Dysplasia in oral lichen planus: relevance, controversies and challenges. A position paper.

BACKGROUND: Patients with oral lichen planus (OLP) have an increased risk of oral cancer. For this reason, OLP is classified as an oral potentially malignant disorder. However, the precise personal (or individual) risk is unknown. Recent meta-analytical studies have reported that dysplastic OLP may transform to cancer in around 6% of cases, while the rate of transformation is lower (<1.5%) in non-dysplastic cases. The presence of epithelial dysplasia has emerged as the most powerful indicator for assessing cancer risk in oral potentially malignant disorders in routine practice. However, the general acceptance of epithelial dysplasia as an accompanying histologic feature in OLP is subject to great controversy. Many pathologists consider the presence of dysplasia as a criterion to exclude OLP when routinely reporting on this disease. This practice, widespread among oral pathology professionals, has resulted in the underestimation of the potential for malignancy of OLP. MATERIAL AND METHODS: A review of the literature was carried out in order to critically analyze the relevance, controversies and challenges encountered across the diagnosis of epithelial dysplasia in OLP. RESULTS: 12 studies have been published examining dysplastic changes in OLP, reporting figures ranging from 0.54% to 25% of cases with dysplasia in the first diagnostic biopsy. The diagnosis of dysplasia in the OLP poses an additional difficulty due to the fact that the affected oral epithelium per se develops changes related to autoimmune aggression. Among the most frequent histological features of OLP that develops dysplasia are basal cell hyperplasia with basaloid appearance, loss of basal cells polarity, cellular and nuclear pleomorphism and irregular stratification. CONCLUSIONS: Epithelial dysplasia should not be considered an exclusion criterion for OLP; its evaluation requires experienced pathologists in this field.

Prevalence and virulence of Vibrio species isolated from raw shrimp from retail markets in Reynosa, Mexico.

In this study, the prevalence of Vibrio cholerae, Vibrio parahaemolyticus, Vibrio mimicus, Vibrio vulnificus and Vibrio spp. in shrimp from retail markets in Reynosa, Mexico was determined. A total of 765 isolates, identified as Vibrio spp. (59·1%), V. cholerae (17·8%), V. mimicus (6·7%) and V. parahaemolyticus (4·6%), were obtained; V. vulnificus was not detected. Most of the strains were isolated from supermarkets (48·1%), followed by street vendors (37·3%) and retail stores (14·6%). Moreover, several virulence genes were identified in V. cholerae: toxR (100%), OmpU (76·5%), hlyA (76·5%), VPI (19·9%) and tcpA (5·1%); in V. mimicus: vmh (100%), wzb (74·5%), pilF (54·9%), VPI (43·1%), OmpU (29·4%) and tdh (9·8%); and in V. parahaemolyticus: toxR (100%), tlh (100%), VP1680 (51·4%) and VPI (11·4%). These results show the low safety of this food and the potential risk to consumers' health, since this product in Mexican cuisine is sometimes served raw or semi-cooked. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows the prevalence of pathogenic Vibrio cholerae, Vibrio mimicus and Vibrio parahaemolyticus isolated from shrimp that is commercialized in Reynosa city. This could represent a risk to consumers' health, since outbreaks related to shrimp contaminated with Vibrio have been previously reported. Additionally, shrimp fishing has a major role in Mexico's economy.

Isolation and identification of Vibrio species in the Rio Bravo/Grande and water bodies from Reynosa, Tamaulipas.

The Rio Bravo (Rio Grande) adjoins various states in the Mexican region and has a great importance in water distribution in the northeast Tamaulipas (Mexico). In this work 161 strains were isolated, identified and characterized from the water samples taken from the flow of the Rio Bravo and the two inner canals that cover Reynosa city. The strains were identified as Vibrio cholerae (74·5%), Vibrio spp. (1·2%) and Vibrio mimicus (0·6%). Furthermore, the detected virulence genes in the V. cholerae strains, were the hlyA, ompU, tcpA, toxR genes in 78·3, 62·5, 15·8 and 90·8% respectively. Only the ompU and vmh genes were detected in the V. mimicus strain. These results indicate the presence of multi-toxigenic V. cholerae strains in the Rio Bravo/Grande and in the water bodies from Reynosa city, which could represent a risk for the exposed population. SIGNIFICANCE AND IMPACT OF THE STUDY: Water quality is associated with public health, as it plays an important role in the transmission and epidemiology of pathogens such as Vibrio, since this species have been responsible for human diseases around the world. This study demonstrated the presence of toxigenic Vibrio species in water bodies in Reynosa surroundings, indicating that water bodies may be a source of public health risk.

