EXPRESS: Landmark Publications in Analytical Atomic Spectrometry: Fundamentals and Instrumentation Development.

The almost-two-centuries history of spectrochemical analysis has generated a body of literature so vast that it has become nearly intractable for experts, much less for those wishing to enter the field. Authoritative, focused reviews help to address this problem but become so granular that the overall directions of the field are lost. This broader perspective can be provided partially by general overviews but then the thinking, experimental details, theoretical underpinnings and instrumental innovations of the original work must be sacrificed. In the present compilation, this dilemma is overcome by assembling the most impactful publications in the area of analytical atomic spectrometry. Each entry was proposed by at least one current expert in the field and supported by a narrative that justifies its inclusion. The entries were then assembled into a coherent sequence and returned to contributors for a round-robin review.

Evaluation of highly adsorptive Guefoams (multifunctional guest-containing foams) as a potential sorbent for determination of volatile organic compounds (VOCs) by means of thermal desorption.

The present work delves into the feasibility of employing a novel structured sorbent referred to as GFAD (Guefoam Adsorption Device) for the determination of volatile organic compounds (VOCs) in liquid samples. The chosen method has been static headspace sorptive extraction-thermal desorption gas chromatography mass spectrometry (HSSE-TD-GC-MS). The GFAD comprises an aluminum cellular material with a distinct replication structure and a solid guest phase consisting of activated carbon particles dispersed within the cavities of the cellular aluminum. The extensive specific surface area, robustness, and exceptional thermal conductivity of this pioneering material offer distinct advantages over commercially available polydimethylsiloxane-based Twister® devices. Therefore, the trapping efficiency for volatile organic compounds is enhanced, and it is possible to perform the analysis of concentrated samples. According to computational simulations, it has been demonstrated that GFAD has a high heat conductivity. As a result, the desorption efficiency is improved, and minimal temperature gradients are generated throughout the GFAD during the heating process. Besides, the energy consumption is significantly lowered, thus aligning with environmentally conscientious and sustainable analytical practices.The experimental results give a proof of the suitability of the GFAD for determining gaseous compounds in liquid samples through HSSE-TD-GC-MS. For volatile species, the new material provides higher peak areas and lower limits of detection than a commercially available Twister® device. Furthermore, the GFAD is reusable, its adsorbing properties remaining unchanged during, at least, 100 consecutive analyses. In addition, unlike to the Twister®, no intense siloxane peaks are observed in the chromatograms obtained with the GFAD. The feasibility of qualitative and semi-quantitative analysis with the new accessory has been demonstrated with both standards and a cereal bioethanol real sample.

Application of Dispersive Liquid-Liquid Aerosol Phase Extraction to the Analysis of Total and Individual Phenolic Compounds in Fried Extra Virgin Olive Oils.

Seventeen extra virgin olive oil samples from Valencian Community (Spain) were submitted to a domestic-frying process (180 °C) during different degradation times (5, 10, 30, 60, 120 min). A dispersive liquid-liquid aerosol phase extraction by using a methanol/water (50:50) extracting solution was used to isolate the polyphenol fraction. Total phenolic content (TPC) was determined, whereas the determination of seven individual target polyphenolic compounds (hydroxytyrosol, tyrosol, oleuropein, vanillic acid, p-coumaric acid, ferulic acid, and vanillin) was carried out by using ultrahigh-performance liquid chromatography coupled to a tandem mass spectrometer. Statistically significant differences in the TPC values were found for Blanqueta and Manzanilla samples from different harvesting years. The domestic-frying process impacted the TPC and the individual phenolic compounds content. Thermal treatment for 2 h gave rise to a 94% decrease in the TPC. A first-order kinetic model was suitable to accurately describe the degradation of the individual phenolic compounds.

Efficacy and Safety of Anakinra Plus Standard of Care for Patients With Severe COVID-19: A Randomized Phase 2/3 Clinical Trial.

