus has the potential to be used as a prophylactic cervical cancer vaccine. Methylotrophic yeasts are known to be excellent producers of recombinant proteins due to their strongly inducible promoters that allow culturing of these yeasts to very high cell densities. Pichia pastoris and Hansenula polymorpha have been employed in several studies for heterologous protein production and levels of protein higher than 1 g/L have been reported. These yeasts also have GRAS status and can therefore be used to manufacture products for use in humans. In this study, the potential of H. polymorpha and P. pastoris to produce SAF intracellularly was evaluated. The effect of increased gene dosage and peroxisomal targeting on SAF production was examined as possible strategies to increase the yield of SAF. Peroxisomal targeting was achieved by fusing the SAF gene at the C-terminal end with the Peroxisomal Targeting Sequence 1 (PTS1) which consists of a short tri-peptide: –SKL. The functionality of PTS1 was confirmed using green fluorescent protein (GFP), fluorescence microscopy and peroxisome isolation. Peroxisomal targeting was shown to have a negative effect on SAF production levels in both H. polymorpha and P. pastoris. An increase in gene dosage had no discernable effect on SAF yield in H. polymorpha which is in contrast to previous research. The highest production levels were achieved by P. pastoris KM71 (24.86 mg/L) which compares well to levels of L1 achieved by other research groups. The most significant insight emerging from this work was that all the strains that produced SAF at detectable levels were equally efficient at the production of SAF. Increased biomass was therefore the biggest contributor to high SAF levels (mg/L) in the P. pastoris strains as significantly higher cell densities were achieved during culturing of these strains. With the necessary optimisation, the methylotrophic yeasts have the potential to be used as hosts for the production of a broad-spectrum HPV vaccine.
AFRIKAANSE OPSOMMING: Die skakel tussen infeksie met Mens Papilloomvirus (HPV) en die ontwikkeling van servikale kanker is deur verskeie epidemiologiese studies bevestig. Servikale kanker is die tweede mees algemene kanker onder vroue en dit kom voor teen ‘n tempo van 22.8 gevalle per 100 000 vroue in Suid Afrika. Ongeveer 86% van alle nuwe gevalle kom voor in ontwikkelende lande waar beperkte toegang tot mediese fasiliteite pogings om HPV infeksie te voorkom en te behandel, belemmer. Twee pseudovirale-partikel (VLP) entstowwe teen HPV is tans op die mark beskikbaar en hierdie entstowwe verleen immuniteit teen die mees algemene hoë-risiko HPV tipes. Die hoë koste en nou spektrum van hierdie entstowwe het dit nodig gemaak om ‘n goedkoop, wye-spektrum HPV entstof te ontwikkel. Navorsing het bewys dat die insluiting van die strukturele L2 proteïen in die VLP entstof, lei tot die indusering van neutraliserende teenliggame, wat wye spektrum antigenisiteit tot gevolg het. ‘n Chimeriese proteïen wat ‘n epitoop van L2 binne die L1 volgorde bevat is gekonstrueer, en hierdie proteïen is benoem SAF. SAF het hoë immunogenisiteit en kan dus potensieel as ‘n voorkomende servikale kanker entstof gebruik word. Metielotrofiese giste is bekend vir hulle vermoë om hoë vlakke rekombinante proteïene te produseer as gevolg van hulle induseerbare promotors wat groei tot baie hoë sel digthede toelaat. Pichia pastoris en Hansenula polymorpha is in menigte studies gebruik om heteroloë proteïene te produseer tot vlakke bo 1 g/L. Hierdie giste en die proteïen produkte wat hulle vorm word algemeen aanvaar as veilig vir menslike gebruik. In hierdie studie het ons die potensiaal van H. polymorpha en P. pastoris om SAF intrasellulêr te produseer, geevalueer. Die effek op SAF produksie van verhoogde geen dosering asook die teiken van SAF na die peroksisoom was ondersoek as moontlike strategieë om die opbrengs van SAF te verhoog. Die teiken van SAF na die peroksisoom is behaal deur die Peroksisomale Teiken Volgorde 1 (PTS1) aan die C-terminaal van SAF te heg. Die funksionaliteit van PTS1 was bevestig deur gebruik te maak van groen fluoroserende proteïen (GFP), fluoressensie mikroskopie en isolering van peroksisome. Teiken van SAF na die peroksisoom het ‘n negatiewe uitwerking gehad op SAF uitdrukking in beide H. polymorpha en P. pastoris. ‘n Verhoging in geen dosering het geen onderskeibare effek gehad op SAF opbrengs in H. polymorpha nie wat in teenstelling is met vorige navorsing. Die hoogste produksie vlakke is opgelewer deur P. pastoris KM71 (24.86 mg/L) wat goed vergelyk met vlakke van L1 wat deur ander navorsings groepe behaal is. Die belangrikste gevolgtrekking wat gemaak kan word uit hierdie studie is dat al die rasse wat SAF geproduseer het in meetbare hoeveelhede ewe effektief was. Verhoogde biomassa was dus die grootste bydraende faktor tot hoë SAF vlakke (mg/L) in die P. pastoris rasse as gevolg van die hoë sel digthede wat hierdie rasse kan bereik. Dit is duidelik dat metielotrofiese giste, met die nodige optimisering, oor die potensiaal beskik om as gasheer sisteme te dien vir die produksie van ‘n wye spektrum HPV entstof.
The NRF and the Department of Microbiology for financial support
Yeh, Hsin-Hsien. "Utility and validation of the histone deacetylase (HDAC) substrate, [18F]FAHA, as a positron emission tomography (PET) imaging biomarker in non-human primates and HD transgenic mice for evaluation of neurodegenerative diseases and HDAC inhibitor treatment." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/utility-and-validation-of-the-histone-deacetylase-hdac-substrate-18ffaha-as-a-positron-emission-tomography-pet-imaging-biomarker-in-nonhuman-primates-and-hd-transgenic-mice-for-evaluation-of-neurodegenerative-diseases-and-hdac-inhibitor-treatment(69cbe9a1-aa64-45d6-947f-9368eabb071c).html.
Повний текст джерелаFrench, Cynthia L. "Examining Change in Symptoms of Depression, Anxiety, and Stress in Adults after Treatment of Chronic Cough: A Dissertation." eScholarship@UMMS, 2014. https://escholarship.umassmed.edu/gsn_diss/31.
Повний текст джерелаFouche, Celeste. "Differential effects of TNfα on satellite cell differentiation". Thesis, Stellenbosch : Stellenbosch University, 2007. http://hdl.handle.net/10019.1/19596.
