Current concepts of enzyme histochemistry in modern pathology

Enzyme histochemistry serves as a link between biochemistry and morphology. It is based on metabolization of a substrate provided to a tissue enzyme in its orthotopic localization. Visualization is accomplished with an insoluble dye product. It is a sensitive dynamic technique that mirrors even early metabolic imbalance of a pathological tissue lesion, combined with the advantage of histotopographic enzyme localization. With the advent of immunohistochemistry and DNA-oriented molecular pathology techniques, the potential of enzyme histochemistry currently tends to be underrecognized. This review aims to draw attention to the broad range of applications of this simple, rapid and inexpensive method. Alkaline phosphatase represents tissue barrier functions in brain capillaries, duodenal enterocyte and proximal kidney tubule brush borders. Decrease in enzyme histochemical alkaline phosphatase activity indicates serious functional impairment. Enzyme histochemical increase in lysosomal acid phosphatase activity is an early marker of ischemic tissue lesions. Over the last four decades, acetylcholinesterase enzyme histochemistry has proven to be the gold standard for the diagnosis of Hirschsprung disease and is one of the most commonly applied enzyme histochemical methods today. Chloroacetate esterase and tartrate-resistant phosphatase are both resistant to formalin fixation, EDTA decalcification and paraffin embedding. Early enzyme histochemical insight into development of a pathologic tissue lesion and evaluation of function and vitality of tissue enhance our understanding of the pathophysiology of diseases. In this process, enzyme histochemistry constitutes a valuable complement to conventional histology, immunohistochemistry and molecular pathology for both diagnostic and experimental pathology

ZwanzigJahre diagnostisches Hirschsprung-Kompetenzzentrum in Basel

Zusammenfassung: Hintergrund: In vorliegendem Bericht werden die in 20 Jahren gesammelten Erfahrungen des Basler Hirschsprung-Kompetenzzentrums zusammengestellt. Methodik: Zwischen 1987 und 2006 wurden 19.365 Rektumschleimhautbiopsien untersucht. Die Biopsien stammten von 6615 Kindern mit chronischer Obstipation im Alter von einer Woche bis zu 4Jahren. Die Biopsien wurden in Lehrkrankenhäusern in ganz Deutschland gewonnen und auf Trockeneis per Intercity-Kurierdienst nach Basel transportiert. Das gefrorene Gewebe wurde im Kryostaten in Serienschnitten verarbeitet. An den Biopsien wurden enzymhistochemische Reaktionen durchgeführt. Ergebnis: Insgesamt wurden in 20Jahren 935 Morbus-Hirschsprung-Fälle (14%) diagnostiziert (769 klassische Hirschsprung-Erkrankungen, 68 totale Aganglionosen des Kolons, 98 ultrakurze Hirschsprung-Erkrankungen). Im Interesse einer Qualitätssicherung wurden alle Befunde durch einen zweiten unabhängigen Untersucher beurteilt. Es gab keine falsch-positiven oder falsch-negativen Diagnosen. Die Schnittpräparate waren innerhalb von 2h nach Erhalt auswertbar. Eine Acetylcholinesterase-Reaktion diente der Darstellung der Nervenfasern, die bei Vorliegen eines Hirschsprungs charakteristisch erhöht ist. Succinat- und Lactat-Dehydrogenase sowie Nitroxid-Synthetase ermöglichten eine elektive Nervenzellfärbung des Plexus submucosus und dienten als zweite Bestätigung einer Aganglionose. Schlussfolgerung: Von 100 chronisch obstipierten Kindern hatten im Mittel 12 eine Hirschsprung-Erkrankung. 2% der Kinder wiesen eine totale Kolonaganglionose oder einen ultrakurzen Hirschsprung auf. Die enzymhistochemische Hirschsprung-Diagnostik erwies sich als 100% zuverlässig und zeitsparen

Isolated adult hypoganglionosis presenting as sigmoid volvulus: a case report

<p>Abstract</p> <p>Introduction</p> <p>Isolated hypoganglionosis is a rare cause of intestinal innervation defects. It is characterized by sparse and small myenteric ganglia, absent or low acetylcholinesterase activity in the lamina propria and hypertrophy of the muscularis mucosae, principally in the region of the colon and rectum. It accounts for 5% of all intestinal neuronal malformations. To the best of our knowledge, only 92 cases of isolated hypoganglionosis were reported from 1978 to 2009. Isolated hypoganglionosis usually manifests as enterocolitis or poor bowel function, and is diagnosed in infancy or childhood. We report the first case of isolated hypoganglionosis presenting with sigmoid volvulus in a 34-year-old woman.</p> <p>Case presentation</p> <p>A 34-year-old Asian woman had progressively increasing abdominal pain and had not passed stool or flatus for two days. A physical examination revealed a distended abdomen with sluggish gut sounds. A computerized tomography (CT) scan demonstrated gross dilatation of the sigmoid colon (maximal diameter 14.3 cm) suggestive of sigmoid volvulus. During emergency laparotomy, sigmoidectomy with a side-to-side colorectal anastomosis was performed. Histopathology of the resected specimen showed occasional ganglion cells and hypertrophied nerve bundles in the muscle layers, suggesting hypoganglionosis. Colonoscopy was performed, and multiple full-thickness biopsies were taken that showed hypoganglionosis of the entire large bowel. Our patient underwent total colectomy with an ileorectal anastomosis. Subsequently our patient reported a dramatic improvement in her bowel function.</p> <p>Conclusions</p> <p>Isolated hypoganglionosis is a rare cause of intestinal dysganglionosis and cannot be differentiated from Hirschsprung's disease based on clinical presentation. This case report describes an atypical presentation of the disease. A definitive diagnosis requires histopathological analysis of full-thickness intestinal biopsies. Treatment should be tailored to the extent of hypoganglionosis.</p