Importance: COVID-19 pneumonia is often associated with hyperinflammation. The efficacy and safety of anakinra in treating patients with severe COVID-19 pneumonia and hyperinflammation are still unclear. Objective: To assess the efficacy and safety of anakinra vs standard of care alone for patients with severe COVID-19 pneumonia and hyperinflammation. Design, Setting, and Participants: The Clinical Trial of the Use of Anakinra in Cytokine Storm Syndrome Secondary to COVID-19 (ANA-COVID-GEAS) was a multicenter, randomized, open-label, 2-group, phase 2/3 clinical trial conducted at 12 hospitals in Spain between May 8, 2020, and March 1, 2021, with a follow-up of 1 month. Participants were adult patients with severe COVID-19 pneumonia and hyperinflammation. Hyperinflammation was defined as interleukin-6 greater than 40 pg/mL, ferritin greater than 500 ng/mL, C-reactive protein greater than 3 mg/dL (rationale, ≥5 upper normal limit), and/or lactate dehydrogenase greater than 300 U/L. Severe pneumonia was considered if at least 1 of the following conditions was met: ambient air oxygen saturation 94% or less measured with a pulse oximeter, ratio of partial pressure O2 to fraction of inspired O2 of 300 or less, and/or a ratio of O2 saturation measured with pulse oximeter to fraction of inspired O2 of 350 or less. Data analysis was performed from April to October 2021. Interventions: Usual standard of care plus anakinra (anakinra group) or usual standard of care alone (SoC group). Anakinra was given at a dose of 100 mg 4 times a day intravenously. Main Outcomes and Measures: The primary outcome was the proportion of patients not requiring mechanical ventilation up to 15 days after treatment initiation, assessed on an intention-to-treat basis. Results: A total of 179 patients (123 men [69.9%]; mean [SD] age, 60.5 [11.5] years) were randomly assigned to the anakinra group (92 patients) or to the SoC group (87 patients). The proportion of patients not requiring mechanical ventilation up to day 15 was not significantly different between groups (64 of 83 patients [77.1%] in the anakinra group vs 67 of 78 patients [85.9%] in the SoC group; risk ratio [RR], 0.90; 95% CI, 0.77-1.04; P = .16). Anakinra did not result in any difference in time to mechanical ventilation (hazard ratio, 1.72; 95% CI, 0.82-3.62; P = .14). There was no significant difference between groups in the proportion of patients not requiring invasive mechanical ventilation up to day 15 (RR, 0.99; 95% CI, 0.88-1.11; P > .99). Conclusions and Relevance: In this randomized clinical trial, anakinra did not prevent the need for mechanical ventilation or reduce mortality risk compared with standard of care alone among hospitalized patients with severe COVID-19 pneumonia. Trial Registration: ClinicalTrials.gov Identifier: NCT04443881.

High temperature total consumption sample introduction system coupled to microwave plasma optical emission spectrometry (MIP-OES) for the analysis of aqueous samples.

The high temperature torch integrated sample introduction system (hTISIS) is coupled to microwave plasma optical emission spectrometry (MIP-OES) for the first time. The goal of this work is to develop an accurate analysis of digested samples under continuous sample aspiration mode by coupling the hTISIS to a MIP-OES instrument. To achieve this, different operating conditions such as, nebulization flow rate, liquid flow rate and the spray chamber temperature were optimized in terms of sensitivity, limits of quantification (LOQs) and background equivalent concentration (BECs) for the determination of Ca, Cr, Cu Fe, K, Mg, Mn, Na, Pb and Zn, and these values were compared with those reported with a conventional sample introduction system. Under optimum conditions (0.8-1 L min-1, 100 µL min-1 and 400 ᵒC, respectively), the hTISIS improved MIP-OES analytical figures of merit and shortened 4-times wash out times with respect to a conventional cyclonic spray chamber, reporting an enhancement factor in the sensitivity among 2-47 times and LOQs from 0.9 to 360 µg kg-1. Once the best operating conditions were set, the magnitude of the interference caused by 15 different acid matrices (2, 5 and 10% w/w of HNO3, H2SO4, HCl and mixtures of HNO3 with H2SO4 and HNO3 with HCl) was significantly lower for the former device. Finally, 6 different digested oily samples (used cooking oil, animal fat, corn oil and the same samples after a filtration step) were analyzed by means of an external calibration approach based on the use of multielemental standards prepared in 3% (w/w) HCl solution. The obtained results were compared against those supplied by a conventional methodology employing an inductively coupled plasma optical emission spectrometry, ICP-OES, instrument. It was clearly concluded that the hTISIS coupled to MIP-OES afforded similar concentrations as compared to the conventional methodology.

