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Cantharidin is a poisonous substance secreted by blister beetles, including the 'Spanish fly'. Historically, cantharidin was used as an aphrodisiac, vesicant and abortifacient. Symptoms of poisoning include gastrointestinal and genitourinary mucosal irritation along with renal dysfunction. We present the case of a reckless 23-year-old soldier who accepted the challenge of eating a beetle (Berberomeloe majalis). Six hours later he was admitted to the emergency room with abdominal pain, dysuria, gross haematuria with clots, hypotension, fever and renal insufficiency. With intravenous fluid therapy, he recovered clinically. Laboratory parameters returned to normal within 1 week.

Background and purpose: Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been associated with Parkinson’s disease (PD), and the majority of the pathogenic variants are located in the ROC and MAPKKK domains. Methods: Exons 29–31 and 38–44 (ROC and MAPKKK domains) were sequenced in 204 patients with PD, mostly Brazilian. Results: We identified four polymorphisms, a novel silent variant p.R1398R and four substitutions: p.T1410M, p.G2019S, p.Y2189C and the novel variant p.C2139S. Conclusions: The most prevalent mutation was the p.G2019S (2.4%). We consider that the p.T1410M and the p.Y2189C variants are probably polymorphisms and that the p.C2139S mutation is potentially pathogenic.

Cardiovascular (CV) disease is the major cause of mortality in patients undergoing renal replacement therapy. The primary aim of the study was to evaluate the CV risk profile and prevalence of CV disease in patients on peritoneal dialysis (PD) in Portugal. The secondary goal was to establish parameters most associated with CV disease.Retrospective, multicenter study of the prevalent adult population on PD. Six hundred patients were included (56.7% male; mean age 53.5 ± 15.3 years), on PD for 25.6 ± 21.9 months. Patients were divided into two groups: group 1 (n=166) with CV disease and group 2 (n=434) without CV disease. Comparisons were made regarding traditional CV risk factors and those associated with uremia and PD itself, and a multivariate analysis was performed to determine variables independently associated with CV disease.At the end of the study, the prevalence of CV disease was 28%. At univariate analysis, group 1 presented a higher frequency of males (p.01), older patients (p.01), diabetics (p.01), occurrence of left ventricular hypertrophy (LVH) (p.01), mean C-reactive protein (CRP) (p=.04), lower mean parathormone level (p=.014), lower serum phosphorus (p=.02), lower daily urine output (p=.04), lower weekly Kt/V (p=.008), increased use of icodextrin and hypertonic glucose-based PD solutions (p.001 and p=.006, respectively) and more were under continuous ambulatory PD (CAPD) (p=.014) and had a high peritoneal transport status (p=.02). Multivariate analysis provided a significant discriminatory influence pertaining to age50 years, CRP0.6 mg/dl, male gender, diabetes, LVH, CAPD and anuria, when comparing group 1 and group 2.Risk factors most related to the development of CV disease in PD in Portugal are age50 years, CRP0.6 mg/dL, male gender, diabetes, LVH, CAPD and anuria.

The encapsulating peritoneal sclerosis is a rare but serious complication of peritoneal dialysis. The incident rate varies between 0.5 to 4.4%. This entity is associated with significant morbidity and mortality. The diagnosis requires the presence of clinical features of intestinal obstruction or disturbed gastrointestinal function with pathological and radiological evidence of bowel encapsulation. The exact pathogenic mechanism of EPS remains unknown, although itrsquo;s strongest associated with duration of peritoneal dialysis. We present a clinical case of EPS and discuss the clinical manifestations, diagnosis, treatment, prognosis and prevention.

Parkinson’s disease is one of the most common neurodegenerative disorders associated with aging, reaching ∼ 2% of individuals over 65 years. Knowledge achieved in the last decade about the genetic basis of Parkinson’s disease clearly shows that genetic factors play an important role in the etiology of this disorder. Exon dosage variations account for a high proportion of Parkinson’s disease mutations, mainly for PARKIN gene. In the present study, we screened genomic rearrangements in SNCA, PARKIN, PINK1 and DJ-1 genes in 102 Brazilian Parkinson’s disease patients with early onset (age of onset ≤ 50 years), using the multiplex ligation-dependent probe amplification method. Family history was reported by 24 patients, while 78 were sporadic cases. Screening of exon dosage revealed PARKIN and PINK1 copy number variations, but no dosage alteration was found in SNCA and DJ-1 genes. Most of the carriers harbor heterozygous deletions or duplications in the PARKIN gene and only one patient was found to have a deletion in PINK1 exon 1. Data about dosage changes are scarce in the Brazilian population, which stresses the importance of including exon dosage analysis in Parkinson’s disease genetic studies.

