Search PubMed⌕ Search

Biomedical subjects

S Lin

Publications and source records attributed to S Lin.

At least 19 recordsLinked to original sources
PubMed2007

Antibodies to a novel antigen in acute hepatitis C virus infections.

BACKGROUND: Conformational viral proteins potentially play an important role in the immunobiology of acute hepatitis C virus (HCV) infection and may enable earlier antibody detection. MATERIALS AND METHODS: HCV RNA was detected using nucleic acid testing. Early antibody production was evaluated using three enzyme immunoassays (EIAs) containing antigenic proteins not present in licensed EIAs. Respectively, these contained: (1) multiple-epitope fusion antigen (MEFA) 7.1-NS3/4a, (2) F and Core, and (3) E1/E2 proteins. NS3/4a is a conformational antigen retaining protease and helicase enzymatic activities. MEFA 7.1 contains the linear epitopes used in licenced EIAs, including the latest EIA-3.0, in combination with genotype 1-3 specific epitopes. Forty-two RNA positive, EIA-3.0 negative samples, including two persistently serosilent cases, were used to evaluate these research EIAs. As controls, 54 EIA-3.0 negative/RNA negative and three HCV RNA+/antibody positive specimens were included. RESULTS: Only the MEFA 7.1-NS3/4a EIA was positive in seven (17%) of the 42 HCV RNA + specimens, in all three EIA-3.0 positive controls but in none of 54 EIA-3.0 negative/HCV RNA negative controls. Notably, six of the seven (86%) specimens had evidence of active hepatitis (ALT > 210 IU/l). The two serosilent cases were research EIA negative. CONCLUSION: A novel EIA with conformational and linear epitopes detected HCV antibodies in 17% of viraemic specimens missed by the standard reference EIA-3.0. Our research EIA appears to detect HCV antibodies closer to the initiation of acute hepatitis. Given that the average RNA-positive, antibody-negative window period is 56.4 days, this 17% yield would translate into a 10-day earlier detection of antibodies.

Blood Donors↗
PubMed2006

Evaluation of the impact of shielding materials in radiation protection in transgenic animals.

We are using a plasmid-based transgenic mouse mutation model system to evaluate the effectiveness of aluminum or low-density polyethylene (LDPE) shielding after 250 MeV/u protons or 1 GeV/u iron ion irradiation. Transgenic mice, with multiple copies of the plasmid pUR288 lacZ transgene integrated into the genome of every cell of the animal, were either irradiated or sham-treated. Multiple endpoints, including early cytogenetic damage in erythrocytes at 48 h after exposure, chromosome aberrations in bone marrow lymphocytes, and lacZ mutant frequencies (MF) in brain and spleen tissues were measured in the same animals. The frequency of total circulating reticulocytes (fRET) dropped precipitously at 48 h after 2 Gy of proton irradiation. The average level of micronucleated reticulocytes (fMN-RET) was fivefold higher in the irradiated samples relative to the controls at the same time point. There was an increase in total chromosome aberrations in bone marrow lymphocytes at 8 weeks after proton irradiation but this increase was not statistically significant relative to the controls. Evaluation of the lacZ MF in the brain and spleen tissues showed that proton irradiation induced a twofold increase in MF in each tissue. Similar samples were collected from animals that were shielded from the proton beam by aluminum. Compared to the unshielded treatment group, we noted no difference in fRET, fMN-RET, chromosome aberrations in lymphocytes and lacZ MF in brain and spleen tissues obtained from these animals. In a separate study, animals were exposed to high-energy iron ions with or without 10 or 15 cm LDPE. Using the same approach, we noted a precipitous drop in fRET, and an elevation in fMN-RET within 48 h after 1 Gy of iron ions. Total chromosome aberrations in bone marrow lymphocytes were slightly elevated but not significant at 8 weeks after iron ion exposure. Shielding animals with 10 or 15 cm of polyethylene appeared to have no effect on the level of RET, MN-RET or chromosome aberrations in these animals. LacZ MF in brain and spleen tissues increased 1.5-2-fold above control levels after 1 Gy iron ions at 8 weeks after treatment. On the other hand, MF in tissues harvested from shielded animals appeared to be lower than their unshielded litermates, suggesting the polyethylene shielding was effective in reducing the iron-induced genomic damage in tissues. Although shielding may be effective, in some cases, in reducing the physical dose of particle radiation, our cytogenetic results showed that the biological impact of the particle beam remain unchanged. On the other hand, reduction in transgene MF in tissues from LDPE-shielded animals but not in the aluminum-shielded animals strongly suggests that careful consideration of the biological endpoints used is necessary in the evaluation of the efficacy of the selected shielding material.

