Submitted by Bruno Giorno Eberhardt (bruno.giorno@agricultura.gov.br) on 2018-04-21T01:40:57Z No. of bitstreams: 1 TESE DOUTORADO - BRUNO GIORNO EBERHARDT.pdf: 3876871 bytes, checksum: 3c2c7eac21349ce401f54a1cb03fae4f (MD5) / Approved for entry into archive by Maria Lucia Martins Frederico null (mlucia@fca.unesp.br) on 2018-04-23T12:55:33Z (GMT) No. of bitstreams: 1 eberhardt_bg_dr_botfca.pdf: 2911225 bytes, checksum: 9f9ad5ea743405838741796482e9ab66 (MD5) / Made available in DSpace on 2018-04-23T12:55:33Z (GMT). No. of bitstreams: 1 eberhardt_bg_dr_botfca.pdf: 2911225 bytes, checksum: 9f9ad5ea743405838741796482e9ab66 (MD5) Previous issue date: 2018-03-01 / EBERHARDT, B.G. Avaliação de micro-organismos zoonóticos em filés de tilápia do Nilo (Oreochromis niloticus). Botucatu, 2018. 71p. Tese (Doutorado) – Faculdade de Medicina Veterinária e Zootecnia, Campus de Botucatu, Universidade Estadual Paulista. RESUMO Cinquenta filés de tilápia do Nilo (Oreochromis niloticus) obtidos em mercado de peixes no município de Ourinhos, Estado de São Paulo, foram analisados quanto à prevalência para Aeromonas hydrophila, Edwardsiella tarda, Mycobacterium spp. e Cianobactérias. Amostras de músculo foram avaliadas por PCR para Aeromonas hydrophila, Edwardsiella tarda e Mycobacterium spp., enquanto que as amostras para cianobactérias foram analisadas por PCR em Tempo Real (qPCR). Os resultados obtidos demonstraram ausência de Aeromonas hydrophila e Edwardsiella tarda nas amostras de filés. A prevalência para Mycobacterium spp. foi de 100% (50/50). Realização posterior de sequenciamento revelou Mycobacterium gordonae. Esta bactéria é considerada um colonizador comum, normalmente não patogênico, porém, há relatos de literatura que demonstram risco de infecção em indivíduos imunossuprimidos e até mesmo imunocompetentes. A taxa de prevalência para cianobactérias foi de 48% (24/50). As cianobactérias (algas azuis) produzem grande quantidade de metabólitos bioativos ou mesmo tóxicos, incluindo toxinas associadas a problemas ambientais e de saúde pública. Considerando a natureza e o papel das cianobactérias como patógenos emergentes, a elevada prevalência deste organismo em um alimento popular como o filé de tilápia do Nilo desperta preocupação, uma vez que os métodos tradicionais de inspeção são incapazes de detectar o patógeno, pelo fato de não provocar alterações macroscópicas nos produtos, bem como pelo potencial de toxicidade para humanos. Entretanto, estudos adicionais são necessários a fim de entender se estes compostos tóxicos estão presentes nos peixes e, caso estejam, se podem sofrer bioacumulação em níveis suficientes para afetar a saúde humana. Palavras-chave: Aeromonas hydrophila, Edwardsiella tarda, Mycobacterium spp, Mycobacterium gordonae, cianobactéria, cianotoxina, tilápia do Nilo, Oreochromis niloticus, diagnóstico. / Fifty fillets of Nile tilapia (Oreochromis niloticus) from a Ourinhos fish market, Sao Paulo State (Southeast Brazil) were analyzed for the prevalence of Aeromonas hydrophila, Edwardsiella tarda, Mycobacterium spp. and cyanobacteria. Muscle samples were evaluated by PCR for Aeromonas hydrophila, Edwardsiella tarda and Mycobacterium spp. Samples for cyanobacteria were analyzed by real time PCR. Both Aeromonas hydrophila and Edwardsiella tarda were not present in fish samples. The prevalence of Mycobacterium spp. was 100% (50/50). Sequencing revealed Mycobacterium gordonae. This agent is usually a ubiquitous and commonly nonpathogenic colonizing organism, although many research publications have reported disease in immunocompromised or even in immunocompetent patients. Prevalence for cyanobacteria was 48% (24/50). Cyanobacteria (blue-green algae) produce a diversity of toxic or otherwise bioactive metabolites, including a number of toxins that have been associated with human and environmental health concerns. Considering the nature and role of cyanobacteria as a pathogen of emerging importance, the high prevalence of this organism in a popular food item such as Nile tilapia raises concern, since no macroscopic alterations can be detected through regular food inspection methods. However, further studies are necessary in order to understand whether these compounds are present in fish and, if so, if they could accumulate sufficiently to affect human health.

