1,720,976 research outputs found
Association between up-regulated expression proteins and circulating steroidal hormones in leiomyoma
No full textSeveral studies have shown that both ovarian hormones estrogen and progesterone and various proteins are involved in uterine leiomyoma growth. We hereby describe a study carried out to investigate the possible relation between progesterone, estrone, 17β-estradiol and the seven dysregulated proteins in the leiomyoma. Statistical analyses showed a significant inverse rank correlation between desmin expressed in leiomyoma and progesterone (ρ = −0.9276; p = 0.0077) and between alpha-1-antitrypsin expressed in leiomyoma and 17β-estradiol (ρ = −0.8571; p = 0.0137). Our data suggest that decreased levels of 17-β-estradiol involve an increasing of the inflammation response stimulating alpha-1-antitrypsin expression in leiomyoma and that lower levels of progesterone associated with increasing of desmin expression may be related to increase of inflammation response, and to the role played by desmin in signal transduction inducing leiomyoma growth
Analysis of the cAMP-PCT-CGRP axis in normal and pathological pregnancy
No full textThe pro-hormone Procalcitonin (PCT) is one of the best diagnostic and prognostic markers in clinical practice, which exerts an immunomodulatory role during inflammation. We previously showed that PCT has turned out to be a powerful tool to study the ability of pregnant serum to regulate mononuclear phagocytes function. The modulation of PCT may help us to understand the mechanisms responsible for the imbalance in the immune-endocrine crosstalk in pregnancy and encourage further research to identify effective therapeutic strategies in pre-eclampsia (PE). Our recent findings show that PCT levels are higher in PE sera compared to those of healthy pregnant women. We demonstrated the local synthesis of PCT in normal and PE placenta due to macrophages and trophoblast cells. PE sera have the ability to upregulate the PCT production in trophoblasts cells and MΦ. TNFα, IL-1β and IL-6 are more concentrated in PE serum, their expression is upregulated in M1 MΦ, and seem to drive together the regulation of the synthesis of PCT and CGRP. We show that TNFα alone is not able to increase the PCT expression in human MΦ. A mAb to TNFα completely abrogated the ability of PE sera to upregulate PCT production in these cells. These data emphasize that additional factors in the gravid serum play a role in the PCT synthesis, indicating that its regulation might have an impact on the use of this laboratory marker for the analysis of the inflammatory status in healthy and pathological pregnancy
Predittività dell'emoglobina glicata nei confronti dell'OGTT in una popolazione pediatrica italiana sovrappeso/obesa
No full textBackground. Recently glycated hemoglobin (A1c) ≥ 48 mmol/mol
has been included among the diagnostic criteria for type 2 diabetes
mellitus (DM2) in adults, while borderline levels of 39-47
mmol/mol indicate impaired glycemia (pre-diabetes). In overweight/
obese children an oral glucose tolerance test (OGTT) is
used to screen for DM2 and pre-diabetic status (impaired fasting
glucose [IFG] and impaired glucose tolerance [IGT]). A1c could
therefore theoretically replace OGTT as a screening test in children
at risk for DM2, IFG, IGT, or insulin resistance (IR).
Methods. Italian patients aged less than 18 years, consecutively
assessed for overweight/obesity (BMI > 85th percentile) in our Pediatric
Endocrinology Outpatient Care Unit between July 2011
and December 2012, were included. A1c was determined for each
patient (IFCC method) and an OGTT was done (blood glucose
and insulin levels at 0, 60 and 120 min).
Results. Data were collected from 225 patients (105 males),
mean age 11.2 ± 3.2 years and mean BMI 27.6 ± 4.7 (77% with
BMI > 95th percentile). Mean A1c was 36.2 ± 4.9 mmol/mol (range
16-50). Three cases had IFG, 12 IGT and 83 IR. In 71 cases
(32%) with borderline A1c, none had IFG, 5 had IGT, and 37 had
IR. The only child known to be diabetic had borderline A1c. Sensitivity
and specificity were 0, 67.6% for IFG, 41.6, 68.8% for IGT,
45.1, 76.1% for IR.