Localized Quantitative Analysis of Polymeric Films through Laser Ablation-Inductively Coupled Plasma Mass Spectrometry.

The present work shows, for the first time, the application of laser ablation connected to inductively coupled plasma mass spectrometry (LA-ICP-MS) to the localized quantitative analysis of inclusions in polymeric industrial films. The multielemental mapping capabilities of LA-ICP-MS has allowed to chemically examine unique defects appeared during the plastic processing. This analytical tool is perfectly suited to detect elements such as Al, Mg, Zr, Ti, Cr, P, Pb, Sb, Zn, and Si in those inclusions. A method for multielemental quantitative analysis of these defects has been developed in the present work. The profiling for more than 100 different defects in three samples has demonstrated that more than 50% of these inclusions contain aggregates of some of the aforementioned elements. Therefore, the distribution of elements used as additives or present in catalysts must be carefully controlled during the production of polymeric films in order to avoid degradation in their performance.

Prospect on Rare Earth Elements and Metals Fingerprint for the Geographical Discrimination of Commercial Spanish Wines.

This paper presents a novel tool for Spanish commercial wine discrimination according to their designation of origin (PDO). A total of 65 commercial wines from different Spanish designation of origin (Alicante, Bullas, Campo de Borja, Jumilla, Castilla la Mancha, Ribeiro, Ribera de Duero, Rioja, Rueda, Utiel-Requena, Valdepeñas and Valencia) were characterized. The rare earth elements (REEs) content was determined by a high-temperature torch integrated sample introduction system (hTISIS) coupled to inductively coupled plasma mass spectrometry (ICP-MS). The REE content was used to draw characteristic PDOs radar charts. Results indicated that the REEs fingerprint provides a good prospect to discriminate the different Spanish PDOs, except for Alicante, Castilla la Mancha, Jumilla, Utiel-Requena and Valdepeñas. Finally, for those PDOs that were not properly distinguished, a second fingerprint obtained from Ba, Co, Cr, Mn, Ni, Pb and V content was used for discrimination purposes.

Profiling of Organic Compounds in Bioethanol Samples of Different Nature and the Related Fractions.

Forty-one bioethanol real samples and related fractions, together with a biobutanol sample, have been analyzed with gas chromatography coupled to either mass spectrometry (GC-MS) or flame ionization detection (GC-FID). Bioethanol with different water contents, samples originated from several sources of biomass, first- as well as second-generation specimens, distillation fractions, samples stocked in containers made of four different materials, and, finally, a biobutanol sample have been analyzed. The number of the compounds found through GC-MS has been 130, including alcohols, aldehydes, ketones, esters, ethers, nitrogen compounds, organic acids, furane derivates as well as other species (e.g., limonene). Afterward, a quantitative determination of major components of bioethanol has been carried out. The achieved results have revealed that, besides ethanol and, in some cases, water, species such as acetaldehyde, methanol, and higher alcohols, as well as 1,1-diethoxyethane, may be present at concentrations above 500 mg L-1. While the source of bioethanol (nature of the raw material, ethanol generation, or water content) has a direct impact on its volatile organic compound (VOC) profile, the material of the container where the biofuel has been stored does not play a significant role. Finally, the results have demonstrated that, for a given production process, different distillation fractions contain unequal VOC profiles.

