Melanoma Inhibitory Activity (MIA) Is Able to Induce Vitiligo-Like Depigmentation in an in vivo Mouse Model by Direct Injection in the Tail.

In the complex pathogenesis of vitiligo, the exact mechanism of the dermatosis is still to be clarified. We previously demonstrated that a protein called melanoma inhibitory activity (MIA) is present in non-segmental vitiligo skin and seems to cause the detachment of melanocytes, consequently creating the depigmented macules. In this study, we present an animal model of vitiligo on the basis of the ability of the MIA protein to induce vitiligo-like lesions. Twenty pigmented mice were chosen for the experiments and received injections in the tail with saline (control group) or with saline + MIA protein (treated group). The control group did not show any sign of depigmentation. The treated group showed, instead, clear zones of complete depigmentation in the injected areas in each mouse, with the appearance of white patches with whitening of the hair and a clear-cut edge. Histological examination of the tail in the treated zone showed the absence of melanocytes, without the presence of any inflammatory cell or any sign of skin inflammation patterns, confirming the detachment of the melanocyte operated by the MIA protein. These data seem to confirm a possible role played by the MIA protein in the pathogenesis of vitiligo and may support the development of treatments able to inhibit its action as an alternative therapeutic strategy for this disorder.

Radiological and histological analysis of two replaced interphalangeal joints with active subchondral bone resorption in erosive hand osteoarthritis: a novel mechanism?

The aim of this study was to describe the histological features of erosive hand osteoarthritis (EHOA), which is considered an aggressive subset of hand osteoarthritis (OA) characterized by severe local inflammation and degeneration of the distal and proximal interphalangeal joints. Two patients with EHOA underwent replacement with a cement-free press fit ceramic prosthesis of a proximal interphalangeal joint (PIPJ). Clinical and radiological data were collected and histological examination was performed. Radiological examination with histological correlation showed complete erosion of the articular cartilage with focal presence of peripheral fibrocartilaginous resurfacing, sclerosis, and remodeling of the exposed bone, osteoclastic activity with resorptive lacunae in the subchondral bone and around degenerative fibromyxoid pseudocysts, coarse trabeculation of the cancellous bone, and marginal osteophytes. The synovial membrane showed non-specific mild hypertrophy and mildly cellular fibromyxoid stroma. The histological findings in patients with EHOA suggest a pathogenesis of cartilage resorption from the subchondral bone, via osteoclastic-mediated activity and formation of periarticular reactive fibrocartilaginous proliferation with partial resurfacing of the articular surface.

Ultrasound findings of BK polyomavirus-associated nephropathy in renal transplant patients.

BK polyomavirus (BKV) is an emerging pathogen in immunocompromised patients. BKV infection occurs in 1-9 % of renal transplants and causes chronic nephropathy or graft loss. Diagnosis of BKV-associated nephropathy (BKVAN) is based on detection of viruria then viremia and at least a tubule-interstitial nephritis at renal biopsy. This paper describes the ultrasound and color Doppler (US-CD) features of BKVAN. Seventeen patients affected by BKVAN were studied using a linear bandwidth 7-12 MHz probe. Ultrasound showed a widespread streak-like pattern with alternating normal echoic and hypoechoic streaks with irregular edges from the papilla to the cortex. Renal biopsy performed in hypoechoic areas highlighted the typical viral inclusions in tubular epithelial cells. Our experience suggests a possible role for US-CD in the non-invasive diagnosis of BKVAN when combined with blood and urine screening tests. US-CD must be performed with a high-frequency linear probe to highlight the streak-like pattern of the renal parenchyma.

Cardiorenal Syndrome Type 1: Activation of Dual Apoptotic Pathways.