Conclusions. A1c is not sensitive enough for detecting diabetic
and pre-diabetic status, so it would not be a reliable tool. Given the
intermediate specificity of borderline A1c 39-47 mmol/mol to identify
pre-diabetic status, confirmation with an OGTT is always advisable.
In our series, borderline A1c was better at predicting IR
Analysis of the molecular mechanisms of C1-inhibitor deficiency induced angioedema
No full textPurpose: Angioedema (AE) due to inherited or acquired
deficiencies of C1 inhibitor (C1-INH) is characterized by localized
swelling of deeper layers of the skin or submucosal tissues,
becoming particularly life threatening if it occurs in the upper
respiratory tract. C1-INH regulates the release of bradykinin
which can enhance permeability of post-capillary venules
interacting with its receptors. The drugs currently used are
more symptomatic than curative, so we sought to identify the
molecular mechanisms responsible for the induction of vascular
permeability.
Methods: We used a transwell in vitro model with a filter covered
by primary human endothelial cells (EC), in the upper chamber
we add the fluorescent-BSA and the stimuli and the BSA leaked
into the lower chamber was evaluated using a Fluorescence
reader.
Results: EC were incubated with plasma collected from patients
during attack (APL) and the presence of C1-INH in the majority
of the patients was able to block the permeability. To mimic the
in vivo situation we stimulated the EC with the APL for 30 min
and then the SN was collected and used to stimulate the ECs in
the transwell model. In that case the inhibition of the leakage
by C1-INH was not seen in all the patients. This observation was
further confirmed by using the plasma collected from 1 patient
before and 1 h after the clinical treatment with C1-INH, indeed
there is no difference in the EC leakage induced by the plasma
before and after the treatment.
Discussions: The inhibition of endothelial leakage induced by
APL stimulation by C1-INH indicates the involvement of that
molecule in controlling the onset of AE attacks, although the
inability of C1-INH to completely block the permeabilizing effect
of the SN indicates that after the activation of the cells there are
other molecules involved.
Conclusion: Since the clinical treatment of AE can be done with
different drugs besides C1-INH we have to analyze the most
appropriate therapeutic approach
Fecal Calprotectin: Diagnostic Accuracy of the Immunochromatographic CalFast Assay in a Pediatric Population
No full textBACKGROUND:
Fecal calprotectin is a noninvasive marker for bowel diseases and it is high valuable to follow disease activity in Crohn's disease (CD) and ulcerative colitis (UC). In this study, we evaluated the diagnostic performance of the recently introduced immunochromatographic assay CalFast in comparison to the well-known ELISA tests for calprotectin assay to obtain a rapid diagnosis of bowel inflammation in pediatric patients.
METHODS:
CalFast was tested in parallel to the classic ELISA tests CalPrest and PhiCal (gold standards for the calprotectin determination) on 148 fecal samples from pediatric subjects including 104 healthy subjects, 29 with CD, and 15 with UC.
RESULTS:
In this study, the sensitivity and specificity of CalFast, CalPrest, and PhiCal were 86.4%, 88.6%, and 93.2% and 86.6%, 74%, and 64.4%, respectively. The area under the curve, obtained from receiver operating characteristic analysis, indicated the lack of significant difference among all the kits used.
