Fetal neurosonography at 31-35 weeks reveals altered cortical development in pre-eclampsia with and without small-for-gestational-age fetus.

OBJECTIVE: To explore the pattern of fetal cortical development in pregnancies complicated by pre-eclampsia (PE), with and without a small-for-gestational-age (SGA) fetus, compared to uncomplicated pregnancies. METHODS: This was a prospective observational study including singleton pregnancies complicated by normotensive SGA (birth weight < 10th centile) (n = 77), PE with an appropriate-for-gestational-age (AGA) fetus (n = 76) or PE with a SGA fetus (n = 67), and 128 uncomplicated pregnancies (normotensive AGA) matched by gestational age at ultrasound. All pregnancies underwent detailed neurosonography, using a transabdominal and transvaginal approach, at 31-35 weeks' gestation to assess the depth of the insula, Sylvian fissure, parieto-occipital sulcus, cingulate sulcus and calcarine sulcus. All measurements were adjusted for biparietal diameter (BPD). In addition, a grading score of cortical development was assigned to each brain structure, ranging from Grade 0 (no development) to Grade 5 (maximum development). Univariate and multiple regression analyses were conducted. RESULTS: Similar to findings in previous studies, normotensive pregnancies with a SGA fetus showed significant differences in cortical development compared with controls, with reduced Sylvian fissure depth adjusted for BPD (14.5 ± 2.4 vs 16.6 ± 2.3; P < 0.001) and increased insula depth adjusted for BPD (33.2 ± 2.0 vs 31.8 ± 2.0; P < 0.001). Interestingly, a similar cortical development pattern was observed in PE pregnancies with a SGA fetus and in PE pregnancies with an AGA fetus, manifested by reduced Sylvian fissure depth adjusted for BPD (14.2 ± 2.3 and 14.3 ± 2.3 vs 16.6 ± 2.3; P < 0.001 for both) and greater insula depth adjusted for BPD (33.2 ± 2.1 and 32.8 ± 1.7 vs 31.8 ± 2.0; P < 0.001 for both) compared with controls. No significant differences were observed in parieto-occipital, cingulate sulcus or calcarine sulcus depth across the study groups. The Sylvian fissure was scored as Grade 4 in significantly more (93.2% vs 59.5%) and as Grade 5 in significantly fewer (2.7% vs 37.3%) PE pregnancies with an AGA fetus compared with controls (P < 0.05 for both). These differences remained significant even after statistical adjustment for potential confounders, including ethnicity, low socioeconomic status, nulliparity, chronic hypertension, pregestational diabetes, assisted reproductive technologies, smoking and fetal gender, with the application of Benjamini-Hochberg procedure for multiple comparisons. CONCLUSIONS: PE with or without SGA is associated with a differential fetal cortical development pattern which is similar to that described previously in small fetuses. Future research is warranted to elucidate better the mechanism(s) underlying these changes. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Crotoxin down-modulates pro-inflammatory cells and alleviates pain on the MOG35-55-induced experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.

Multiple sclerosis (MS) is a Central Nervous System inflammatory demyelinating disease that has as primary symptoms losses of sensory and motor functions, including chronic pain. To date, however, few studies have investigated the mechanisms of chronic pain in animal models of MS since locomotor impairments render difficult its evaluation. It was previously demonstrated that in the MOG35-55-induced EAE, an animal model of MS, the hypernociception appears before the onset of motor disability, allowing for the study of these two phenomena separately. Here, we evaluated the effect of crotoxin (CTX), a neurotoxin isolated from the Crotalus durissus terrificus snake venom that displays, at non-toxic dose, antinociceptive, anti-inflammatory and immunomodulatory effects, in the pain and in symptoms progression of EAE. The pain threshold of female C57BL/6 mice decreased at the 4th day after immunization, while the first sign of disease appeared around the 11st-12nd days, coinciding with the onset of motor abnormalities. CTX (40 µg/kg, s.c.) administered in a single dose on the 5th day after immunization, induced a long-lasting analgesic effect (5 days), without interfering with the clinical signs of the disease. On the other hand, when crotoxin was administered for 5 consecutive days, from 5th-9th day after immunization, it induced analgesia and also reduced EAE progression. The antinociceptive effect of crotoxin was blocked by Boc-2 (0.5 mg/kg, i.p.), a selective antagonist of formyl peptide receptors, by NDGA (30 µg/kg, i.p.), a lipoxygenase inhibitor and by atropine sulfate (10 mg/kg, i.p.), an antagonist of muscarinic receptors, administered 30 min before CTX. CTX was also effective in decreasing EAE clinical signs even when administered after its onset. Regarding the interactions between neurons and immunocompetent cells, CTX, in vitro, was able to reduce T cell proliferation, decreasing Th1 and Th17 and increasing Treg cell differentiation. Furthermore, in EAE model, the treatment with 5 consecutive doses of CTX inhibited IFN-γ-producing T cells, GM-CSF-producing T cells, reduced the frequency of activated microglia/macrophages within the CNS and decreased the number of migrating cell to spinal cord and cerebellum at the peak of the disease. These results suggest that CTX is a potential treatment not only for pain alteration but also for clinical progression induced by the disease as well as an useful tool for the development of new therapeutic approaches for the multiple sclerosis control.