A Porfiria Cutânea Tardia (PCT) é uma desordem dermatológica, caracterizada por fotossensibilidade induzida pela circulação de porfirinas que se depositam na pele. Tanto a forma familial como a esporádica são desordens dependentes do acúmulo de ferro. A presença da mutação do gene da Hemocromatose (HFE) é um importante fator de risco para o acúmulo de ferro e pouco se sabe sobre sua prevalência na população brasileira. Da mesma forma, existem poucos relatos a respeito da associação entre mutação do gene HFE e Porfiria Cutânea Tardia. No presente trabalho descrevemos as frequências dos principais alelos e genótipos do gene da Hemocromatose HFE1 em uma coorte de 25 pacientes brasileiros atendidos no HUPE, com Porfiria Cutânea Tardia, durante o período de janeiro 1990 à dezembro 2012, realizando uma correlação da presença desta mutação com a sobrecarga de ferro neste grupo de pacientes. Neste estudo foi utilizado um grupo controle da população fluminense pareado por idade, sexo e grupo étnico informado, para comparar com os dados avaliados dos pacientes com PCT. A pesquisa das mutações genéticas C282Y e H63D do gene da hemocromatose ocorreu através de técnicas de PCR tempo real e e os resultados ratificados por sequenciamento de Sanger. Dos resultados encontrados, não ocorreram diferenças estatísticas significativas nas frequências alélicas e genotípicas das mutações C282Y e H63D entre a coorte com PCT e a população controle. Entretanto, há um forte indício da participação da mutação H63D em um paciente homozigoto, para desenvolvimento da doença, conforme observado na literatura. Dos ensaios bioquímicos, os níveis de ferritina encontrados entre os pacientes portadores de PCT com a mutação H63D foram maiores que os indivíduos sem a mutação. / Porphyria cutanea tarda (PCT) is a dermatological disorder characterized by photosensitivity induced by circulating porphyrins being deposited on the skin. Both the familial form, as sporadic disorders are dependent on the accumulation of iron. Although the cause of this excess hepatic iron is still unknown, the presence of the mutation of the hemochromatosis gene (HFE) is an important risk factor for iron accumulation. Likewise, little is known about the association between HFE gene mutation and porphyria cutanea tarda. In this paper we describe the main frequencies of genotypes and alleles of the gene for hemochromatosis HFE1 in a cohort of 25 patients treated at a dermatology outpatient clinic with Porphyria Cutaneous Late during the period of 1990-2012, performing a correlation with the presence of this mutation and iron overload in these patients. This study used a control group matched for age, sex and ethnic group reported, to compare with the data evaluated in patients with PCT. The research of genetic mutations C282Y and H63D mutations of the hemochromatosis gene occurred through real-time PCR results and ratified by Sanger sequencing. Results found no statistically significant differences in allele and genotype frequencies of the C282Y and H63D between the PCT cohort and population control. However, there is a strong indication of the participation of the H63D mutation in a patient homozygous for disease development, as noted in the literature. Of biochemical analysis, ferritin levels found among patients with PCT with the H63D mutation were higher than those without the mutation.