Cardiorenal syndrome type 1 (CRS1) pathophysiology is complex, and immune-mediated damage, including alterations in the immune response with monocyte apoptosis and cytokine release, has been reported as a potential mechanism. In this study, we examined the putative role of renal tubular epithelial cell (RTC) apoptosis as a pathogenic mechanism in CRS1. In particular, we investigated the caspase pathways involved in induced apoptosis. We enrolled 29 patients with acute heart failure (AHF), 11 patients with CRS1, and 15 controls (CTR) without AHF or acute kidney injury (AKI). Patients who had AKI prior to the episode of AHF or who had any other potential causes of AKI were excluded. Plasma from different groups was incubated with RTCs for 24 h. Subsequently, cell apoptosis, DNA fragmentation, and caspase-3, -8, and -9 activities were investigated in RTCs incubated with AHF, CRS1, and CTR plasma. A p value <0.5 was considered statistically significant. A quantitative analysis of apoptosis showed significantly higher apoptosis rates in CRS1 patients compared to AHF patients and CTR (p < 0.01). This increase in apoptosis was strongly confirmed by caspase-3 levels (ρ = 0.73). Caspase-8 and -9 were significantly higher in CRS1 patients compared to AHF patients and CTR (p < 0.01). Furthermore, caspase-3 levels showed a significantly positive correlation with caspase-8 (ρ = 0.57) and -9 (ρ = 0.47; p < 0.001). This study demonstrated the significantly heightened presence of dual apoptotic disequilibrium in CRS1. Our findings indicated that apoptosis may have a central role in the mechanism of CRS1, and it could be a potential therapeutic target in this syndrome.

Phase II study of afatinib, an irreversible ErbB family blocker, in EGFR FISH-positive non-small-cell lung cancer.

INTRODUCTION: Afatinib, an oral irreversible ErbB Family Blocker, has demonstrated efficacy and safety in epidermal growth factor receptor (EGFR) mutation-positive advanced lung adenocarcinoma. It is unknown whether such activity also occurs in patients with EGFR gene overexpression, regardless of mutation status. This phase II study investigated the activity and safety of afatinib in advanced non-small-cell lung cancer with increased EGFR gene copy number and/or gene amplification by fluorescence in situ hybridization (FISH), with or without EGFR mutation. METHODS: EGFR gene overexpression was assessed by FISH analysis; patients with high polysomy or gene amplification were considered FISH positive. Patients received daily afatinib less than or equal to 50 mg (monotherapy). Endpoints included objective response rate (ORR; primary), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Of 223 patients screened, 69 patients were FISH-positive and met eligibility criteria for treatment. The ORR was 13.0% overall (n =9 of 69). Higher ORRs were observed in patients with gene amplification (20.0%; n =5 of 25) and EGFR mutation-positive tumors (25.0%; n =3 of 12). The DCR was 50.7% overall (n = 35 of 69; median duration: 24.9 weeks) with higher DCRs observed in patients with gene amplification 64.0%; (n = 16 of 25), and in patients with EGFR mutation-positive tumors 66.7% (n = 8 of 12). In the overall population, median PFS was 8.4 weeks and median OS was 50.4 weeks. The most common afatinib-related adverse events were rash/acne (83%) and diarrhea (78%). CONCLUSIONS: First- or second-line afatinib demonstrated preliminary activity and manageable safety in EGFR FISH-positive patients with advanced non-small-cell lung cancer.

A construção do perfil da clientela numa clínica-escola / The profile construction of clientele in a school clinic

A caracterização da demanda na instituição de prestação de serviços é fundamental para a proposta de melhoria da qualidade desses serviços, em particular quando se aborda o trabalho desenvolvido nos Serviços Escola de Psicologia, voltados ao atendimento da população. Este trabalho faz uma análise sobre o processo de recepção a pacientes e apresenta o levantamento da demanda que chega ao Centro de Pesquisa e Psicologia Aplicada (CPPA) "Dra. Betti Katzenstein" da UNESP de Assis. Por meio de pesquisa documental, analisaram-se as fichas de triagem dos anos de 2008 a 2012 e foram tabuladas as variáveis sociodemográficas (sexo, idade, núcleo familiar), motivo da procura pelo serviço, segundo a faixa etária, constituição familiar das crianças, e profissão, nos adultos. O objetivo foi esboçar o perfil da clientela que busca auxílio no CPPA, compreender melhor a realidade dos conflitos que essa população enfrenta e, obtendo-se melhor compreensão da demanda, orientar ações no sentido de melhor atendê-la favorecendo a prevenção da saúde mental...