Animals↗
PubMed2006

Speech and language delay are early manifestations of juvenile-onset Huntington disease.

The neurocognitive features of juvenile-onset Huntington disease (HD) are not well understood. We present three patients with onset of HD symptoms before age 10 years in whom speech delay was the first symptom. Speech delay predated motor symptoms by at least 2 years, and language function was consistently impaired on formal testing. Screening for speech delay is particularly important in children with a family history of HD.

Child↗
PubMed2006

Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis.

Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein that induces apoptosis utilizing both insulin-like growth factor receptor (IGF)-dependent and -independent mechanisms. We investigated the effects of IGFBP-3 on tumor growth and angiogenesis utilizing a human CaP xenograft model in severe-combined immunodeficiency mice. A 16-day course of IGFBP-3 injections reduced tumor size and increased apoptosis and also led to a reduction in the number of vessels stained with CD31. In vitro, IGFBP-3 inhibited both vascular endothelial growth factor- and IGF-stimulated human umbilical vein endothelial cells vascular network formation in a matrigel assay. This action is primarily IGF independent as shown by studies utilizing the non-IGFBP-binding IGF-1 analog Long-R3. Additionally, we used a fibroblast growth factor-enriched matrigel-plug assay and chick allantoic membrane assays to show that IGFBP-3 has potent antiangiogenic actions in vivo. Finally, overexpression of IGFBP-3 or the non-IGF-binding GGG-IGFBP-3 mutant in Zebrafish embryos confirmed that both IGFBP-3 and the non-IGF-binding mutant inhibited vessel formation in vivo, indicating that the antiangiogenic effect of IGFBP-3 is an IGF-independent phenomenon. Together, these studies provide the first evidence that IGFBP-3 has direct, IGF-independent inhibitory effects on angiogenesis providing an additional mechanism by which it exerts its tumor suppressive effects and further supporting its development for clinical use in the therapy of patients with prostate cancer.

Animals↗
PubMed2006

Zebrafish dax1 is required for development of the interrenal organ, the adrenal cortex equivalent.

Mutations in the human nuclear receptor, DAX1, cause X-linked adrenal hypoplasia congenita (AHC). We report the isolation and characterization of a DAX1 homolog, dax1, in zebrafish. The dax1 cDNA encodes a protein of 264 amino acids, including the conserved carboxy-terminal ligand binding-like motif; but the amino-terminal region lacks the unusual repeats of the DNA binding-like domain in mammals. Genomic sequence analysis indicates that the dax1 gene structure is conserved also. Whole-mount in situ hybridization revealed the onset of dax1 expression in the developing hypothalamus at approximately 26 h post fertilization (hpf). Later, at about 28 hpf, a novel expression domain for dax1 appeared in the trunk. This bilateral dax1-expressing structure was located immediately above the yolk sac, between the otic vesicle and the pronephros. Interestingly, weak and transient expression of dax1 was observed in the interrenal glands (adrenal cortical equivalents) at approximately 31 hpf. This gene was also expressed in the liver after 3 dpf in the zebrafish larvae. Disruption of dax1 function by morpholino oligonucleotides (MO) down-regulated expression of steroidogenic genes, cyp11a and star, and led to severe phenotypes similar to ff1b (SF1) MO-injected embryos. Injection of dax1 MO did not affect ff1b expression, whereas ff1b MO abolished dax1 expression in the interrenal organ. Based on these results, we propose that dax1 is the mammalian DAX1 ortholog, functions downstream of ff1b in the regulatory cascades, and is required for normal development and function of the zebrafish interrenal organ.

Adrenal Cortex↗
PubMed2006

Cigarette smoke toxicants alter growth and survival of cultured mammalian cells.