Evolution of the Multielemental Content along the Red Wine Production Process from Tempranillo and Grenache Grape Varieties.

In the present work, 38 elements were quantified in the different fractions generated by applying amateur winemaking methods. Inductively Coupled Plasma Mass Spectrometry was used as detection technique. Grapes were analyzed and separate metal profiles were also obtained for the skin and seeds. Additional vinification fractions included musts before and after the fermentation process. Meanwhile, solid fractions corresponded to the so-called hat, pressed pomace and the lees obtained after gravitational settling at the tank bottom. Wine was further analyzed. The obtained results revealed a different repartition depending on the particular element and winemaking solid and liquid fraction evaluated. The studies included vinification in presence and in absence of added yeast and grape geographical origin. Principal component analysis helped to discriminate among fractions and to determine the critical elements behaving differently. Finally, a mass balance allowed to unequivocally detect the migration of a given element to the winemaking fractions.

Total polyphenol content and metals determination in Spanish virgin olive oils by means of a dispersive liquid-liquid aerosol phase extraction method and ICP-MS.

This report presents a study on the determination of total polyphenols together with metals in several samples of olive oil produced in Spain. The results provided by applying a conventional extraction method were compared against those encountered by means of the so-called Dispersive Liquid-Liquid Aerosol Phase Extraction method. The novel method is based on the dispersion of the extracting solution in the sample. To accomplish this, an aerosol is pneumatically generated and directed against the surface of the oil sample. The aerosol was generated in order to increase as much as possible the surface area of the interface between the two involved non-miscible phases. As a result, the partition equilibrium was quickly achieved. The critical variables dictating the characteristics of the obtained aerosols as well as those influencing the partition equilibrium state were studied. With the aerosol phase extraction method, the values corresponding to the total polyphenols and metals in real samples were not statistically different as compared to those obtained by the conventional liquid - liquid extraction method. The new method provided shorter extraction times and lower mass of consumed reagents than the conventional one, thus giving rise to a more environmentally friendly method. For polyphenols, calculated limits of detection and quantification were 0.48 and 1.5 mg of gallic acid kg-1, respectively. The absorbance linearity, in turn, was kept from 0 to 50 mg kg-1 (R2 = 0.998). In the case of metal and metalloid quantification, the limits of detection found with a sample digestion method ranged from 1.3 (Cu) to 291 (Na) ng mL-1. Meanwhile, because of the lower dilution factor, this parameter was one order of magnitude lower when these elements were extracted according to the new method. The new extraction method was applied to the analysis of 42 extra virgin olive oils both bottled and directly collected from the oil press, containing single cultivars or blends and produced from different areas. Fresh oils were analyzed and a preliminary study on the oil thermal degradation was also done. Dispersing the extracting solution as an aerosol into the sample can be considered a versatile method able to provide extensive oil chemical information in a rapid way what is especially important in the case of polyphenols.

Comparative evaluation of ICP sample introduction systems to be used in the metabolite profiling of chlorine-containing pharmaceuticals via HPLC-ICP-MS.