Повний текст джерелаENGLISH ABSTRACT: Tumour necrosis factor alpha (TNFα) is a pleiotropic cytokine and has a wide variety of dose dependent cellular effects ranging from cell growth and differentiation, to inducing apoptosis. It has long been implicated in muscle and non-muscle inflammatory disorders, such as muscle wasting in chronic disease states, and rheumatoid arthritis. However, a physiological role for TNFα in muscle regeneration has been proposed as elevated levels of the cytokine are present when muscle regeneration processes are initiated: TNFα is secreted by infiltrating inflammatory cells, and by injured muscle fibres. Adult skeletal muscle contains a population of resident stem cell-like cells called satellite cells, which become activated, proliferate and differentiate following muscle injury to bring about repair of damaged muscle. Much research on the effects of TNFα on satellite cell differentiation has been conducted in recent years. It is however difficult to get a complete characterisation of the cytokine’s action as all models used slightly differ. We aimed therefore at providing comprehensive assessment of the effects of increasing doses of chronically supplemented TNFα on differentiating C2C12 cells. Cells were allowed to differentiate with or without TNFα supplementation for 7 days. Differentiation was induced at day 0. The effect on differentiation was assessed at days 1, 3, 5, and 7 by western blot analysis, and supplementary immunohistochemical analysis at days 1, 4, and 7 of markers of differentiation - muscle regulatory factors: MyoD and myogenin, markers of the cell cycle p21, PCNA, and the integral signalling molecule, p38MAPK. TNFα supplementation at day 1 tended to positively regulate early markers of differentiation. With continued supplementation however, markers of differentiation decreased dose dependently in treated cultures as the initial effect appeared to be reversed: A trend towards a dose dependent decrease in MyoD, myogenin and p21 protein existed in treated cultures at days 3, 5, and 7. These findings were significant at day 5 (p21, p<0.05), and day 7 (myogenin, p<0.05). A significant dose dependent decrease in p38 phosphorylation was evident at day 3 (p<0.05), while phospho-p38 was dose dependently increased at day 7 (p<0.05). Taken together, these data show that TNFα supplementation for 24 hours following the induction of differentiation in vitro, tends to increase levels of early markers of differentiation, and with continued TNFα supplementation decrease markers of differentiation in a dose dependent fashion. This study provides a comprehensive characterisation of the dose and time dependent effects of TNFα on satellite cell differentiaton in vitro. The model system used in the current study, allows us to make conclusions on more chronic disease states.
AFRIKAANSE OPSOMMING: Tumor nekrose faktor alfa (TNFα) is ‘n pleiotropiese sitokien wat ‘n wye verskeidenheid, dosis afhanklike, sellulêre effekte te weeg bring. Hierdie sellulêre effekte sluit sel groei en differensiasie tot sel dood in. TNFα is by beide spier en niespier inflammatoriese stoornisse soos spier tering in kroniese siektetoestande, en rumatiese artritis betrek. ‘n Fisiologiese rol vir TNFα is egter voorgestel aangesien verhoogde vlakke van die sitokien tydens inisiasie van spier herstel meganismes teenwoordig is: TNFα word deur infiltrerende inflammatoriese selle, asook deur beseerde spier vesels afgeskei. Volwasse skeletspier bevat ‘n populasie stamselagtige selle, sogenoemde satelliet selle. Laasgenoemde word geaktiveer, prolifereer en differensieër volgende spierbesering, om sodoende herstel van beskadigde spier te weeg te bring. Baie navorsing op die effekte van TNFα op satelliet sel differensiasie is onlangs uitgevoer. Dit is egter aansienlik moeilik om volgens hierdie navorsing‘n algehele beeld van TNFα se aksies te vorm aangesien alle modelle wat gebruik word verskil. Ons doel was daarom om ‘n omvangryke assessering van toenemende konsentrasies kronies gesupplementeerde TNFα op differensieërende C2C12 selle op ‘n enkele model uit te voer. Selle was vir 7 dae met of sonder TNFα supplementasie gedifferentieër. Differensiasie was by Dag 0 geïnduseer. TNFα se effek op differensiasie is op dae 1, 3, 5, en 7 deur middel van western blot analise geassesseer. Aanvullende immunohistochemiese bepalings op dae 1, 4, en 7 is verder deurgevoer. Merkers vir differensiasie het die spier regulatoriese faktore MyoD en miogenien, sel siklus merkers p21 en PCNA, asook die integrale sein transduksie molekule p38MAPK ingesluit. TNFα supplementasie by dag 1 het geneig om vroeë merkers van differensiasie positief te reguleer. Met voortdurende supplementasie is die vroeë positiewe effekte (op ‘n dosis afhanklike manier) egter omgekeer: ‘n neiging teenoor (‘n dosis afhanklike) vermindering in MyoD, miogenien en p21 proteïen het in behandelde kulture op dae 3, 5, en 7 bestaan. Hierdie bevindinge was beduidend by dag 5 (p21, p<0.05), en dag 7 (miogenien, p<0.05). A beduidende dosis afhanklike afname in p38 fosforilasie was duidelik by dag 3 (p<0.05), terwyl fosfo-p38 by dag 7 verhoog het met verhoogde konsentrasie TNFα (p<0.05). Bogenoemde saamgevat, dui aan dat TNFα supplementasie 24h volgende die induksie van differensiasie in vitro, verhoogde vlakke van vroeë differnsiasie merkers te weeg bring. Met voortdurende TNFα supplementasie, word differensiasie merkers egter met toenemende dosis verminder. Hierdie studie voorsien ‘n omvattende karakterisering van die dosis- en tyd afhanklike effekte van TNFα op satelliet sel differesiasie in vitro. Die model sisteem in hierdie studie gebruik, maak afleidings oor meer kroniese siektetoestande moontlik.
Leishman, Alison Jane. "Harnessing the immunomodulatory capacity of dendritic cells differentiated from human induced pluripotent stem cells and the therapeutic potential of dendritic cell-derived exosomes for the treatment of lysosomal storage diseases." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:97f6791f-ff69-4645-9a3d-2ff23ce69529.
Повний текст джерелаLeishman, Alison Jane. "Harnessing the immonomodulatory capacity of dendritic cells differentiated from human induced pluripotent stem cells and the therapeutic potential of dendritic cell-derived exosomes for the treatment of lysosomal storage diseases." Thesis, University of Oxford, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711748.
