A zinc-doped endodontic cement facilitates functional mineralization and stress dissipation at the dentin surface.

BACKGROUND: The purpose of this study was to evaluate nanohardness and viscoelastic behavior of dentin surfaces treated with two canal sealer cements for dentin remineralization. MATERIAL AND METHODS: Dentin surfaces were subjected to: i) 37% phosphoric acid (PA) or ii) 0.5 M ethylenediaminetetraacetic acid (EDTA) conditioning prior to the application of two experimental hydroxyapatite-based cements, containing sodium hydroxide (calcypatite) or zinc oxide (oxipatite), respectively. Samples were stored in simulated body fluid during 24 h or 21 d. The intertubular and peritubular dentin were evaluated using a nanoindenter to assess nanohardness (Hi). The load/displacement responses were used for the nano-dynamic mechanical analysis to estimate complex modulus (E*) and tan delta (δ). The modulus mapping was obtained by imposing a quasistatic force setpoint to which a sinusoidal force was superimposed. AFM imaging and FESEM analysis were performed. RESULTS: After 21 d of storage, dentin surfaces treated with EDTA+calcypatite, PA+calcypatite and EDTA+oxipatite showed viscoelastic discrepancies between peritubular and intertubular dentin, meaning a risk for cracking and breakdown of the surface. At both 24 h and 21 d, tan δ values at intertubular dentin treated with the four treatments performed similar. At 21 d time point, intertubular dentin treated with PA+oxipatite achieved the highest complex modulus and nanohardness, i.e., highest resistance to deformation and functional mineralization, among groups. CONCLUSIONS: Intertubular and peritubular dentin treated with PA+oxipatite showed similar values of tan δ after 21 d of storage. This produced a favorable dissipation of energy with minimal energy concentration, preserving the structural integrity at the dentin surface.

A zinc oxide-modified hydroxyapatite-based cement facilitated new crystalline-stoichiometric and amorphous apatite precipitation on dentine.

AIM: To evaluate the remineralization ability of two endodontic sealer cements. METHODOLOGY: Mid-coronal dentine surfaces were subjected to: (i) 37% phosphoric acid (PA) or (ii) 0.5 mol L-1 ethylenediaminetetraacetic acid (EDTA) conditioning prior to the application of two experimental hydroxyapatite-based cements, containing sodium hydroxide (calcypatite) or zinc oxide oxiapatite respectively. Samples were stored in simulated body fluid for 24 h or 21 days. Remineralization of the dentine surfaces were studied by Raman spectroscopy (mapping with K-means cluster and hierarchical cluster analysis) was undertaken. Nanoroughness and collagen fibril width measurements were performed with an atomic force microscopy. ANOVA and Student-Newman-Keuls test were performed (α=0.05). RESULTS: Phosphoric acid+oxiapatite promoted both the highest dentine mineralization (P < 0.05) and crystallographic maturity at the dentine surface. Noncrystalline amorphous-like apatites were also formed. Dentine treated with PA+calcypatite attained the roughest surface (P < 0.05) with minimal fibril width (P < 0.05). Cross-linking of collagen only became greater in the group PA+oxiapatite after 21 days. The maximum relative mineral concentration and structure of collagen linked to the amide I and ratio amide III/AGEs was obtained after using PA+calcypatite at 21-days time-point (P < 0.05). EDTA produced a lower stoichiometric hydroxyapatite (P < 0.05) with decreased maturity, at the expense of carbonate band widening, although it favoured the nucleation of carbonated calcium phosphate. CONCLUSIONS: Dentine surfaces treated with PA+oxiapatite attained the highest dentine remineralization with both crystalline-stoichiometric and amorphous apatites, at 21 days. EDTA conditioning facilitated amorphous-bulk mineral precipitation. The amorphization was more intense after using oxiapatite and provided an ion-rich environment favouring in situ dentine remineralization.

Synthesis and evaluation of hybrid molecules targeting the vinca domain of tubulin.