Our purpose was to determine the effects of six cigarette toxicants (pyridine, nicotine, 2-ethylpyridine, 3-ethylpyridine, p-cresol, and pyrazine) on three types of cultured mammalian cells (human umbilical vein endothelial cells [HUVECs], human microvascular endothelial cells [HMVECs], and NIH 3T3 cells) using a cell proliferation/survival assay. Synchronized cells were cultured in proliferation or survival medium containing various doses (10(-18)M-10(-2)M) of the tested chemicals. After 48 h, cells were counted using a hemacytometer. The no observable adverse effect level (NOAEL), lowest observable adverse effect level (LOAEL), and the efficacy were determined for each compound in the cell proliferation and survival assays. Pyridine and p-cresol did not show significant effects with any cell types, except at high doses. Derivitization of the pyridine ring altered its potency, especially when an ethyl group or nitrogen was added. In survival medium, nicotine stimulated proliferation of all three cell types at doses found in smoker's serum (10(-8)M-10(-7)M). For HUVEC and HMVEC, 2-ethylpyridine, 3-ethylpyridine, and pyrazine inhibited proliferation in proliferation medium and induced cell death in survival medium at attomolar and femtomolar doses. All chemicals, except pyridine and pyrazine, stimulated NIH 3T3 cell proliferation at low doses and induced cell death at high doses. LOAELs and efficacies revealed that endothelial cells from a developing organ (umbilical cord) were more sensitive to these chemicals than endothelial cells from an adult organ (lung). 3-Ethylpyridine and pyrazine, which induced cell death at low doses, are added to consumer products and should be subjected to further toxicological testing.

Animals↗
PubMed2006

Gene expression profiling in vLINCL CLN6-deficient fibroblasts: Insights into pathobiology.

The CLN6 vLINCL is caused by molecular defects in CLN6 gene coding for an ER resident transmembrane protein whose function is unknown. In the present study gene expression profiling of CLN6-deficient fibroblasts using cDNA microarray was undertaken in order to provide novel insights into the molecular mechanisms underlying this neurodegenerative fatal disease. Data were validated by qRT-PCR. Statistically significant alterations of expression were observed for 12 transcripts. The two most overexpressed genes, versican and tissue factor pathway inhibitor 2, are related to extracellular matrix (ECM), predicting changes in ECM-related proteins in CLN6-deficient cells. Transcript profiling also suggested alterations in signal transduction pathways, apoptosis and the immune/inflammatory response. Up-regulated genes related to steroidogenesis or signalling, and the relationship between cholesterol dynamics and glycosphingolipid sorting, led to investigation of free cholesterol and gangliosides in CLN6-deficient fibroblasts. Cholesterol accumulation in lysosomes suggests a homeostasis block as a result of CLN6p deficiency. The cholesterol imbalance may affect structure/function of caveolae and lipid rafts, disrupting signalling transduction pathways and sorting cell mechanisms. Alterations in protein/lipid intracellular trafficking would affect the composition and function of endocytic compartments, including lysosomes. Dysfunctional endosomal/lysosomal vesicles may act as one of the triggers for apoptosis and cell death, and for a secondary protective inflammatory response. In conclusion, the data reported provide novel clues into molecular pathophysiological mechanisms of CLN6-deficiency, and may also help in developing disease biomarkers and therapies for this and other neurodegenerative diseases.

Cells, Cultured↗
PubMed2006

Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity.

AIMS/HYPOTHESIS: Obese people exhibit reduced circulating peptide YY (PYY) levels, but it is unclear whether this is a consequence or cause of obesity. We therefore investigated the effect of Pyy ablation on energy homeostasis. METHODS: Body composition, i.p. glucose tolerance, food intake and hypothalamic neuropeptide expression were determined in Pyy knock-out and wild-type mice on a normal or high-fat diet. RESULTS: Pyy knock-out significantly increased bodyweight and increased fat mass by 50% in aged females on a normal diet. Male chow-fed Pyy (-/-) mice were resistant to obesity but became significantly fatter and glucose-intolerant compared with wild-types when fed a high-fat diet. Pyy knock-out animals exhibited significantly elevated fasting or glucose-stimulated serum insulin concentrations vs wild-types, with no increase in basal or fasting-induced food intake. Pyy knock-out decreased or had no effect on neuropeptide Y expression in the arcuate nucleus of the hypothalamus, and significantly increased proopiomelanocortin expression in this region. Male but not female knock-outs exhibited significantly increased growth hormone-releasing hormone expression in the ventromedial hypothalamus and significantly elevated serum IGF-I and testosterone levels. This sex difference in activation of the hypothalamo-pituitary somatotrophic axis by Pyy ablation may contribute to the resistance of chow-fed male knock-outs to late-onset obesity. CONCLUSIONS/INTERPRETATION: PYY signalling is important in the regulation of energy balance and glucose homeostasis, possibly via regulation of insulin release. Therefore reduced PYY levels may predispose to the development of obesity, particularly with ageing or under conditions of high-fat feeding.