The demand characterization in service institutions is fundamental to improve their quality, particularly when discussing the work of Psychology School Services, focused on people's attendance. This paper makes an analysis on the process of patients' reception and shows the demand survey that arrives at Centro de Pesquisa e Psicologia Aplicada (CPPA)2 "Dr. Betti Katzenstein" at UNESP in Assis. Through documentary research, screening records from 2008 to 2012 were analyzed and sociodemographic variables (gender, age, household) were tabulated, as well as the reason for seeking treatment, age, children's family constitution, and profession in the case of adults. The objective was to outline the clientele profile who seeks for assistance in CPPA, to understand better the reality of conflicts those people face and, when better understanding of the demand is achieved, guide actions to serve them better, providing prevention to mental health...

A construção do perfil da clientela numa clínica-escola / The profile construction of clientele in a school clinic

A caracterização da demanda na instituição de prestação de serviços é fundamental para a proposta de melhoria da qualidade desses serviços, em particular quando se aborda o trabalho desenvolvido nos Serviços Escola de Psicologia, voltados ao atendimento da população. Este trabalho faz uma análise sobre o processo de recepção a pacientes e apresenta o levantamento da demanda que chega ao Centro de Pesquisa e Psicologia Aplicada (CPPA) "Dra. Betti Katzenstein" da UNESP de Assis. Por meio de pesquisa documental, analisaram-se as fichas de triagem dos anos de 2008 a 2012 e foram tabuladas as variáveis sociodemográficas (sexo, idade, núcleo familiar), motivo da procura pelo serviço, segundo a faixa etária, constituição familiar das crianças, e profissão, nos adultos. O objetivo foi esboçar o perfil da clientela que busca auxílio no CPPA, compreender melhor a realidade dos conflitos que essa população enfrenta e, obtendo-se melhor compreensão da demanda, orientar ações no sentido de melhor atendê-la favorecendo a prevenção da saúde mental.(AU)

The demand characterization in service institutions is fundamental to improve their quality, particularly when discussing the work of Psychology School Services, focused on people's attendance. This paper makes an analysis on the process of patients' reception and shows the demand survey that arrives at Centro de Pesquisa e Psicologia Aplicada (CPPA)2 "Dr. Betti Katzenstein" at UNESP in Assis. Through documentary research, screening records from 2008 to 2012 were analyzed and sociodemographic variables (gender, age, household) were tabulated, as well as the reason for seeking treatment, age, children's family constitution, and profession in the case of adults. The objective was to outline the clientele profile who seeks for assistance in CPPA, to understand better the reality of conflicts those people face and, when better understanding of the demand is achieved, guide actions to serve them better, providing prevention to mental health.(AU)

Comparison of reasorbeable mini anchor versus non reasorbeable: histological evaluation in an experimental rabbit model.

PURPOSE: Experimental animal study to evaluate the osseo integration, inflammatory response, dislocation and the reabsorption timing of the reasorbeable Mitek(®) mini anchor, in comparison with the non reasorbeable titanium based. METHODS: TWENTY RABBITS WERE USED: divided into two groups of ten. Each animal underwent sectioning and reinsertion of the Achilles tendon bilaterally, using a reasorbeable mini anchor on one side and a controlateral non reasorbeable mini anchor. The first group was sacrificed after 40 days and the other after 120 days. The bone tendon complex was subjected to histological study. RESULTS: No histological and statistical significative difference were observed in each group, with a lower inflammation response in the reasorbeable implant. Electronic microscopy evaluation demonstrates good stability of the implant in each group. At day 120 the reasorbeable anchors were not yet disappeared. CONCLUSION: Reasorbeable Mitek mini anchors are to be considered to guarantee a similar response and similar bone stability than non reasorbeable ones.