Some hybrids of vinca alkaloids and phomopsin A, linked by a glycine pattern, have been synthesized in one or two steps, by an insertion reaction and shown to inhibit microtubule assembly. These compounds have been elaborated in order to interact with both the "vinca site" and the "peptide site" of the vinca domain in tubulin. Two out of three hybrids are potent inhibitors of microtubules assembly and they present good cytotoxicity against different cell lines. Molecular modelling studies show that they could bind, within the vinca domain, in similar spatial regions as those of vinca and phomopsin thanks to the flexibility provided by the glycine linker used to elaborate these hybrids.

Cloning and characterization of the Mx1, Mx2 and Mx3 promoters from gilthead seabream (Sparus aurata).

Mx proteins are main effectors of the antiviral innate immune response mediated by type I interferon (IFN I). Actually, diverse Mx proteins from fish proved highly active against fish viruses, standing out among them the Mx1, Mx2 and Mx3 from gilthead seabream (Sparus aurata), a species exhibiting a natural resistance to viral diseases. In this study, the structure and functional activity of their corresponding promoters (pMx1, pMx2 and pMx3) have been assessed. The three promoters present an identical 3' region of 157 bp, exhibiting a single canonical interferon-stimulated response element (ISRE), which is indispensible for the poli:IC induction of pMx1 and pMx3, while not for that of pMx2. In the remaining part of the three promoters other regulatory motifs were identified, as gamma IFN activated sites in variable number (1, 4 and 2 in pMx1, pMx2 and pMx3, respectively), as well as several independent GAAA elements or ISRE core sequences (13, 15 and 12 in pMx1, pMx2 and pMx3, respectively). The structural dissimilarities shown by the three promoters parallels with the differences observed in their response profiles, in terms of the time course of the induction, and basal and induced expression levels of each promoter. Altogether, these findings indicate that the expression of Mx1, Mx2 and Mx3 genes from the gilthead seabream might be specifically regulated, in accordance with the functional role of each Mx protein in the successful antiviral response shown by this species.

[Translated article] The effect of showing preoperative photographs on patient satisfaction following forefoot surgery.

BACKGROUND: Postoperative outcome measurement typically relies on postoperative radiological results and clinical-functional scales; however, there is a growing interest in considering patient satisfaction (including subjective aspects) as part of the success of forefoot surgery. OBJECTIVE: To determine whether showing a preoperative photograph improves satisfaction in postoperative forefoot surgery patients. MATERIAL AND METHODS: An observational, cross-sectional, analytical study was conducted in the foot and ankle unit of our centre. We included 120 participants between 18 and 90 years old who underwent forefoot surgery. The degree of satisfaction was compared using the PSQ-10 questionnaire between a group of patients who received a preoperative foot appearance image at their 3-month postoperative follow-up and those who did not receive it. RESULTS: The overall satisfaction rate was 78.33% at 3 months after the intervention. The 93.6% of patients who received the photograph were satisfied at the postoperative follow-up, while in the control group, it was 86.2% with a p value of 0.218. CONCLUSION: The degree of satisfaction in patients undergoing forefoot surgery is not associated with the presentation of preoperative photographs.

Morphological and clinical findings in placentas and newborns with a history of tobacco, alcohol, and other substance abuse during pregnancy.

BACKGROUND: Exposure to toxins during pregnancy is the main modifiable behavior that affects the placenta and, consequently, the fetus. In particular, smoking is a recognized risk factor for negative outcomes. Our study pretended to examine gross and microscopic placental features in women who reported exposure to tobacco, alcohol, or other psychoactive substances. METHODS: In this observational case-control study, we collected 706 placentas to assess precise substance exposure histological-interaction features of in the placenta. We examined gross and microscopic placental features, and then recorded maternal and newborn clinical conditions. RESULTS: We found that 4.8% of mothers admitted to consumption of some type of (harmful) substance. The most common pre-existing maternal condition was obesity (20.3%); predominant complications included amniotic infection (32.3%), urinary tract infection (14.5%) and hypertensive disorders of pregnancy (14.5%). In newborns, we discovered positive associations as respiratory distress syndrome. Macroscopically, exposed mothers had heavier placentas, more true knots, and single umbilical artery; microscopically, they were more likely to exhibit fetal vascular malperfusion (FVM). CONCLUSIONS: Until our present study, no research linked umbilical cord defects to toxic substance exposure; our study results do confirm association with adverse outcomes in neonates and alterations in the neuro-cardio-placental circuit through FVM. IMPLICATIONS: The results are confirming the importance of this modifiable risk factor and how its presence may potentially affect the course of pregnancy, as well as the health of both mother and child.