Adipose Tissue↗
PubMed2006

Factors affecting growth factor activity in goat milk.

Growth factors that are present in goat milk may be responsible for its beneficial effects on the digestive system as described in ancient Chinese medical texts. To develop a nutraceutical product rich in growth factors for promoting gastrointestinal health, it is essential to collect milk with consistently high growth factor activity. Therefore, we investigated the factors affecting growth factor activity in goat milk. Among the 5 breeds of dairy goats tested, milk from Nubian goats had the highest growth factor activity. Tight-junction leakage induced by a 24-h milking interval did not increase growth factor activity in the milk. Milk collected from pregnant does had a significantly higher growth factor activity than milk collected postpartum. Growth factor activity decreased during the first 8 wk of lactation, fluctuated thereafter, and then increased dramatically after natural mating. During wk 1 to 8, growth factor activity was inversely correlated with milk yield and week of lactation. No correlation was observed during wk 9 to 29. After natural mating of the goats, the growth factor activity in the milk correlated significantly with somatic cell count and conductivity (a measure of membrane permeability), and correlated inversely with milk yield. Based on the above data, goat milk with higher growth factor activity could be selectively collected from Nubian pregnant does.

Animals↗
PubMed2006

[Dental trauma protocol--treatment of avulsion and luxation injury].

The goal of this protocol is to provide clear instructions which simplify the process of decision making and treatment of Luxation and Avulsion. In teeth with a closed apex, one should perform root canal therapy at the second appointment in teeth with injuries of luxation and avulsion (except for injuries of subluxation and concussion). The tooth should be reimplanted at site of accident if it possible. For avulsed teeth, the preferred storage medium is milk. One should condition the roots of teeth which have been avulsed. In teeth which have not finished development, the preferred treatment is to allow the continued development of the root.

Animals↗
PubMed2005

Minocycline alleviates hypoxic-ischemic injury to developing oligodendrocytes in the neonatal rat brain.

The role of minocycline in preventing white matter injury, in particular the injury to developing oligodendrocytes was examined in a neonatal rat model of hypoxia-ischemia. Hypoxia-ischemia was achieved through bilateral carotid artery occlusion followed by exposure to hypoxia (8% oxygen) for 15 min in postnatal day 4 Sprague-Dawley rats. A sham operation was performed in control rats. Minocycline (45 mg/kg) or normal phosphate-buffered saline was administered intraperitoneally 12 h before and immediately after bilateral carotid artery occlusion+hypoxia and then every 24 h for 3 days. Nissl staining revealed pyknotic cells in the white matter area of the rat brain 1 and 5 days after hypoxia-ischemia. Hypoxia-ischemia insult also resulted in apoptotic oligodendrocyte cell death, loss of O4+ and O1+ oligodendrocyte immunoreactivity, and hypomyelination as indicated by decreased myelin basic protein immunostaining and by loss of mature oligodendrocytes in the rat brain. Minocycline significantly attenuated hypoxia-ischemia-induced brain injury. The protective effect of minocycline was associated with suppression of hypoxia-ischemia-induced microglial activation as indicated by the decreased number of activated microglia, which were also interleukin-1beta and inducible nitric oxide synthase expressing cells. The protective effect of minocycline was also linked with reduction in hypoxia-ischemia-induced oxidative and nitrosative stress as indicated by 4-hydroxynonenal and nitrotyrosine positive oligodendrocytes, respectively. The reduction in hypoxia-ischemia-induced oxidative stress was also evidenced by the decreases in the content of 8-isoprostane in the minocycline-treated hypoxia-ischemia rat brain as compared with that in the vehicle-treated hypoxia-ischemia rat brain. The overall results suggest that reduction in microglial activation may protect developing oligodendrocytes in the neonatal brain from hypoxia-ischemia injury.

Animals↗
PubMed2005

Placental alkaline phosphatase (PLAP) enzyme activity and binding to IgG in Chagas' disease.