Immunomodulatory activity of ß-glucan-containing exopolysaccharides from Auricularia auricular in phagocytes and mice infected with Cryptococcus neoformans.

Current antifungal drugs present poor effectiveness and there is no available vaccine for fungal infections. Thus, novel strategies to treat or prevent invasive mycosis, such as cryptococcosis, are highly desirable. One strategy is the use of immunomodulators of polysaccharide nature isolated from mushrooms. The purpose of the present work was to evaluate the immunostimulatory activity of ß-(1,3)-glucan-containing exopolysaccharides (EPS) from the edible mushrooms Auricularia auricula in phagocytes and mice infected with Cryptococcus neoformans. EPS triggered macrophages and dendritic cell activation upon binding to Dectin-1, a pattern recognition receptor of the C-type lectin receptor family. Engagement of Dectin-1 culminated in pro-inflammatory cytokine production and cell maturation via its canonical Syk-dependent pathway signaling. Furthermore, upon EPS treatment, M2-like phenotype macrophages, known to support intracellular survival and replication of C. neoformans, repolarize to M1 macrophage pattern associated with enhanced production of the microbicidal molecule nitric oxide that results in efficient killing of C. neoformans. Treatment with EPS also upregulated transcript levels of genes encoding products associated with host protection against C. neoformans and Dectin-1 mediated signaling in macrophages. Finally, orally administrated ß-glucan-containing EPS from A. auricular enhanced the survival of mice infected with C. neoformans. In conclusion, the results demonstrate that EPS from A. auricula exert immunostimulatory activity in phagocytes and induce host protection against C. neoformans, suggesting that polysaccharides from this mushroom may be promising as an adjuvant for vaccines or antifungal therapy.

Degradation of estriol (E3) and transformation pathways after applying photochemical removal processes in natural surface water.

Steroidal hormones such as estriol (E3), are resistant to biodegradation; hence their removal by conventional treatment systems (aerobic and anaerobic) facilities is limited. These substances are detected in surface water, and present risks to the aquatic ecosystem and humans via potential biological activity. Photochemical treatments can be used to remove E3; however, just a few studies have analyzed the kinetics, intermediates, and E3 degradation pathways in natural surface water. In this study, the behavior of E3 under ultraviolet irradiation associated with H2O2, O3 or TiO2 was investigated to determine the degradation potential and the transformation pathways in reactions performed with a natural surface water sample. E3 degradation kinetics (200 ppb) fitted well to the pseudo-first-order kinetics model, with kinetic constant k in the following order: kUV/O3 > kUV/TiO2 > kUV/H2O2 > kUV. The mechanism of degradation using different advanced oxidative processes seemed to be similar and 12 transformation byproducts were identified, with 11 of them being reported here for the first time. The byproducts could be formed by the opening of the aromatic ring and addition of a hydroxyl radical. A possible route of E3 degradation was proposed based on the byproducts identified, and some of the byproducts presented chronic toxicity to aquatic organisms, demonstrating the risks of exposure.

Molecular characteristics of granulosa and cumulus cells and oocyte competence in Nelore cows with low and high numbers of antral follicles.