Is oral cancer incidence among patients with oral lichen planus/oral lichenoid lesions underestimated?

BACKGROUND: Oral lichen planus (OLP) and oral lichenoid lesions (OLL) are considered potentially malignant disorders with a cancer incidence of around 1% of cases, although this estimation is controversial. The aim of this study was to analyze the cancer incidence in a case series of patients with OLP and OLL and to explore clinicopathological aspects that may cause underestimation of the cancer incidence in these diseases. METHODS: A retrospective study was conducted of 102 patients diagnosed with OLP (n = 21, 20.58%) or OLL (n = 81) between January 2006 and January 2016. Patients were informed of the risk of malignization and followed up annually. The number of sessions programmed for each patient was compared with the number actually attended. Follow-up was classified as complete (100% attendance), good (75-99%), moderate (25-74%), or poor (<25% attendance) compliance. RESULTS: Cancer was developed by four patients (3.9%), three males and one male. One of these developed three carcinomas, which were diagnosed at the follow-up visit (two in lower gingiva, one in floor of mouth); one had OLL and the other three had OLP. The carcinoma developed in mucosal areas with no OLP or OLL involvement in three of these patients, while OLP and cancer were diagnosed simultaneously in the fourth. Of the six carcinomas diagnosed, five (83.3%) were T1 and one (16.7%) T2. None were N+, and all patients remain alive and disease-free. CONCLUSIONS: The cancer incidence in OLP and OLL appears to be underestimated due to the strict exclusion criteria usually imposed.

Asymmetrical proliferative pattern loss linked to cyclin D1 overexpression during malignant transformation of the lip epithelium.

BACKGROUND: There is inadequate knowledge on the involvement of oncogenic mechanisms linked to the cyclin (CCND1) gene in lip squamous cell carcinoma (LSCC). OBJECTIVE: The aim of this study was to analyse the implication of cyclin D1 in the malignant transformation of lip lesions. METHODS: We immunohistochemically studied 45 actinic cheilitis cases (15 mild dysplasia, 15 moderate dysplasia, 15 severe dysplasia/carcinoma in situ), 30 LSCC cases with adjacent non-tumour epithelium and 15 normal oral epithelium samples for detection of cyclin D1, ß-catenin and Ki-67. RESULTS: Cyclin D1 and Ki-67 expressions were significantly increased in the basal layer of premalignant epithelia and peripheral layers of tumour nests vs. CONTROLS: Premalignant epithelia had lost their asymmetrical proliferative pattern. CONCLUSION: Lip carcinogenesis was associated with loss of the asymmetrical proliferative pattern, a preventive mechanism against lip oncogenesis, and with cyclin D1 overexpression.

Genotypic and phenotypic diversity of Alicyclobacillus acidocaldarius isolates.

