Secukinumab-induced pompholyx in a psoriasis patient.

With a prevalence of up to 20%, eczematous lesions are the most common skin adverse events of tumor necrosis factor alpha inhibitors. Eczematous lesions triggered by more modern biologics such as the IL17A antagonist secukinumab have been rarely reported. Herein, a case of secukinumab-induced pompholyx in a psoriasis patient is presented.

Slowly developing toxic epidermal necrolysis-like reaction associated with pemetrexed and carboplatin.

Most cutaneous adverse drug reactions reported in association with chemotherapy, such as a limited maculopapular rash, are considered mild and do not affect the continuation of the treatment. Toxic epidermal necrolysis (TEN), however, is a life-threatening reaction that needs treatment discontinuation. The present case shows the slow progression from a pemetrexed and carboplatin-associated maculopapular rash to a TEN-like reaction.

Brunsting-Perry Pemphigoid as Differential Diagnosis of Nonmelanoma Skin Cancer.

Brunsting-Perry pemphigoid is a rare autoimmune blistering skin disease. Similar to nonmelanoma skin cancers, Brunsting-Perry pemphigoid has a predilection for the head and neck. Herein, a case of solitary Brunsting-Perry pemphigoid treated as cutaneous squamous cell carcinoma (SCC) with subsequent excision is reported.

Warfarin-induced skin necrosis within psoriatic plaques.

A myriad of different phenomena exist in the dermatological literature which are based on the concept of locus minores resistentiae. The most commonly described phenomenon is the Koebner phenomenon, which is classically associated with the emergence of psoriatic lesions post trauma. Warfarin-induced skin necrosis (WISN) is a rare but severe side effect that leads to necrosis of the skin, predominantly on areas with increased subcutaneous fat. The presented case reports on WISN within psoriatic plaques.

Psoriatic Arthritis and Nail Psoriasis in a Patient with Concomitant Atopic Dermatitis.

Coincidence of psoriasis and atopic dermatitis (AD) is considered to be very rare, as a result of the different underlying immunopathology. This case report describes a patient with long history of atopy and AD who developed psoriatic nail changes and psoriatic arthritis (PsA). The patient's skin, however, revealed only eczematous lesions without manifestation of psoriasis.

Two-photon imaging of neural networks in a mouse model of Alzheimer's disease.

In humans, Alzheimer's disease (AD) develops over many years. It comprises a chain of subtle yet irreversible alterations in brain function, finally leading to impairment of memory and cognition. Presymptomatic and thus invisible in humans, these alterations can be studied in the animal models of AD. Mouse models of the disease expressing AD-related proteins with familial mutations reproduce several pathological hallmarks of AD. Although the models do not recapitulate the abundant neuronal loss seen in humans, they offer a unique opportunity to learn more about synaptic and cellular mechanisms underlying the disease (both in their essence and in their temporal sequence) through in vivo analyses of brain function. This, however, requires in vivo monitoring of brain function in aged living animals at both a single-cell and network level. Tools developed over the last several decades can be used to selectively mark and to visualize in vivo many important elements of the diseased brain parenchyma, such as amyloid plaques, individual neurons, and glial and microglial cells. Here we describe a method in which cell-type-specific labeling of neurons and glia is combined with in vivo two-photon calcium imaging and fluorescent labeling of amyloid plaques to study functional properties of cortical circuits in a mouse model of AD.

Microglial calcium signal acts as a rapid sensor of single neuron damage in vivo.

In the healthy adult brain microglia, the main immune-competent cells of the CNS, have a distinct (so-called resting or surveying) phenotype. Resting microglia can only be studied in vivo since any isolation of brain tissue inevitably triggers microglial activation. Here we used in vivo two-photon imaging to obtain a first insight into Ca(2+) signaling in resting cortical microglia. The majority (80%) of microglial cells showed no spontaneous Ca(2+) transients at rest and in conditions of strong neuronal activity. However, they reliably responded with large, generalized Ca(2+) transients to damage of an individual neuron. These damage-induced responses had a short latency (0.4-4s) and were localized to the immediate vicinity of the damaged neuron (< 50 µm cell body-to-cell body distance). They were occluded by the application of ATPγS as well as UDP and 2-MeSADP, the agonists of metabotropic P2Y receptors, and they required Ca(2+) release from the intracellular Ca(2+) stores. Thus, our in vivo data suggest that microglial Ca(2+) signals occur mostly under pathological conditions and identify a Ca(2+) store-operated signal, which represents a very sensitive, rapid, and highly localized response of microglial cells to brain damage. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.

Intracellular calcium signalling in Alzheimer's disease.

More than two decades ago, dysregulation of the intracellular Ca(2+) homeostasis was suggested to underlie the development of Alzheimer's disease (AD). This hypothesis was tested in numerous in vitro studies, which revealed multiple Ca(2+) signalling pathways able to contribute to AD pathology. It remained, however, unclear whether these pathways are also activated in vivo, in cells involved in signal processing in the living brain. Here we review recent data analysing intracellular Ca(2+) signalling in vivo in the context of previous in vitro findings. We particularly focus on the processes taking place in the immediate vicinity of amyloid plaques and on their possible role for AD-mediated brain dysfunction.

Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease.

The neurodegeneration observed in Alzheimer's disease has been associated with synaptic dismantling and progressive decrease in neuronal activity. We tested this hypothesis in vivo by using two-photon Ca2+ imaging in a mouse model of Alzheimer's disease. Although a decrease in neuronal activity was seen in 29% of layer 2/3 cortical neurons, 21% of neurons displayed an unexpected increase in the frequency of spontaneous Ca2+ transients. These "hyperactive" neurons were found exclusively near the plaques of amyloid beta-depositing mice. The hyperactivity appeared to be due to a relative decrease in synaptic inhibition. Thus, we suggest that a redistribution of synaptic drive between silent and hyperactive neurons, rather than an overall decrease in synaptic activity, provides a mechanism for the disturbed cortical function in Alzheimer's disease.

In vivo calcium imaging of the aging and diseased brain.

PURPOSE: Over the last decade, in vivo calcium imaging became a powerful tool for studying brain function. With the use of two-photon microscopy and modern labelling techniques, it allows functional studies of individual living cells, their processes and their interactions within neuronal networks. In vivo calcium imaging is even more important for studying the aged brain, which is hard to investigate in situ due to the fragility of neuronal tissue. METHODS: In this article, we give a brief overview of the techniques applicable to image aged rodent brain at cellular resolution. RESULTS: We use multicolor imaging to visualize specific cell types (neurons, astrocytes, microglia) as well as the autofluorescence of the "aging pigment" lipofuscin. CONCLUSIONS: Further, we illustrate an approach for simultaneous imaging of cortical cells and senile plaques in mouse models of Alzheimer's disease.