Usefulness of Community Pharmacy for Early Detection of Cognitive Impairment in Older People Using the IQ-CODE Questionnaire.

BACKGROUND: People with cognitive impairment (CI) need to be identified early because of the risk of progression to dementia. OBJECTIVES: The primary objective of the study was to analyze the usefulness of the community pharmacy for early detection of CI in older people through their caregivers. As secondary objective the risk factors related to IQ-CODE classification of risk of CI were identified. DESIGN: A cross-sectional observational study was designed. SETTING: Caregivers were selected by pharmacists from Spanish community pharmacies. PARTICIPANTS: Subjects with a close relationship to persons over 70 years of age who were not previously diagnosed with CI and who did not live in a nursing home or were hospitalized participated in the study. MEASUREMENTS: The proportion of older people who were classified as "at risk of CI" was assessed using the Informant Questionnaire on Cognitive Decline in the Elderly (IQ-CODE), which was completed by the caregiver. RESULTS: A total of 197 pharmacists selected 910 caregivers with an average age of 53 years, 75.5% of whom were women. In 324 people over the age of 70 (38.5%), "risk of CI" was observed, increasing with age. The risk of CI was 4.3 times higher in older people who complained of memory loss (p<0.001), 2.5 times higher if they had had a stroke in the last two years (p=0.007), 1.9 times higher if they were smokers (p=0.045) and 1.6 times higher if they were diabetic (p=0.028). CONCLUSION: Detection of risk of CI from the community pharmacy showed prevalence figures consistent with the CI figures observed in the Spanish primary care setting, demonstrating the capacity of the community pharmacy to contribute to early detection of CI.

The effect of showing preoperative photographs on patient satisfaction following forefoot surgery. / Influencia de la fotografía preoperatoria en el grado de satisfacción en pacientes postoperados de cirugía de antepié.

BACKGROUND: Postoperative outcome measurement typically relies on postoperative radiological results and clinical-functional scales; however, there is a growing interest in considering patient satisfaction (including subjective aspects) as part of the success of forefoot surgery. OBJECTIVE: To determine whether showing a preoperative photograph improves satisfaction in postoperative forefoot surgery patients. MATERIAL AND METHODS: An observational, cross-sectional, analytical study was conducted in the foot and ankle unit of our center. We included 120 participants between 18 and 90 years old who underwent forefoot surgery. The degree of satisfaction was compared using the PSQ-10 questionnaire between a group of patients who received a preoperative foot appearance image at their 3-month postoperative follow-up and those who did not receive it. RESULTS: The overall satisfaction rate was 78.33% at 3 months after the intervention. The 93.6% of patients who received the photograph were satisfied at the postoperative follow-up, while in the control group, it was 86.2% with a p-value of 0.218. CONCLUSION: The degree of satisfaction in patients undergoing forefoot surgery is not associated with the presentation of preoperative photographs.

Changes in complement responses in Gilthead seabream (Sparus aurata) and European seabass (Dicentrarchus labrax) under crowding stress, plus viral and bacterial challenges.

