Neuroinflammatory processes, A1 astrocyte activation and protein aggregation in the retina of Alzheimer’s disease patients, possible biomarkers for early diagnosis

Alzheimer's disease (AD), a primary cause of dementia in the aging population, is characterized by extracellular amyloid-beta peptides aggregation, intracellular deposits of hyperphosphorylated tau, neurodegeneration and glial activation in the brain. It is commonly thought that the lack of early diagnostic criteria is among the main causes of pharmacological therapy and clinical trials failure; therefore, the actual challenge is to define new biomarkers and non-invasive technologies to measure neuropathological changes in vivo at pre-symptomatic stages. Recent evidences obtained from human samples and mouse models indicate the possibility to detect protein aggregates and other pathological features in the retina, paving the road for non-invasive rapid detection of AD biomarkers. Here, we report the presence of amyloid beta plaques, tau tangles, neurodegeneration and detrimental astrocyte and microglia activation according to a disease associated microglia phenotype (DAM). Thus, we propose the human retina as a useful site for the detection of cellular and molecular changes associated with Alzheimer's disease

KPNB1 (karyopherin (importin) beta 1)

Review on KPNB1 (karyopherin (importin) beta 1), with data on DNA, on the protein encoded, and where the gene is implicated

Essential Role of the Small GTPase Ran in Postnatal Pancreatic Islet Development

The small GTPase Ran orchestrates pleiotropic cellular responses of nucleo-cytoplasmic shuttling, mitosis and subcellular trafficking, but whether deregulation of these pathways contributes to disease pathogenesis has remained elusive. Here, we generated transgenic mice expressing wild type (WT) Ran, loss-of-function Ran T24N mutant or constitutively active Ran G19V mutant in pancreatic islet β cells under the control of the rat insulin promoter. Embryonic pancreas and islet development, including emergence of insulin+ β cells, was indistinguishable in control or transgenic mice. However, by one month after birth, transgenic mice expressing any of the three Ran variants exhibited overt diabetes, with hyperglycemia, reduced insulin production, and nearly complete loss of islet number and islet mass, in vivo. Deregulated Ran signaling in transgenic mice, adenoviral over-expression of WT or mutant Ran in isolated islets, or short hairpin RNA (shRNA) silencing of endogenous Ran in model insulinoma INS-1 cells, all resulted in decreased expression of the pancreatic and duodenal homeobox transcription factor, PDX-1, and reduced β cell proliferation, in vivo. These data demonstrate that a finely-tuned balance of Ran GTPase signaling is essential for postnatal pancreatic islet development and glucose homeostasis, in vivo

Multiple skin ulcers due to Serratia marcescens in an immunocompetent patient

Serratia marcescens is a species of gram negative bacillus, classified as a member of the Enterobacteriaceae, mainly involved in opportunistic infections, particulary in the hospital environment. Cutaneous infections have rarely reported in literature and are predominantly observed in elderly or in immunocompromised patients. The clinical manifestations of skin infections include granulomatous lesions, necrotizing fasciitis, nodules, cellulitis, ulcers, dermal abscesses. Infections caused by S. marcescens may be difficult to treat because of resistance to a variety of antibiotics, including ampicillin and first and second generation cephalosporins. Aminoglycosides have good activity against S. marcescens, but resistant strains have also been described. We report a very intriguing case of S. marcescens infection, in an immunocompetent 18-year-old man, causing multiple rounded ulcers of varying sizes, along with few pustular lesions that both clinically and histopathologically mimic a pyoderma gangrenosum (PG). This is a non infectious neutrophilic skin disorder, characterized by painful and rapidly progressing skin ulceration. According to our experience, we would strongly recommend to perform cultures of multiple skin ulcers resembling PG, even in young healthy patients, to ensure correct diagnosis and treatment, since resistant to conventional antibiotics bacteria such as S. marcescens may be the cause of these lesions, like in the case here reported

A Rare Case of Sarcoidosis and Morphea

In the last decades several cases of association between sarcoidosis and various autoimmune diseases have been described, leading us to stress the concept of a possible common genetic “soil” of predisposition. The majority of these cases were association between sarcoidosis and generalized scleroderma, but only one case of localized scleroderma and sarcoidosis. In this report, we describe a case of a female patient in which a diagnosis of pulmonary sarcoidosis and morphea was made

Cutaneous venous malformations related to KRIT1 mutation: Case report and literature review

Cavernous malformations (CMs) are vascular anomalies of the nervous system mostly located in the brain. Cerebral cavernous malformations can present sporadically or familial, as a consequence of an autosomal dominant condition, with incomplete penetrance and variable clinical expression. Occasionally, extraneural manifestations of CMs involving the skin have been described. We report the case of two siblings presenting in adulthood diffuse cutaneous vascular lesions associated with cerebral CMs that, after surgical excision and histopathologic analysis, resulted to cavernous haemangiomas. Genomic DNA was extracted from peripheral blood, and molecular evaluation of KRIT1 gene was performed. Although no signs of neurological impairment were reported, cerebral MRI revealed multiple images in both patients, suggestive of cavernous haemangiomas. The genetic study demonstrated a nonsense mutation (c.535C > T) in the KRIT1 (Krev-1/rap1 interaction trapped 1) gene. Few reports describe extraneural manifestations of Cavernous malformation syndrome (CMs) related to a KRIT1 mutation; these involve the skin and are associated with hyperkeratotic cutaneous capillary-venous malformation. CMs should be suspected in patients developing multiple nodular cutaneous venous lesions in adulthood

A RARE CASE OF SARCOIDOSIS AND MORPHEA

In the last decades several cases of association between sarcoidosis and various autoimmune diseases have been described, leading us to stress the concept of a possible common genetic "soil" of predisposition. The majority of these cases were association between sarcoidosis and generalized scleroderma, but only one case of localized scleroderma and sarcoidosis. In this report, we describe a case of a female patient in which a diagnosis of pulmonary sarcoidosis and morphea was made