Повний текст джерелаOdendaal, Louise. "The effect of dietary Red Palm Oil on the functional recovery and the PKB/Akt pathway in the ischaemic/reperfused isolated rat heart." Thesis, Stellenbosch : Stellenbosch University, 2007. http://hdl.handle.net/10019.1/21745.
Повний текст джерелаENGLISH ABSTRACT: Introduction Cardiovascular disease is one of the leading causes of death in the world. Formation of harmful reactive oxygen species (ROS) is associated with several pathological conditions, and contributes to ischaemia/reperfusion injury. Antioxidants can be added to the diet in an attempt to decrease the prevalence of cardiovascular disease by decreasing the harmful effects of ischaemia/reperfusion injury. Red Palm Oil (RPO) consists of saturated, monounsaturated and polyunsaturated fatty acids and is rich in antioxidants such as -carotene, tocopherols and tocotrienols. It has previously been shown that RPO-supplementation improved reperfusion mechanical function. In these studies it was found that RPO might exert its beneficial effects during reperfusion through increased PKB/Akt pathway activity, which may lead to inhibition of apoptosis and improved mechanical function. Aims The aims of this study were: 1) to determine whether RPO-supplementation protected against ischaemia/reperfusion injury in the isolated perfused rat heart, 2) to confirm RPO-supplementation’s effect on the PKB/Akt pathway activity and, 3) to elucidate the regulators in the PKB/Akt pathway that RPOsupplementation influenced. Methods Male Wistar rats were divided into 4 groups, 2 control groups and 2 experimental groups. The 2 control groups were fed a standard rat chow (SRC) for 4 weeks. The two experimental groups received SRC and RPOsupplementation for 4 weeks. Hearts were excised and transferred to a Langendorff perfusion apparatus and perfused with Krebs-Henseleit buffer. Mechanical functional recovery was measured after 25 min of total global noflow ischaemia. The following parameters were also measured during various time points in the protocol: left ventricular develop pressure, heart rate, coronary flow, rate pressure product. Hearts were also freeze-clamped for biochemical analysis at 10 min during reperfusion. The biochemical analysis was aimed at determining PKB/Akt involvement. In a second protocol, hearts were subjected to the same perfusion protocol, but wortmannin was also added to the perfusion fluid, in order to inhibit PI3- kinase. Results Hearts from the RPO-supplemented rats showed an improved RPP recovery (92.26 ± 5.89 % vs 63.86 ± 7.74 %) after 10 min of reperfusion. This finding corroborated the findings of previous studies. Hearts of the RPOsupplemented rats perfused with wortmannin, showed increased RPP recoveries at several time points. Biochemical results showed that wortmannin did indeed inhibit PI3-K phosphorylation in the RPO-supplemented group, as was expected. The RPO-supplemented group that was perfused with wortmannin had an increased PKB/Akt (Ser473) phosphoyrylation, when compared to the wortmannin control group. It was also found that the combination of RPO and wortmannin had prosurvival effects. Discussion This study showed that RPO-supplementation offered protection against ischaemia/reperfusion injury in the Langendorff-perfusion apparatus at 10 min into reperfusion. Thereafter the significance of the protection was lost. This protection has been confirmed in several previous studies and several mechanisms have been proposed for this protection. Since no conclusive evidence exists on the precise mechanism of protection, our investigation focused on the regulators of the pro-survival PKB/Akt pathway. An improved functional recovery was also seen in the RPO-supplemented group that was perfused with wortmannin. This was an unexpected finding, because Wortmannin is a known PI3-kinase inhibitor (as was confirmed by our biochemical data). PI3-kinase phosphorylation leads to PKB/Akt phosphorylation and therefore, activation of a pro-survival pathway. It would be expected that wortmannin would inhibit PKB/Akt and thus decrease the survival of the cells. The RPO-supplementation thus reversed wortmannin’s detrimental effect to such an extent that the functional recovery was far better than RPO-supplementation alone. In the RPO + wortmannin group, PKB/Akt (Ser473) phosphorylation was increased, contrary to previous findings. This is an indication that RPO may have the ability to override wortmannin’s inhibitory effect on PI3-kinase, or that PKB/Akt (Ser473) may be phosphorylated independently of PI3-kinase.
AFRIKAANSE OPSOMMING: Inleiding Kardiovaskulêre siektes is een van die hoof oorsake van sterftes in die wêreld. Die vorming van skadelike reaktiewe suurstof spesies word geassosieer met verskeie patologiese kondisies en dra ook by tot isgemie/reperfusie skade. ‘n Moontlike manier om die voorkoms van isgemie/herperfusie skade asook kardiovaskulêre siektes te voorkom, is om antioksidante by die dieet te voeg. Rooi Palm Olie (RPO) bevat versadigde, mono-onversadigde en polionversadigde vetsure. RPO bevat ook ‘n oorvloed van antioksidante soos β- karoteen en tokoferole en tokotriënole. Dit is bewys in vorige studies dat RPO-aanvulling verbeter funksionele herstel. Hierdie voordelige effekte mag dalk wees agv verhoogde PKB/Akt pad aktiwiteit. Die PKB/Akt pad word geassosieer met die inhibisie van apoptose en verhoogde meganiese funksie. Doelwitte Die doelwitte van hierdie studie was om te bepaal of 1) RPO-aanvulling beskermende effekte teen isgemie/herperfusie skade in die geisoleerde rotharte het, 2) Bevestig of RPO-aanvulling wel die PKB/Akt pad beïnvloed 3). om die effekte wat RPO-aanvulling het op die reguleerders van die PKB/Akt pad te onthul. Metodes Manlike Wistar rotte is in 4 groepe verdeel. 