Carolina Guzmán

Immunoendocrine host-parasite interactions during helminth infections: from the basic knowledge to its possible therapeutic applications.

Most of the current research on parasitic infections that affect humans and domestic animals has been focused on vaccines, diagnostic methods, epidemiology, new drug design, and recently, with the advancement of genomics and proteomics, on the evolutionary origins of parasites. However, the basic biology of many parasites of medical and veterinary importance has not been intensively studied. Some efforts have been made to obtain information on the parasite–host relationship; however, knowledge of the intricate neuroimmunoendocrine interactions of the host–parasite network, the consequences of this interaction on the host and parasite physiology, and its possible applications needs further investigation. We review here the literature, our own studies on the host–parasite neuroimmunoendocrine network, and how this basic knowledge can be used to design new treatments, by way of using hormones, antihormones, and hormone analogues as a possible novel therapy during parasitic diseases, with special emphasis on helminth parasites. Besides the biological interest, these investigations may contribute to the future identification of alternative treatments for several parasitic diseases. This complicated neuroimmunoendocrine network management during parasitic infections, and its physiological and behavioural consequences upon the host, may be operative in other mammalian infections. Such complexity may also help to explain the often conflicting results, observed between infections with respect to the role of the host sex and age, and hints to other avenues of research and strategies for their treatment and control.

Neuroprotective Role of Estradiol against Neuronal Death Induced by Glucose Deprivation in Cultured Rat Hippocampal Neurons

Studies have reported the protective effect of estradiol (E2) against neuronal death induced by several insults including oxygen deprivation, mitochondrial toxins and activation of glutamate receptors. Glucose deprivation (GD) is associated with ischemia and hypoglycemia, and to date there is no effective therapeutic agent able to prevent neuronal damage induced by these conditions. In this study, we have investigated the effects of 17β-E2 and the selective agonists of the alpha (ERα) and beta (ERβ) estrogen receptors, propyl pyrazole triol (PPT) and diarylpropionitrile (DPN), respectively, on neuronal death induced by GD in cultured rat hippocampal neurons. We have also analyzed the expression of both ER isoforms after GD. Results show that GD for 2 and 4 h reduces cell survival by 42 and 55%, respectively. Treatment with 17β-E2 (10 nM to 10 µM) induces a dose-dependent protective effect that is blocked by ICI 182,780, an ER antagonist, and by 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(-piperidinylethoxy)phenol]-1H′pyrazole dihydrochloride (MPP) and 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP), selective ERα and ERβ antagonists, respectively. The ERα and ERβ agonists PPT and DPN show a similar neuroprotective effect to that of 17β-E2, but DPN is more efficient. In addition, hippocampal neurons under normal conditions show a higher expression of the ERβ isoform. When exposed to GD during 4 h, the expression of both ER isoforms is increased, while only that of the ERβ isoform significantly increases after 2 h of GD. Results demonstrate that E2 prevents neuronal death induced by GD through its interaction with ER, although the ERβ isoform might have a predominant role. Results also suggest that GD differentially alters the expression of ERα and ERβ in hippocampal neurons.

In vivo assessment of liver fibrosis using diffuse reflectance and fluorescence spectroscopy: A proof of concept

A novel application of diffuse reflectance and fluorescence spectroscopy in the assessment of liver fibrosis is here reported. To induce different stages of liver fibrosis, a sufficient number of male Wistar rats were differentially exposed to chronic administration with carbon tetrachloride. Then, diffuse reflectance and fluorescence spectra were in vivo measured from the liver surface of each animal by a minimal invasive laparoscopic procedure. The liver fibrosis degree was conventionally determined by means of histological examination using the Masons Trichrome stain, accompanied by hepatic expression of α-sma, and evaluation of the ALT/AST serum levels. The liver from rats exhibiting higher grades of fibrosis showed a significant increase in diffuse reflectance and fluorescence intensity when compared with control animals. At 365 nm, the diffuse reflectance spectrum exhibited an increase of 4 and 3-fold in mild and advanced fibrotic rats, respectively, when compared to the control group. Similarly, the fluorescence emission at 493 nm was 2-fold higher in fibrotic animals than in controls. By using fluorescence intensity, discrimination algorithms indicated 73% sensitivity and 94% specificity for recognition of hepatic fibrosis, while for diffuse reflectance, these values increased up to 85% and 100%, respectively. Taking into consideration there is a special need for developing new diagnostic approaches focused on detecting different stages of liver fibrosis with minimal invasiveness, these results suggest that diffuse reflectance and fluorescence spectroscopy could be worthy of further exploration in patients with liver disease.

Liver exhibits thermal variations according to the stage of fibrosis progression: A novel use of modulated‐differential scanning calorimetry for research in hepatology

Liver fibrosis results in a disproportion of the hepatic composition and architecture, characterized by a progressive accumulation of fibrillar proteins at the liver parenchyma. Modulated‐differential scanning calorimetry (mDSC) is an experimental methodology able to determine the specific thermal signature from any biological substance, based on the variation in heat flow and heat capacity. As these physicochemical properties are directly influenced by compositional and structural changes, we decided to study the thermal behavior of the liver during fibrosis using mDSC.

Prenatal exposure to persistent organic compounds and their association with anogenital distance in infants

RESEARCH QUESTION What is the association between prenatal exposure to persistent organic pollutants, separately and combined, and anogenital distance (in-utero endocrine disruption marker). DESIGN A cohort study conducted in Sonora, Mexico. Blood concentrations of polychlorobiphenyls (PCB) 28, 74, 118, 138/158, 153, 170, 180 and the isomers of dichlorodiphenyltrichloroethane (DDT) and its metabolites were determined in women in the third trimester of pregnancy; three variants of anogenital distance were measured on five occasions during the first year of life of their infants: 82 girls (402 observations) and 74 boys (356 observations). RESULTS Boys had negative and significant associations between anogenital distance/height and the concentrations of PCB 28 (beta = - 0.005;P = 0.006), PCB 74 (beta = - 0.003;P = 0.013), and PCB 170 (beta = - 0.005;P = 0.001) when analysed individually. Negative and significant associations were also found using statistical models applied to mixtures of compounds. The latter associations were sometimes larger in magnitude and significance, suggesting a possible potentiation of the compounds. No associations were observed between anogenital distance and DDT in either sex or with PCB in girls. CONCLUSIONS The decreased anogenital distance associated with prenatal exposure to the persistent organic pollutants, observed consistently in different analyses, suggests an under-masculinizing effect of these environmental pollutants in boys.