Alterations of brain and cerebellar proteomes linked to Aβ and tau pathology in a female triple-transgenic murine model of Alzheimer's disease

The triple-transgenic Alzheimer (3 × Tg-AD) mouse expresses mutant PS1M146V, APPswe, and tauP301L transgenes and progressively develops plaques and neurofibrillary tangles with a temporal- and region-specific profile that resembles the neuropathological progression of Alzheimer's disease (AD). In this study, we used proteomic approaches such as two-dimensional gel electrophoresis and mass spectrometry to investigate the alterations in protein expression occurring in the brain and cerebellum of 3 × Tg-AD and presenilin-1 (PS1) knock-in mice (animals that do not develop Aβ- or tau-dependent pathology nor cognitive decline and were used as control). Finally, using the Ingenuity Pathway Analysis we evaluated novel networks and molecular pathways involved in this AD model. We identified several differentially expressed spots and analysis of 3 × Tg-AD brains showed a significant downregulation of synaptic proteins that are involved in neurotransmitter synthesis, storage and release, as well as a set of proteins that are associated with cytoskeleton assembly and energy metabolism. Interestingly, in the cerebellum, a structure not affected by AD, we found an upregulation of proteins involved in carbohydrate metabolism and protein catabolism. Our findings help to unravel the pathogenic brain mechanisms set in motion by mutant amyloid precursor protein (APP) and hyperphosphorylated tau. These data also reveal cerebellar pathways that may be important to counteract the pathogenic actions of Aβ and tau, and ultimately offer novel targets for therapeutic intervention

Toxic effects of phenothiazines on the eye

Publications about the retinotoxic action of phenothiazine derivatives led the author to undertake an ophthalmological investigation in two psychiatric hospitals in The Netherlands. The pharmacological actions of phenothiazine preparations are listed and a survey of the phenothiazine derivatives which are at present in use is given. Some retinotoxic substances are discussed and a survey is given of the literature on the ocular complications of phenothiazine therapy. The eyes of 561 patients were examined. of whom 541 are included in this study. 343 of these patients(63.4 %) were found to have retinopathy. The correlation between the retinopathy and the total dose of phenothiazine preparations taken. and between the retinopathy and the duration of treatment. was highly significant. The correlation between the retinopathy and the average daily dose taken was significant. The retinopathy was associated with a reduced standing potential of the eye. as determined by electro-oculography. It was possibly responsible for diminished visual acuity in some cases, and for an abnormally large proportion of protans in the group of patients with colour defects. It was not possible to ascribe a more severe retinotoxic action to one or more specific phenothiazine derivatives than to others. In the author's opinion regular examination of the eyes of patients who are being treated with phenothiazine preparations in high dosage and for for a long period of time is indicated

Frontally mediated inhibitory processing and white matter microstructure: age and alcoholism effects

RationaleThe NOGO P3 event-related potential is a sensitive marker of alcoholism, relates to EEG oscillation in the δ and θ frequency ranges, and reflects activation of an inhibitory processing network. Degradation of white matter tracts related to age or alcoholism should negatively affect the oscillatory activity within the network.ObjectiveThis study aims to evaluate the effect of alcoholism and age on δ and θ oscillations and the relationship between these oscillations and measures of white matter microstructural integrity.MethodsData from ten long-term alcoholics to 25 nonalcoholic controls were used to derive P3 from Fz, Cz, and Pz using a visual GO/NOGO protocol. Total power and across trial phase synchrony measures were calculated for δ and θ frequencies. DTI, 1.5 T, data formed the basis of quantitative fiber tracking in the left and right cingulate bundles and the genu and splenium of the corpus callosum. Fractional anisotropy and diffusivity (λL and λT) measures were calculated from each tract.ResultsNOGO P3 amplitude and δ power at Cz were smaller in alcoholics than controls. Lower δ total power was related to higher λT in the left and right cingulate bundles. GO P3 amplitude was lower and GO P3 latency was longer with advancing age, but none of the time-frequency analysis measures displayed significant age or diagnosis effects.ConclusionsThe relation of δ total power at CZ with λT in the cingulate bundles provides correlational evidence for a functional role of fronto-parietal white matter tracts in inhibitory processing

2 nd Brazilian Consensus on Chagas Disease, 2015

Abstract Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research