The incidence of acute kidney injury in pregnancy declined significantly over the second half of the 20th century; however, it is still associated with major maternal and perinatal morbidity and mortality. A set of systemic and renal physiological adaptive mechanisms occur during a normal gestation that will constrain several changes in laboratory parameters of renal function, electrolytes, fluid and acid-base balances. The diagnosis of acute kidney injury in pregnancy is based on the serum creatinine increase. The usual formulas for estimating glomerular filtration rate are not validated in this population. During the first trimester of gestation, acute kidney injury develops most often due to hyperemesis gravidarum or septic abortion. In the third trimester, the differential diagnosis is more challenging for the obstetrician and the nephrologist and comprises some pathologies that are reviewed in this article: preeclampsia/HELLP syndrome, acute fatty liver of pregnancy and thrombotic microangiopathies.

Mutations in the Jumonji AT-rich interactive domain 1C (JARID1C/SMCX/KDM5C) gene, located at Xp11.22, are emerging as frequent causes of X-linked intellectual disability (XLID). KDM5C encodes for a member of an ARID protein family that harbors conserved DNA-binding motifs and acts as a histone H3 lysine 4 demethylase, suggesting a potential role in epigenetic regulation during development, cell growth and differentiation. In this study, we describe clinical and genetic findings of a Brazilian family co-segregating a novel nonsense mutation (c.2172C>A) in exon 15 of KDM5C gene with the intellectual disability phenotype. The transition resulted in replacement of the normal cysteine by a premature termination codon at position 724 of the protein (p.Cys724X), leading to reduced levels of KDM5C transcript probably due to nonsense mediated mRNA decay. The clinical phenotype of the proband, who has two affected brothers and a mild cognitively impaired mother, consisted of short stature, speech delay, hyperactivity, violent behavior and high palate, besides severe mental retardation. Our findings extend the number of KDM5C mutations implicated in XLID and highlight its promise for understanding neural function and unexplained cases of XLID.

Point mutations and genomic rearrangements in the MECP2 gene are the major cause of Rett syndrome (RTT), a pervasive developmental disorder affecting almost exclusively females. MECP2 mutations were also identified in patients with autism without RTT. In this study, we present a mutational and gene dosage analysis of the MECP2 in a cohort of 60 Brazilian males with autistic features but not RTT. No duplication or deletion was identified. Sequencing analysis, however, revealed four MECP2 sequence variations. Three of them were previously discussed as non disease causing mutations and one mutation (p.T160S) was novel. It affects a highly conserved amino acid located within the MBD domain, a region of the protein involved in specific recognition and interaction with methylated CpG dinucleotides. The p.T160S variation was not found in the control sample. This mutation may represent a potential genetic factor for autistic phenotype and should be object of further studies.

There is good evidence that long-term graft survival is superior when living donors are used for kidney transplantation. Nevertheless, an assessment of potential risks associated with living donation is of particular interest.In this single-center study, we evaluated the renal function of 31 kidney living donors (1997-2003) at 2-13.2 years after nephrectomy. The purpose of this study was to evaluate perioperative complications, renal function, new-onset proteinuria, and hypertension.Living related donation was performed in all cases. The average time after donation was 5.7 +/- 2.4 years. The mean age at nephrectomy was 46.3 +/- 9.0 years (range, 25-64), and 26 (83.9%) donors were females. Twelve patients (29%) were older than 50 years. The left kidney was used in 25 patients (80.6%). Surgical complications occurred in 2 patients. Glomerular filtration rate (GFR) decreased from 116.9 +/- 23 to 77.7 +/- 19.2 mL/min/1.73 m(2) (P.001). Five patients (16.1%) developed a postdonation GFR between 50 and 60 mL/min/1.73 m(2). Patients with lower GFR values after uninephrectomy showed lower predonation values (P.05). Older patients (50 years) displayed lower postdonation GFR than younger ones. We did not observe an increased prevalence of low postdonation GFR over time nor significant differences in protein excretion and blood pressure.Living donor nephrectomy appears to be an acceptably safe intervention. Despite a reduction in GFR, the postdonation incidence of hypertension was low and proteinuria was not observed in any donor, even among previously hypertensive patients. Rigorous donor follow-up is recommended to identify persons at risk.