Magister Artium (Development Studies) - MA(DVS) / Participatory Monitoring and Evaluation (PME) is an integral part for the success of any government community development initiative as it helps foster a sense of ownership and at the same time promotes meaningful development at grass-root level. The Government of Kenya (GOK), through the Ministry of Regional Development has established Regional Development Authorities (RDA’s) that are mandated to promote development within their areas of jurisdiction by implementing integrated programmes and enhancement of community participation. It is against this backdrop that this research investigation is using Tana and Athi River Development Authority (TARDA) in Kenya as a case study in order to appraise how PME is applied in this process. The people-centred development theory constituted the theoretical grounding of the study, and in addition implementation approaches to PME were discussed in relation to the various project management areas of knowledge. Qualitative methods of research were applied throughout the study in assessing the level of stakeholders’ participation in monitoring and evaluation. A mix of interviews and focus group discussions were utilized. More specifically, individual interviews were conducted with the project beneficiaries/community, TARDA management, project management facilitators, as well as monitoring and evaluation specialists in an attempt to unravel how and to what extent Tana County residents are involved in the monitoring and evaluation process of TARDA projects. Empirical findings gathered from the study were reflected upon through concrete grounded discussions on the contribution of PME in increasing community participation, empowerment and decision-making in various development projects. The research findings also indicated that PME plays a pivotal role in ensuring accountability and transparency of institutions thus creating investor confidence and promoting regional-balanced development. Furthermore, the findings also revealed that an effective PME system gives decision makers an additional public sector management tool, while at the same time building on the capacities of the beneficiaries. Finally, it is proposed that PME should be a standard practice among public sector institutions that embrace PME techniques, also in order to document and share PME experiences for purposes of information generation and future sustainable development.

Porphyria is a group of inherited metabolic disorders due to enzymatic defect of the heme biosynthesis resulting in the overproduction of the heme precursors' porphyrins in different body organs. The enzymes of the heme biosynthesis are encoded by corresponding genes in which any defect in any of these genes lead to a specific type of porphyria. Numerous mutations were detected in these genes leading to impairment in the enzyme function and therefore developing of the clinical manifestations of porphyria. The aim of the present work was to investigate the UROD gene in patients with porphyria cutanea tarda (PCT) and hepatoerythropoietic protoporphyria (HEP) as well as the FECH gene in patients with erythropoietic protoporphyria (EPP) on a molecular level. We identified numerous mutations in the FECH and the UROD genes in three different populations, Czech, Slovak, and Egyptian. We described the novel mutations in the UROD gene in HEP Arabic patients from Egypt as well in the FECH gene in patients with EPP of Czech and Slovak origin. We expressed mutatted UROD protein in prokaryotic system and found 19 % of the wild-type enzymatic activity. Moreover, the current study presents for the first time the frequency of the low expression allele IVS3-48c in the FECH gene in healthy controls from the Czech...

Porphyria is a group of inherited metabolic disorders due to enzymatic defect of the heme biosynthesis resulting in the overproduction of the heme precursors' porphyrins in different body organs. The enzymes of the heme biosynthesis are encoded by corresponding genes in which any defect in any of these genes lead to a specific type of porphyria. Numerous mutations were detected in these genes leading to impairment in the enzyme function and therefore developing of the clinical manifestations of porphyria. The aim of the present work was to investigate the UROD gene in patients with porphyria cutanea tarda (PCT) and hepatoerythropoietic protoporphyria (HEP) as well as the FECH gene in patients with erythropoietic protoporphyria (EPP) on a molecular level. We identified numerous mutations in the FECH and the UROD genes in three different populations, Czech, Slovak, and Egyptian. We described the novel mutations in the UROD gene in HEP Arabic patients from Egypt as well in the FECH gene in patients with EPP of Czech and Slovak origin. We expressed mutatted UROD protein in prokaryotic system and found 19 % of the wild-type enzymatic activity. Moreover, the current study presents for the first time the frequency of the low expression allele IVS3-48c in the FECH gene in healthy controls from the Czech...