CONCLUSION:
The immunochromatographic assay demonstrated good diagnostic predictive values, comparable to those of the ELISA methods, and may represent a valid alternative in order to save operators' time. The test, in fact, has a short turnaround time and does not need a specific ELISA instrumentation
Combined use of AFM and soft X-ray microscopy to reveal fibres' internalization in mesothelial cells
No full textNanotoxicology and nanomedicine investigations often require the probing of nano-objects such as
fibres and particles in biological samples and cells, whilst internalization and intracellular destiny are the
main issues for in vitro cellular studies. Various high resolution microscopy techniques are well suited for
providing this highly sought-after information. However, sample preparation, nanomaterial composition
and sectioning challenges make it often difficult to establish whether the fibres or particles have been
internalized or they are simply overlaying or underlying the biological matter. In this paper we suggest a
novel suitable combination of two different microscopic techniques to reveal in intact cells the uptake of
asbestos fibres by mesothelial cells. After exposure to asbestos fibres and fixation, cells were first analysed
under the AFM instrument and then imaged under the TwinMic soft X-ray microscope at Elettra
Sincrotrone. The suggested approach combines standard soft X-ray microscopy imaging and AFM
microscopy, with a common non-invasive sample preparation protocol which drastically reduces the
experimental uncertainty and provides a quick and definitive answer to the nanoparticle cellular and
tissue uptake
Clinical significance of hyper-IgA in a paediatric laboratory series
No full textThe causes of extremely elevated IgA, whether isolated or associated with an increase in other classes of immunoglobulin, are poorly defined in paediatrics. We reviewed the diagnostic significance of very high IgA levels (greater than 3 SD above the mean for age) in a cohort of patients referred to a tertiary care children's hospital. Hyper-IgA was found in 91 of 6364 subjects (1.4%) and in 68 cases was not associated with an increased IgG and/or IgM level. Most subjects with hyper-IgA (73.5%) had a severe immune defect, a chronic rheumatic disease or inflammatory bowel disease, while these conditions were very rare in a control group with normal IgA values (8%). Although our results may in part reflect the experience of a tertiary care centre, we suggest that hyper-IgA in children should always arouse suspicion of a serious disease
A proteomic approach for the identification of biomarkers in endometrial cancer uterine aspirate
Full text linkEndometrial cancer arises from the endometrium. It has a slow progression and a reported survival rate of 75%. The identification of soluble biomarkers in the uterine aspirate may be very useful for its early diagnosis. Uterine aspirates from 10 patients with endometrial cancer and 6 non-endometrial cancer controls were analyzed by two-dimensional gel electrophoresis coupled with mass spectrometry and western blotting for data verification. A total of 25 proteins with fold change in %V ≥2 or ≤0.5 in intensity were observed to change significantly (P<0.05). From the discovery phase, four proteins (costars family protein ABRACL, phosphoglycerate mutase 2, fibrinogen beta chain, annexin A3) were found to be present in the uterine aspirate of endometrial cancers and not in healthy aspirates. Western blotting verification data demonstrated that costars family protein ABRACL, phosphoglycerate mutase 2 were present only in endometrial cancer uterine aspirate while fibrinogen beta chain, annexin A3 were also present in healthy aspirates. To our knowledge, phosphoglycerate mutase 2 has not been previously associated with endometrial cancer. In this study we demonstrate that uterine aspirates are a promising biological fluid in which to identify endometrial cancer biomarkers. In our opinion proteins like costars family protein ABRACL and phosphoglycerate mutase 2 have a great potential to reach the clinical phase after a validation phase
C1q is involved in human trophoblast invasion
No full textDuring the development of human placenta, extravillous trophoblast (EVT) departs from anchoring chorionic villi and invades the maternal decidua. Immunohistochemical analysis of decidua obtained from voluntary abortions showed that C1q was widely distributed in the decidual stroma with intense staining around invading trophoblast, while undetectable in non pregnant uterus. Based on these findings, we hypothesized that C1q may be involved in the migration of EVT. To this end, we investigated the ability of EVT to adhere to solid-phase bound C1q and to migrate using a transwell model system with inserts coated with C1q. Our results showed that EVT strongly adhered to C1q to an extent similar to that observed for cell adhesion to fibronectin, a component of the extracellular matrix of decidua. Adhesion of EVT to C1q was inhibited by antibodies to gC1qR, which was detected on these cells by FACS analysis. Cells bound to C1q and to FN exhibited a markedly different morphological appearance. The cells attached to FN were spread out whereas those bound to C1q were much smaller with wide ruffles extending in multiple direction. EVT spread on FN contained a high number of actin-containing stress fibers as revealed by phalloidin staining as opposed to the peripheral distribution of actin in cells bound to C1q.
C1q was also found to promote the migration of EVT, though to a lesser extent than FN. Interestingly, RT-PCR analysis showed that EVT expressed mRNA for the three chains of C1q.
In conclusion, our results suggest that C1q is produced by EVT of maternal decidua and play a role in the migration and adhesion of these cells to the extracellular matrix of the decidua
Activation of hepatic stem cells compartment during hepatocarcinogenesis in a HBsAg HBV-transgenic mouse model
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