Gilthead seabream (Sparus aurata) and European seabass (Dicentrarchus labrax) were subjected to either experimental infection with Photobacterium damselae subsp. piscicida or Nodavirus after a period of 2 weeks of crowding in which fish were subjected to a 5-fold increase in density (10-50 kg/m(3)). Samples were obtained before the crowding period (0 h or control) and at 24h and 72 h after crowding from both groups of infected fish. The Complement haemolytic activity and the expression of the C3 gene were evaluated in blood and liver samples respectively. The bacteriolytic and lysozyme activities were also assessed. The results showed that Complement haemolytic activity was reduced at 72 h with both bacteria and virus in high density Gilthead seabream, and a similar increase was observed at low density. Bacteriolytic activity under both bacterial and viral challenges for both species was increased at 24h, under low density. At high density, the bacterial challenge did not induce significant changes. C3 mRNA abundance was substantially increased after pathogen treatments in low density groups at 24h but no significant changes were detected at high densities. These results support the idea of the suppressor effect of stressors on the immune system since a reduction of Complement activity under virus and high density, or lack of response in C3 expression under high density were observed.

Molecular cloning and characterization of European seabass (Dicentrarchus labrax) and Gilthead seabream (Sparus aurata) complement component C3.

We present the complete C3 cDNA sequence of Gilthead seabream (Sparus aurata) and European seabass (Dicentrarchus labrax) and its molecular characterization with a descriptive analysis of their structural elements. We obtained one sequence for Gilthead seabream (gsbC3) which encodes a predicted protein of 1656 amino acids, and two sequences for European seabass (esbC3_1 and esbC3_2) which encode two predicted proteins of 1654 and 1587 amino acids respectively. All sequences present the characteristic structural features of C3 but interestingly esbC3_2 lacks the anaphylotoxin domain and the cysteine residue responsible for thiolester bond formation. Moreover, we have detected and quantified (by real-time PCR-based absolute quantification) specific isoform expression in European seabass depending on pathogen and density conditions in vivo. In addition, we have analyzed the tissue distribution pattern of European seabass and Gilthead seabream C3 genes under crowding stress and under pathological challenges in vivo, and we have observed that crowding and infection status provoke changes in expression levels, tissue expression pattern and C3 isoform expression balance.

[Functional results in the orthopedic treatment of acute ruptures of the Achilles tendon]. / Resultados funcionales en el tratamiento ortopédico de las roturas agudas del tendón de Aquiles.

OBJECTIVE: The purpose of this study is to assess the clinical and functional results of patients with acute middle third of Achilles tendon rupture treated conservatively by orthopedic boot and early weight-bearing. MATERIAL AND METHODS: This is a prospective observational study with 19 patients with acute Achilles tendon rupture treated by conservative treatment. Demographic variables, ATRS score, function using heel-rise test, calf circumference and Achilles tendon resting angle were analyzed. The clinical and functional registration was performed at six weeks, three, six and 12 months of injury. A statistical analysis was performed. RESULTS: At one year follow-up, the 94% of patients were capable of standing single heel rise, the mean of twin atrophy was 1.03 cm ± 0.51 compared to uninjured side and the difference of Achilles tendon resting angle was 5.63 degrees ± 4.17 compared to contralateral limb. The 83.24% of patients returned to play and the mean of ATRS score was 87.41 points ± 17.78. Two partial re-rupture (11%) were occurred at three months of follow-up, which continued with orthopedic treatment. CONCLUSIONS: Based on the results, functional orthopedic treatment using orthopedic boot and early weight-bearing presents good clinical and functional outcomes, considering it a valid treatment for acute Achilles tendon ruptures.

