Hepatolithiasis with biliary ascariasis – a case report

Background  

Biliary ascariasis is regarded as possible etiological factor for hepatolithiasis. Here we report one case of a patient with hepatolithiasis with biliary ascariasis who developed a liver abscess, which was treated with partial hepatectomy.     

Proliferative and inflammatory factors in the vitreous of patients with proliferative diabetic retinopathy

Purpose:

The purpose was to measure the concentrations of various cytokines and growth factors (including vascular endothelial growth factor [VEGF] and pigment epithelium-derived factor [PEDF]) in the vitreous of patients with proliferative diabetic retinopathy (PDR) and to investigate interaction between inflammatory and proliferative factors in the genesis of PDR.

Materials and Methods:

Vitreous samples from 32 eyes with PDR and 25 eyes without diabetes mellitus and signs of DR (control) were collected. Vitreous concentrations of VEGF, PEDF, monocyte chemotactic protein-1 (MCP-1), interleukin-4 (IL-4), IL-6, IL-8, IL-10, IL-17A, and secretory immunoglobulin A (sIgA) were simultaneously measured using enzyme-linked immunoassay.

Results:

Vitreous levels of VEGF, PEDF, IL-17A, IL-6, IL-8, IL-4, and sIgA were significantly (Π < 0.05) higher in eyes with PDR compared to control. The concentration of VEGF was more than 17-times higher than in control, and the concentration of PEDF was not changed oppositely and was also higher (1.45-times) compared to control, that may indicate disturbances of compensatory mechanisms in angiogenesis regulation in PDR. Significant (P < 0.05) positive correlations were observed between vitreous concentrations of VEGF and IL-17A (r = 0.45), VEGF and IL-8 (r = 0.48), VEGF and IL-4 (r = 0.51), PEDF and IL-17A (r = 0.48), PEDF and IL-8 (r = 0.59), MCP-1 and PEDF (r = 0.72), MCP-1 and IL-8 (r = 0.45), IL-4 and IL-17A (r = 0.65), IL-4 and IL-8 (r = 0.71), IL-8 and IL-17A (r = 0.59).

Conclusions:

Significantly raised levels of inflammatory and proliferative factors and numerous positive correlations between them may demonstrate a significant role of activation of vascular proliferation and local inflammation in the pathogenesis of PDR.     

A preliminary study of the whole-genome expression profile of sporadic and monogenic early-onset Alzheimer's disease

Alzheimer's disease (AD) is the most common neurodegenerative dementia. Approximately 10% of cases present at an age of onset before 65 years old, which in turn can be monogenic familial AD (FAD) or sporadic early-onset AD (sEOAD). Mutations in PSEN1, PSEN2, and APP genes have been linked with FAD. The aim of our study is to describe the brain whole-genome RNA expression profile of the posterior cingulate area in sEOAD and FAD caused by PSEN1 mutations (FAD-PSEN1). Fourteen patients (7 sEOAD and 7 FAD-PSEN1) and 7 neurologically healthy control subjects were selected and whole-genome expression was measured using Affymetrix Human Gene 1.1 microarrays. We identified statistically significant expression changes in sEOAD and FAD-PSEN1 brains with respect to control subjects (3183 and 3350 differentially expressed genes [DEG] respectively, false discovery rate-corrected p < 0.05). Of them, 1916 DEG were common between the 2 comparisons. We did not identify DEG between sEOAD and FAD-PSEN1. Microarray data were validated through real-time quantitative polymerase chain reaction. In silico analysis of DEG revealed an alteration in biological pathways related to intracellular signaling pathways (particularly calcium signaling), neuroactive ligand-receptor interactions, axon guidance, and long-term potentiation in both groups of patients. In conclusion, the altered biological final pathways in sEOAD and FAD-PSEN1 are mainly related with cell signaling cascades, synaptic plasticity, and learning and memory processes. We hypothesize that these 2 groups of early-onset AD with distinct etiologies and likely different could present a neurodegenerative process with potential different pathways that might converge in a common and similar final stage of the disease.     