O desenho da figura humana e o TAT em adolescentes grávidas: um estudo no hospital geral / The human figure drawing and TAT of pregnant adolescents: a study in the general hospital

A gestação na adolescência é uma questão de saúde pública e um desafio para a Psicologia, que pode contribuir propondo ações de prevenção da saúde junto a essa população. Visando oferecer subsídios para isso, este trabalho teve o objetivo de investigar o funcionamento psíquico de 10 adolescentes gestantes por meio da análise do Desenho da Figura Humana (DFH) segundo Machover e do Teste de Apercepção Temática (TAT). Os resultados no DFH indicaram alto nível de ansiedade vivido pelas gestantes demonstrado no traçado, no sombreamento e na pobreza de detalhes, que pode levar ao surgimento de problemas relacionados à gestação e à relação entre a família, a adolescente e o bebê. Quanto ao TAT, em geral as adolescentes mostraram dificuldades em contar histórias elaboradas, as produzidas eram pobres de conteúdo, pouco estruturadas e com finais magicamente felizes. Concluiu-se que o DFH e o TAT mostraram-se sensíveis e adequados para avaliar a psicodinâmica dessas adolescentes e permitem oferecer indicações para subsidiar ações preventivas nesta área...

The adolescent pregnancy is a public health problem and a challenge to Psychology, that could contribute proposing health prevention actions to this population. The present study intended to investigate the psychological functioning of 10 pregnant adolescents through analysis of Human Figure Drawing (HFD) and Thematic Apperception Test (TAT). It was observed a high level of anxiety experienced by the pregnant adolescents verified in tracing, in shading and in the poverty of details, that can lead to the development of problems related to pregnancy and the relationship between the family, the adolescent and the baby. As for the TAT, the stories, in general constructed by the teenagers, were poorly structured with reduced content and a magical happy ending. It was concluded that the HFD and the TAT are discriminating and adequate to evaluate these adolescents’ psychodynamics and allow to indicate supporting preventive actions in this area...

O desenho da figura humana e o TAT em adolescentes grávidas: um estudo no hospital geral / The human figure drawing and TAT of pregnant adolescents: a study in the general hospital

A gestação na adolescência é uma questão de saúde pública e um desafio para a Psicologia, que pode contribuir propondo ações de prevenção da saúde junto a essa população. Visando oferecer subsídios para isso, este trabalho teve o objetivo de investigar o funcionamento psíquico de 10 adolescentes gestantes por meio da análise do Desenho da Figura Humana (DFH) segundo Machover e do Teste de Apercepção Temática (TAT). Os resultados no DFH indicaram alto nível de ansiedade vivido pelas gestantes demonstrado no traçado, no sombreamento e na pobreza de detalhes, que pode levar ao surgimento de problemas relacionados à gestação e à relação entre a família, a adolescente e o bebê. Quanto ao TAT, em geral as adolescentes mostraram dificuldades em contar histórias elaboradas, as produzidas eram pobres de conteúdo, pouco estruturadas e com finais magicamente felizes. Concluiu-se que o DFH e o TAT mostraram-se sensíveis e adequados para avaliar a psicodinâmica dessas adolescentes e permitem oferecer indicações para subsidiar ações preventivas nesta área.(AU)

The adolescent pregnancy is a public health problem and a challenge to Psychology, that could contribute proposing health prevention actions to this population. The present study intended to investigate the psychological functioning of 10 pregnant adolescents through analysis of Human Figure Drawing (HFD) and Thematic Apperception Test (TAT). It was observed a high level of anxiety experienced by the pregnant adolescents verified in tracing, in shading and in the poverty of details, that can lead to the development of problems related to pregnancy and the relationship between the family, the adolescent and the baby. As for the TAT, the stories, in general constructed by the teenagers, were poorly structured with reduced content and a magical happy ending. It was concluded that the HFD and the TAT are discriminating and adequate to evaluate these adolescents’ psychodynamics and allow to indicate supporting preventive actions in this area.(AU)

Família e gênero na contemporaneidade / Family and gender in contemporary

O presente estudo é resultado de um relato de pesquisa bibliográfica sobre o tema “ família”, a ser apresentado no Seminário “Pensando os Gêneros II”: desterritorializando as normatividades "acáYallá", pensando a questão de gênero através das novas possibilidades de constituição familiar e formas de parentalidade presentes na atualidade, visando, dessa forma, ao maior entendimento e divulgação da questão. Sabemos que a família é uma instituição que sempre existiu, mas se constitui de diferentes formas, de acordo com o momento histórico e social. No entanto, vemos que, ainda hoje, a imagem que frequentemente ocorre à maioria das pessoas, quando se fala de família, é a da família nuclear, constituída pelo pai e mãe heterossexuais e seus filhos, ainda que atualmente existam várias formas de arranjos familiares, como famílias sem a presença de pelo menos uma das figuras parentais, famílias formadas a partir de um casal homossexual, formas de parentalidade como adoção, homoparentalidade, coparentalidade, inseminação artificial, entre outras tantas formas que constituem os novos arranjos familiares, na contemporaneidade. (AU)