The aims of this study were to investigate whether the number of antral follicles (AF) in the ovaries of Nelore cows is influenced with the developmental competence of oocytes to reach the blastocyst stage and to quantify the mRNA abundance of genes associated with folliculogenesis and oogenesis in granulosa and cumulus cells. A total of 168 cows were distributed into two experimental groups according to the number of AF, low (≤31) and high AF (≥92), which were determined based on the mean number of AF (61.14) ± SD (30.43). Granulosa and cumulus cells were used to assess the mRNA expression of 16 genes. Cumulus cells from cows with low AF had higher mRNA expression of genes involved in meiosis resumption (NPR-2, NPR-3) and cumulus cell expansion (FGF10), as well as a transcription factor involved in the regulation of oocyte maturation and cell proliferation (STAT3). Conversely, granulosa cells from females with high AF had higher expression of PGR and AMHR2a, which are involved in meiosis resumption and cumulus cell expansion. Cumulus-oocyte complexes (COCs) were collected from 356 cows with low and high AF populations to evaluate embryo development. Cleavage and blastocyst rates did not differ between the groups. In conclusion, our findings revealed that genes involved in folliculogenesis and oogenesis are differently expressed in cumulus and granulosa cells of cows having low and high numbers of AF. These molecular differences suggest that the regulation of oocyte maturation, meiotic resumption and cumulus expansion may be influenced by the number of AFs. However, the variations in gene expression were not associated with in vitro oocyte developmental competence to reach the blastocyst stage, which confirms that oocytes from Nelore cows with low and high numbers of AF are similarly able to mature, regulate the fertilization process and support pre-implantation embryo development.

Main biomarkers associated with age-related plasma zinc decrease and copper/zinc ratio in healthy elderly from ZincAge study.

PURPOSE: Zinc (Zn) plays an essential role in many biological processes including immune response. Impaired Zn status promotes immune dysfunction, and it has been associated with enhanced chronic inflammation during aging. It has been suggested that the measurement of circulating Zn by itself could not reflect the real Zn status of an individual. It is therefore necessary to identify other determinants associated with plasma Zn to better understanding how physiopathological conditions during aging may affect the concentration of this metal. METHODS: We have investigated the association between Zn levels and some biomarkers in 1090 healthy elderly from five European countries to increase the accuracy in the assessment of the Zn status. Stepwise multivariate linear regression models were used to analyze the influence of factors such as age, dietary intake, inflammatory mediators, laboratory parameters and polymorphisms previously associated with Zn homeostasis. RESULTS: Plasma Zn decrement was most strongly predicted by age, while positive correlations were found with albumin, RANTES and Zn intake after adjustment for multiple confounders. HSP70 +1267 AA genotype was an independent factor associated with Zn plasma concentrations. Cu/Zn ratio was positively associated with markers of systemic inflammation and age and negatively associated with albumin serum levels. CONCLUSIONS: Our findings show the most important independent determinants of plasma Zn concentration and Cu/Zn ratio variability in elderly population and suggest that the decline with age of Zn circulating levels is more dependent on physiopathological changes occurring with aging rather than to its nutritional intake.

Lavandula angustifolia Mill. Essential Oil Exerts Antibacterial and Anti-Inflammatory Effect in Macrophage Mediated Immune Response to Staphylococcus aureus.

Different studies described the antibacterial properties of Lavandula angustifolia (Mill.) essential oil and its anti-inflammatory effects. Besides, no data exist on its ability to activate human macrophages during the innate response against Staphylococcus aureus. The discovery of promising regulators of macrophage-mediated inflammatory response, without side effects, could be useful for the prevention of, or as therapeutic remedy for, various inflammation-mediated diseases. This study investigated, by transcriptional analysis, how a L. angustifolia essential oil treatment influences the macrophage response to Staphylococcus aureus infection. The results showed that the treatment increases the phagocytic rate and stimulates the containment of intracellular bacterial replication by macrophages. Our data showed that this stimulation is coupled with expression of genes involved in reactive oxygen species production (i.e., CYBB and NCF4). Moreover, the essential oil treatment balanced the inflammatory signaling induced by S. aureus by repressing the principal pro-inflammatory cytokines and their receptors and inducing the heme oxygenase-1 gene transcription. These data showed that the L. angustifolia essential oil can stimulate the human innate macrophage response to a bacterium which is responsible for one of the most important nosocomial infection and might suggest the potential development of this plant extract as an anti-inflammatory and immune regulatory coadjutant drug.

A comparison of methods to estimate genomic relationships using pedigree and markers in livestock populations.