A systematic evaluation of four different ICP sample introduction systems to be used in the context of metabolite profiling of chlorine-containing pharmaceuticals via HPLC-ICP-MS was carried out using diclofenac and its major metabolite, 4'-hydroxy-diclofenac, as model compounds. The strict requirements for GMP validation of chromatographic methods in the pharmaceutical industry were adhered to in this context. The final aim of this investigation is an extension of the applicability and validatability of HPLC-ICP-MS in the field of pharmaceutical R&D. Five different gradient programmes were tested while the baseline peak width (wb), peak capacity (P), USP tailing factor (As) and USP signal-to-noise ratio (USP S/N) were determined as major indicators of the chromatographic performance and the values obtained were compared to the corresponding FDA recommendations (if applicable). Four different ICP-MS sample introductions systems were investigated involving two units typically working at higher flow rates (∼1.0 mL min-1) and another two systems working at lower flow rates (∼0.1 mL min-1). Optimal conditions with potential for applicability under GMP conditions were found at a mobile phase flow rate of 1.0 mL min-1 by using a pneumatic micro-flow LC nebulizer mounted onto a Peltier-cooled cyclonic spray chamber cooled to -1 °C for sample introduction. Under these conditions, HPLC-ICP-MS provided a chromatographic performance similar to that of HPLC with UV detection. The peak shape (USP tailing factor = 1.1-1.4) was significantly improved compared to that obtained with the Peltier-cooled Scott-type spray chamber. Two alternative sample introduction systems - a POINT® and a High-Temperature Torch-Integrated Sample Introduction System (hTISIS) - were also tested at a flow rate of 0.1 mL min-1 using a chromatographic column with 1.0 mm ID. Although these systems allowed the peak shape to be improved compared to that obtained with the traditional Scott-type spray chamber, the limits of detection and of quantification achievable were strongly compromised due to the significantly lower sensitivity observed for Cl. In addition to a comparison of the aforementioned sample introduction systems, also the effect of spray chamber temperature was evaluated and it was demonstrated that proper temperature control plays an essential role in the optimization of HPLC-ICP-MS methods.

Aerosol-Phase Extraction Method for Determination of Ca, K, Mg, and Na in Biodiesel through Inductively Coupled Plasma Optical Emission Spectrometry.

A novel extraction method was developed, optimized, and validated for the elemental analysis of organic samples. The method, called aerosol-phase extraction (APE), is based on nebulization of the extracting aqueous solution (0.1 mol·L-1 nitric acid) on the sample. Extraction was performed at the interface of generated extractant droplets as they entered into contact with the samples. Afterward, the phases were allowed to separate and Ca, K, Na, and Mg were determined in aqueous phase by means of inductively coupled plasma optical emission spectroscopy (ICP-OES). Measurement of aerosol characteristics demonstrated that a water-in-oil emulsion was generated. Therefore, once the aqueous solution was dispersed into the sample, the phases spontaneously separated. Furthermore, the interfacial specific surface area exhibited values on the order of 1 m2·mL-1, hence enhancing the extraction kinetics over conventional extraction methods. Key variables affecting the extraction yield were the nebulization gas flow rate, liquid flow rate, extraction time, acid concentration, nebulizer tip to sample surface gap, and morg/maq ratio. Once the optimal conditions were selected, the method was applied and validated for the determination of Ca, K, Na, and Mg by ICP-OES in 0.5 mL biodiesel samples with an expanded uncertainty lower than 2%. With the APE method, the extraction time was around 1 min, whereas conventional methods employed to perform this kind of extraction required from 4 to 50 min. Additionally, the APE involved preconcentration of analytes, thus lowering the limit of detection (LOD) to the nanograms per milliliter level (i.e., LODs based on the 3sb criterion were 32, 20, 19, and 24 ng·mL-1 for Ca, K, Na, and Mg, respectively). Furthermore, accuracy of quantification of Ca, K, Na, and Mg concentration by APE was not significantly different as compared to that afforded by conventional liquid-liquid extraction. Finally, Ca, K, Na, and Mg contents were determined in four real samples in the 0.5-13 mg·kg-1 range. The obtained results were not statistically different from those encountered with a microwave-based digestion method.

Fully Automatic In-Syringe Magnetic Stirring-Assisted Dispersive Liquid-Liquid Microextraction Hyphenated to High-Temperature Torch Integrated Sample Introduction System-Inductively Coupled Plasma Spectrometer with Direct Injection of the Organic Phase.