This study is the result of a research report literature on the subject family to be presented at the “Pensando os Gêneros II”: desterritorializando as normatividades "acáYallá" thinking on gender issues through the creation of new possibilities and forms of family present in our parenting, in order thus to greater understanding and disclosure of the issue. We know that the family is an institution that has always existed, but it is in different ways according to the historical and social moment. We, however, even today, the image that often occurs to most people when talking about family is the nuclear family, consisting of the father and mother heterosexuals and their children, even today, there are various forms of family arrangements such as the existence of families without the presence of at least one of the parental figures, families formed from a homosexual couple, forms of parenthood such as adoption, artificial insemination among many other forms which are the new family in contemporary. (AU)

O caminho da loucura e a transformação da assistência aos portadores de sofrimento mental / Los caminos de la locura y la transformación de la atención a los portadores de sufrimiento mental / The course of madness and changes in the care provided to patients in mental suffering

O texto parte de novos conceitos e práticas da psiquiatria que atravessam o contexto da saúde mental coletiva, aborda o desenvolvimento histórico que favorece o entendimento para a construção de novas formas sociais e técnicas no lidar com a loucura, a doença mental e o sofrimento humano. Destaca, ainda, que o atendimento ao portador de transtorno mental sofreu vários processos de transformação, passando da institucionalização para os serviços de atenção psicossocial, realizando a mudança do paradigma ôdoença-curaõ pelo ôexistência-sofrimentoõ.

El texto parte de nuevos conceptos y prácticas de la psiquiatría que atraviesan el contexto de la salud mental colectiva, considerando el desarrollo histórico que favorece el entendimiento para la construcción de nuevos maneras sociales y técnicas en el lidiar con la locura, la enfermedad mental y el sufrimiento humano. También destaca que la atención al enfermo mental pasó por varios procesos de transformación, cambiando de la institucionalización para los Servicios de Atención Psicosocial, realizando el cambio del paradigma ôenfermedad-curaõ para aquel de ôexistencia-sufrimientoõ.

This paper departs from new psychiatry concepts and practices crossing the context of collective mental health, considering the historical development that favors the understanding for the construction of new social and technical ways of dealing with madness, mental disease and human suffering. It also emphasizes that mental health care went through various changes, from institutionalization to Psychosocial Care Services, bringing about a change from the ôdisease-cureõ to the ôexistence-sufferingõ paradigm.

O caminho da loucura e a transformação da assistência aos portadores de sofrimento mental / The course of madness and changes in the care provided to patients in mental suffering / Los caminos de la locura y la transformación de la atención a los portadores de sufrimiento mental

O texto parte de novos conceitos e práticas da psiquiatria que atravessam o contexto da saúde mental coletiva, aborda o desenvolvimento histórico que favorece o entendimento para a construção de novas formas sociais e técnicas no lidar com a loucura, a doença mental e o sofrimento humano. Destaca, ainda, que o atendimento ao portador de transtorno mental sofreu vários processos de transformação, passando da institucionalização para os serviços de atenção psicossocial, realizando a mudança do paradigma ôdoença-curaõ pelo ôexistência-sofrimentoõ.(AU)

This paper departs from new psychiatry concepts and practices crossing the context of collective mental health, considering the historical development that favors the understanding for the construction of new social and technical ways of dealing with madness, mental disease and human suffering. It also emphasizes that mental health care went through various changes, from institutionalization to Psychosocial Care Services, bringing about a change from the ôdisease-cureõ to the ôexistence-sufferingõ paradigm.(AU)