Accurate prediction of breeding values depends on capturing the variability in genome sharing of relatives with the same pedigree relationship. Here, we compare two approaches to set up genomic relationship matrices for precision of genomic relationships (GR) and accuracy of estimated breeding values (GEBV). Real and simulated data (pigs, 60k SNP) were analysed, and GR were estimated using two approaches: (i) identity by state, corrected with either the observed (GVR-O ) or the base population (GVR-B ) allele frequencies and (ii) identity by descent using linkage analysis (GIBD-L ). Estimators were evaluated for precision and empirical bias with respect to true pedigree IBD GR. All three estimators had very low bias. GIBD-L displayed the lowest sampling error and the highest correlation with true genome-shared values. GVR-B approximated GIBD-L 's correlation and had lower error than GVR-O . Accuracy of GEBV for selection candidates was significantly higher when GIBD-L was used and identical between GVR-O and GVR-B . In real data, GIBD-L 's sampling standard deviation was the closest to the theoretical value for each pedigree relationship. Use of pedigree to calculate GR improved the precision of estimates and the accuracy of GEBV.

Pregnancy Rates to Fixed Embryo Transfer of Vitrified IVP Bos indicus, Bos taurus or Bos indicus × Bos taurus Embryos.

The pregnancy rates obtained after the transfer of cryopreserved in vitro-produced (IVP) embryos are usually low and/or inconsistent. The objective of this study was to evaluate the pregnancy rates of Holstein, Gyr and Holstein × Gyr cattle after the transfer of vitrified IVP embryos produced with X-sorted sperm. Seventy-two Gyr and 703 Holstein females were subjected to ovum pickup (OPU) sessions, followed by in vitro embryo production using semen from sires of the same breeds. Embryos (1636 Holstein, 241 Gyr and 1515 Holstein × Gyr) were exposed to forskolin for 48 h prior to vitrification. The pregnancy rate achieved with Gyr dam and sire was 46.1%, which was similar (p = 0.11) to that of Holstein dam and Gyr sire (40.3%). Crossing Gyr dams with Holstein sires resulted in a pregnancy rate of 38.9% and did not differ (p = 0.58) from the pregnancy rate obtained with the cross between Holstein dams and Gyr sires. The rate obtained with Holstein dam and sire was 32.5%. The average pregnancy rate was 36.6%, and no difference was found in the proportion of female foetuses (88.8%, in average) among breeds (p > 0.05). In conclusion, transfer of cryopreserved X-sorted embryos represents an interesting choice for dairy cattle. Despite the small differences between pregnancy rates, we highlight the efficiency of this strategy for all of the racial groups studied.

Association among 1267 A/G HSP70-2, -308 G/A TNF-α polymorphisms and pro-inflammatory plasma mediators in old ZincAge population.

Proinflammatory cytokines and heat shock proteins play relevant roles in the pathogenesis of inflammatory diseases. We investigated whether Hsp70 1267 A/G and TNF-α -308 G/A polymorphisms are associated with proinflammatory mediators, zinc status and laboratory parameters in 1,078 healthy elderly from ZincAge study. Hsp70 1267 A/G genotype and allele distribution were similar among various European countries, while a TNF-α genetic heterogeneity was observed between the Northern and the Southern European populations, with a major frequency of the -308 A variant in France, Germany and Poland. We used linear regression models to test additive, dominant or recessive associations of each SNP with proinflammatory mediators, laboratory parameters, metallothioneins and zinc status. Hsp70 1267 A/G SNP, but not TNF-α -308 G/A SNP, influences TNF-α and IL-6 plasma levels under additive, dominant and recessive models (for TNF-α only). An association between Hsp70 1267 A/G SNP and zinc plasma levels was observed in the dominant model. In particular, G allele carriers showed increased circulating pro-inflammatory cytokines and zinc. Moreover, both these SNPs affect creatinine levels suggesting a possible influence on renal function. In conclusion, Hsp70 1267 A/G SNP is associated with pro-inflammatory cytokine production in healthy elderly and might represent a possible determinant of individual susceptibility to inflammatory diseases.

Leptin deficiency modulates allograft survival by favoring a Th2 and a regulatory immune profile. [corrected].

Leptin, an adipose-secreted hormone, links metabolism and immunity. Our aim was to determine whether leptin affects the alloimmune response. We used an allogeneic skin transplant model as a means to analyze the allograft immune response in Lep(ob/ob) and wild-type mice. Leptin deficiency results in an increased frequency of Treg and Th2 cells and a prolonged graft survival. These effects of leptin deficiency indicate the importance of leptin and obesity in modulating the allograft immune responses. Our data suggest a possible explanation for the increased susceptibility of hyperleptinemic obese patients to acute and chronic graft rejection.