2 Groepe kontrole rotte is ‘n standaard rotkosmengsel gevoer vir 4 weke. Die 2 eksperimentele groepe het ook ‘n standaard rotkosmengsel gekry plus ‘n RPO-aanvulling vir 4 weke. Harte is uitgesny en op ‘n Langendorff perfusie sisteem gemonteer en met Krebs-Henseleit buffer geperfuseer. Meganiese funksie herstel is gemeet na 25 min totale globale geen-vloei isgemie. Linker ventrikulêre ontwikkelde druk, harttempo, koronêre vloei en tempo druk produk is gemeet by verskillende tydpunte. Sommige harte is na 10 min herperfusie vir biochemiese analiese gevriesklamp. Die biochemiese analisiese was beoog om die PKB/Akt pad betrokkenheid te bepaal. ‘n Tweede stel harte is aan dieselfde perfusie protokol blootgestel, maar wortmannin (PI3-kinase inhibitor) is ook bygevoeg by die perfusie vloeistof. Resultate Die groep wat met RPO aangevul is, het na 10 min herperfusie, ‘n verbeterde tempo druk produk herstel getoon (92.26 ± 5.89 % vs 63.86 ± 7.74. Hierdie bevinding is ook met ander studies bevestig. ‘n Interessante bevinding was dat die groep wat met RPO aangevul is en met wortmannin geperfuseer is, ‘n verbeterde meganiese funksionele herstel getoon het. Biochemiese resultate het getoon dat wortmannin wel PI3-K fosforilering geinhibeer het. Die harte van die rotte in die groep wat aangevul is met RPO en daarna met wortmannin geperfuseer is, het ‘n toename in PKB/Akt (Ser473) fosforilering getoon, relatief tot die wortmannin geperfuseerde harte van die rotte in die kontrole groep. Hierdie groep (RPO-aanvulling en wortmannin perfusie) het beskermende effekte getoon. Bespreking Hierdie studie het getoon dat RPO-aanvulling beskerming gebied het teen isgemie/herperfusie skade in die Langendorff geperfuseerde rothart na 10 min herperfusie. Daarna is die beduidenheid van die beskerming verloor. Hierdie bevindings ondersteun die resultate van vorige studies. Verskeie moontlike meganismes is voorgestel vir die beskerming, maar die presiese meganisme is nog nie duidelik nie. In hierdie studie is daar gekyk na die reguleerders van die PKB/Akt pad. Geen vorige studies het al gefokus op RPO-aanvulling en sy effek op die reguleerders van die PKB/Akt pad nie. ‘n Onverwagte bevinding is dat harte van die rotte in die RPO + wortmannin groep ‘n verbeterde funksionele herstel getoon het. Wortmannin is ‘n PI3- kinase inhibitor. PI3-K fosforilering lei tot PKB/Akt fosforilering, wat tot sel beskerming lei. Dus, aangesien wortmannin PI3-K inhibeer, sou dit verwag word dat wortmannin sel beskerming sal verminder. Die RPO het egter die wortmannin se nadelige effekte tot so ‘n mate oorskrei dat die funksionele herstel baie beter was as die RPO-aanvulling alleen. Die verhoogde PKB/Akt (Ser473) fosforilering, wat gesien is in die RPO + wortmannin groep kan toegeskryf word aan RPO se vermoë om wortmannin se nadelige effekte te oorskrei. ‘n Moontlike verduideliking vir hierdie bevinding mag wees dat rooi palm olie PKB/Akt (Ser473) op ‘n PI3-K onafhanklike manier fosforileer.
Awad, Hamza H. "Use of Multinational Registries to Assess and Compare Outcomes of Patients with an Acute Coronary Syndrome: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/546.
Повний текст джерелаDjalali, Mahmoud. "Contribution à l'étude du métabolisme digestif des corrinoïdes chez l'homme dans les conditions physiologiques et pathologiques." Nancy 1, 1988. http://www.theses.fr/1988NAN10030.
Повний текст джерелаHarmon, Amanda L. "Preventing Mother-to-Child Transmission of Human Immunodeficiency Virus-1 (HIV-1): Effects of Intrapartum and Neonatal Single-Dose Nevirapine Prophylaxis and Subsequent HIV-1 Drug Resistance at Antiretroviral Treatment Initiation." Scholarship @ Claremont, 2011. http://scholarship.claremont.edu/cmc_theses/305.
Повний текст джерелаHurlimann, Thierry. "The duty to treat very defective neonates as "persons" : from the legal and moral personhood of very defective neonates to their best interests in medical treatment." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=80929.
Повний текст джерелаNguyen, Hoa L. "Age and Sex Differences in Duration of Pre-Hospital Delay, Hospital Treatment Practices, and Short-Term Outcomes in Patients Hospitalized with an Acute Coronary Syndrome/Acute Myocardial Infarction: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/471.
Повний текст джерелаNunes, Mérces da Silva. "A função social da empresa: a indústria farmacêutica, os medicamentos de alto custo e doenças raras." Pontifícia Universidade Católica de São Paulo, 2014. https://tede2.pucsp.br/handle/handle/6412.
Повний текст джерелаIn a Democratic Constitutional State - which elected the human being as the ultimate end of everything and the greatest value of all forms of coexistence, human dignity is the mother principle that inspires, guides and radiates all the legal and social order, is the value that drives and directs the society and its members to commit actions aimed at effecting and promoting the welfare of the human person. Therefore, at the time the Constitution states the dignity of the human being as the founding principle of the Federative Republic of Brazil, it is actually explaining that Brazilian society as a whole has the duty to protect, support and respect the citizen in what the they have as the most sacred and essential to their existence, which is the equality of all human beings in their personal dignity. Recognizing the equality of the human being, in his personal dignity implies that this equality must be respected and observed in all its aspects, especially the political, economic, legal and social conditions regardless of the nature and differences of gender, race, belief, color, language, wealth, birth, national or social origin, as stated in Section II of the Universal Declaration of Human Rights, from 1948. Due to this, the human being must be protected by society and all its members, not only in the sense that this protection has to be a guarantee for them to remain alive, but mainly not to be attacked in their dignity of human people, because their right to live with dignity and the right to a dignified existence is ensured. Regarding the delimitation and scope of the present study, it is crucial to emphasize that when providing the Unified Health System SUS, free of charge, with expensive drugs for rare diseases and treatment of needy people, the pharmaceutical industry gives to the Property a social function - that in a Democratic Constitutional State goes far beyond the payment of taxes and the availability of vacancies, since the hiring of employees and the payment of taxes are prerequisites to the exercise of the economic activity itself without which even the existence of the company would not be considered. In fact, the business activity directed to the exploration of drugs, as in the pharmaceutical industry, should be developed seeking the social interest, to the recovery and improvement of human health . Thus, for the property to meet its social function, as determined by the article 170, III of the Federal Constitution, the pharmaceutical industry has the duty to participate and engage with the state, sharing the responsibility for ensuring the right to health - fundamental social right, and contributing to the achievement of the basic objectives stated in the article 3 of the Federal Constitution