Fundamentos: A porfiria cutânea tardia é a forma mais comum das porfirias e caracteriza-se pela diminuição da atividade da enzima uroporfirinogênio descarboxilase. Há vários relatos da associação das mutações do gene HFE da hemocromatose hereditária com porfiria cutânea tardia no mundo, mas até hoje apenas um estudo foi realizado no Brasil. Objetivo: Estudar a associação da porfiria cutânea tardia com as mutações C282Y e H63D do gene HFE da hemocromatose hereditária. Identificar a associação com etilismo, hepatite C, hepatite B e infecção pelo HIV e relacioná-los com a presença ou não das mutações do gene HFE e estudar retrospectivamente a resposta terapêutica à cloroquina. Métodos: Estudo ambispectivo para detectar as mutações C282Y e H63D em 60 pacientes com porfiria cutânea tardia no período de 2003 até 2012. O histórico familiar, etilismo, hepatite C, hepatite B e anti-HIV foram investigados. O estudo das mutações HFE foi realizado com PCR em tempo real. A resposta terapêutica foi avaliada utilizando a dosagem das porfirinas urinárias (urina de 24 horas), o perfil de ferro (ferro sérico, ferritina e saturação de transferrina) e as enzimas hepáticas antes e após a remissão bioquímica. Resultados: A frequência dos alelos das mutações foi significativamente mais elevada nos pacientes com PCT para C282Y (8,3% versus 1,77%, odds ratio 5,02, IC [95%] = [4,1%; 14,8%], p=0,0001) e H63D (27,5% versus 14,05, odds ratio 2,32, IC [95%] = [19,7%; 36,4%], p=0,0004) em relação à população grupo controle. A hepatite C estava presente em 41,7% dos pacientes e estava associada à ingestão de álcool em 71,7% dos casos. Conclusões: As mutações HFE e a expressão clínica da hemocromatose hereditária podem contribuir isoladamente para o desencadeamento da PCT, independente-mente da presença de outros fatores precipitantes; o que torna a pesquisa das mutações HFE um exame necessário nos pacientes com PCT. Nos pacientes homozigotos para C282Y e heterozigotos compostos (C282Y/H63D) a flebotomia é o tratamento de primeira escolha. A porfiria cutânea tardia pode ser um marcador cutâneo para a hemocromatose e o dermatologista pode auxiliar no seu diagnóstico e tratamento precoce. / Background: Porphyria cutanea tarda (PCT) is the most common form of porphyria and is characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with PCT worldwide, although up to date only one study has been conducted in Brazil. Objective: Study the association between porphyria cutanea tarda and C282Y and H63D mutations in the HFE gene of hereditary hemochromatosis. Identify the association with alcoholism, hepatitis C, hepatitis B and HIV infection and relate them with the presence or absence of the HFE gene mutations and study retrospectively the therapeutic response to chloroquine. Methods: Ambispective study in the period from 2003 to 2012 to detect the C282Y and H63D mutations in 60 patients with porphyria cutanea tarda. The family history, alcoholism, hepatitis C, hepatitis B and HIV were investigated. HFE mutations were held with real-time PCR. The therapeutic response was assessed using the urinary porphyrins (24h urine), the iron profile (serum iron, ferritin and transferrin saturation) and the liver enzymes, before and after biochemical remission. Results: The frequency of alleles of the mutations were significantly higher in patients with PCT for C282Y (8.3% vs. 1.77%, odds ratio 5.02, CI [95%] = [4.1%; 14.8%], p = 0.0001) and H63D (27.5% vs. 14.05, odds ratio 2.32, CI [95%] = [19.7% and 36.4%], p = 0.0004) in relation to group control population. Hepatitis C was found in 41.7% of the patients and was associated with the ingestion of alcohol in 71.7% of cases. Conclusions: The HFE mutations and clinical expression of hereditary hemochromatosis can contribute in an isolated manner to the outbreak of PCT, independently of the existence of other precipitating factors. This makes the search for HFE mutations necessary in patients with PCT. In patients who are homozygous for C282Y and compound heterozygotes (C282Y/H63D) phlebotomy is the treatment of first choice. Porphyria cutanea tarda can be a cutaneous marker for hemochromatosis and the dermatologist can help in its diagnosis and early treatment.

