Adrenomedullin plasma concentrations in patients with retinitis pigmentosa

PURPOSE: To evaluate the relationship between retinitis pigmentosa (RP) and plasma adrenomedullin (ADM) levels. METHODS: Blood samples were obtained from a group of 40 consecutive patients with RP matched with 35 healthy subjects (HS) as control. We carried out a complete ophtalmological examination. The study group included 26 patients with RP and 14 patients with syndromic RP. Plasma ADM levels were determined in duplicate with a specific radioimmunoassay method. RESULTS: In the HS plasma ADM levels were 13.7 +/- 6.1 pg/mL. The mean of plasma ADM concentrations in all patients with RP (23.4 +/- 10.7 pg/mL) was significantly (P < 0.0001) higher than that of HS. Moreover, in the syndromic RP patients, plasma ADM levels (28.6 +/- 14.35 pg/ml) were higher than those of HS and RP patients (P < 0.0017). CONCLUSION: The increase of plasma ADM levels in RP patients may be a response to photoreceptor damage.     

Adrenomedullin increases in term asphyxiated newborns developing intraventricular hemorrhage

OBJECTIVES: Adrenomedullin (AM) is a newly discovered vasodilator peptide that participates in the regulation of cerebral blood flow. The aim of this study was to investigate whether circulating AM was increased in infants with prenatal asphyxia who developed intraventricular hemorrhage (IVH). DESIGN AND METHOD:: A case-control study was performed on 40 full-term asphyxiated newborns: 20 developed IVH (group A) and 20 did not (group B). Forty term healthy newborns represented the control group. Biochemical laboratory parameters, neurological patterns, cerebral ultrasound scanning, and Doppler velocimetry were assessed at 12 and 72 h from birth. Plasma AM concentration was measured at 12 h from birth by means of a specific RIA. RESULTS: AM levels were significantly higher in group A (20.2 +/- 5.2 fmol/ml) than in group B (8.4 +/- 2.1 fmol/ml) or controls (9.3 +/- 2.6 fmol/ml). In asphyxiated newborns, AM concentration was correlated with middle cerebral artery PI value only in group B. CONCLUSIONS: Increased concentration of AM at 12 h from birth in asphyxiated newborns who later developed IVH suggests that this peptide may participate in the loss of cerebral vascular autoregulation in response to hypoxia and could be useful to discriminate, among newborns at risk, those with an adverse neurological outcome.     

Understanding the changes of cone reflectance in adaptive optics flood illumination retinal images over three years

Although there is increasing interest in the investigation of cone reflectance variability, little is understood about its characteristics over long time scales. Cone detection and its automation is now becoming a fundamental step in the assessment and monitoring of the health of the retina and in the understanding of the photoreceptor physiology. In this work we provide an insight into the cone reflectance variability over time scales ranging from minutes to three years on the same eye, and for large areas of the retina (≥ 2.0 × 2.0 degrees) at two different retinal eccentricities using a commercial adaptive optics (AO) flood illumination retinal camera. We observed that the difference in reflectance observed in the cones increases with the time separation between the data acquisitions and this may have a negative impact on algorithms attempting to track cones over time. In addition, we determined that displacements of the light source within 0.35 mm of the pupil center, which is the farthest location from the pupil center used by operators of the AO camera to acquire high-quality images of the cone mosaic in clinical studies, does not significantly affect the cone detection and density estimation.OCIS codes: (110.1080) Active or adaptive optics, (330.7331) Visual optics, receptor optics, (170.3880) Medical and biological imaging     

Molecular analysis of minimal residual disease in adult acute lymphoblastic leukaemia

Despite intensive chemotherapy and stem cell transplantation (SCT) programmes, overall survival in adult acute lymphoblastic leukaemia (ALL) remains poor compared to that in childhood ALL. Despite clinical and morphological remission being achieved by over 80% of patients, 5-year survival is limited to 40% of patients, clearly indicating that morphology is insufficient in predicting future outcome. Molecular assessment of residual disease in bone marrow using immunoglobulin genes as markers of clonality has recently been evaluated in a large adult ALL study in our institution. Analysis of disease-free survival (DFS) rates for minimal residual disease-(MRD-) positive and -negative patients established that MRD positivity was associated with increased relapse rates at all times, being most significant at 3-5 months post-induction and beyond. Pre-autologous SCT tests are predictive of outcome, but for allogeneic SCT outcome is related to results of the tests after the procedure rather than before. The association of MRD test results and DFS was independent of, and greater than, other standard predictors of outcome and is therefore important in determining treatment for individual patients.     