UNLABELLED: The fruit juice industry recognizes Alicyclobacillus as a major quality control target micro-organism. In this study, we analysed 19 bacterial isolates to identify Alicyclobacillus species by polymerase chain reaction (PCR) and sequencing analyses. Phenotypic and genomic diversity among isolates were investigated by API 50CHB system and ERIC-PCR (enterobacterial repetitive intergenic consensus-PCR) respectively. All bacterial isolates were identified as Alicyclobacillus acidocaldarius, and almost all showed identical DNA sequences according to their 16S rRNA (rDNA) gene partial sequences. Only few carbohydrates were fermented by A. acidocaldarius isolates, and there was little variability in the biochemical profile. Genotypic fingerprinting of the A. acidocaldarius isolates showed high diversity, and clusters by ERIC-PCR were distinct to those obtained from the 16S rRNA gene phylogenetic tree. There was no correlation between phenotypic and genotypic variability in the A. acidocaldarius isolates analysed in this study. SIGNIFICANCE AND IMPACT OF THE STUDY: Detection of Alicyclobacillus strains is imperative in fruit concentrates and juices due to the production of guaiacol. Identification of the genera originates rejection of the product by processing industry. However, not all the Alicyclobacillus species are deteriorative and hence the importance to differentiate among them. In this study, partial 16S ribosomal RNA sequence alignment allowed the differentiation of species. In addition, ERIC-PCR was introduced for the genotypic characterization of Alicyclobacillus, as an alternative for differentiation among isolates from the same species.

Identification of predominant yeasts associated with artisan Mexican cocoa fermentations using culture-dependent and culture-independent approaches.

The process of cocoa fermentation is a very important step for the generation or aromatic compounds, which are attributable to the metabolism of the microorganisms involved. There are some reports about this process and the identification of microorganisms; however, there are no reports identifying the yeasts involved in a Mexican cocoa fermentation process using molecular biology techniques, including restricted fragment length polymorphism (RFLP) and denaturing gradient gel electrophoresis (DGGE). The aim of this study was to identify the main yeast species associated with Mexican cocoa fermentations employing culture-dependent and -independent techniques achieving two samplings with a 1 year time difference at the same site. Isolation of the microorganisms was performed in situ. Molecular identification of yeast isolates was achieved by RFLP analysis and rDNA sequencing. Total DNA from the microorganisms on the cocoa beans was utilized for the DGGE analysis. Bands from the DGGE gels were excised and sequenced. Nineteen isolated yeasts were identified (al specie level), three of which had never before been associated with cocoa fermentations worldwide. The detected predominant yeast varied from one technique to another. Hanseniaspora sp. resulted dominant in DGGE however Saccharomyces cerevisiae was the principal isolated species. In conclusion, the culture-dependent and -independent techniques complement each other showing differences in the main yeasts involved in spontaneous cocoa fermentation, probably due to the physiological states of the viable but non culturable yeasts. Furthermore important differences between the species detected in the two samplings were detected.

Asymmetrical proliferative pattern loss during malignant transformation of the oral mucosa.

OBJECTIVES: The aim of this study was to study the loss of asymmetrical proliferation in oral tumorigenesis. MATERIALS AND METHODS: Samples: 92 oral squamous cell carcinomas (OSCC) with associated non-tumor epithelia (NTE). NTE and tumor were classified as distant from or close to the invasion point. Immunohistochemistry was performed using Mib-1 antibody. Ki-67 was assessed in basal, parabasal layer, medium and upper third, counting total and positive cells. Proliferative patterns were classified according to the ki-67 expression: 1 = expression in parabasal layers of well-differentiated tumor nest (WDTN); 2 = expression in parabasal and basal layers of WDTN; 3 = ki-67 expression in <20% cells in tumor tissue without WDTN; 4 = ki-67 expression in ≥20% of cells in tumor tissue without WDTN; and 5 = ki-67 expression exclusively found in basal layers of WDTN. RESULTS: Ki-67 expression was highest in parabasal layers of both close and distant NTE (39.7 ± 27.6 and 30.1 ± 20) and was also elevated in the close (43.4 ± 21.3) and distant (48.8 ± 21.9) tumor tissue samples. Close tumors largely corresponded to proliferation patterns 2 and 4, while distant tumors generally followed pattern 4. Of the 92 close NTE samples, 23 showed reduced basal proliferation with increased parabasal proliferation. Tumors derived from these epithelia followed patterns 2 (52%, 12/23 cases) or 4 (30.4%, 7/23 cases). Parabasal proliferation in distant NTE was significantly increased in patients with multiple vs. single tumors (36.7% vs. 25.4%; P = 0.032). CONCLUSION: The change from asymmetrical to symmetrical division appears to be an oncogenic mechanism in oral carcinogenesis.