Fundamentos: A porfiria cutânea tardia é a forma mais comum das porfirias e caracteriza-se pela diminuição da atividade da enzima uroporfirinogênio descarboxilase. Há vários relatos da associação das mutações do gene HFE da hemocromatose hereditária com porfiria cutânea tardia no mundo, mas até hoje apenas um estudo foi realizado no Brasil. Objetivo: Estudar a associação da porfiria cutânea tardia com as mutações C282Y e H63D do gene HFE da hemocromatose hereditária. Identificar a associação com etilismo, hepatite C, hepatite B e infecção pelo HIV e relacioná-los com a presença ou não das mutações do gene HFE e estudar retrospectivamente a resposta terapêutica à cloroquina. Métodos: Estudo ambispectivo para detectar as mutações C282Y e H63D em 60 pacientes com porfiria cutânea tardia no período de 2003 até 2012. O histórico familiar, etilismo, hepatite C, hepatite B e anti-HIV foram investigados. O estudo das mutações HFE foi realizado com PCR em tempo real. A resposta terapêutica foi avaliada utilizando a dosagem das porfirinas urinárias (urina de 24 horas), o perfil de ferro (ferro sérico, ferritina e saturação de transferrina) e as enzimas hepáticas antes e após a remissão bioquímica. Resultados: A frequência dos alelos das mutações foi significativamente mais elevada nos pacientes com PCT para C282Y (8,3% versus 1,77%, odds ratio 5,02, IC [95%] = [4,1%; 14,8%], p=0,0001) e H63D (27,5% versus 14,05, odds ratio 2,32, IC [95%] = [19,7%; 36,4%], p=0,0004) em relação à população grupo controle. A hepatite C estava presente em 41,7% dos pacientes e estava associada à ingestão de álcool em 71,7% dos casos. Conclusões: As mutações HFE e a expressão clínica da hemocromatose hereditária podem contribuir isoladamente para o desencadeamento da PCT, independente-mente da presença de outros fatores precipitantes; o que torna a pesquisa das mutações HFE um exame necessário nos pacientes com PCT. Nos pacientes homozigotos para C282Y e heterozigotos compostos (C282Y/H63D) a flebotomia é o tratamento de primeira escolha. A porfiria cutânea tardia pode ser um marcador cutâneo para a hemocromatose e o dermatologista pode auxiliar no seu diagnóstico e tratamento precoce. / Background: Porphyria cutanea tarda (PCT) is the most common form of porphyria and is characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with PCT worldwide, although up to date only one study has been conducted in Brazil. Objective: Study the association between porphyria cutanea tarda and C282Y and H63D mutations in the HFE gene of hereditary hemochromatosis. Identify the association with alcoholism, hepatitis C, hepatitis B and HIV infection and relate them with the presence or absence of the HFE gene mutations and study retrospectively the therapeutic response to chloroquine. Methods: Ambispective study in the period from 2003 to 2012 to detect the C282Y and H63D mutations in 60 patients with porphyria cutanea tarda. The family history, alcoholism, hepatitis C, hepatitis B and HIV were investigated. HFE mutations were held with real-time PCR. The therapeutic response was assessed using the urinary porphyrins (24h urine), the iron profile (serum iron, ferritin and transferrin saturation) and the liver enzymes, before and after biochemical remission. Results: The frequency of alleles of the mutations were significantly higher in patients with PCT for C282Y (8.3% vs. 1.77%, odds ratio 5.02, CI [95%] = [4.1%; 14.8%], p = 0.0001) and H63D (27.5% vs. 14.05, odds ratio 2.32, CI [95%] = [19.7% and 36.4%], p = 0.0004) in relation to group control population. Hepatitis C was found in 41.7% of the patients and was associated with the ingestion of alcohol in 71.7% of cases. Conclusions: The HFE mutations and clinical expression of hereditary hemochromatosis can contribute in an isolated manner to the outbreak of PCT, independently of the existence of other precipitating factors. This makes the search for HFE mutations necessary in patients with PCT. In patients who are homozygous for C282Y and compound heterozygotes (C282Y/H63D) phlebotomy is the treatment of first choice. Porphyria cutanea tarda can be a cutaneous marker for hemochromatosis and the dermatologist can help in its diagnosis and early treatment.