Structural variations that affect the copy number of the MECP2 gene were shown to cause mental retardation in males by driving the overexpression of this gene. To access the impact of these rearrangements in males with unexplained mental retardation, we have performed a quantitative real-time polymerase chain reaction assay using SYBR Green I chemistry to quantify MECP2 gene copy number in 145 Brazilian males with mental retardation of unknown cause. Three patients carrying MECP2 duplications (approximately 2%) were identified. The analysis of additional markers flanking the MECP2 region showed that the duplications observed are nonrecurrent. Expression studies in two of these patients revealed the overexpression of the MECP2 gene compared to the expression level observed in controls. These findings corroborate other recent reports in the literature and highlight that the overexpression of MECP2 caused by duplications involving this gene is a relatively frequent genetic cause of mental retardation in males, highlighting the importance of MECP2 gene dosage for diagnostic purposes in such cases.

MeCP2 is a protein that functions as a key factor in epigenetic transcriptional regulation. Mutations in MECP2 gene have been reported as being the major cause of Rett syndrome. These mutations may also cause a wide spectrum of neurological disorders in males. Here, we report the identification of the mutation p.P405L in a 19-year-old Brazilian male with mental retardation. This variant is localized in a highly conserved aminoacid from the carboxy terminal domain and may affect the protein function. Segregation analysis on the patient's mother revealed that this is a de novo mutation and it was not identified in the control sample. The programs SIFT, PolyPhen and A-GVGD considered that the p.P405L may be damaging. Despite the high frequency of non pathogenic variants that have been identified in this gene, our data lead us to consider the p.P405L a disease-causing mutation.

MeCP2 is a protein that selectively binds to methylated cytosines through its methyl-CpG-binding domain (MBD) and connects DNA methylation to transcriptional repression. Mutations in MECP2 gene, located in Xq28, have been reported as being the major cause of Rett syndrome and are also associated with some cases of X-linked mental retardation in both males and females. In this study, we present the first screening in the MECP2 gene in a Brazilian cohort of 239 unrelated males with idiopathic mental retardation. Eight sequence variations were observed in 10 patients: one novel putative pathogenic variant, two never described variants of unknown pathogenic value and five non-pathogenic variations. We conclude that in mentally retarded Brazilian males, non-pathogenic variants in the MECP2 gene are more common than actual pathogenic mutations, and therefore alterations in this gene have a weak relationship with mental retardation in males.

Myocarditis is one of the many possible forms of cardiac involvement in systemic lupus erythematosus. Its clinical presentation ranges from asymptomatic patients with self-limited disease to fulminant heart failure that can lead to death. In most cases treatment consists of supportive care only. The authors present the case of a patient with lupus myocarditis.

FRAXE fragile site associated mental retardation (FRAXE MR) belongs to a group of non-syndromic X-linked mental retardation. Two genes, FMR2 and FMR3 (likely a non-coding RNA) are transcribed from the FRAXE CpG island in the opposite directions. While the contribution of the FMR2 gene to FRAXE MR has been demonstrated, the role of the FMR3 gene is not known. We have screened 441 Brazilian mentally handicapped males for CCG repeat expansions in the FMR2 gene and identified a boy with a mutation (c.-414_-357del58) immediately distal to the FRAXE CCG repeat. We have established a skin fibroblast cell line from this patient and tested expression of both FMR2 and FMR3 genes. Reverse transcriptase PCR studies on the FMR2 and FMR3 genes showed that only the FMR3 gene transcription was abolished, suggesting a possible causal relationship between the lack of FMR3 expression and mental retardation in this patient. In the literature, there have been few deletions described near the FRAXE CCG repeat, but none was followed with expression studies. This is the first study showing missing expression in the FMR3 gene with normal FMR2 transcription leading to FRAXE mutation-likely phenotype. The FMR3 gene is likely a non-coding RNA gene. So far all individuals with FRAXE CCG repeat expansions and cytogenetically detectable FRAXE fragile site have both FMR2 and FMR3 gene expression abolished. Although the function of the FMR3 gene is not known, our present study together with previous studies on FRAXE MR suggest that it may play role in the processes underpinning normal learning and memory.