o valor maior de todas as formas de convivência, a dignidade da pessoa humana é o princípio matriz que inspira, norteia e irradia todo o ordenamento jurídico e social, é o valor que move e direciona a sociedade e seus integrantes à prática de ações destinadas à efetivação e promoção do bem estar da pessoa humana. Bem por isso, no momento em que a Constituição Federal explicita a dignidade da pessoa humana como princípio fundante da República Federativa do Brasil, na verdade, está afirmando que a sociedade brasileira, como um todo, tem o dever de proteger, amparar e respeitar o cidadão naquilo que o Homem tem de mais sagrado e essencial à sua existência, que é a igualdade de todo ser humano em sua dignidade de pessoa. Reconhecer a igualdade do ser humano, em sua dignidade de pessoa, implica dizer que essa igualdade deve ser respeitada e observada em todos os seus aspectos, sobretudo, os de natureza política, econômica, jurídica e social independentemente das condições e diferenças de sexo, raça, credo, cor, língua, riqueza, nascimento, origem nacional ou social, tal como explicitado no Artigo II, da Declaração Universal dos Direitos Humanos, de 1948. Por essa razão, o ser humano deve ser protegido pela sociedade e por todos os seus integrantes, não apenas no sentido de essa proteção ser uma garantia de que o ser humano permaneça vivo, mas, principalmente, para que não seja atingido em sua dignidade de pessoa humana, porquanto lhe é assegurado o direito de viver de forma digna, o direito a uma existência digna. No que concerne à delimitação e ao alcance do presente estudo, imperioso destacar que ao destinar, gratuitamente, em favor do Sistema Único de Saúde - SUS- medicamentos de alto custo e doenças raras para tratamento de pessoas carentes, a indústria farmacêutica confere à propriedade uma função social que, num Estado Democrático de Direito, vai muito além do pagamento de tributos e da disposição em oferecer postos de trabalho, uma vez que a contratação de funcionários e/ou colaboradores e o pagamento de tributos são condições indispensáveis ao exercício da própria atividade econômica sem as quais sequer a existência da empresa haveria de ser considerada. Na verdade, a atividade empresarial voltada para a exploração de medicamentos, como é o caso da indústria farmacêutica, deve ser desenvolvida no interesse social, visando a recuperação e a melhoria da saúde humana. Assim, para que a propriedade atenda a sua função social, como determina o artigo 170, III da Constituição Federal, a indústria farmacêutica tem o dever de participar e de agir em conjunto com o Estado, compartilhando a responsabilidade pela efetivação do direito à saúde - direito fundamental social e contribuindo para a consecução dos objetivos fundamentais explicitados no art. 3º da Constituição Federal
Borg, Karin. "Sickness Absence with Musculoskeletal Diagnoses : An Eleven-Year Follow-Up of Young Persons." Doctoral thesis, Linköping : Univ, 2003. http://www.ep.liu.se/diss/med/07/86/index.html.
Повний текст джерела"Plant-Made Biologics: Human Butyrylcholinesterase Mutants for the Treatment of Cocaine Addiction-Related Diseases." Doctoral diss., 2015. http://hdl.handle.net/2286/R.I.29972.
Повний текст джерелаDissertation/Thesis
Doctoral Dissertation Molecular and Cellular Biology 2015
Mota, Catarina. "Towards the therapeutic use of regulatory T cells for the treatment of human autoimmune diseases." Doctoral thesis, 2015. http://hdl.handle.net/10451/23654.
Повний текст джерелаRegulatory T Cells (Treg), constitutively expressing the transcription factor Foxp3/FOXP3, play a crucial role in maintaining self-tolerance, assuming particular relevance in the context of autoimmunity. Adoptive transfer of Treg has been shown to be highly efficient in the prevention and treatment of autoimmunity in rodents and clinical trials exploring Treg-based adoptive therapy in Type I Diabetes (T1D) are currently ongoing. These therapies require large numbers of Treg, stressing the importance of a better knowledge of the molecular and cellular requirements for human thymic and peripheral Treg development. Moreover, widespread application of Treg-based therapy dealt with several limitations regarding the stability and function of in vitro expanded populations for in vivo use. The creation of efficient protocols enabling stable FOXP3 acquisition by human non-regulatory cells could overcome the limited availability of thymus-derived (t)Treg and would facilitate the generation of antigen-specific Treg, an ideal candidate in autoimmune diseases (AID) setting. The overall objective of this work was to provide new insights into the principles dictating human thymic and peripheral Treg development and homeostasis, thus facilitating the progress of Treg-based immunotherapy. First, we proposed to investigate the capacity of human non-regulatory memory CD4+ T cells to differentiate in vitro into bona-fide FOXP3-expressing cells and to assess the role of the Notch signaling pathway in modulating this conversion. We showed that stable and functional bona-fide Treg can be generated from memory CD4+ T cells and that Delta like (DL)1-mediated Notch signaling activation enhanced this conversion. We additionally showed that DL1 increased Treg proliferation, reinforcing the possible role of Notch in the homeostasis of the human peripheral Treg compartment. Importantly, we also demonstrated that DL1 enhanced the expression of function-related molecules within these cells, contributing to the maintenance of their regulatory phenotype. In order to better clarify the principles governing Treg development in the human thymus, we investigated the role of common gamma-chain (c) cytokines in human tTreg differentiation. We identified interleukin (IL)-2 and IL-15 as key molecular determinants in this process and excluded a major function for IL-4, IL-7 and IL-21. Moreover, we revealed that IL-2 and IL-15 are expressed in a non-overlapping pattern in the human thymus, with the former produced mainly by mature αβ and γδ thymocytes and the latter by monocyte/macrophages and B lymphocytes. Overall, this work has provided a better understading of the core mechanisms governing human Treg differentiation and homeostasis that should facilitate the further establishment of Treg-based therapies.