Expression of proliferative markers in ameloblastomas and malignant odontogenic tumors.

OBJECTIVE: To compare the proliferative activity in ameloblastoma and malignant odontogenic tumors, as assessed by Ki-67 immunostaining and determine whether expression of substance P (SP) and NK-1 receptor (NK-1R) is related to cell proliferation in these tumors. MATERIALS AND METHODS: Immunohistochemistry was used to evaluate protein expression in 44 benign and malignant odontogenic tumors from 39 patients. Immunohistochemistry was performed with anti-SP, anti-NK-1R, and anti-Ki-67 monoclonal antibodies, and the clinical and pathological data of the patients with odontogenic tumor were evaluated. RESULTS: Expression of Ki-67 in malignant odontogenic tumors was significantly higher than in ameloblastomas (P < 0.001), and the expression level was associated with higher expression of NK-1R. Among the ameloblastomas, there was significantly higher expression of Ki-67 in peripheral ameloblastic-like cells (3.3 ± 4.1) than in stellate reticulum-like cells (2.6 ± 3.7) (P = 0.04). In the majority of tissue locations of the malignant tumors, expression of SP and NK-1R was positively correlated with higher expression of Ki-67. CONCLUSION: These findings show that the expression level of Ki-67 in ameloblastomas was positively correlated with the rate of growth of odontogenic tumors. Overexpression of NK-1R complex in malignant odontogenic tumors could be part of the trigger stimulus that results in higher proliferative activity of the tumor.

Defining metabolic flexibility in hair follicle stem cell induced squamous cell carcinoma.

Among the numerous changes associated with the transformation to cancer, cellular metabolism is one of the first discovered and most prominent[1, 2]. However, despite the knowledge that nearly every cancer is associated with the strong upregulation of various metabolic pathways, there has yet to be much clinical progress on the treatment of cancer by targeting a single metabolic enzyme directly[3-6]. We previously showed that inhibition of glycolysis through lactate dehydrogenase (LDHA) deletion in cancer cells of origin had no effect on the initiation or progression of cutaneous squamous cell carcinoma[7], suggesting that these cancers are metabolically flexible enough to produce the necessary metabolites required for sustained growth in the absence of glycolysis. Here we focused on glutaminolysis, another metabolic pathway frequently implicated as important for tumorigenesis in correlative studies. We genetically blocked glutaminolysis through glutaminase (GLS) deletion in cancer cells of origin, and found that this had little effect on tumorigenesis, similar to what we previously showed for blocking glycolysis. Tumors with genetic deletion of glutaminolysis instead upregulated lactate consumption and utilization for the TCA cycle, providing further evidence of metabolic flexibility. We also found that the metabolic flexibility observed upon inhibition of glycolysis or glutaminolysis is due to post-transcriptional changes in the levels of plasma membrane lactate and glutamine transporters. To define the limits of metabolic flexibility in cancer initiating hair follicle stem cells, we genetically blocked both glycolysis and glutaminolysis simultaneously and found that frank carcinoma was not compatible with abrogation of both of these carbon utilization pathways. These data point towards metabolic flexibility mediated by regulation of nutrient consumption, and suggest that treatment of cancer through metabolic manipulation will require multiple interventions on distinct pathways.

Molecular findings in oral premalignant fields: update on their diagnostic and clinical implications.

The development of multiple oral tumours, seen in up to 30% of patients with a primary oral squamous cell carcinoma, is sometimes attributable to the presence of genetically altered premalignant fields and has important prognostic implications. Molecular techniques available for the definitive diagnosis of such a field (loss of heterozygosity analysis of 3p, 9p and 17p and study of TP53 tumour suppressor gene mutation) are expensive, complex and not universally available, hampering their routine application. Nevertheless, molecular diagnosis is essential for modern assessment of the risk of multiple tumours and for decisions on the appropriate preventive and therapeutic approaches. This article reviews current knowledge on molecular findings in premalignant fields in the oral cavity and oropharynx and provides an update on criteria for their identification, discussing the clinical and therapeutic implications.

Cell apoptosis and proliferation in salivary glands of Sjögren's syndrome.