OBJETIVO: Analizar los resultados clínicos y funcionales de los pacientes con rotura aguda del cuerpo del tendón de Aquiles tratados de forma conservadora mediante bota ortopédica y carga precoz. MATERIAL Y MÉTODOS: Estudio observacional prospectivo con 19 pacientes con rotura aguda de tendón de Aquiles tratados de forma ortopédica. Se analizaron las variables demográficas, la escala ATRS (Achilles tendon Total Rupture Score), la función mediante el test de puntillas, masa muscular gemelar y el equino en reposo residual. Los registros clínicos y funcionales se realizaron a las seis semanas, tres, seis y 12 meses. Se realizó un análisis estadístico mediante Stata 14. RESULTADOS: A los 12 meses, 94% de los pacientes realizaban puntillas monopodales, la media de la atrofia gemelar fue de 1.03 cm ± 0.51 respecto a extremidad contralateral y la diferencia de equino residual respecto el lado sano era de 5.63 grados ± 4.17, 83.24% de los pacientes realizaban su práctica deportiva habitual previa a la rotura. La media de ATRS de la muestra era de 87.41 puntos ± 17.78. Se registraron dos rerroturas parciales (11%) a los tres meses de seguimiento que continuaron con tratamiento ortopédico. CONCLUSIONES: El tratamiento ortopédico funcional mediante bota ortopédica y carga precoz presenta buenos resultados clínicos y funcionales, considerándolo un tratamiento válido para las roturas agudas del tendón de Aquiles.

Cellular and molecular immune responses of the sea bass (Dicentrarchus labrax) experimentally infected with betanodavirus.

Naïve sea bass juveniles (38.4 + or - 4.5 g) were intramuscularly infected with a sublethal dose of betanodavirus isolate 378/I03, followed after 43 days by a similar boosting. This infection resulted in an overall mortality of 7.6%. At various intervals, sampling of fish tissues was performed to investigate: i) B and T lymphocyte content in organs and tissues; ii), proliferation of leucocytes re-stimulated in vitro with inactivated virus; iii) presence of serum antibody specific for betanodavirus; iv) expression of genes coding for the following immunoregulatory molecules involved in innate and acquired responses: type I IFN, Mx, IL-1, Cox-2; IL-10, TGF-beta, TCRbeta, CD4, CD8alpha, IgM, by using a quantitative PCR array system developed for sea bass. The obtained results showed a detectable increase of T cells and B cells in PBL during betanodavirus infection. Furthermore, leucocytes obtained from blood, head kidney, and gills showed a detectable "in vitro" increase in viability upon addition of inactivated viral particles, as determined by measuring intracellular ATP concentration. ELISA analysis of sera showed that exposure to nodavirus induced a low, but specific antibody titer measured 43 days after infection, despite the presence of measurable levels of natural antibody. Finally, a strong upregulation of genes coding for type I IFN, Mx, and IgM was identified after both infection and boosting. Interestingly, an upregulation of Cox-2 until boosting, and of TGF-beta and IL-10 after boosting was also observed, while the other tested genes did not show any significant variations with respect to mock-treated fish. Overall, our work represents a first comprehensive analysis of cellular and molecular immune parameters in a fish species exposed to a pathogenic virus.

Optimization of hollow-fiber liquid phase microextraction for polychlorinated biphenyls in human breast milk.

A reliable and sensitive analytical approach has been optimized for the extraction of seven polychlorinated biphenyls (PCBs) from human breast milk. Hollow fiber liquid phase microextraction (HF-LPME) was applied for the first time for the extraction and pre-concentration of the analytes. Analytes were separated by gas chromatography with electron capture detector (GC-µECD) for the sensitive detection and mass spectrometry for the unequivocal identification. A rotable central composite design (RCCD) was performed for the multivariate optimization of the method. The best results were obtained at 40 °C during 30 min and 600 rpm of stirring speed using a hollow fiber length of 5 cm and toluene as an extractant phase and salt addition was not required. The detection limits were in the range 7-14 ng L-1 for PCBs. The coefficients of determination of the calibration curves indicated good linearity (R2> 0.96) and the enrichment factors ranged from 74 to 143. This type of study is of great importance due to the deleterious effect that the presence of contaminants can produce in infants health related to the immature character of the defense system. Moreover, exclusive breastfeeding is recommended by neonatologists up to six months of life and as complementary food during the first two years.

Influence of Helicobacter pylori infection on the expression of MLH1 and MGMT in patients with chronic gastritis and gastric cancer.