As Células T Reguladoras (T Regs), expressando constitutivamente o factor de transcrição Foxp3/ FOXP3, desempenham um papel crucial na manutenção da auto-tolerância, assumindo particular relevância no contexto de auto-imunidade. A transferência adoptiva de T Regs demonstrou ser altamente eficaz na prevenção e no tratamento de autoimunidade em roedores e ensaios clínicos explorando terapêuticas baseadas em T Regs na Diabetes Tipo I estão actualmente em curso. Estas terapias exigem um grande número de células, pelo que é essencial um melhor conhecimento dos requisitos moleculares e celulares para o desenvolvimento no timo humano e na periferia de T Regs. Além disso, a aplicação generalizada desta terapêutica tem ainda várias limitações no que respeita à estabilidade e função das populações expandidas in vitro para utilização in vivo. A criação de protocolos eficientes que permitam a aquisição estável de FOXP3 por células não-reguladoras poderá ultrapassar a disponibilidade limitada de T Regs de origem tímica e facilitar a geração de T Regs com especificidade antigénica, potencialmente ideais no contexto de doenças auto-imunes. O objetivo global deste trabalho foi investigar os princípios que ditam o desenvolvimento tímico e periférico e a homeostasia das T Regs humanas, facilitando assim o progresso da imunoterapia utilizando T Regs. Em primeiro lugar, propusemo-nos investigar a capacidade das células T CD4+ de memória não-reguladoras para se diferenciarem in vitro em células que expressam FOXP3, avaliando o papel da via de sinalização Notch na modulação desta conversão. Revelámos que T Regs estáveis e funcionais podem ser geradas a partir de células T CD4+ de memória isoladas do sangue periférico de indivíduos saudáveis e que a activação de Notch mediada por DL1 aumenta esta conversão. Adicionalmente, demonstrámos que DL1 aumenta a proliferação de T Regs circulantes, reforçando o possível papel de Notch na homeostasia do compartimento periférico de T Regs. Mostrámos também que DL1 aumenta a expressão de moléculas relacionadas com a função de T Regs circulantes, contribuindo para a manutenção do fenótipo das T Regs. Com a finalidade de clarificar os princípios que regem o desenvolvimento de T Regs no timo humano, investigámos o papel das citocinas que utilizam um receptor com cadeia gama comum na diferenciação de T Regs humanas. Identificámos as interleucinas IL-2 e IL-15 como determinantes moleculares chave neste processo, tendo sido excluída uma função de relevo para IL-4, IL-7 e IL-21. Mais ainda, revelámos que IL-2 e IL-15 são expressas num padrão não sobreposto no timo humano, sendo a primeira produzida principalmente por timócitos maduros αβ e γδ e a última por monócitos/ macrófagos e linfócitos B. Em conclusão, este trabalho proporcionou um melhor conhecimento dos mecanismos fundamentais que regem o desenvolvimento, a homeostasia e manipulação in vitro das T Regs em humanos, contribuindo para o estabelecimento das terapêuticas baseadas em T Regs.
Park, Joon-Hyuk. "Wearable Torso Exoskeletons for Human Load Carriage and Correction of Spinal Deformities." Thesis, 2016. https://doi.org/10.7916/D81V5F5G.
Повний текст джерела"Apoptotic mechanism of anti-tumor treatment in human laryngeal squamous cell cancer infected with human papillomavirus type 16 (HPV16)." Thesis, 2006. http://library.cuhk.edu.hk/record=b6074228.
Повний текст джерелаOur results suggest that HPV16 E6 and E7 oncoproteins do not prevent 5Fu medicated apoptosis and G1/S cell arrest in laryngeal cancers. The anti-cancer effect of 5Fu is probably decided by the level of p21 WAF1/CIP1 while the sensitivity of laryngeal cancer cells responded to 5Fu treatment is associated with the increase of Bak or/and the decrease in Bcl-2, not with the HPV16 viral proteins and p53 status. 5Fu also presented some effects on the E6 and E7 oncoproteins of HPV16 in laryngeal cancer. However, the anti-viral effect of 5Fu still needs further investigation.
Our study indicated that (1) the evasion of apoptosis mediated by HPV16 E6 and E7 plays a critical role in laryngeal carcinogenesis; (2) HPV16 E6 or E7 plays an important role in regulating the expression of Bak, Bax and Bcl-2; (3) The degradation of Bak by HPV16 E6 is not caused by interacting with the promoter of Bak; (4) The induction of Bcl-2 is mediated through HPV16 E7; (5) HPV16 transfection does not interfere with the apoptosis and cell cycle arrest mediated by 5Fu in human laryngeal squamous cancer cells.
There is a growing body of evidence that human papillomavirus type 16 (HPV16) is involved in the development of human laryngeal cancer, especially in Chinese population. The two oncoproteins, HPV16 E6 and E7 that target host cell tumor suppressor proteins p53 and Rb respectively, may generate antiapoptotic effects and induce cell immortalization. However, the effect of both oncoproteins on apoptosis in laryngeal cancers is not completely clear. In this study, we demonstrated the possible mechanism of high risk HPV16 in laryngeal carcinogenesis and evaluated the effect of 5Fu on HPV16-positive laryngeal cancer cells.
We employed two human laryngeal cancer cell lines---UMSCC12 (with truncated p53) and UMSCC11A (with mutant but functional p53) in this study. These two cell lines were stably transfected with HPV16 E6, E7 or empty vector, pcDNA3.1, which provided a good foundation for further study on the carcinogenic mechanism of HPV16 E6 or E7 in human laryngeal cancers. Through Annexin V staining and protein stability assay, we found that the transfection of HPV16 E6 and E7 induced fewer spontaneous apoptosis in both UMSCC11A and UMSCC12 cells accompanied with enhanced protein stability of Bcl-2 and increased protein degradation of Bak. Similar results were obtained when E6- and E7-transfected cells exposed to apoptosis stimuli---TNF-alpha/CHX. These results indicate that stable transfection of E6 and E7 in human laryngeal cancer cells on one hand shortened the half-life of Bak protein, and on the other hand, enhanced the steady-state levels of Bcl-2 protein. In order to gain insight into the role of Bak and Bcl-2 in regulating apoptosis in HPV-associated laryngeal cancer cells, we performed transient transfection of Bcl-2 into E6- and E7-transfected cells. It is found that HPV16 E7 statistically enhanced the expression of Bcl-2 in laryngeal cancer, indicating that the induction of Bcl-2 require the transfection of HPV16 E7. Furthermore, Luciferase assay was performed to investigate whether the viral proteins E6 and E7 altered the stability of Bak through interaction with the promoter of Bak. Negative results were obtained, suggesting that E6 or E7 do not alter the transcription activity of Bak, indicating the degradation of Bak by E6 or E7 may be mediated through other mechanisms.
Liu Han-ching.
"August 2006."
Advisers: C. A. van Hasselt; George G. Chen.
Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1569.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2006.
Includes bibliographical references (p. 245-274).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstracts in English and Chinese.
School code: 1307.
Ratzeburg, Brenda. "A medical perspective of chiropractic, based on a survey conducted amongst medical professionals in the western region of Johannesburg and how they view chiropractic compared to physiotherapy in the treatment of neuromusculoskeletal conditions." Thesis, 2008. http://hdl.handle.net/10210/974.
Повний текст джерелаDr. M. Moodley Dr. J. Mitchell
Aina-Badejo, Danielle. "Elucidating the Unknown Role of Cyclin Dependent Kinase 5 in Cardiac Pathophysiological Conditions." Thesis, 2021. https://doi.org/10.7916/d8-j79v-jk33.