BACKGROUND: Sjögren's syndrome (SS) occurs associated with parotid neoplasm, non-Hodgkin's B-cell lymphoma, which could impair the condition or be life-threatening for patients. The aim of this work was to analyze cell proliferation and apoptosis modifications in acinar, ductal and inflammatory infiltrate in salivary glands (SG) in patients with Sjögren Syndrome, keratoconjunctivitis, or stomatitis sicca or in healthy subjects, to establish parameters that indicate the likelihood of malignancy of the disease in populations at risk. METHODS: A study was performed with n = 58 histological samples of lower lip SG from patients diagnosed with SS, keratoconjunctivitis, or stomatitis sicca (SICCA) and from healthy subjects (C). Ki67 and caspase-3 immunolabeling were performed. RESULTS: The most important result was significant differences between the three study groups in Ki67 and caspase-3 markers (P < 0.0001) in infiltrated lymphocytes. CONCLUSION: The results of this work are indicative of a high degree of proliferation (85%) in infiltrated lymphocytes (IL) associated with SS which, according the literature, could be considered a risk. Furthermore, the markers used in this work are widely known and represent a lower cost than others and can be used to determine risk groups within the population of SS patients, enabling their follow-up.

Hospitalization of Cuban children for giardiasis: a retrospective study in a paediatric hospital in Havana.

The medical records of the 185 children who, in 2007, were admitted to the Academic Paediatric Hospital 'Centro Habana', in the Cuban capital of Havana, because of giardiasis were analysed retrospectively. A standardized form was used to collect data on the socio-demographic characteristics, clinical features, laboratory diagnosis, treatment and length of stay of each child. Information on the 15 children who had incomplete medical records was excluded from the data analysis. Of the remaining 170 children, 85 (50·0%) were aged 1-4 years, 97 (57·1%) were male, and 106 (62·4%), 92 (54·1%) and 69 (40·6%) had presented with diarrhoea, vomiting, and/or abdominal pain, respectively. Most (91·2%) of the cases had been diagnosed by the microscopical examination of a duodenal aspirate, and the drugs that had been most used frequently were quinacrine and tinidazole, which had been given to 72 (42·4%) and 62 (36·5%) of the cases, respectively. The mean length of hospital stay was 4·9 days. Such information on the clinical characteristics of giardiasis among children living in an endemic area may be valuable to paediatricians and public-health officials who wish to screen for the disease.

The Southern Ocean Exchange: porous boundaries between humpback whale breeding populations in southern polar waters.

Humpback whales (Megaptera novaeangliae) are a cosmopolitan species and perform long annual migrations between low-latitude breeding areas and high-latitude feeding areas. Their breeding populations appear to be spatially and genetically segregated due to long-term, maternally inherited fidelity to natal breeding areas. In the Southern Hemisphere, some humpback whale breeding populations mix in Southern Ocean waters in summer, but very little movement between Pacific and Atlantic waters has been identified to date, suggesting these waters constituted an oceanic boundary between genetically distinct populations. Here, we present new evidence of summer co-occurrence in the West Antarctic Peninsula feeding area of two recovering humpback whale breeding populations from the Atlantic (Brazil) and Pacific (Central and South America). As humpback whale populations recover, observations like this point to the need to revise our perceptions of boundaries between stocks, particularly on high latitude feeding grounds. We suggest that this "Southern Ocean Exchange" may become more frequent as populations recover from commercial whaling and climate change modifies environmental dynamics and humpback whale prey availability.

Ki-67 expression in non-tumour epithelium adjacent to oral cancer as risk marker for multiple oral tumours.