Genetics of acute and chronic pancreatitis: An update

Progress made in identifying the genetic susceptibility underlying acute and chronic pancreatitis has benefitted the clinicians in understanding the pathogenesis of the disease in a better way. The identification of mutations in cationic trypsinogen gene(PRSS1 gene; functional gain mutations) and serine protease inhibitor kazal type 1(SPINK1 gene; functional loss mutations) and other potential susceptibility factors in genes that play an important role in the pancreatic secretory functions or response to inflammation during pancreatic injury has changed the current concepts and understanding of a complex multifactorial disease like pancreatitis. An indi-vidual's susceptibility to the disease is governed by ge-netic factors in combination with environmental factors. Candidate gene and genetic linkage studies have iden-tified polymorphisms in cationic trypsinogen(PRSS1), SPINK1, cystic fibrosis trans-membrane conductance regulator(CFTR), Chymotrypsinogen C(CTRC), Ca-thepsin B(CTSB) and calcium sensing receptor(CASR). Individuals with polymorphisms in the mentioned genes and other as yet identified genes are at an enhanced risk for the disease. Recently, polymorphisms in genes other than those involved in "intra-pancreatic trypsin regulatory mechanism" namely Claudin-2(CLDN2) andCarboxypeptidase A1(CPA1) gene have also been iden-tified for their association with pancreatitis. With ever growing number of studies trying to identify the genetic susceptibility in the form of single nucleotide polymor-phisms, this review is an attempt to compile the avail-able information on the topic.     

Enteroendocrine K Cells Exert Complementary Effects to Control Bone Quality and Mass in Mice

The involvement of a gut-bone axis in controlling bone physiology has been long suspected, although the exact mechanisms are unclear. We explored whether glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine K cells were involved in this process. The bone phenotype of transgenic mouse models lacking GIP secretion (GIP-GFP-KI) or enteroendocrine K cells (GIP-DT) was investigated. Mice deficient in GIP secretion exhibited lower bone strength, trabecular bone mass, trabecular number, and cortical thickness, notably due to higher bone resorption. Alterations of microstructure, modifications of bone compositional parameters, represented by lower collagen cross-linking, were also apparent. None of these alterations were observed in GIP-DT mice lacking enteroendocrine K cells, suggesting that another K-cell secretory product acts to counteract GIP action. To assess this, stable analogues of the known K-cell peptide hormones, xenin and GIP, were administered to mature NIH Swiss male mice. Both were capable of modulating bone strength mostly by altering bone microstructure, bone gene expression, and bone compositional parameters. However, the two molecules exhibited opposite actions on bone physiology, with evidence that xenin effects are mediated indirectly, possibly via neural networks. Our data highlight a previously unknown interaction between GIP and xenin, which both moderate gut-bone connectivity. © 2020 American Society for Bone and Mineral Research.     

Contribution of CSF biomarkers to early‐onset Alzheimer's disease and frontotemporal dementia neuroimaging signatures

Prior studies have described distinct patterns of brain gray matter and white matter alterations in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), as well as differences in their cerebrospinal fluid (CSF) biomarkers profiles. We aim to investigate the relationship between early‐onset AD (EOAD) and FTLD structural alterations and CSF biomarker levels. We included 138 subjects (64 EOAD, 26 FTLD, and 48 controls), all of them with a 3T MRI brain scan and CSF biomarkers available (the 42 amino acid‐long form of the amyloid‐beta protein [Aβ42], total‐tau protein [T‐tau], neurofilament light chain [NfL], neurogranin [Ng], and 14‐3‐3 levels). We used FreeSurfer and FSL to obtain cortical thickness (CTh) and fraction anisotropy (FA) maps. We studied group differences in CTh and FA and described the “AD signature” and “FTLD signature.” We tested multiple regression models to find which CSF‐biomarkers better explained each disease neuroimaging signature. CTh and FA maps corresponding to the AD and FTLD signatures were in accordance with previous literature. Multiple regression analyses showed that the biomarkers that better explained CTh values within the AD signature were Aβ and 14‐3‐3; whereas NfL and 14‐3‐3 levels explained CTh values within the FTLD signature. Similarly, NfL levels explained FA values in the FTLD signature. Ng levels were not predictive in any of the models. Biochemical markers contribute differently to structural (CTh and FA) changes typical of AD and FTLD.