A 38-year-old man with a history of myeloperoxidase antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presented after 4 days of fever >38°C, red eye, arthralgias and skin lesions. The patient's vasculitis was initially treated with a 7-month course of intravenous cyclophosphamide and oral corticosteroids, reaching complete remission. The patient had been transferred, 2 weeks before, to oral azathioprine (200 mg/day) as maintenance therapy. The physical examination found fever, conjunctivitis and painful erythematous edematous papules, with occasional pustules, involving the neck, upper back and extremities (Figure 1). In the lower legs, there were also erythematous, tender deep nodules (Figure 2). Laboratory findings revealed 12.2 × 109/L leukocytes with 85% neutrophils, elevation of both erythrocyte sedimentation rate and C-reactive protein, acute kidney injury, haematoproteinuria and leukocyturia. Infectious disease was ruled out. A skin biopsy, from an erythematous papule, showed a dense neutrophilic infiltrate in the upper dermis, junctional oedema and focal karyorrhexis. There was no vasculitis in the biopsy specimen and testing for ANCAs was negative. Fig. 1. Erythematous papules, involving the neck and upper back, typical of Sweet syndrome, with occasional pustules. Fig. 2. Erythematous deep nodules in the lower legs (mimic erythema nodosum) typical of the subcutaneous presentation of Sweet syndrome. The diagnosis of Sweet syndrome was established, and the temporal relationship between azathioprine administration and clinical presentation raised the suspicion for drug-induced Sweet syndrome. Azathioprine was withdrawn and high-dose prednisolone was initiated with a rapid and dramatic response of both cutaneous and extracutaneous manifestations. The diagnosis of azathioprine-induced Sweet syndrome was confirmed. Methotrexate was selected as maintenance therapy. Azathioprine treats a variety of autoimmune conditions, and, in nephrology, its main indication is maintenance therapy of ANCA-associated vasculitis. Sweet syndrome is one of the several recognized clinical patterns of azathioprine hypersensitivity syndrome. Sweet syndrome is characterized by fever, constitutional symptoms, peripheral neutrophilia and abrupt onset of erythematous papules, plaques or nodules [1]. Sweet syndrome presents in three clinical settings: classical, malignancy-associated and drug-induced. The criteria for drug-induced Sweet syndrome include: (i) abrupt onset of painful erythematous plaques or nodules, (ii) histopathological evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis, (iii) fever >38°C, (iv) temporal relationship between drug ingestion and clinical presentation and (v) temporal resolution of lesions after drug withdrawal or treatment with systemic corticosteroids [2]. The first case of azathioprine-induced Sweet syndrome was reported in 2003 [3] and since then only 18 [4] cases have been described. We emphasize the importance of considering azathioprine-induced Sweet syndrome, within weeks of azathioprine initiation, in the differential diagnosis of infection and disease flare in patients with ANCA-associated vasculitis. Subsequent azathioprine avoidance is crucial as rechallenge can lead to anaphylaxis [5].

Dynamic mutation involves the expansion of a tandem arrayed DNA sequence that is polymorphic in the population. This mechanism is associated with neurological/neuromuscular disorders and the pathology depends on the extension of the repeated tract, with a specific threshold for each disease. We made a PCR-based characterization of allelic polymorphism of SCA1 and SCA2 loci in a sample of 200 pairs of chromosomes in a population in Rio de Janeiro and found 23 different alleles at the SCA1 locus, varying from 10 to 39 CAG repeats (mean 27.7 +/- 3.3, mode 28) and 10 different alleles ranging from 19 to 29 CAG (mean 22.1 +/- 1.0, mode 22) at the SCA2 locus. The level of heterozygosis was 53% (SCA1) and 8% (SCA2).

