Levels of plasma homocysteine in pseudoexfoliation glaucoma.

BACKGROUND: To examine levels of serum homocysteine (Hcy), vitamin B12 and folic acid in patients with pseudoexfoliation glaucoma (PEXG), primary open-angle glaucoma (POAG), and healthy control subjects. METHODS: This study included 36 patients with PEXG, 40 with POAG, and 40 age-matched healthy subjects. Fasting plasma Hcy concentrations and levels of serum vitamin B12 and folic acid were measured using competitive chemiluminescent enzyme immunoassay; values exceeding 14 μm/l were considered elevated. RESULTS: Mean plasma Hcy was significantly higher in PEXG (16.55 ± 7.23 μm/l) compared with POAG (13.91 ± 3.61 μm/l) and controls (13.12 ± 5.13 μm/l) (p = 0.03 and p = 0.0007 respectively). There were no statistical differences in serum vitamin B12 and folic acid levels among PEXG, POAG and control subjects (p > 0.05). A moderate, although statistically significant, relationship between Hcy and folic acid levels was found in the PEXG group (R(2) = 0.23, p = 0.003). Hcy levels were found not to be related with folic acid or vitamin B12 in either POAG or control subjects. CONCLUSIONS: In this study, plasma Hcy is significantly higher in PEXG group than the POAG and control groups. Hyper-Hcy might play a role in the pathogenesis of PEXG. Hyper-Hcy may be an independent factor stressing vasculopathy in addition to pseudoexfoliation, so might be a modifiable risk factor for PEXG

HLA allele frequencies and susceptibility to COVID-19 in a group of 99 Italian patients

With the aim to individuate alleles that may reflect a higher susceptibility to the disease, in the present study we analyzed the HLA allele frequency distribution in a group of 99 Italian patients affected by a severe or extremely severe form of COVID-19. After the application of Bonferroni's correction for multiple tests, a significant association was found for HLA-DRB1*15:01, -DQB1*06:02 and -B*27:07, after comparing the results to a reference group of 1017 Italian individuals, previously typed in our laboratory. The increased frequencies observed may contribute to identify potential markers of susceptibility to the disease, although controversial results on the role of single HLA alleles in COVID-19 patients have been recently reported

The influence of PON1 192 polymorphism on endothelial function in diabetic subjects with or without hypertension.

Hypertension and type 2 diabetes mellitus (T2DM) cause endothelial dysfunction probably through increased oxidant stress. Paraoxonase (PON1) is an high-density lipoprotein (HDL)-linked anti-oxidant enzyme whose capacity is influenced by a genetic polymorphism at codon 192. In the present study we have investigated the role of PON1 polymorphism on endothelial function in subjects with T2DM with or without hypertension. Three groups of male subjects were enrolled: 65 healthy control subjects without T2DM or hypertension (CON), 51 with only T2DM (DM), and 67 with both hypertension and T2DM (HYP+DM). The PON1 Gln192Arg polymorphism was determined by polymerase chain reaction (PCR) amplification and restriction analysis. Endothelial function was evaluated as flow-mediated vasodilatation (FMD) of the brachial artery after forearm ischemia. Data were analyzed according to the presence or absence of the Arg allele. Subjects with T2DM had markedly impaired FMD, compared with those of the CON group. In the CON and HYP+DM groups no difference was observed in FMD between subjects homozygous for the Gln allele and those carrying the Arg allele. In the DM group FMD was lower among those carrying the Arg allele compared with Gln/Gln homozygotes (2.1+/-2.4% vs. 6.2+/-5.2%, p=0.002). In conclusion, the present findings demonstrated that FMD was less impaired in normotensive diabetic subjects homozygous for the Gln allele, consistent with the notion that this isoform has a more effective antioxidant action that serves to protect circulating low-density lipoprotein (LDL). Hypertension seems to abolish the protective effect of the Gln isoform. These findings, however, warrant further investigation to clarify their clinical import

A Novel Mini-invasive Approach to the Treatment of Neuropathic Pain: The PENS Study

Background: Peripheral neuromodulation is often used as chronic neuropathic pain treatment. Percutaneous electrical nerve stimulation (PENS) is generally utilized with several probes at the same time and repeated treatments.Objectives: Evaluate the short-and long-term efficacy of a single probe and single shot PENS approach. Study Design: Multicenter, prospective, observational study.Setting: Four Italian pain therapy centers.Methods: Inclusion criteria were age >= 18 and <= 80 years, presence of severe peripheral neuropathic pain lasting more than 3 months, localized and refractory to pharmacological therapies. Patients with infection, coagulopathies, psychiatric disorders, pacemakers, or implantable cardiac defibrillators were excluded.Patients: Seventy-six patients (47 women, 29 men), mean age 62 +/- 14 years, affected by neuralgia (21 herpes zoster infection, 31 causalgia, 24 postoperative pain) were enrolled in the study. Intervention: After localization of trigger point and/or allodynic/hyperalgesic area, PENS therapy was achieved with a single 21 gauge conductive probe tunneled percutaneously and a neurostimulator device.Measurement: Numerical Rating Scale (NRS) and Neuropathic Pain Scale (NPS) were assessed at baseline, 60 minutes after PENS, at one week, after one, 3, and 6 months; perceived health outcome was measured with Euroqol-5 dimension (EQ-5D) questionnaire at baseline and at 6 months. Adverse events and patient satisfaction were reported.Results: NRS and NPS decreased significantly after 60 minutes and the reduction remained constant over time at follow-up. EQ-5D increased significantly with respect to the baseline. Two nonclinically significant adverse events (one contralateral dysestesia and one self-resolving hematoma) were observed.Limitations: Small sample size and non-randomized observational study; high prevalence of post-herpetic and occipital neuralgias.Conclusion: PENS therapy produced significant and long-lasting pain relief in chronic peripheral neuropathic pains of different etiology. The present study confirms the feasibility, safety, and repeatability of this minimally invasive technique