OBJECTIVE: The aim of this study was to determine whether the differential assessment of epithelial proliferation is useful to diagnose premalignant fields and assess the risk of multiple tumours. MATERIAL AND METHODS: We analysed 83 oral carcinomas with associated non-tumour epithelium classified as distant or close according to its distance (> or <1 cm) from the invasion point, and as squamous hyperplasia, mild, moderate, severe dysplasia or carcinoma in situ. Twenty-five healthy oral mucosa samples were used as controls. An immunohistochemical technique was applied using Mib-1. Ki-67 in premalignant epithelium was assessed in basal layer, parabasal layer, medium and upper third. RESULTS: Parabasal expression was significantly higher or showed a tendency to be higher in close and distant epithelia with any histological grade than in the controls. Parabasal Ki-67 significantly differed between distant epithelia associated with multiple vs single tumours (P < 0.001) and between distant epithelia associated with multiple tumours vs controls (P < 0.001). This difference was not observed between distant epithelia associated with single tumours and controls (P = 0.175). The cut-off point that differentiated epithelia associated with multiple tumours was >50% of Ki-67 + parabasal cells in distant epithelia, which yielded 0.88 sensitivity and 0.79 specificity. CONCLUSIONS: The concept of a precancerous field may be linked to an increase in the proliferative activity of parabasal cells.

Effect of supplementation with corn oil on postpartum ovarian activity, pregnancy rate, and serum concentration of progesterone and lipid metabolites in F1 (Bos taurus x Bos indicus) cows.

The aim was to evaluate the effect of corn oil supplementation during postpartum anoestrus on ovarian activity, pregnancy rate, progesterone (P(4)), and lipid metabolites (cholesterol, CHO; low and high density lipoproteins; LDL and HDL, respectively) concentrations in blood of F(1) (Bos taurus x Bos indicus) grazing cows. Cows were randomly assigned to an experimental group, fed with a supplement containing 4% corn oil on dry matter basis (OG, n = 11), and a control group with the same supplement without corn oil (CG, n = 12). Both supplements contained equivalent amounts of crude protein and metabolizable energy and were fed for 34 days continuously. All cows were induced to estrous 12 days after beginning of supplementation by using a synthetic progestagen and artificially inseminated 56 h after retiring the implants. Pregnancy diagnosis was performed by transrectal palpation 45 days after insemination, evaluating simultaneously ovarian activity. P(4) and lipid metabolites (CHO, HDL, LDL) concentrations were determined in blood samples collected at 3-day intervals, from the beginning of corn oil supplementation and up to 10 days after artificial insemination. Ovarian activity was affected by treatment (p < 0.05), finding ovarian structures in 72.7% of OG cows and in 50% of CG cows. Concentration of P(4) and CHO was higher for OG with respect to CG (2.52 +/- 0.65 vs 1.88 +/- 0.62 ng/ml and 117.79 +/- 11.57 vs 85.71 +/- 12.11 mg/dl, respectively), whereas pregnancy rate and blood concentrations of HDL and LDL were not affected by treatment (p > 0.05). Addition of corn oil to the supplement stimulated ovarian activity and increased serum concentrations of progesterone and cholesterol in grazing B. taurus x B. indicus cows with low body condition score showing postpartum anoestrus.

A role for the substance P/NK-1 receptor complex in cell proliferation and apoptosis in oral lichen planus.

OBJECTIVES: To determine whether substance P (SP) and NK-1 receptor (NK-1R) are expressed in oral lichen planus (OLP) and are related to cell proliferation and apoptosis in this disease. MATERIAL AND METHODS: Tissue samples from 50 OLP patients and 26 healthy controls were studied. Immunohistochemistry was performed with anti-SP, anti-NK-1R, anti-ki-67 and anti-caspase-3 monoclonal antibodies and the clinical and pathological data of the OLP patients were evaluated. RESULTS: With the exception of NK-1R expression in epithelial cell membrane and cytoplasm, all markers were more frequently present in OLP patients than in controls (P < 0.05). Higher cytoplasmatic expression of NK-1R was associated with higher epithelial expression of caspase-3 (P < 0.05). Higher epithelial expression of NK-1R and SP was associated with higher suprabasal and basal epithelial expression of ki-67 (P < 0.05 and P < 0.005, respectively). CONCLUSIONS: Actions of the SP/NK-1R complex may contribute to the immune disorder underlying OLP and trigger stimuli to induce cell proliferation. These results indicate that this complex might play a role in the malignant transformation of OLP.