La tesi indaga la produzione e la messa in opera delle tessere musive e dei sectilia parietali in paste vitree in epoca tardoantica e altomedievale, studiando in particolare il caso di Milano. Nella prima parte viene esaminato il processo di produzione del vetro musivo, poco noto nella documentazione edita, ma estremamente fecondo per la ricostruzione degli scambi commerciali e culturali del periodo esaminato. Con vari strumenti (etnoarcheologia, ricettari, analisi archeometriche, resti archeologici, fonti economiche, stime quantitative, documentazione di restauro) vengono rintracciati gli indicatori di riconoscibilità di un atelier che produce piastre musive colorate e a foglia d’oro, i marker di cronologia, provenienza e tecnologia ottenibili dalle analisi chimiche sul vetro musivo e l’esito materiale dei gesti eseguiti da chi mette in opera rintracciabili sui frammenti. Nella seconda parte sono affrontate le problematiche specifiche del caso milanese. In particolare viene riconsiderata l’ipotesi dell’esistenza di una bottega milanese per la realizzazione e la posa di tessellata vitrea. A fronte di una bibliografia contraddittoria sulla datazione e il contesto culturale in seno a cui sarebbero nate queste competenze, vengono valutati i resti archeologici di decorazioni musive parietali (lacerti e tessere sciolte) e vengono caratterizzati con analisi archeometriche. Viene così determinata la diffusione dell’arte, contestualizzato quanto ancora conservato e stabilito quali apporti commerciali e culturali ha comportato la realizzazione dei mosaici milanesi. I resti archeologici, le fonti letterarie, le attestazioni iconografiche, le analisi archeometriche, pur nella loro difficile lettura, permettono di riconoscere tre momenti di diffusione dell’arte musiva: l’età tardo-imperiale, l’età gota e i secoli finali dell’altomedioevo. Per ogni periodo vengono analizzati tre casi significativi: la basilica di San Lorenzo (fine IV-inizi V sec.), il battistero di San Giovanni alle Fonti (fine V-VI sec.) e la basilica di Sant’Ambrogio (V-VI e X sec.). La ricerca contribuisce a diverse problematiche aperte: la tecnologia del vetro, gli elementi di continuità e innovazione rispetto alle tecniche romane, la decorazione parietale dei monumenti milanesi, le scelte dei committenti che hanno finanziato gli edifici, l’investimento necessario, le relazioni intraprese per realizzare le opere. / The thesis studies the production and layout of wall mosaic tesserae and of glass paste sectilia in late antique and early medieval times, focusing in particular on the case of Milan. The first part examines the productive process of glass mosaics to reconstruct the commercial and cultural exchanges of the studied period. Different tools (ethnoarchaeology, technical recipes, archaeometric analyses, archaeological remains, economic sources, quantitative estimates, restoration reports) are used to track the indicators of a workshop producing coloured and gold-leaf mosaic plates, to identify the markers of mosaic glass history and technology from chemical analysis, and to detect the material results on the remains of the actions performed by the craftsmen. The second part investigates the specific issues of the case of Milan. In particular, it reconsiders the hypothesis of the existence of a Milanese workshop that manufactures and lays out glass tesserae, approached so far in a contradictory literature in term of chronology and cultural framework. The archaeological remains, literary sources, iconographic testimonies, and archaeometric analyses, despite their difficult interpretation, allow identifying three stages of diffusion of mosaic art in Milan: the late Imperial age, the age of the Goths, and the final centuries of the Early Middle Ages. Three significant cases are analyzed for each of these periods: the Basilica of San Lorenzo (late 4th-early 5th c.), the baptistery of San Giovanni alle Fonti (end 5th-6th c.) and the Basilica of Sant’Ambrogio (5th-6th and 10th c.). This research contributes to the state of several open questions: the technology of glass, the preserved or innovative features with respect to Roman techniques, the mural decoration of Milanese buildings, the choices of the customers who have financed the buildings, the investment required, the social and commercial relations established in order to carry out the works.

ABSTRACT The porphyrias are a diverse group of metabolic disorders arising from diminished activity of enzymes in the heme biosynthetic pathway. They can present with acute neurovisceral symptoms, cutaneous symptoms, or both. The complexity of these disorders is demonstrated by the fact that some acute porphyria patients with the underlying genetic defect(s) are latent and asymptomatic while others present with severe symptoms. This indicates that there is at least one other risk factor required in addition to the genetic defect for symptom manifestation. A systematic review of the heme biosynthetic pathway highlighted the involvement of a number of micronutrient cofactors. An exhaustive review of the medical literature uncovered numerous reports of micronutrient deficiencies in the porphyrias as well as successful case reports of treatments with micronutrients. Many micronutrient deficiencies present with symptoms similar to those in porphyria, in particular vitamin B6. It is hypothesized that a vitamin B6 deficiency and related micronutrient deficiencies may play a major role in the pathogenesis of the acute porphyrias. In order to further investigate the porphyrias, a computational model of the heme biosynthetic pathway was developed based on kinetic parameters derived from a careful analysis of the literature. This model demonstrated aspects of normal heme biosynthesis and illustrated some of the disordered biochemistry of acute intermittent porphyria (AIP). The testing of this model highlighted the modifications necessary to develop a more comprehensive model with the potential to investigated hypotheses of the disordered biochemistry of the porphyrias as well as the discovery of new methods of treatment and symptom control. It is concluded that vitamin B6 deficiency might be the risk factor necessary in conjunction with the genetic defect to trigger porphyria symptoms.