GENETIC CONTROL OF SUSCEPTIBILITY IN CLINICAL AND EXPERIMENTAL UVEITIS

Genetic association of some immune-mediated human uveitic diseases with histocompatibility antigens, ethnic origin, familial background, or gender have suggested the presence of a hereditary component in susceptibility to uveitis. Uveitis is a genetically complex disease, in which genes and environment contribute to the phenotype appearance. In complex traits, genotypes of particular sets of genes, together with environmental factors, alter the probability that an individual will express the characteristic, although each individual factor is typically insufficient to cause the disease. The main susceptibility genes for clinical and experimental uveitis seem to be located within the major histocompatibility complex (MHC) region, but genes possibly regulating responses to lymphokines, hypothalamic-adrenal-pituitary axis hormones, vascular effects, and possibly T cell repertoire and other pathways play a role to determine "permissiveness" or "nonpermissiveness" to the disease.     

Biobanking in the digital pathology era

Digital Pathology is becoming more and more important to achieve the goal of precision medicine. Advances in whole-slide imaging, software integration, and the accessibility of storage solutions have changed the pathologists’ clinical practice, not only in terms of laboratory workflow but also for diagnosis and biomarkers analysis. In parallel with the pathology setting advancement, translational medicine is approaching the unprecedented opportunities unrevealed by artificial intelligence (AI). Indeed, the increased usage of biobanks’ datasets in research provided new challenges for AI applications, such as advanced algorithms, and computer-aided techniques. In this scenario, machine learning-based approaches are being propose in order to improve biobanks from biospecimens collection repositories to computational datasets. To date, evidence on how to implement digital biobanks in translational medicine is still lacking. This viewpoint article summarizes the currently available literature that supports the biobanks’ role in the digital pathology era, and to provide possible practical applications of digital biobanks.     

Different Trends of Changes in Heart Rate Variability in Patients with Anterior and Inferior Acute Myocardial Infarction

Modifications in heart rate variability (HRV) parameters occur after acute myocardial infarction. The aim of this study was to evaluate the trend of HRV change during the acute phase and the first month after myocardial infarction, and establish whether they were affected by the anterior or inferior location of the infarction. The time-domain HRV measures of 59 patients with a first uncomplicated acute myocardial infarction were computed from 24-hour ECG recordings made on days 1, 2, 10, and 28 after hospital admission. At day 1, the mean RR cycle length (NN), the standard deviation of the NN intervals (SDNN), and the root mean square successive difference of NN intervals (RMSSD) were lower in the patients with anterior myocardial infarction. Although the parameters were similar in all of the patients at day 28, their behavior over time was different (P = 0.01): the SDNN in the patients with inferior myocardial infarction had decreased to the values found in anterior myocardial infarction patients by day 2 but, at day 10, both NN and SDNN tended to recover in both groups; RMSSD had diminished in both groups by day 2, but at day 10, had increased in the patients with anterior, but not in those with inferior myocardial infarction. These findings suggest that (1) in the very early phase of myocardial infarction, HRV is different in the two locations, (2) during the first hours of myocardial infarction patients with inferior location showed a greater vagal activity than patients with anterior location that became lower at day 10, and (3) the recovery of HRV is an early phenomenon in both groups, being already evident by the second week after myocardial infarction.     

Carcinoembryonic Antigen as a Monitor in Breast Cancer

ABSTRACT: Carcinoembryonic antigen (CEA) levels were serially determined in 125 patients with breast cancer in order to study the diagnostic and prognostic use of serum CEA levels before and/or after surgery and during treatment with hormonal and chemotherapy. Serum CEA levels were elevated in 15.5% of nonmetastatic patients. Carcinoembryonic antigen increased according to stage (TNM classification); and a direct relationship between positive CEA levels and subsequent recurrence was found. After a three-year postoperative interval a 50% survival rate was exhibited in CEA-positive patients vs an 88% survival rate in those patients found to be CEA negative. There is a definite correlation between the trend of serial CEA values and the response to therapy and the development of metastases despite the fact that metastases occurred in CEA-negative patients. Therefore CEA assay is a useful and simple adjuvant test of monitoring metastatic and nonmetastatic breast cancer.     

Antigenic and Cytochemical Characterization of Cells Adhering to Intrauterine Contraceptive Devices

ABSTRACT: Eighteen copper intrauterine devices (IUDs), removed after 25 months of use, were examined to evaluate cells adhering to them (IAC). By means of monoclonal antibodies, the antigenic phenotype of IAC was studied, along with some IAC cytochemical properties. Sixty percent of IAC were identified as granulocytes based on morphological, cytochemical, and antigenic characteristics. A small proportion of IAC were shaped like large foreign-body macrophages, with multiple picnotic nuclei, and diffused alpha naphtyl acetate esterase (ANAE) activity. Some IAC identified as macrophages from a morphological view point also showed dipeptidil-diaminopeptidase IV (DAPIV) reactivity, previously described only in T-helper lymphocytes. Most IAC identified as macrophages reacted with the monoclonal antibodies OKM1 and HLA-DR, and showed ANAE activity in the form of small multiple granules. The hypothesis that IUD-adhering macrophages with an ANAE +, DAPIV+, OKM1 +, and HLA-DR + phenotype could play a role in the inactivation of spermatozoa can be proposed.     

EFFECT OF SHORT COURSE OF 1,25-DIHYDROXYVITAMIN D3ON BIOCHEMICAL MARKERS OF BONE REMODELLING IN POSTMENOPAUSAL WOMEN

This study was designed to test the hypothesis that a short treatment course of 1,25(OH)₂D₃elicits a stimulation of osteoblast activity without any action on the osteoclast. To test this, oral daily doses of 0.5μg or 1μg of 1,25(OH)₂D₃were administered for 7 days to two groups (n=5 andn=7, respectively) of postmenopausal women with low bone mineral density. Markers of osteoblast activity, i.e. osteocalcin (BGP), total alkaline phosphatase activity (ALP) and bone alkaline phosphatase activity (BALP), and markers of osteoclast activity, i.e. hydroxylysyl-pyridinoline (Pyr), lysyl-pyridoline (D-Pyr), and galactosyl-hydroxylysine (GHyl) were measured in plasma and in fasting urinary samples, respectively, at sequential times during and after 1,25(OH)₂D₃administration. It resulted that short term 1μg 1,25(OH)₂D₃oral administration induced a significant (P<0.05) rise of BGP serum level without any associated increase ofD-Pyr and GHyl, the latter also expressed as GHyl to GGHyl ratio. Urinary Pyr increased significantly after 1μg daily doses of 1,25(OH)₂D₃. Thus, a short course of 1μg daily doses of 1,25(OH)₂D₃elicits a stimulation of osteoblast activity without any enhancement ofD-Pyr, the most specific marker of osteoclast activity. The enhancement of Pyr after 1μg daily doses of 1,25(OH)₂D₃might be due to the activation of extraosseous metabolic pathways rather than to the activation of osteoclast.