Comparison of synthetic oviductal fluid and G1/G2 medium under low-1 oxygen atmosphere on embryo production and pregnancy rates in Nelore (Bos indicus) cattle.

In this work, we evaluated whether embryo development and pregnancy rates would be affected by culturing bovine Bos indicus embryos in Synthetic Oviductal Fluid with amino acids (SOFaa) or G1/G2 sequential medium under a low-oxygen atmosphere. Using Ovum Pick Up, we obtained 1,538 oocytes, divided into G1/G2 (n = 783) and SOFaa (n = 755). No difference was observed for blastocyst development among the groups (27.8% ± 14.6 and 34.9% ± 20.0 for G1/G2 and SOFaa respectively, p > 0.05). Transferring the embryos (n = 450) from both groups to recipients resulted in similar pregnancy rates for the G1/G2 (38.4% n = 78/203) compared to the SOFaa (39.7% n = 98/247). Our findings confirm that Bos indicus embryos cultured in SOFaa and G1/G2 under low-oxygen atmosphere have similar in vitro (blastocyst rate) and in vivo (pregnancy rate) developmental capacity. However, embryos cultured in G1/G2 medium have higher cleavage than those cultured in SOFaa medium.

Nonhormonal management of postmenopausal women: effects of a red clover based isoflavones supplementation on climacteric syndrome and cardiovascular risk serum profile.

PURPOSE OF INVESTIGATION: The aim of this prospective randomized study was to evaluate a red clover based isoflavones supplementation in the treatment of climacteric syndrome and its effects on cardiovascular risk serum profile. MATERIALS AND METHODS: The study included 150 healthy postmenopausal women that were randomly assigned to receive phytoestrogens tablets, amounting in a total daily intake of 60.8 mg red clover isoflavones plus 19.2 mg soy isoflavones (n = 75), or placebo (n = 75). The authors evaluated teh following: daily number of hot flushes and Kupperman Index at baseline and after one and three months; serum total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, and antithrombin III (ATIII) at baseline and after three and six months. RESULTS: One hundred twenty-eight patients completed the study: 67 in the active group and 61 in the placebo group. The treatment led to a progressive significant reduction (p < 0.05) of the number of hot flushes in the active group compared to placebo already after one month, while Kupperman Index was statistically reduced after three months. No significant variation in total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, PT, PTT, fibrinogen, and ATIII were found. CONCLUSION: The present findings suggest that a red clover based isoflavones supplementation in healthy postmenopausal women is promptly effective on climacteric syndrome, improves neurovegetative symptoms, safe on cardiovascular risk serum profile, and does not modify lipids and coagulation.

Immune effects of polychlorinated biphenyls, smoking and alcohol.

Polychlorinated biphenyls (PCB) have been shown to exert some immune effects. Here we analysed their effects also on immune parameters not previously studied such as TCR alpha-beta, TCR gamma-delta and regulatory T cells (Treg), taking into account the specific and cumulative interference of smoking and alcohol. The study subjects consisted of 26 male workers in a steel works factory, employed in the electrical maintenance sector, with previous exposure to a mixture of PCB (exposed subjects), and 30 male workers with no occupational exposure to PCB (controls). All subjects were given a questionnaire and peripheral venous blood samples were taken to determine serum PCB (33 congeners), total cholesterol and triglycerides, leukocytes, total lymphocytes and the T lymphocyte subpopulations (TCR alpha-beta, TCRgamma-delta, CD4+ and Treg lymphocytes). PCB, even though at a very low concentration, were significantly higher in exposed subjects than controls, and were significantly correlated with age. Monocytes% and CD4+ were significantly reduced in the exposed subjects as compared to the controls. The serum concentration of PCB positively correlated with TCR alpha-beta, and negatively with TCRgamma-delta. Treg lymphocytes showed a positive dependence on tobacco smoking, while the monocytes percentage and CD4+ showed a negative and positive dependence, respectively, on alcohol intake. Our results seem to show some effects of slight exposure to PCB in particular reducing the relative concentration of TCRgamma-delta. This effect can favour indirectly the increase in Treg induced by smoking, the anti-inflammatory or proinflammatory/fibrogenetic/angiogenetic effect of which, exerted by produced cytokines, particularly TGF-beta, deserves further clarification.