Placentas and plasma from women with and without Chagas' disease and cultures of human placental villi with Trypanosoma cruzi, neuraminidase, phospholipase A2 and phospholipase C were analyzed in order to verify if the alterations in placental alkaline phosphatase (PLAP) enzyme activity are caused by T. cruzi as observed in previous works. As IgG receptivity happens to be one of the proposed functions of PLAP, general IgG binding ability of the placentas treated with the mentioned enzymes, which are present on the parasite's surface, were also tested. The phospholipases caused an increase of PLAP's enzyme activity in the supernatant of infected placentas and a decrease of enzyme activity in the membrane of cultured placentas, therefore suggesting the cleavage of PLAP by parasitic enzymes. Desialylation could also partially inhibit PLAP's enzyme activity in supernatant and membrane of placenta culture. Placentas from healthy patients presented higher IgG receptivity than those from patients with Chagas' disease. In vitro infection of healthy placentas with T. cruzi caused no difference in IgG receptivity in placental sections with respect to controls but the phospholipases and neuraminidase increased the IgG receptivity of cultured placentas. The IgG transference index was higher for patients with Chagas' disease than for those without it. Although binding to IgG does not completely inhibit the enzyme activity of PLAP, it interferes with the enzyme activity of PLAP. We concluded that the enzymes on the surface of T. cruzi trypomastigotes can not only affect PLAP's enzyme activity but also increase the IgG binding ability of the placenta and this can be related to the actions of neuraminidase-transsialidase, phospholipase A2 and phospholipase C on the parasite surface. The modification of PLAP from women with Chagas' disease should be considered as a result of multiple factors.

Alkaline Phosphatase↗
PubMed2005

Minocycline attenuates lipopolysaccharide-induced white matter injury in the neonatal rat brain.

Our previous studies have shown that intracerebral administration of endotoxin, lipopolysaccharide (LPS), induces selective white matter injury and hypomyelination in the neonatal rat brain and that the LPS-induced brain injury is associated with activation of microglia. To test the hypothesis that inhibition of microglial activation may protect against LPS-induced white matter injury, we examined roles of minocycline, a putative suppressor of microglial activation, on LPS-induced brain injury in the neonatal rat. A stereotactic intracerebral injection of LPS (1 mg/kg) was performed in postnatal day 5 Sprague-Dawley rats and control rats were injected with sterile saline. Minocycline (45 mg/kg) was administered intraperitoneally 12 h before and immediately after LPS injection and then every 24 h for 3 days. Inflammatory responses, activation of microglia and brain injury were examined 1 and 3 days after LPS injection. LPS injection resulted in brain injury in selective brain areas, including bilateral ventricular enlargement, cell death at the sub- and periventricular areas, loss of O4+ and O1+ oligodendrocyte (OL) immunoreactivity and hypomyelination, as indicated by decreased myelin basic protein immunostaining, in the neonatal rat brain. Minocycline administration significantly attenuated LPS-induced brain injury in these rat brains. The protective effect of minocycline was associated with suppressed microglial activation as indicated by the decreased number of activated microglial cells following LPS stimulation and with consequently decreased elevation of interleukin 1beta and tumor necrosis factor-alpha concentrations induced by LPS and a reduced number of inducible nitric oxide synthase expressing cells. Protection of minocycline was also linked with the reduction in LPS-induced oxidative stress, as indicated by 4-hydroxynonenal positive OLs. The overall results suggest that reduction in microglial activation may protect the neonatal brain from LPS-induced white matter injury and inhibition of microglial activation might be an effective approach for the therapeutic treatment of infection-induced white matter injury.

Animals↗
PubMed2005

Experimental characterization and physical modelling of the dose distribution of scanned proton pencil beams.

In this paper we present the pencil beam dose model used for treatment planning at the PSI proton gantry, the only system presently applying proton therapy with a beam scanning technique. The scope of the paper is to give a general overview on the various components of the dose model, on the related measurements and on the practical parametrization of the results. The physical model estimates from first physical principles absolute dose normalized to the number of incident protons. The proton beam flux is measured in practice by plane-parallel ionization chambers (ICs) normalized to protons via Faraday-cup measurements. It is therefore possible to predict and deliver absolute dose directly from this model without other means. The dose predicted in this way agrees very well with the results obtained with ICs calibrated in a cobalt beam. Emphasis is given in this paper to the characterization of nuclear interaction effects, which play a significant role in the model and are the major source of uncertainty in the direct estimation of the absolute dose. Nuclear interactions attenuate the primary proton flux, they modify the shape of the depth-dose curve and produce a faint beam halo of secondary dose around the primary proton pencil beam in water. A very simple beam halo model has been developed and used at PSI to eliminate the systematic dependences of the dose observed as a function of the size of the target volume. We show typical results for the relative (using a CCD system) and absolute (using calibrated ICs) dosimetry, routinely applied for the verification of patient plans. With the dose model including the nuclear beam halo we can predict quite precisely the dose directly from treatment planning without renormalization measurements, independently of the dose, shape and size of the dose fields. This applies also to the complex non-homogeneous dose distributions required for the delivery of range-intensity-modulated proton therapy, a novel therapy technique developed at PSI.