Повний текст джерелаMignon, Charles, N. E. Uzunbajakava, B. Raafs, Natalia V. Botchkareva, and Desmond J. Tobin. "Photobiomodulation of human dermal fibroblasts in vitro: decisive role of cell culture conditions and treatment protocols on experimental outcome." 2017. http://hdl.handle.net/10454/15613.
Повний текст джерелаPhotobiomodulation-based (LLLT) therapies show tantalizing promise for treatment of skin diseases. Confidence in this approach is blighted however by lamentable inconsistency in published experimental designs, and so complicates interpretation. Here we interrogate the appropriateness of a range of previously-reported treatment parameters, including light wavelength, irradiance and radiant exposure, as well as cell culture conditions (e.g., serum concentration, cell confluency, medium refreshment, direct/indirect treatment, oxygen concentration, etc.), in primary cultures of normal human dermal fibroblasts exposed to visible and near infra-red (NIR) light. Apart from irradiance, all study parameters impacted significantly on fibroblast metabolic activity. Moreover, when cells were grown at atmospheric O2 levels (i.e. 20%) short wavelength light inhibited cell metabolism, while negligible effects were seen with long visible and NIR wavelength. By contrast, NIR stimulated cells when exposed to dermal tissue oxygen levels (approx. 2%). The impact of culture conditions was further seen when inhibitory effects of short wavelength light were reduced with increasing serum concentration and cell confluency. We conclude that a significant source of problematic interpretations in photobiomodulation reports derives from poor optimization of study design. Further development of this field using in vitro/ex vivo models should embrace significant standardization of study design, ideally within a design-of-experiment setting.
Pho, Anthony T. "Human Papillomavirus Vaccination, Online Health Information Seeking, and Health Literacy among Transgender and Gender Nonbinary People." Thesis, 2020. https://doi.org/10.7916/d8-e5am-9v36.
Повний текст джерелаYang, Yi Fang, and 楊宜芳. "Systemic exploration of redox proteome in human A431 cells under different Photofrin-mediated photodynamic treatment conditions by quantitative proteomics approach." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/52121421771566331555.
Повний текст джерела長庚大學
生物醫學研究所
100
Photodynamic therapy (PDT) is a minimally invasive therapeutic clinical treatment for some cancer and non-tumor disorders. This process requires a photosensitizer which can absorb light and produce reactive oxygen species to damage biomolecules in target cells. Photofrin is the most widely used photosensitizer. Our previous studies showed that different distribution of Photofrin in cells results in distinct cell death after PDT and Photofrin can selectively interact with some proteins. Using human epidermoid carcinoma A431 cells as model, we herein applied SILAC-based quantitative proteome approach to systemically analyze the relationship between the subcellular location of Photofrin and the Photofrin-PDT-mediated protein oxidization (on Met residues). In addition, we try to identify Photofrin-interacting proteins in A431 cells. Our data showed that when Photofrin mainly localized to plasma membrane (condition I), intracellular organelles (condition II) and whole cell (condition III), there were 116, 84 and 199 proteins quantified greater than mean+2SD Met-oxidized proteins, respectively. Further analysis revealed that (i) the percentage of highly oxidized membrane proteins is significantly higher in condition I (13.33%) than in condition II (3.03%) and III (0.76%); (ii) the percentage of highly oxidized Golgi proteins is drastically higher in condition II (18.18%) than in condition I (3.33%) and III (9.09%); and (iii) the percentage of highly oxidized mitochondrial proteins is largely higher in condition III (30.3%) than in condition I (4.44%) and II (15.66%). The results indicate that PDT with Photofrin targeted to distinct subcellular localizations can affect the redox proteome in a site-specific manner in living cells. Regarding the Photofrin-interacting proteins, we have identified 66 such candidates via in vitro pull down assay (using Photofrin-coupled beads) combined with MS analysis. Among those highly oxidized proteins detected post Photofrin-PDT, we select protein A and B for further study. Mapping the observed oxidized Met residues into the 3D structure of the two proteins showed that these oxidized Met residues mainly distribute on the surface of the protein. We also provided evidence to show that Photofrin-PDT can directly inhibit the activity of protein A in vitro. Collectively, our data demonstrate for the first time that the relationship between protein Met oxidation and PDT with site-specific location of Photofrin in living cells. Our results also unravel many potential Photofrin-interacting proteins that deserve further investigation.
Downs, Matthew. "Focused Ultrasound Mediated Blood-Brain Barrier Opening in Non-Human Primates: Safety, Efficacy and Drug Delivery." Thesis, 2015. https://doi.org/10.7916/D82B8XC7.
Повний текст джерелаGupta, Manav. "Differentiation and characterization of cell types associated with retinal degenerative diseases using human induced pluripotent stem cells." Thesis, 2014. http://hdl.handle.net/1805/4839.
Повний текст джерелаHuman induced pluripotent stem (iPS) cells have the unique ability to differentiate into 200 or so somatic cell types that make up the adult human being. The use of human iPS cells to study development and disease is a highly exciting and interdependent field that holds great promise in understanding and elucidating mechanisms behind cellular differentiation with future applications in drug screening and cell replacement studies for complex and currently incurable cellular degenerative disorders. The recent advent of iPS cell technology allows for the generation of patient-specific cell lines that enable us to model the progression of a disease phenotype in a human in vitro model. Differentiation of iPS cells toward the affected cell type provides an unlimited source of diseased cells for examination, and to further study the developmental progression of the disease in vitro, also called the “disease-in-a-dish” model. In this study, efforts were undertaken to recapitulate the differentiation of distinct retinal cell affected in two highly prevalent retinal diseases, Usher syndrome and glaucoma. Using a line of Type III Usher Syndrome patient derived iPS cells efforts were undertaken to develop such an approach as an effective in vitro model for studies of Usher Syndrome, the most commonly inherited disorder affecting both vision and hearing. Using existing lines of iPS cells, studies were also aimed at differentiation and characterization of the more complex retinal cell types, retinal ganglion cells (RGCs) and astrocytes, the cell types affected in glaucoma, a severe neurodegenerative disease of the retina leading to eventual irreversible blindness. Using a previously described protocol, the iPS cells were directed to differentiate toward a retinal fate through a step-wise process that proceeds through all of the major stages of neuroretinal development. The differentiation process was monitored for a period of 70 days for the differentiation of retinal cell types and 150 days for astrocyte development. The different stages of differentiation and the individually derived somatic cell types were characterized by the expression of developmentally associated transcription factors specific to each cell type. Further approaches were undertaken to characterize the morphological differences between RGCs and other neuroretinal cell types derived in the process. The results of this study successfully demonstrated that Usher syndrome patient derived iPS cells differentiated to the affected photoreceptors of Usher syndrome along with other mature retinal cell types, chronologically analogous to the development of the cell types in a mature human retina. This study also established a robust method for the in vitro derivation of RGCs and astrocytes from human iPS cells and provided novel methodologies and evidence to characterize these individual somatic cell types. Overall, this study provides a unique insight into the application of human pluripotent stem cell biology by establishing a novel platform for future studies of in vitro disease modeling of the retinal degenerative diseases: Usher syndrome and glaucoma. In downstream applications of this study, the disease relevant cell types derived from human iPS cells can be used as tools to further study disease progression, drug screening and cell replacement strategies.