The aim of the present study was to evaluate the influence of Helicobacter pylori on MLH1 and MGMT mRNA levels in patients with chronic gastritis and gastric cancer. The study included 217 patients, of which 26 were uninfected, 127 had chronic gastritis and were H. pylori-positive, and 64 had gastric cancer. Bacterial genotypes were evaluated by polymerase chain reaction (PCR), and the expression levels of MLH1 and MGMT were determined by quantitative real-time PCR and immunohistochemistry. There was an association between infection with cagA, vacA s1m1 strains and gastric cancer development. When the gastric epithelium and associated inflammation were examined for expression of MLH1 and MGMT, an overall increase in expression was observed. On the other hand, these levels decrease significantly among gastric cancer patients. The loss of MLH1 and MGMT expression in gastric cancer patients suggests that it is not an early event in H. pylori-associated gastric carcinogenesis.

[Viral respiratory tract infections in the first six months of life]. / Infecciones virales de vías respiratorias en los primeros seis meses de vida.

BACKGROUND: Respiratory syncytial virus and Influenza virus infections are known causes of hospital admission in infants. It is less well known the pattern of virus infections in infants under 6 months of age in the outpatient setting. OBJECTIVE: To describe the clinical and epidemiological pattern of community-acquired viral respiratory infections in infants under 6 months. PATIENTS AND METHODS: A cohort of infants from the 8 and 9 Madrid Health Districts was followed by telephone calls every two weeks since birth during the epidemic winter season. Clinical and epidemiological data were collected in pre-designed questionnaires. Nasopharyngeal aspirate was obtained in every patient with symptoms compatible with respiratory infection. Diagnosis of the more common virus was made with direct immunofluorescence and nucleic acid amplification test (PCR). RESULTS: Were recruited 316 newborns. The 1,865 phone calls made (median 4 for every child), produced 106 visits, and the illness confirmed in 89 illness. Rhinitis (91%) and cough (69%) were the most common symptoms. Upper respiratory infection was the principal clinical diagnosis (84.5%), and 17 of the 72 samples (23.2%) were positive. Most common viruses were RSV (41.1%) and rhinovirus (35.2%). Of the children visited, 17 out of 106 (16%) (5.3% of the cohort) were admitted to hospital. Diagnoses were febrile syndrome and bronchiolitis. We did not find any epidemiological factor associated with viral respiratory infection in positive cases. CONCLUSIONS: In our population most of the respiratory infections in infants are minor and do not need hospital assistance. Rhinovirus and RSV are the major pathogens. We did not find any epidemiological factor associated with viral respiratory infection.

[Human bocavirus infections in Spanish 0-14 year-old: clinical and epidemiological characteristics of an emerging respiratory virus]. / Infecciones por bocavirus humano en niños españoles: características clínicas y epidemiológicas de un virus respiratorio emergente.

INTRODUCTION: In 2005 a new respiratory virus, called human bocavirus (HBoV), was cloned from respiratory samples from Swedish infants and children with lower respiratory tract infections. OBJECTIVES: To determine whether HBoV has circulated in Spain, estimate the frequency of HBoV infections in patients hospitalized for respiratory infection and describe the clinical and epidemiological characteristics of these patients. PATIENTS AND METHODS: We performed a descriptive prospective study of confirmed HBoV infections in patients aged < 14 years old, hospitalized for respiratory infections between October 2004 and June 2005. Virologic diagnosis was based on multiple RT-PCR for respiratory syncytial virus (RSV) A and B, influenza A,B, and C, parainfluenza 1-4, adenovirus and rhinovirus; PCR was used for human metapneumovirus (hMPV) and PCR in nasopharyngeal aspirates was used for HBoV. The clinical and epidemiological characteristics of patients were analyzed. RESULTS: Fifty-two cases of HBoV infection were detected, representing 17.1% (95% CI: 13% a 21%) of patients hospitalized for respiratory infections. HBoV was the third most frequent viral agent after RSV (30%) and rhinovirus (25%). In 39 patients (71.1%) coinfection with another respiratory virus was detected. Fifty percent of the patients were aged less than 13.6 months and 75% were aged less than 2 years. The most frequent diagnoses were recurrent wheezing (55.8%), bronchiolitis (21.2%) and pneumonia (15.4%). Clinical sepsis with petechial exanthema was found in two patients. Fever > 38 degrees C was found in 72.1% and radiological infiltrate in 44%. Hypoxia was present in 55.8 % of the patients. HBoV was isolated in distinct episodes in two patients. Coinfections were similar to simple infections except that hypoxia was more frequent in the former (p = 0.038). CONCLUSIONS: HBoV is one of the most frequent viruses in severe respiratory infections in patients aged less than 14 years old. Only RSV and rhinovirus are more frequent. Coinfections are highly frequent. Most patients are infants with recurrent wheezing and bronchiolitis.