Differences in the expression of p53 protein in oral lichen planus based on the use of monoclonal antibodies DO7 and pAb 240.

UNLABELLED: A comparison is made of p53 expression in oral lichen planus, detected via monoclonal antibodies pAb240 and DO7, and with cell apoptosis and proliferation markers. An immunohistochemical study was made of 51 cases of oral lichen planus and 26 controls, using monoclonal antibodies DO7 and pAb240, anti-caspase-3 antibody and Mib-1 antibody against Ki-67. The cases showed important p53 expression with D07 (68%, 36 cases), presumably wild p53, and low p53 expression with pAb240 (14.9%, 7 cases), presumably mutated p53. No significant relationship was observed between p53 expression and caspase-3 apoptosis marker, though an association was recorded between p53 expression with DO7 and Ki-67 expression. CONCLUSIONS: In oral lichen planus, p53 protein preferentially activates the cell cycle for DNA repair, this representing a very effective genome vigilance mechanism, in view of the low rate of malignant transformations observed in this disease.

[Acute renal failure in a case of nephrotic syndrome secondary to focal and segmental glomerulosclerosis]. / Fracaso renal agudo en síndrome nefrótico secundario a glomeruloesclerosis focal y segmentaria.

Nephrotic syndrome is infrequently complicated with appearance of acute renal failure and minimal change disease is the glomerulopathy more usually involved. Pathogenesis is unclear and three possible mechanisms it has been proposed to explain the decrease of glomerular filtration rate: a severe reduction of glomerular permeability, the presence of acute tubular necrosis or an increased intrarenal pressure related with interstitial oedema. Here we present a 36 years-old-male with a nephrotic syndrome caused by focal and segmental glomerulosclerosis who developed an anuric acute renal failure. Renal function did not change despite oedema removal with haemodialysis and only after corticosteroid and cyclophosphamide therapy introduction we observed a rapid recovery of urinary output and resolution of acute renal failure. Renal biopsy did not show signs of tubular damage or obstruction with proteins nor significant interstitial oedema. Therefore, in this case we think acute renal failure was caused by a severe reduction in glomerular ultrafiltration rate and steroids were the effective treatment that allowed recovery of renal function.

Tamoxifen effect on L-DOPA induced response complications in parkinsonian rats and primates.

The contribution of striatal protein kinase C (PKC) isoform changes in levodopa (L-DOPA) induced motor response complications in parkinsonian rats was investigated and the ability of tamoxifen, an antiestrogen with a partial PKC antagonist property, to prevent these response alterations in 6-hydroxydopamine (6-OHDA) lesioned rats as well as in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated cynomologous monkeys was studied. Following treatment of adult male rats with L-DOPA twice daily for 3 weeks, protein levels of left (lesioned) and right (intact) striatal PKC isoforms were measured. Western blot analysis showed increased protein expression of both the novel PKC epsilon isoform and the atypical PKC lambda isoform ipsilateral to the lesion (174+/-17% for epsilon, 140+/-9% for lambda, of intact striatum in 6-OHDA lesioned plus chronic L-DOPA treated animals) in acute L-DOPA treated rats. No enhancement was observed in PKC immunoreactivity for other isoforms. Tamoxifen (5.0 mg/kg p.o.) significantly attenuated the L-DOPA induced augmentation of protein expression of PKC epsilon and PKC lambda, but had no effect on immunoreactivity for other PKC isoforms. In chronic L-DOPA treated parkinsonian rats, tamoxifen prevented (5.0 mg/kg p.o.) as well as ameliorated (5.0 mg/kg p.o.) the characteristic shortening in duration of motor response to L-DOPA challenge. In MPTP lesioned primates, similar to the ameliorative effect seen in rats, tamoxifen (1 and 3 mg/kg p.o) reduced the appearance of L-DOPA induced dyskinesia by 61% and 55% respectively (p<0.05). These results suggest that changes in specific striatal PKC isoforms contribute to the pathogenesis of L-DOPA induced motor complications and further that drugs able to selectively inhibit these signaling kinases might provide adjunctive benefit in the treatment of Parkinson's disease.