El texto parte de nuevos conceptos y prácticas de la psiquiatría que atraviesan el contexto de la salud mental colectiva, considerando el desarrollo histórico que favorece el entendimiento para la construcción de nuevos maneras sociales y técnicas en el lidiar con la locura, la enfermedad mental y el sufrimiento humano. También destaca que la atención al enfermo mental pasó por varios procesos de transformación, cambiando de la institucionalización para los Servicios de Atención Psicosocial, realizando el cambio del paradigma ôenfermedad-curaõ para aquel de ôexistencia-sufrimientoõ.(AU)

A família e a internação em UTI: a doença e a morte no hospital regional de Assis - SP / The family and the ICU impatient: the disease and death at Assis, Regional hospital - SP

O presente trabalho apresenta reflexões sobre a doença e a morte, pontuando os momentos de internação em uma Unidade de Terapia Intensiva, considerando o significado de adoecer, da história pessoal, familiar e social e de morte. Teóricos mostram a evolução do significado da morte ao longo dos anos, enquanto buscamos compreender os sentimentos dos pacientes e de seus familiares diante da internação na UTI. Ressaltamos a necessidade de atuação da equipe inerdisciplinar para o trabalho de atendimento sistematizado e individualizado, com o intuito de dar sentido às diferenças do outro, de cada paciente, com diferentes doenças e as diversas famílias.

COQ2 nephropathy: a newly described inherited mitochondriopathy with primary renal involvement.

Primary coenzyme Q(10) (CoQ(10)) deficiency includes a group of rare autosomal recessive disorders primarily characterized by neurological and muscular symptoms. Rarely, glomerular involvement has been reported. The COQ2 gene encodes the para-hydroxybenzoate-polyprenyl-transferase enzyme of the CoQ(10) synthesis pathway. We identified two patients with early-onset glomerular lesions that harbored mutations in the COQ2 gene. The first patient presented with steroid-resistant nephrotic syndrome at the age of 18 months as a result of collapsing glomerulopathy, with no extrarenal symptoms. The second patient presented at five days of life with oliguria, had severe extracapillary proliferation on renal biopsy, rapidly developed end-stage renal disease, and died at the age of 6 months after a course complicated by progressive epileptic encephalopathy. Ultrastructural examination of renal specimens from these cases, as well as from two previously reported patients, showed an increased number of dysmorphic mitochondria in glomerular cells. Biochemical analyses demonstrated decreased activities of respiratory chain complexes [II+III] and decreased CoQ(10) concentrations in skeletal muscle and renal cortex. In conclusion, we suggest that inherited COQ2 mutations cause a primary glomerular disease with renal lesions that vary in severity and are not necessarily associated with neurological signs. COQ2 nephropathy should be suspected when electron microscopy shows an increased number of abnormal mitochondria in podocytes and other glomerular cells.

Calcineurin inhibitor-free immunosuppression in dual kidney transplantation from elderly donors.

BACKGROUND: Kidneys from expanded-criteria donors may be particularly susceptible to calcineurin inhibitor (CI)-mediated vasoconstriction and nephrotoxicity. In the early post-transplant phase, using CI may prolong ischemic injury and, in the long term, chronic CI nephrotoxicity is an even greater concern. To avoid the acute and chronic consequences of CI in kidneys from marginal donors, CI-free protocols have been introduced for maintenance immunosuppressive therapy. A CI-free protocol of anti-thymocyte globulin (ATG) induction, sirolimus, mycophenolate mofetil (MMF) and steroids has been adopted at our center in recipients of dual kidney transplantation (DKT) from elderly donors (EDs). METHODS: Dual kidney transplantations performed since April 2003 on CI-free immunosuppression (group 1 = 31) were compared with earlier DKTs in recipients treated with CI-based therapy (group 2 = 25), retrospectively analyzing patient and graft survival, surgical and medical complications, rejection episodes and renal function. RESULTS: No deaths occurred after a mean follow-up of 10.1 +/- 7.6 (group 1) and 48.2 +/- 17.4 months (group 2). Graft loss occurred in one patient in group 1 (bilateral renal vein thrombosis) and in three patients in group 2 (one primary non-function [PNF], one chronic rejection, one Kaposi's sarcoma). The incidence of acute rejection was 19% in group 1 and 16% in group 2. Delayed graft function (DGF) was recorded in 16% and 48%, respectively. Renal function was better in group 1, with a mean S-Cr of 135 +/- 48 vs. 210 +/- 141 micromol/L at one month and 116 +/- 30 vs. 149 +/- 49 micromol/L at six months. CONCLUSIONS: After DKT from EDs, a CI-free immunosuppressive regimen including ATG induction, sirolimus, MMF and steroids affords excellent results, with a lower DGF rate and a better renal function.