A proof of concept study involving the online coupling of automatic dispersive liquid-liquid microextraction (DLLME) to inductively coupled plasma optical emission spectrometry (ICP OES) with direct introduction and analysis of the organic extract is herein reported for the first time. The flow-based analyzer features a lab-in-syringe (LIS) setup with an integrated stirring system, a Meinhard nebulizer in combination with a heated single-pass spray chamber, and a rotary injection valve, used as an online interface between the microextraction system and the detection instrument. Air-segmented flow was used for delivery of a fraction of the nonwater miscible extraction phase, 12 µL of xylene, to the nebulizer. All sample preparative steps including magnetic stirring assisted DLLME were carried out inside the syringe void volume as a size-adaptable yet sealed mixing and extraction chamber. Determination of trace level concentrations of cadmium, copper, lead, and silver as model analytes has been demonstrated by microextraction as diethyldithiophosphate (DDTP) complexes. The automatic LIS-DLLME method features quantitative metal extraction, even in troublesome sample matrixes, such as seawater, salt, and fruit juices, with relative recoveries within the range of 94-103%, 93-100%, and 92-99%, respectively. Furthermore, no statistically significant differences at the 0.05 significance level were found between concentration values experimentally obtained and the certified values of two serum standard reference materials.

Determination of fat-soluble vitamins in vegetable oils through microwave-assisted high-performance liquid chromatography.

In this manuscript, a study of the effect of microwave radiation on the high-performance liquid chromatography separation of tocopherols and vitamin K1 was conducted. The novelty of the application was the use of a relatively low polarity mobile phase in which the dielectric heating effect was minimized to evaluate the nonthermal effect of the microwave radiation over the separation process. Results obtained show that microwave-assisted high-performance liquid chromatography had a shorter analysis time from 31.5 to 13.3 min when the lowest microwave power was used. Moreover, narrower peaks were obtained; hence the separation was more efficient maintaining or even increasing the resolution between the peaks. This result confirms that the increase in mobile phase temperature is not the only variable for improving the separation process but also other nonthermal processes must intervene. Fluorescence detection demonstrated better signal-to-noise compared to photodiode arrayed detection mainly due to the independent effect of microwave pulses on the baseline noise, but photodiode array detection was finally chosen as it allowed a simultaneous detection of nonfluorescent compounds. Finally, a determination of the content of the vitamin E homologs was carried out in different vegetable oils. Results were coherent with those found in the literature.

Increased circulating endothelial cells and microparticles in patients with psoriasis.

INTRODUCTION: Psoriasis is a chronic pathology characterized by increased inflammation that can be associated with changes in the vascular endothelium. We quantified the levels of circulating endothelial cells (CECs) and microparticles (MPs) in patients with psoriasis in order to analyze their relationship with endothelial and inflammation markers, subclinical atherosclerosis and microcirculation. METHODS: We studied 20 patients and 20 controls. Circulating markers of endothelial damage (CEC, MPs and von Willebrand factor, vWF) and inflammation (E-selectin, E-sel; Interleukin-6, IL-6 and C-reactive protein, CRP) were determined. Subclinical atherosclerosis was assessed by carotid ultrasound to obtain intima-media thickness. Microcirculation was evaluated by nailfold capillaroscopy. RESULTS: CECs, MPs, vWF, CRP and E-sel levels were significantly elevated in patients when compared with controls (p <  0.05). Ninety-four and fifty-three percentage of patients had CEC and MP levels higher than 99th percentile in controls. Forty-seven percent of patients simultaneously showed increased CEC and MP levels. MPs correlate with the inflammatory markers and with the intima-media thickness. CECs correlate with the capillaries loops per mm (p <  0.05). CONCLUSION: Psoriasis patients show elevated CECs and MPs, as a sign of endothelial dysfunction, which correlates with inflammatory markers as well as subclinical atherosclerosis and some capillaroscopy findings.

Haematological, biochemical and inflammatory parameters in inactive Behçet's disease. Its association with red blood cell distribution width.