Stromelysin gene promoter polymorphism and common carotid geometry in diabetic subjects.

AIM: Stromelysin (MMP3), through its action on collagen and other matrix metalloproteinases, influences arterial wall remodeling. In healthy subjects, the 5A/6A polymorphism located in the promoter of the MMP3 gene is associated with common carotid remodeling, 6A/6A subjects having increased arterial diameter, wall thickness (intima-media thickness, IMT) and decreased wall shear stress (WSS). In the present study, we have investigated the influence of the 5A/6A polymorphism on common carotid remodeling in subjects with diabetes mellitus. METHODS: Diabetic subjects (N.=136) and age-matched healthy male controls (N.=101) have been studied. Common carotid diameter, IMT and flow velocity have been measured by echo-Doppler. Blood viscosity has been measured by a cone/plate viscometer. WSS has been calculated. RESULTS: Diabetic patients had increased common carotid diameter, IMT, and decreased flow velocity and WSS (all P<0.05), compared with controls. In controls, subjects homozygous for the 6A allele had increased diameter, IMT and decreased WSS. In diabetics, no difference was observed in vascular parameters among the three genotypes. CONCLUSION: The 5A/6A polymorphism of the MMP3 gene influences arterial remodeling of the common carotid artery in healthy subjects, but not in patients with diabetes mellitus. Therefore, the significance of the 5A/6A polymorphism as a marker of risk in this high cardiovascular risk population seems to be somehow blunted

Selective Adsorption of Homocysteine Using an HFR-ON LINE Technique

HFR-ON LINE (double chamber HDF with reinfusion of ultrafiltrate regenerated through a charcoalresin cartridge) is a novel method which combines the processes of diffusion, convection, and adsorbance. We have investigated the effect of such a treatment on the homocysteine (Hcy) levels in ten patients with a mean Hcy level of 57.6 mmol/L (range 24.1–119.7 mmol/L). We have measured the Hcy, folate, and vitamin B12 predialysis and postdialysis, and in the ultrafiltrate precartridge and postcartridge at 10, 120, and 240 min. The mean Hcy levels were 57.6 and 35.3 mmol/L (range 9.9–80.3 mmol/L) (P = 0.005) predialysis and postdialysis, respectively, while folate and vitamin B12 were unchanged. Precartridge and postcartridge Hcy levels were 11.6 vs. 2.5 mmol/L (P = 0.005), 9.3 vs. 3.9 mmol/L (P = 0.005), and 7.7 vs. 4.6 mmol/L (P = 0.012) at the three time points considered, while folate and vitamin B12 were essentially undetectable.These preliminary data, which need confirmation in a long-term study, seem to indicate that HFRONLINE is able to reduce Hcy levels not only through a likely reduction of uremic toxins, but also through an actual removal of Hcy by adsorbance onto the charcoalresin cartridge

Beta-sitosterolaemia: a new nonsense mutation in the ABCG5 gene.

BACKGROUND: Sitosterolaemia is a rare autosomal recessive disorder characterised by elevated plasma levels of plant sterols and cholesterol. Sitosterolaemia is caused by gene mutations in either of two ATP-binding cassette (ABC) half transporters, ABCG5 and ABCG8. The plasma sterol profile and genetic analysis of a 10-year-old girl who had tuberous xanthomas is the subject of this report. MATERIALS AND METHODS: Genomic DNA was isolated from white blood cells from the proband, her family and a control group of healthy people. All exons of ABCG5 and ABCG8 were sequenced. Plasma cholesterol and triglycerides were measured by routine methods. All other plasma sterols were measured by Gas Chromatography coupled to Mass Spectrometry. RESULTS: The proband was found to be homozygous for a single nucleotide mutation in exon 10 of the ABCG5 gene, consisting of a C to T transition at nucleotide 1336 of the coding sequence, which results in the premature termination of the ABCG5 protein at amino acid 446 (Arg446X). Her mother and brother were also homozygous for the same mutation and all had elevated plasma beta-sitosterol levels. The father was heterozygous and showed normal beta-sitosterol levels. This mutation was not found in healthy normolipidaemic subjects. CONCLUSIONS: We describe a novel nonsense mutation in exon 10 of the ABCG5 gene in a 10-year-old girl showing clinical and biochemical features of sitosterolaemia. This family study broadens the spectrum of the ABCG5/ABCG8 mutations causing sitosterolaemia and helps highlight the correlations between such gene mutations, biochemical phenotype and the development of cardiovascular \ud disease