Mild tubular damage induces calcium oxalate crystalluria in a model of subtle hyperoxaluria: Evidence that a second hit is necessary for renal lithogenesis.

Environment and diet have a major role in calcium nephrolithiasis by affecting urine saturation, but this is not enough to cause lithogenesis; the crystals must adhere to the tubular epithelium (TE), but it is hard to say how environment and nutrition may be involved in this step. The hypothesis that TE damage (known to enhance crystal attachment) is lithogenic in mild hyperoxaluria was tested. Mild hyperoxaluria was induced in male Wistar rats using ethylene glycol (EG; 0.5% in water) for 21 d, and TE damage was induced by intraperitoneal administration of hexachloro-1:3-butadiene (HCBD; an industrial nephrotoxin) at 10, 25, and 50 mg/kg body wt on days 7 and 14. These EG and HCBD concentrations were chosen to span from suboptimal to very low doses as far as effects on crystalluria and TE damage are concerned. Enzymuria, proteinuria, oxaluria, crystalluria, and renal pathology were investigated. All HCBD dosages induced crystalluria in mildly hyperoxaluric rats, but no intrarenal crystals were found. EG alone induced very mild hyperoxaluria but no damage to the renal tubule observable on transmission electron microscopy, and it did not cause crystalluria or intrarenal crystals. HCBD with the concomitant administration of EG caused apoptosis of the TE at the two highest dosages after the second injection. Apoptosis did not correlate with crystalluria. A TE toxin is needed for crystallogenesis to occur in borderline metabolic conditions. It may take more than just a metabolic predisposition for calcium nephrolithiasis to occur, and the second hit could come from an environmental pollutant such as HCBD.

Isolated hepatocyte transplantation for Crigler-Najjar syndrome type 1.

Crigler-Najjar syndrome type 1 (CN1) is an inherited disorder characterized by the absence of hepatic uridine diphosphoglucuronate glucuronosyltransferase (UDPGT), the enzyme responsible for the conjugation and excretion of bilirubin. We performed allogenic hepatocyte transplantation (AHT) in a child with CN1, aiming to improve bilirubin glucuronidation in this condition. A 9-year-old boy with CN1 was prepared with plasmapheresis and immunosuppression with prednisolone and tacrolimus. When a graft was made available, 7.5 x 10(9) hepatocytes were isolated and infused into the portal vein percutaneously. After 2 weeks phenobarbitone was added to promote the enzymatic activity of UDPGT of the transplanted hepatocytes. Nocturnal phototherapy was continued throughout the studied period. Total bilirubin was considered a reliable marker of allogenic cell function. There was no significant variation of vital signs nor complications during the infusion. Mean +/- SD bilirubin level was 530 +/- 38 micromol/L before and 359 +/- 46 micromol/L after AHT (t-test, p < 0.001). However, the introduction of phenobarbitone was followed by a drop of tacrolimus level with increase of alanine aminotransferase (ALT) and increase of bilirubin. After standard treatment of cellular rejection bilirubin fell again but from then on it was maintained at a greater level. After discharge the patient experienced a further increase of bilirubin that returned to predischarge levels after readmission to the hospital. This was interpreted as poor compliance with phototherapy. Only partial correction of clinical jaundice and the poor tolerability to nocturnal phototherapy led the parents to refuse further hepatocyte infusions and request an orthotopic liver transplant. After 24 months the child is well, with good liver function on tacrolimus and prednisolone-based immunosuppression. Isolated AHT, though effective and safe, is not sufficient to correct CN1. Maintenance of adequate immunosuppression and family compliance are the main factors hampering the success of this procedure.