Sun, Shu. "The Evaluation of Chinese therapeutic food for the treatment of dyslipidemia." Thesis, 2010. https://vuir.vu.edu.au/7689/.
Повний текст джерелаCraven, Kelly E. "Angiogenic gene signature in human pancreatic cancer correlates with TGF-beta and inflammatory transcriptomes." Diss., 2016. http://hdl.handle.net/1805/10984.
Повний текст джерелаPancreatic ductal adenocarcinoma (PDAC), which comprises 85% of pancreatic cancers, is the 4th leading cause of cancer death in the United States with a 5-year survival rate of 8%. While human PDACs (hPDACs) are hypovascular, they also overexpress a number of angiogenic growth factors and receptors. Additionally, the use of anti-angiogenic agents in murine models of PDAC leads to reduced tumor volume, tumor spread, and microvessel density (MVD), and improved survival. Nonetheless, clinical trials using anti-angiogenic therapy have been overwhelmingly unsuccessful in hPDAC. On the other hand, pancreatic neuroendocrine tumors (PNETs) account for only 2% of pancreatic tumors, yet they are very vascular and classically angiogenic, respond to anti-angiogenic therapy, and confer a better prognosis than PDAC even in the metastatic setting. In an effort to compare and contrast the angiogenic transcriptomes of these two tumor types, we analyzed RNA-Sequencing (RNA-Seq) data from The Cancer Genome Atlas (TCGA) and found that a pro-angiogenic gene signature is present in 35% of PDACs and that it is mostly distinct from the angiogenic signature present in PNETs. The pro-angiogenic PDAC subgroup also exhibits a transcriptome that reflects active TGF-β signaling, less frequent SMAD4 inactivation than PDACs without the signature, and up-regulation of several pro-inflammatory genes, including members of JAK signaling pathways. Consequently, targeting the TGF-β receptor type-1 kinase with SB505124 and JAK1/2 with ruxolitinib blocks proliferative crosstalk between human pancreatic cancer cells (PCCs) and human endothelial cells (ECs). Additionally, treatment of the KRC (oncogenic Kras, homozygous deletion of Rb1) and KPC (oncogenic Kras, mutated Trp53) genetically engineered PDAC mouse models with ruxolitinib suppresses murine PDAC (mPDAC) progression only in the KRC model, which shows superior enrichment and differential expression of the human pro-angiogenic gene signature as compared to KPC tumors. These findings suggest that targeting both TGF-β and JAK signaling in the 35% of PDAC patients whose cancers exhibit an pro-angiogenic gene signature should be explored in a clinical trial.
"Innovative options for the treatment of non-melanoma skin cancer : Investigations on the activity of antimicrobial peptides against topical diseases and study of peptide penetration into human skin ex vivo." Berlin : Freie Universität Berlin, 2014. http://d-nb.info/1063934591/34.
Повний текст джерелаBaldwin, P. Clive. "Narrative, ethics and severe mental illness." 2005. http://hdl.handle.net/10454/3268.
Повний текст джерелаStarting from the premise that people are essentially narrative beings, I argue that the onset of severe mental illness compromises the narrative enterprise of being able to construct one's Self and one's relationships inmeaningful and coherent ways. This is due to both the curtailment of opportunities for narrative engagement and the dispossession of those whose narratives do not conform to the current conceptualization of narrative and narrativity. In these circumstances, supporting the narrative enterprise is an ethical endeavour that requires that we examine not only which narratives we construct, but also how we construct them. This requires a re-thinking of what might constitute narrative and how we might facilitate or enhance the narrativity of people with severe mental illness. Following this, I suggest four means to support the narrativity of people with severe mental illness: through maintaining narrative continuity, maintaining narrative agency, countering master narratives and attention to small stories.
Marukutira, Tafireyi. "Factors influencing adherence to antiretroviral therapy in adolescents at Botswana-Baylor Children's Clinical Centre of Excellence : a qualitative study." Diss., 2012. http://hdl.handle.net/10500/6036.
Повний текст джерелаHealth Studies
M.A. (Public Health)
"Dietary intake, diet-related knowledge and metabolic control of children with type 1 diabetes mellitus, aged 6-10 years attending the paediatric diabetic clinics at Grey's Hospital, Pietermaritzburg and Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu-Natal." Thesis, 2007. http://hdl.handle.net/10413/3445.
Повний текст джерелаThesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2007.
Ribeiro, Isabel Patrícia Magalhães. "Implicações da COVID-19 no estado de saúde oral." Master's thesis, 2021. http://hdl.handle.net/10284/10572.
Повний текст джерелаIn the context of the SARS-CoV-2 pandemic, in 2020 measures were implemented for a controlled management of the spread of contagion, minimizing the risk of virus transmission as much as possible. The General Directorate of Health legislated norms and recommendations that led to the interruption of activity in dental offices and clinics in March of that year, and the resumption of that activity two months later. In which, in addition to universal precautions, the adoption of measures to ensure protection from contagion through contaminated droplets and aerosols was recommended. This disease is easy and fast to spread, as its main transmission route is through direct contact with salivary droplets carrying the virus. The results of this review revealed that the main oral alterations associated with COVID-19 are taste disturbances, xerostomia and ulcerations. Several oral manifestations were observed, however, there is insufficient evidence to prove a causal relationship with COVID-19 infection. The implications of COVID-19 in the oral health status are based on the deprivation of access to oral health care in the mitigation phase of COVID-19, the underdiagnosis of oral manifestations in the initial phase of the pandemic, and currently, a scientific association is unknown. consistent between COVID-19 and the oral manifestations of the disease.