Biology subjects

Locatelli, C.

Publications and source records attributed to Locatelli, C..

4 recordsLinked to original sources

bioRxiv2021

Folate pathway metabolites are altered in the plasma of subjects with Down syndrome: relation to chromosomal dosage

Down syndrome (DS) is the most common chromosomal disorder and it is caused by trisomy of chromosome 21 (Hsa21). Subjects with DS show a large heterogeneity of phenotypes and the most constant clinical features present are typical facies and intellectual disability (ID). Several studies demonstrated that trisomy 21 causes an alteration in the metabolic profile, involving among all one-carbon cycle. We performed enzyme-linked immunosorbent assays (ELISAs) to identify the concentration of 5 different intermediates of the one-carbon cycle in plasma samples obtained from a total of 164 subjects with DS compared to 54 euploid subjects. We investigated: tetrahydrofolate (THF; DS n=108, control n=41), 5-methyltetrahydrofolate (5-methyl-THF; DS n=140, control n=34), 5-formyltetrahydrofolate (5-formyl-THF; DS n=80, control n=21), S-adenosyl-homocysteine (SAH; DS n=94, control n=20) and S-adenosyl-methionine (SAM; DS n=24, control n=15). Results highlight specific alterations of THF with a median concentration ratio DS/control of 2:3, a decrease of a necessary molecule perfectly consistent with a chromosomal dosage effect. Moreover, SAM and SAH show a ratio DS/control of 1.82:1 and 3.6:1, respectively. The relevance of these results for the biology of intelligence and its impairment in trisomy 21 is discussed, leading to the final proposal of 5-methyl-THF as the best candidate for a clinical trial aimed at restoring the dysregulation of one-carbon cycle in trisomy 21, possibly improving cognitive skills of subjects with DS.

genetics↗

bioRxiv2021

Echocardiographic mitral valve association with morphometric measurements in Cavalier King Charles Spaniels via Inverse Probability Weighting analysis

Development and progression of myxomatous mitral valve disease (MMVD) in Cavalier King Charles Spaniels (CKCS) are difficult to predict. Identification at a young age of dogs with a morphotype associated with more severe mitral disease is desirable. The aims of this study were to: 1) describe the physical, morphometric, and echocardiographic features of MMVD affected Cavalier King Charles Spaniels (CKCS) in American College of Veterinary Internal Medicine (ACVIM) class B1; 2) evaluate the influence of morphometric physical measurements on murmur intensity, mitral valve prolapse (MVP), regurgitant jet size and indexed mitral valve and annulus measurements. Fifty-two MMVD affected CKCS in ACVIM class B1 were included. This is a prospective clinical cross-sectional study. Morphometric measurements, which included body, thorax, and the head sizing of each dog, have been investigated to establish the association with heart murmur intensity, valvular and annular echocardiographic measurements, MVP and regurgitant jet size using inverse probability weighting (IPW) analyses to adjust for confounding. The IPW analyses showed that when head length and nose length decreased, dogs had more severe regurgitant jet size. Furthermore, subjects with more pronounced head stop angle had thicker anterior mitral valve leaflets. A brachycephalic morphotype, with dogs more similar to King Charles Spaniel breed in cephalic morphology, is associated with a more severe regurgitant jet size and with valvular characteristics related to worse forms of MMVD.

pathology↗

bioRxiv2020

Prospective evaluation of renal function in dogs with chronic mitral valve disease

The coexistence of renal and cardiac disease has been defined in dogs and cats as cardiovascular-renal disorders (CvRD). In humans, renal function is affected by recurrent episodes of acute congestive heart failure (CHF). The aim of this prospective, case-control study was to evaluate the appearance and influence of worsening cardiac disease (WCD), defined on echocardiographic and radiographic parameters, on renal function (defined as worsening renal function [WRF], on the basis of serum creatinine level and presence of proteinuria) in two population: 21 dogs with chronic mitral valve disease (CMVD) and 20 healthy dogs. Dogs were sorted into groups according to the presence/absence of WRF or WCD. Statistical analysis was performed between CMVD dogs and healthy dogs and inside the CMVD dogs group. There was no statistically significant difference in developing WRF between dogs with/without WCD and no statistical evidence to support a difference in WRF parameters in dogs experiencing CHF and dogs not experiencing it. The prevalence of azotemia in CMVD dogs was significantly higher than the prevalence of azotemia previously reported in the general population of dogs. Diuretics therapy didnt affect renal function. No difference in survival time was seen between groups. In conclusion, CHF, WCD and diuretics therapy didnt directly induce WRF. However, considering the prevalence of azotemia, data suggests a link between heart and kidney function (despite we didnt excluded aged-related coexistence of organ damage). A bigger number of dogs at inclusion is required to reach statistical significance.

pathology↗

bioRxiv2020

Multiple retrospective analysis of survival and evaluation of cardiac death predictors in a population of dogs affected by degenerative mitral valve disease in ACVIM class C treated with different therapeutic protocols

Clinical records of dogs with spontaneous degenerative mitral valve disease (DMVD) with clinical signs related to congestive heart failure (CHF) that had been recruited during routine clinical practice, between 2001 and 2018 at the Cardiology Unit of the Veterinary Teaching Hospital (University of Milan) were included in this retrospective cohort study. Baseline echocardiographic data were evaluated. Median survival times (MSTs) were calculated. Data on therapeutic treatment, ISACHC or ACVIM classes were reviewed based on the inclusion period and type of endpoint (i.e. cardiac death or death for other causes). The main goal of this data review was to retrospectively evaluate 259 clinical records of subjects belonging to ACVIM C class examined between 2001 to 2018 together with the 202 examined between 2010 to 2018. The MSTs of these subjects was 531 d (2001-2018) and 335.5 d (2010-2018), respectively. Univariate survival regression analysis for subjects included from 2010 to 2018 showed the following variables as being significantly related to cardiac death (CD): LA/Ao ratio (HR 2.754, p=0.000), E wave (HR 2.961, p=0.000), E/A ratio (HR 1.372, p=0.000), EDVI (HR 1.007, p=0.000), ESVI (HR 1.012, p=0.026), Allo(d) (HR 4.018, p=0.000) and Allo(s) (HR 2.674, p=0.049), age (HR 1.006, p=0.009) and PH severity (HR=1.309, p=0.012). Multivariate analysis, adjusted for age, showed that the only variable that determined a statistically significant difference in MST was PH severity (HR 1.334, p=0.033). The type of therapeutic treatment within this class was not significant for the MST of the subjects.

pathology↗