Calibration↗
PubMed2005

Instant MR labeling of stem cells using magnetoelectroporation.

For cellular MR imaging, conventional approaches to intracellular magnetic labeling of nonphagocytic cells rely on the use of secondary compounds such as transfection agents and prolonged incubation of cells. Magnetoelectroporation (MEP) was investigated as an alternative method to achieve instant (<1 s) endosomal labeling with the FDA-approved formulation Feridex, without the need for adjunct agents or initiating cell cultures. While MEP was harmful at higher voltages or pulse durations, the procedure could be properly calibrated using a pulse of 130 V and 17 ms. Labeling was demonstrated for stem cells from mice, rats, and humans; the uptake of iron was in the picogram range and comparable to values obtained using transfection agents. MEP-labeled stem cells exhibited an unaltered viability, proliferation, and mitochondrial metabolic rate. Labeled mesenchymal stem cells (MSCs) and neural stem cells (NSCs) differentiated into adipogenic, osteogenic, and neural lineages in an identical fashion as unlabeled cells, while containing Feridex particles as demonstrated by double immunofluorescent staining. MEP-labeled NSCs proliferated normally following intrastriatal transplantation and could be readily detected by MR imaging in vivo. As MEP circumvents the use of secondary agents, obviating the need for clinical approval, MEP labeling may be ideally suitable for bedside implementation.

Animals↗
PubMed2005

Components of honeybee royal jelly as deterrents of the parasitic Varroa mite, Varroa destructor.

The parasitic mite Varroa destructor Anderson & Trueman reproduces on the immature stage of the honeybee, Apis mellifera L. Mites are found more often on drone brood than worker brood and only infrequently on queen brood. We investigated the chemical basis for the low incidence of mites on queen brood. V. destructor mites were deterred by a crude extract of royal jelly, a glandular secretion produced by nurse bees and fed to queen larvae. Bioassay-driven fractionation of the crude extract via column chromatography resulted in one active fraction that was as active as the crude extract. Compounds in the active fraction were identified using gas chromatography (GC) and coupled gas chromatography/mass spectrometry (GC-MS). Before injection, compounds were esterified with MeOH/sulfuric acid, followed by silylation of any hydroxyl groups present. The active fraction contained at least 22 compounds, all fatty acids, several of which contained an additional hydroxyl group on the alkyl chain. Synthesis of some of these compounds that are not commercially available is described. A synthetic mixture containing most of the compounds in the active fraction was as active as the active fraction in the bioassay.

Animals↗
PubMed2005

Placental alkaline phosphatase (PLAP) study in diabetic human placental villi infected with Trypanosoma cruzi.

Previous work has demonstrated that PLAP activity decreases in serum and placental villi from term chagasic and diabetic pregnant women. In vitro, T. cruzi induces changes in human syncytiotrophoblast's PLAP. Our aim was to determine if infection with T. cruzi induces changes in PLAP activity in diabetic and chagasic women's placenta, in order to elucidate if PLAP plays a role in the mechanisms of interaction between placenta and T. cruzi, and whether hyperglycemic conditions could worsen the placental infection. Using zymogrammes, Western blot, biochemical and immunohistological techniques, PLAP activity was determined in placental villi from diabetic and chagasic women, and in normal placentas cultured under hyperglycemic conditions with or without trypomastigotes. A significant reduction of PLAP expression was immunologically detected in infected diabetic and normal placental villi cultured under hyperglycemic conditions of 71 and 81%, respectively, compared with controls. A significant decrease of PLAP specific activity was registered in homogenates and in the culture media from both infected diabetic and normal placentas under hyperglycemic conditions (of about 50-70%), and in chagasic ones (of about 87%), when compared with controls. Thus, PLAP might be involved in parasite invasion and diabetic and hyperglycemic placentas could be more susceptible to T. cruzi infection.

Adult↗