Why Me? To Be an Ultra-Responder to Antiplatelet Therapy: A Case Report.

Platelet function testing is a valid tool to investigate the clinical response to antiplatelet therapy in different clinical settings; in particular, it might supply helpful information in patients with cerebrovascular disease. Oral antiplatelet treatment, such as Aspirin (ASA) and Clopidogrel, is the gold standard in secondary stroke prevention of non-cardiogenic ischemic stroke; conversely, its application as a primary prevention therapy is not routinely recommended in patients with vascular risk factors. Multiple electrode platelet aggregometry (MEA) impedance aggregometer is a validated device to test platelet inhibition induced by ASA or Clopidogrel.

Platelet Function Monitoring Performed after Carotid Stenting during Endovascular Stroke Treatment Predicts Outcome.

Objectives: Many studies showed that platelet reactivity testing can predict ischemic events after carotid stenting or ischemic stroke. The aim of our study was to assess the role of early platelet function monitoring in predicting 90-days functional outcome, stent thrombosis and hemorrhagic transformation in patients with ischemic stroke treated with endovascular procedures requiring emergent extracranial stenting.

Materials And Methods: We performed a retrospective study on consecutive patients with acute anterior circulation stroke admitted to our hospital between January 2015 and March 2020, in whom platelet reactivity testing was performed within 10 days from stenting.

Platelet Function Testing in Patients with Acute Ischemic Stroke: An Observational Study.

Background: The measurement of platelet reactivity in patients with stroke undergoing antiplatelet therapies is not commonly performed in clinical practice. We assessed the prevalence of therapy responsiveness in patients with stroke and further investigated differences between patients on prevention therapy at stroke onset and patients naive to antiplatelet medications. We also sought differences in responsiveness between etiological subtypes and correlations between Clopidogrel responsiveness and genetic polymorphisms.

Role of cerebrospinal fluid biomarkers to predict conversion to dementia in patients with mild cognitive impairment: a clinical cohort study.

Background: Cerebrospinal fluid (CSF) levels assessment of Aβ1-42 and Tau proteins may be accurate diagnostic biomarkers for the differentiation of preclinical Alzheimer's disease (AD) from age-associated memory impairment, depression and other forms of dementia in patients with mild cognitive impairment (MCI). The aim of our study was to explore the utility of CSF biomarkers in combination with common cognitive markers as predictors for the risk of AD development, and other forms of dementia, and the time to conversion in community patients with MCI.

Methods: A group of 71 MCI patients underwent neurological assessment, extended neuropsychological evaluation, routine blood tests, ApoE determination, and lumbar puncture to dose t-tau, p-tau181, Aβ1-42.

Analysis of two duplications of the LDL receptor gene affecting intracellular transport, catabolism, and surface binding of the LDL receptor.

Two novel mutations of the low density lipoprotein (LDL)-receptor gene were found in two Italian familial hypercholesterolemia (FH)-heterozygotes. The first mutation was an 18 nucleotide duplication in exon 8 which is preceded by an A-->T transversion. The translation product of the mutant allele was predicted to be a receptor with an in-frame insertion of 6 amino acids in repeat B of the epidermal growth factor precursor homology domain.

Cerebrotendinous xanthomatosis caused by two new mutations of the sterol-27-hydroxylase gene that disrupt mRNA splicing.

Cerebrotendinous xanthomatosis (CTX) is an inherited sterol storage disease associated with the accumulation of cholestanol and cholesterol in various tissues. CTX is caused by a deficiency of sterol-27-hydroxylase, a mitochondrial enzyme that oxidizes the side chain of cholesterol in the pathway leading to the formation of bile acids. In the present study we report two mutations of sterol-27-hydroxylase gene (CYP27 gene) found in Italian CTX patients.

Partial deletion of the gene encoding sterol 27-hydroxylase in a subject with cerebrotendinous xanthomatosis.

An Italian subject with cerebrotendinous xanthomatosis (CTX) was found to have a partial deletion of the gene encoding the enzyme sterol 27-hydroxylase (CYP27 gene). Southern blot analysis revealed that this deletion (approximately 2 kb) spans from intron 6 to the 3' flanking (3'FLK) region, eliminating exons 7-9, the last three exons of CYP27 gene. No sterol 27-hydroxylase mRNA was detected in proband cells, either by Northern blot analysis or by reverse transcription polymerase chain reaction (PCR).

Two novel partial deletions of LDL-receptor gene in Italian patients with familial hypercholesterolemia (FH Siracusa and FH Reggio Emilia).