Ukrain Affects Pancreas Cancer Cell Phenotype in vitro by Targeting MMP-9 and Intra-/Extracellular SPARC Expression

Background/Aims: We investigated whether the anticancer drug Ukrain (UK) is able to modulate the expression of some of the key markers of tumor progression in pancreatic cell carcinoma, in order to assess its potential therapeutic effect. Methods: Three cell lines (HPAF-II, PL45,HPAC) were treated with UK (5,10 and 20 μM) for 48 h, or left untreated. Secreted protein acidic and rich in cysteine (SPARC) mRNA levels were assessed by real-time PCR. Matrix metalloproteinases (MMP)-2 and -9 activity was analyzed by SDS zymography; SPARC protein levels in cell lysates and supernatants were determined by Western blot. Cell cycle was determined by flow cytometric analysis, and invasion by matrigel invasion assay. Results: UK down-regulated MMP-2 and MMP-9, suggesting that UK may decrease pancreatic cancer cell invasion, as confirmed by the matrigel invasion assay. SPARC protein down-regulation in supernatants points to an inhibition by UK of extracellular matrix remodeling in the tumor microenvironment. At the same time, SPARC mRNA and cellular protein level up-regulation suggests that UKcan affect cell proliferation by cell cycle inhibition, showing a cell cycle G2/M arrest in UK-treated cells. Conclusion: Our results suggest that UK modulates two major aspects involved in tumorigenesis of pancreatic cancer cells, such as extracellular matrix remodeling and cell proliferation.     

Primary aldosteronism due to adrenocortical adenoma with concurrent ileum carcinoid tumor: case report

Primary aldosteronism (PA) with synchronous carcinoid syndrome is extremely rare occurrence. In this article, we describe a case of PA due to adrenocortical adenoma ("aldosteronoma") and concurrent malignant carcinoid tumor of ileum. The patient was treated with synchronous right adrenalectomy and resection of the ileum. This case is an example of concomitant presence of two types of tumors, effectively managed surgically. We report a case of a nonclassical form of multiple endocrine neoplasia type 1 (MEN 1) syndrome.     

Development and validation of an analytical method based on high performance thin layer chromatography for the simultaneous determination of lamotrigine, zonisamide and levetiracetam in human plasma

Methods based on HPLC technology are the most frequently adopted for monitoring blood levels of novel antiepileptics. Here a rapid method based on HPTLC was developed for quantitative determination of lamotrigine (LTG), zonisamide (ZNS) and levetiracetam (LVT) in human plasma and compared with HPLC and LC-MS/MS methods. Chromatographic separation was achieved on silical gel 60F₂₅₄ plates using ethylacetate:methanol:ammonia (91:10:15 v/v/v) as mobile phase. Quantitative analysis was carried out by densitometry at a wavelength of 312, 240 and 210 nm for LTG, ZNS and LVT, respectively. Calibration curves were linear over range of 0-200 ng for LTG and ZNS and 0-400 ng for and LVT. The limit of quantification of LTG, ZNS and LTV was found to be 3.69, 3.7 and 6.85 μg/ml, respectively. Intra and inter-assay precision provided relative standard deviations lower than 10% for all three analytes. Correlation and Bland-Altman plot showed general agreement between HPTLC and LC-MS/MS quantification, with a mean bias of −0.25, −0.46 and 0.5 μg/ml for LTG ZNS and LVT, respectively. Likewise, comparison between HPLC-UV and LC-MS/MS showed good agreement for all the three compounds analyzed. In conclusion, the proposed HPTLC method is simple, rapid, precise and accurate. It therefore is appropriate for the routine quantification of therapeutic levels of LTG, ZNS and LVT in human plasma.     

The GABAA-BZR complex as target for the development of anxiolytic drugs

Anxiety disorders have been linked to alterations in γ-aminobutyric acid (GABA) neurotransmission. GABA interacts with the ligand-gated ion channels, GABAA receptor (GABAA-R) subtypes, and regulates the flow of chloride into the cell, causing neuron hyperpolarization. GABAA-Rs are assembled from a family of 19 homologous subunit gene products and form mostly hetero-oligomeric pentamers. The major isoforms of the GABAA-Rs contain α, β and γ subunits and show a regional heterogeneity that is associated with distinct physiological effects. A variety of allosteric ligands can modulate the response to GABA by binding at different sites on the GABAA-R complex. The best characterized binding site is the benzodiazepine (BZ) one, which is located at the α/γ subunit interface. BZs are commonly used in therapy for their effects as anxiolytic, anticonvulsants, myorelaxants and hypnotics. The broad range of pharmacological effects of classical BZs are mediated by the selective activation of different GABAA-R subtypes: the α1 subunit containing BZ receptor (BZ-R) mediates sedation, the α2 and α3 subunit containing BZ-R mediates anxiolysis and myorelaxation, and the α5 subunit containing BZ-R mediates cognitive impairment. Based on the current understanding of the diversity of the GABAA-R family, different approaches have been employed to develop drugs that target the GABAA/BZ-R complex with selective anxiolytic action and improved profiles. In this review, we present current knowledge about the role of the GABAA/BZ-R complex in anxiety disorders, new insights into the molecular biology of the receptor complex, and the importance of this target in the development of new therapeutic agents in anxiety.