Red blood cell distribution width (RDW) has been shown to be associated with disease activity in several inflammatory disorders. However only one study to show this has been conducted in patients with Behçet's disease (BD). The aim of the present study was to analyse the association of RDW with BD and its main complications; i.e.; thrombosis and posterior uveitis. A second aim was to analyse the possible correlation between RDW and both haematological and inflammatory parameters. Eighty-nine patients with BD (48 males/41 females) and 94 controls (49 males/45 females) were included in the study. Patients were in an inactive phase of the disease, showing only minimum activity. RDW was statistically higher in patients than in controls (14.02 ± 1.32 vs. 13.15 ± 0.75; p < 0.001) as were CRP, fibrinogen, leucocytes and neutrophils (p < 0.001). No differences in haematimetric indices (MCV, MCH, MCHC) were observed (p > 0.05). RDW correlated negatively with haemoglobin, MCH and MCHC (p < 0.05), and directly with homocysteine (p < 0.01). No correlation was found between RDW and the several inflammatory parameters analysed (p > 0.05). The multivariate regression analysis revealed that haemoglobin and homocysteine were independent predictors of RDW (beta coefficient: -0.310; p = 0.003, beta coefficient: 0.379; p < 0.001, respectively). RDW >14 was associated with neither thrombosis nor uveitis (p = 0.935; p = 0.553, respectively). Our results indicate that BD patients show increased RDW when compared with controls. This increase seems to be related with haematimetric indices and with homocysteine levels. Lack of correlation with inflammatory markers may be due to the fact that patients were in an inactive phase of the disease.

Hemorheological profile in primary and secondary Raynaud's phenomenon. Influence of microangiopathy.

Raynaud's phenomenon (RP) is an episodic peripheral circulatory disorder characterized by local artery spams in subjects exposed to cold or emotional stress. It is not well-established whether RP patients show an altered rheological profile, mostly due to patient classification and clinical severity. We aimed to compare the hemorheological profile in patients with primary and secondary RP with a healthy control group. Eighteen primary RP, 22 secondary RP and 22 healthy controls, were included in the study. RP patients were also divided according to the presence of digital ulcers (7 with, 33 without). Biochemical and hemorheological variables were analyzed, including glucose, triglycerides, total-cholesterol, immunoglobulins, fibrinogen, plasma viscosity, erythrocyte aggregation, erythrocyte deformability and blood viscosity. Age was higher in secondary RP as compared with primary (p = 0.049), while glucose, triglycerides IgA, IgG and plasma viscosity were higher in secondary RP than in healthy subjects (p < 0.05). RP patients with digital ulcers presented higher IgA (p = 0.012), lower erythrocyte aggregation time (p = 0.008) and a trend for higher fibrinogen levels and plasma viscosity (p = 0.064, p = 0.069, respectively). The results of the present study indicate that secondary RP patients show a mild impairment of the rheological profile that aggravates with microangiopathy severity.

Homocysteine levels in patients with primary and secondary Raynaud's phenomenon. Its association with microangiopathy severity.

The association between hyperhomocysteinemia (HHcy) and Raynaud's phenomenon (RP) remains a matter of debate. In 18 primary RP, 23 secondary RP and 41 controls, we investigated homocysteine (Hcy) levels along with biochemical and inflammatory parameters. The Hcy levels in both primary and secondary RP were elevated when compared with controls (p < 0.05 and p < 0.01, respectively). As age was higher in secondary RP as compared with controls (p < 0.01), both primary and secondary RP were age-matched with a corresponding control group, and with Hcy maintaining its statistical significance (p < 0.05). No differences in creatinine, B12 vitamin or folic acid were observed between groups (p > 0.05), or in the prevalence of cardiovascular risk factors (p > 0.05). When patients were classified according to presence or absence of digital ulcers, as a sign of microangiopathy severity, the former showed higher Hcy levels than the latter (p = 0.035). Our results indicate that both primary and secondary RP patients show a mild increase in Hcy levels, which is not related to age, vitamin deficiencies or impaired renal function, but is related to microangiopathy severity. Therefore the association of HHcy and RP suggest that Hcy may contribute to endothelial dysregulation, which characterizes this disease. Specific studies should be designed to elucidate the pathogenesis of HHcy in these patients.