Evolution of echocardiographic and cardiac magnetic resonance imaging abnormalities during follow-up in patients with multisystem inflammatory syndrome in children.

AIMS: Multisystem inflammatory syndrome in children (MIS-C) with cardiovascular manifestations are frequent. However, there is lacking evidence regarding cardiological follow-up of this cohort of patients. The aim of our study was to describe the early and mid-term cardiac abnormalities assessed by standard and speckle-tracking echocardiography (STE), and cardiac MRI (CMR). METHODS AND RESULTS: We enrolled 32 patients (21 male, 11 female), mean age 8.25 ± 4years, with diagnosis of MIS-C. During admission, all children underwent TTE, STE with analysis of left ventricle global longitudinal strain (GLS) and CMR. Patients underwent cardiological evaluation at 2 (T1) and 6 months (T2) after discharge. Cardiac MRI was repeated at 6 months after discharge. Mean left ventricular ejection fraction (LVEF) at baseline was 58.8 ± 10% with 10 patients (31%) below 55%. Speckle-tracking echocardiography showed reduced mean LV GLS (-17.4 ± 4%). On CMR, late gadolinium enhancement (LGE) with non-ischaemic pattern was evident in 8 of 23 patients (35%). Follow-up data showed rapid improvement of LVEF at T1 (62.5 ± 7.5 vs. 58.8 ± 10.6%, P-value 0.044) with only three patients (10%) below ≤ 55% at T1. Left ventricular (LV) GLS remained impaired at T1 (-17.2 ± 2.7 vs.-17.4 ± 4, P-value 0.71) and significantly improved at T2 (-19 ± 2.6% vs. -17.4 ± 4%, P-value 0.009). LV GLS was impaired (>-18%) in 53% of patients at baseline and T1, whereas only 13% showed persistent LV GLS reduction at T2. Follow-up CMR showed LGE persistence in 33.4% of cases. CONCLUSION: Early cardiac involvement significantly improves during follow-up of MIS-C patients. However, subclinical myocardial dysfunction seems to be still detectable after 6 months of follow-up in a not negligible proportion of them.

[Lesser validity of urinary benzene than S-phenylmercapturic acid for measuring occupational and environmental exposure to very low concentrations of benzene]. / Minore validità del benzene urinario rispetto all'acido S-fenilmercapturico nel rilevare l'esposizione occupazionale ed ambientale a concentrazioni molto basse di benzene.

AIM: To study the validity of urinary benzene as a biomarker of low and very low exposure to this toxicant, as compared with t,t-muconic acid (t,t-MA) and S-phenylmercapturic acid (SPMA), also taking into account the influence of cigarette smoking and co-exposure to toluene on the urinary excretion of benzene. MATERIALS AND METHODS: The results obtained in two different studies were compared: in the first, workers occupationally exposed to low concentrations of benzene (18 fuel tanker drivers and 23 filling station attendants) were compared with 31 controls and in the second, workers exposed to very low concentrations of benzene (the same 23 filling station attendants) were compared with the 31 controls. Exposure to airborne benzene and toluene was monitored with passive personal samplers (Radiello). Then the urine collected at the end of the work shift was analyzed for t,t-MA, SPMA and urinary benzene. All participants also filled out a questionnaire about their lifestyle habits. RESULTS: There were no differences among the three groups in terms of age and smoking habit. Occupational exposure to benzene and toluene and the urinary concentrations of t,t-MA, SPMA and urinary benzene were higher in the fuel tanker drivers than the filling station attendants and higher in the latter than in the controls. Cigarette smoking was found to be associated with urinary excretion of t,t-MA, SPMA and urinary benzene at both low and very low exposure to benzene. The biomarkers t,t-MA, SPMA and urinary benzene were almost always correlated, for both low and very low exposure to benzene. Notably, for low exposure to benzene a dependency relation was found with the levels of t,t-MA, SPMA and urinary benzene on both cigarette smoking and airborne benzene, whereas for very low exposure to benzene there was a dependency relation of SPMA on cigarette smoking and airborne benzene, of urinary benzene only on cigarette smoking and of t,t-MA on none of the variables considered. CONCLUSIONS: For occupational exposure to low concentrations of benzene, urinary benzene and SPMA showed a comparable validity, while for exposure to very low concentrations of this toxicant the validity of SPMA was confirmed while urinary benzene was found to be less useful. Cigarette smoking was the main factor conditioning the excretion of all the biomarkers of benzene in conditions of both low and very low exposure to the toxicant, so for the analysis of occupational exposure to benzene it is best to recommend abstention from smoking at least in the hours immediately before urine collection.