In the present study we report two novel partial deletions of the LDL-R gene. The first (FH Siracusa), found in an FH-heterozygote, consists of a 20 kb deletion spanning from the 5' flanking region to the intron 2 of the LDL-receptor gene. The elimination of the promoter and the first two exons prevents the transcription of the deleted allele, as shown by Northern blot analysis of LDL-R mRNA isolated from the proband's fibroblasts.

Occurrence of multiple aberrantly spliced mRNAs of the LDL-receptor gene upon a donor splice site mutation that causes familial hypercholesterolemia (FHBenevento).

A novel point mutation of the LDL-receptor gene was found in an Italian patient with homozygous familial hypercholesterolemia. The SSCP analysis of the promoter and of 16 out of the 18 exons of the LDL-receptor gene was negative, suggesting that the mutation might be located in the region of the gene encompassing exons 14 and 15, a region that had not been amenable to polymerase chain reaction (PCR) amplification from genomic DNA. This region was amplified from cDNA by reverse transcription PCR (RT-PCR).

Partial duplication of the EGF precursor homology domain of the LDL-receptor protein causing familial hypercholesterolemia (FH-Salerno).

A novel mutation of low density lipoprotein (LDL)-receptor gene was found in an Italian family hypercholesterolemia (FH) patient during a screening of 300 FH patients. The proband as well as her daughter were found to be heterozygotes for the mutation. Binding, internalization, and degradation of 125I-labeled LDL by the proband's fibroblasts were reduced to approximately 50% compared to values found in control cells.

A new missense mutation (Cys297-->Phe) of the low density lipoprotein receptor in Italian patients with familial hypercholesterolemia (FHTrieste).

During a survey of the mutations of the low density lipoprotein receptor (LDL-R) gene in Italian patients with familial hypercholesterolemia (FH), we identified a novel point mutation, that creates a new EcoRI site at the 5' end of exon 7, in a heterozygous FH subject (FH-100). The sequence of a cDNA fragment encompassing exon 7 showed the presence of a G-->T transversion in codon 297; this created a new EcoRI site and produced a missense mutation, leading to a Cys297-->Phe substitution in repeat A of the epidermal growth factor (EGF) precursor homology domain of LDL-R. Since the substitution of Cys297 disrupts the intracellular transport of the LDL-R protein, as previously demonstrated by site-directed mutagenesis, we suggest that this mutation is the cause of FH in the FH-100 proband.

Alternative splicing of mutant LDL-receptor mRNA in an Italian patient with familial hypercholesterolemia due to a partial deletion of LDL-receptor gene (FHPotenza).

An analysis of LDL-receptor gene was performed on an Italian patient with heterozygous familial hypercholesterolemia. Restriction enzyme analysis showed that the proband was heterozygous for a deletion of 4.5 kb spanning the 5' end of exon 13 (45 nucleotide residues) to intron 15.

A large deletion in the LDL receptor gene--the cause of familial hypercholesterolemia in three Italian families: a study that dates back to the 17th century (FH-Pavia).

In the LDL-receptor gene, a large rearrangement causing hypercholesterolemia was detected in three apparently unrelated families living in northern Italy. In all probands, binding, internalization, and degradation of 125I-LDL measured in skin fibroblasts were found to be 40%-50% of control values, indicative of heterozygous familial hypercholesterolemia (FH). Southern blot analysis revealed that the probands were heterozygous for a large (25-kb) deletion of the LDL-receptor gene eliminating exons 2-12.

Characterization of three mutations of the low density lipoprotein receptor gene in Italian patients with familial hypercholesterolemia.

Three gross rearrangements of the low density lipoprotein receptor (LDL-R) gene were recognized during a survey of 23 unrelated Italian subjects with familial hypercholesterolemia (FH). Restriction endonuclease data were obtained by Southern blotting and hybridization with exon-specific probes. Proband FH-29 is heterozygous for a 4-kb deletion, which eliminates exons 13 and 14.

Duplication of exons 13, 14 and 15 of the LDL-receptor gene in a patient with heterozygous familial hypercholesterolemia.

During a survey of Italian patients with familial hypercholesterolemia (FH), we identified an FH heterozygous patient with a gross rearrangement of the low density lipoprotein (LDL) receptor gene. Southern blot analysis of the proband's DNA digested with restriction enzymes PvuII, BamHI, BglII and XbaI and hybridization with cDNA probes complementary to the 3' end of the gene revealed the presence of abnormal fragments that were approximately 7 kb larger than their normal counterparts. DNA digestion with other enzymes (EcoRV, NcoI, KpnI and StuI) and hybridization with probes complementary to exons 13-17 generated normal fragments and an abnormal fragment of 6.