Light chain deposition disease (LCDD) and immunoglobulin light chain (AL) amyloidosis are uncommon, and heterogeneous clonal plasma cell (PC) proliferative disorders defined by the different biochemical characteristics of the underlying anomalous immunoglobulin. The deposits are usually multisystemic and the two diseases can coexist. The diagnosis is sometimes made difficult by the absence of a detectable paraprotein by routine immunofixation techniques, and the use of serum-free light chain (FLC) immunoassay brought new value in terms of their diagnosis, prognosis and assessment of treatment response. Association of LCDD and AL amyloidosis with multiple myeloma (MM) at the time of diagnosis is common, but further progression to this condition is considered rare. We present a case of a patient diagnosed with systemic LCDD and AL amyloidosis of atypical biochemical characteristics, with no paraprotein detected in immunoelectrophoresis and immunofixation techniques, who progressed to MM in the later course of her disease.

OBJECTIVE: The impacts of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections on patient and renal graft survivals are controversial. This study sought to evaluate the effects of pretransplantation HCV and HBV infections on renal transplant patients and their grafts at our center. PATIENTS AND METHODS: We retrospectively examined 1224 renal transplantations performed between 1992 and 2006, including 28 HBsAg positive; 64, anti-HCV; 9, anti-HCV plus HBsAg positive; and 1123, negative for anti-HCV and HBsAg. The mean posttransplantation follow-up was 5.6 +/- 4.1 years. RESULTS: The prevalences of HBV infection were 6.2% in 1994 and 2.3% in 2006 and those of HCV infection were 6.8% in 1998 and 5.2% in 2006. The rejection rate was higher among HBV+ (46.4%) and HCV+ (40.6%) groups than the negative groups (31.5%), but it was not significant. There were no significant differences in patient and graft survivals among the groups. The major cause of patient death was liver failure among patients with concomitant HBV+ and HCV+ infections and cardiovascular disease among HCV+ and negative patients. CONCLUSIONS: There has been a decrease in the prevalence of recipients with hepatitis virus infections over the last 15 years. Patient and graft survivals were not affected by HCV or HBV infection.

Dissertação de Mestrado em Gestão e Conservação da Natureza. Neste trabalho são desenvolvidas técnicas de detecção remota, com a finalidade de estudar a evolução da vegetação, os estados fenológicos da vinha e a produtividade de vinho em quatro regiões vitivinícolas de Portugal. Para tal, são obtidos valores de NDVI através do instrumento VEGETATION do satélite SPOT 4 e SPOT 5, dados referentes ao período entre 1998 e 2008. Esses valores são compósitos de 10 dias, resultando em 3 valores de NDVI por mês. São construídas séries temporais, e efetuados ajustamentos para esses valores de NDVI com o propósito de explicar a fenologia da vegetação da vinha. Os estados fenológicos floração e pintor são estimados para a região da DRW e VVR a partir do valor máximo obtido através dos ajustamentos efetuados. Através do modelo obtém-se valores de R2 compreendidos entre 0,65 e 0,74. Para a região de VVR, ainda foi possível efectuar um modelo de previsão com R2 de 0,75 para o estado fenológico pintor. Para as quatro regiões em estudo foi possível ajustar um modelo de previsão de produtividade de vinho com base nos valores de NDVI obtidos para a segunda década do mês de Abril do ano anterior. Para as quatro regiões em estudo os valores de R2 encontram-se compreendidos entre 0,73 e 0,88. ABSTRACT: In this work there are developed remote sensing techniques, with the purpose of studying the evolution of vegetation phenological stages and wine yield in four Portuguese wine producing regions. To this end, NDVI values are obtained through the VEGETATION instrument of SPOT satellite SPOT 4 and 5 relating to the period between 1998 and 2008. These values are composites of 10 days, resulting in 3 values of NDVI per month. Time series are built, and made adjustments for these values of NDVI in order to explain the vegetation phenology of the vine. The phenological stages veraison and flowering are estimated for DWR and VVR regions through the maximum value obtained each year for the SG adjustment. The model produces R2 values that fall between 0.65 and 0.74. For the region of VVR, it was possible to produce a forecast model with a R2 value of 0.75 for the veraison Stage. For the four regions under study it was possible to obtain a predictive model of productivity of wine based on the values of NDVI obtained for the second decade of April of the previous year. For the four regions under study the values of R2 are comprised between 0.73 and 0.88.