Lipids: A Suitable Therapeutic Target in Diabetic Neuropathy?

Diabetic polyneuropathy (DPN) encompasses multiple syndromes with a common pathogenesis. Glycemic control shows a limited correlation with DPN, arguing in favor of major involvement of other factors, one of which is alterations of lipid and lipoprotein metabolism. Consistent associations have been found between plasma triglycerides/remnant lipoproteins and the risk of DPN. Studies in cultured nerve tissue or in murine models of diabetes have unveiled mechanisms linking lipid metabolism to DPN. Deficient insulin action increases fatty acids flux to nerve cells, inducing mitochondrial dysfunction, anomalous protein kinase C signaling, and perturbations in the physicochemical properties of the plasma membrane. Oxidized low-density lipoproteins bind to cellular receptors and promote generation of reactive oxygen species, worsening mitochondrial function and altering the electrical properties of neurons. Supplementation with specific fatty acids has led to prevention or reversal of different modalities of DPN in animal models. Post hoc and secondary analyses of clinical trials have found benefits of cholesterol reducing (statins and ezetimibe), triglyceride-reducing (fibrates), or lipid antioxidant (thioctic acid) therapies over the progression and severity of DPN. However, these findings are mostly hypothesis-generating. Randomized trials are warranted in which the impact of intensive plasma lipids normalization on DPN outcomes is specifically evaluated.

Comparison of plasma pigment epithelium-derived factor (PEDF), retinol binding protein 4 (RBP-4), chitinase-3-like protein 1 (YKL-40) and brain-derived neurotrophic factor (BDNF) for the identification of insulin resistance.

AIMS: To evaluate and compare the association of four potential insulin resistance (IR) biomarkers (pigment-epithelium-derived factor [PEDF], retinol-binding-protein-4 [RBP-4], chitinase-3-like protein 1 [YKL-40] and brain-derived neurotrophic factor [BDNF]) with objective measures of IR. METHODS: We studied 81 subjects with different metabolic profiles. All participants underwent a 5-point OGTT with calculation of multiple IR indexes. A subgroup of 21 participants additionally underwent a hyperinsulinemic-euglycemic clamp. IR was defined as belonging to the highest quartile of incremental area under the insulin curve (iAUCins), or to the lowest quartile of the insulin sensitivity index (ISI). RESULTS: PEDF was associated with adiposity variables. PEDF and RBP4 increased linearly across quartiles of iAUCins (for PEDF p-trend=0.029; for RBP-4 p-trend=0.053). YKL-40 and BDNF were not associated with any adiposity or IR variable. PEDF and RBP-4 levels identified individuals with IR by the iAUCins definition: A PEDF cutoff of 11.9ng/mL had 60% sensitivity and 68% specificity, while a RBP-4 cutoff of 71.6ng/mL had 70% sensitivity and 57% specificity. In multiple regression analyses simultaneously including clinical variables and the studied biomarkers, only BMI, PEDF and RBP-4 remained significant predictors of IR. CONCLUSIONS: Plasma PEDF and RBP4 identified IR in subjects with no prior diagnosis of diabetes.