Pharmacologycal activity of peperina (Minthostachys verticillata) on gastrointestinal tract.

ETHNOPHARMACOLOGICAL RELEVANCE: Minthostachys verticillata (Griseb.) Epling (Lamiaceae), known as Peperina is a medicinal native plant, with a traditional use as a digestive, antispasmodic and antidiarrheic. AIM OF THE STUDY: Despite its folkloric use, no scientific evaluation of this plant related to the gastrointestinal inflammatory process has been carried out to date. The present study aims to assess the effects of M. verticillata on gastrointestinal system in experimental models. MATERIALS AND METHODS: M. verticillata (250 and 500 mg/kg) was orally tested in a colitis model induced by acetic acid. Colon weight/length ratio, oxidative stress (oxidized and reduced glutathione), histological changes using Alcian blue and hematoxylin & eosin staining and expression of IL1ß, TNFα, iNOS, COX-2 were evaluated. The effect of the extract in three additional in vivo models were studied: intestinal motility and diarrhea induced by ricin oil, and visceral pain induced by intracolonic administration of capsaicin. Finally, the activity on concentration response curves of acetylcholine, calcium chloride, potassium and serotonin were achieved in isolated rat jejunum. RESULTS: In the colitis model, M. verticillata induced a significant reduction in the colon weight/length ratio, oxidative stress and expression levels of IL-1ß, iNOS and COX-2. Also, the extract diminished the severity of microscopic tissue damage and showed protective effect on goblet cells. Intestinal motility, diarrhea, visceral pain-related behaviors and referred hyperalgesia were significantly reduced when the animals were treated with the extract. Furthermore, in isolated jejunum, M. verticillata significantly reduced the contraction induced by serotonin and acetylcholine. Likewise, the extract non-competitively inhibited the response-concentration induced by CaCl2 and inhibited both low and high K+-induced contractions. CONCLUSIONS: This is the first study to validate traditional use of M. verticillata for digestive disorders and demonstrated that its aqueous extract could represent a promising strategy in targeting the multifactorial pathophysiology of inflammatory bowel disease.

Self-rated health in individuals with and without disease is associated with multiple biomarkers representing multiple biological domains.

Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual's subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.

Optimized synthesis of phosphatidylserine.

The synthesis of phosphatidyl serine containing saturated fatty acids was thoroughly studied and optimized in order to establish a protocol amenable to large-scale synthesis. The key step was a one-pot multicomponent reaction involving an O-benzyl phosphorodiamidite, protected serine and diacylglycerol, followed by in situ oxidation of the resulting phosphite. In order to replace expensive and poorly stable tetrazole, a screening of substitutes was carried out and imidazolium chloride was selected as the best suited one.

Experience from the Argentine Pegvisomant Observational Study: preliminary data.

The GH receptor antagonist pegvisomant is an efficient agent to achieve biochemical control of acromegaly in those cases refractory to surgery and medical therapy with somatostatin analogs. We conducted an observational multicenter study consisting of data collection in accordance with the standard management of patients with acromegaly in everyday practice. We reviewed the medical records of 28 patients, 23 females, who were treated with pegvisomant due to the lack of biochemical response or intolerance to the somatostatin analogs. The objective was to monitor long-term safety and efficacy of the antagonist. 82% of the patients had previous pituitary surgery, 53.6% radiotherapy and 96.4% received medical therapy for acromegaly. Only 19.2% of the patients had pituitary residual tumor size larger than 1 cm, the remainder harbored a microadenoma or no visible tumor in the pituitary images. In terms of biochemical efficacy, IGF-I levels decreased to normal ranges in 45% and 58.8% of patients after 3 and 6 months of treatment, respectively, the daily mean dose of pegvisomant being 9.6+/-1.1 mg. Adverse events, potentially related to pegvisomant were reported in 6 patients (21.4%), local injection site reaction and elevated liver enzymes being the most frequent. Tumor size did not show enlargement in the evaluated population (15 patients) during the period of the study. This paper presents preliminary data from a small observational study in Argentina which represents the first database in our country.