AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia

Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia  through  the so-called  oxygen-dependent  metabolic  regulation,  which  involves  the competitive  binding  of  deoxyhemoglobin  and  glycolytic  enzymes  to  the  N-terminal  cytosolic domain  of  band  3.  This  mechanism  promotes  the  accumulation  of  2,3-DPG,  stabilizing  the deoxygenated state of hemoglobin, and cytosol acidification, triggering oxygen off-loading through the  Bohr  effect.  Despite  in  vitro  studies,  in  vivo adaptations  to  hypoxia  have  not  yet  been completely elucidated. Within  the  framework  of  the AltitudeOmics  study,  erythrocytes  were  collected  from  21 healthy volunteers at sea level, after exposure to high altitude (5260m) for 1, 7 and 16days, and following  reascent  after  7days  at 1525m.  UHPLC-MS  metabolomics  results  were  correlated  to physiological and athletic performance parameters. Immediate  metabolic  adaptations  were  noted as early as a few hours from ascending  to >5000m, and maintained for 16 days at high altitude.  Consistent with the mechanisms elucidated in vitro, hypoxia promoted glycolysis and deregulated the pentose phosphate pathway, as well purine catabolism, glutathione homeostasis, arginine/nitric oxide and sulphur/H2S metabolism. Metabolic adaptations were preserved one week after descent, consistently with improved physical performances in comparison to the first ascendance, suggesting a mechanism of metabolic memory

A new species of Ochthebius (Cobalius) (Coleoptera: Hydraenidae: Ochthebiinae) inhabiting marine rockpools of NW Sicily

AbstractHere we describe a new species of Ochthebius (Cobalius) from marine rockpools of NW Sicily: O. (C.) senczuki sp. n. This species was first discovered on the basis of molecular evidence, but its taxonomic distinction has been subsequently supported by morphological characters. Ochthebius (C.) senczuki sp. n. shows a clear genetic diversity from the known related species, with an average COI p distance ranging from 5.6% to 10.7%; it exhibits only small morphological differences, mostly limited to dorsal punctation, pronotal and elytral outer edge, and (in males) to the mobile part of the median lobe of the aedeagus. The origin of O. (C.) senczuki sp. n. is estimated to lie in the Late Miocene (~9 Mya); the ancestors of this taxon probably remained isolated from populations of the related taxa of the Ochthebius (Cobalius) subinteger and O. (Cobalius) adriaticus complexes during cycles of regressive and transgressive marine phases that occurred in the SW Mediterranean during Late Miocene and Pliocene. The detailed state of the art of members of the O. (Cobalius) adriaticus complex throughout the Central and Eastern Mediterranean rocky coastal areas is also preliminarily discussed.http://zoobank.org/urn:lsid:zoobank.org:pub:CBFA5063-2FBE-488B-8497-E5DA7DCA936

Rapidly Progressive Renal and Hepatic Failure in AL-Amyloidosis: Bortezomib and Steroid Support in a Young Woman Two Months After Delivery

INTRODUCTION: The epidemiology of amyloidosis is not well known and its diagnosis is difficult, due to unspecific early clinical manifestations. Amyloidosis is considered when organ failure occurs. Renal, cardiac and hepatic involvement usually occurred despite therapy. Presenting this case report, we aimed to underline the need of new treatments for amyloidosis. MATERIALS AND METHODS: We describe a 41 years old woman admitted to the hospital with proteinuria (1280 mg/24h) and rapid deterioration of renal function (serum creatinine from 0.8 to 1.6 mg/dL). Autoantibodies, immunoglobulin and C3/C4 were negative. A renal biopsy showed the presence of AL-Amyloidosis with k-light chains deposition at immunofluorence. Subsequently, the patient showed nephrotic syndrome onset (proteinuria 4000 mg/24h with albuminuria 3400 mg/24h) and increased rates of cholestasis with hepatomegaly and hepatic failure. RESULTS: Treatment with bortezomib and dexamethasone gave a complete hematological response but renal function was not improved. DISCUSSION: This case is very interesting because renal involvement was the initial presentation of amyloidosis and rapid progressive renal and hepatic failure was subsequentely observed; its management was challenging from the clinical approach to the final diagnosis and treatment. CONCLUSIONS: In terms of organ response, it is necessary to develop new strategies to counteract the progressive organ failure due to amyloid deposition

Adipose-Derived Stem Cell: an Innovative Therapeutic Approach in Systemic Sclerosis and Parry-Romberg Syndrome

INTRODUCTION: Cell-based therapies represent a promising therapeutic approach to enhance the regeneration of damaged tissue and the combination with specific soluble mediators and biomaterial scaffolds has allowed the introduction of new treatment strategies in regenerative medicine. Adipose-derived stem cells (ASCs) show the ability to differentiate into several cell lineages such as chondrocytes, osteoblasts, adipocytes, neuronal cells, and muscle cells. These cells are abundant in normal human fat and they can be easily harvested from small amount of liposuction. For these reasons, they are greatly employed in the treatment of cutaneous and musculoskeletal defects are greatly. MATERIALS AND METHODS: ASCs isolated from liposuction aspirate by type I collagenases digestion were successively characterized by FACS analysis in order to verify their mesenchymal origin and test their capacity to differentiate into adipogenic, chondrogenic and osteogenic lineages. Autologous cult

Fibroblast Growth Factor Receptor-2 Expression in Thyroid Tumor Progression: Potential Diagnostic Application

Fibroblast growth factor receptor-2 (FGFR-2) plays an important role in tumorigenesis. In thyroid cancer it has been observed a FGFR-2 down-modulation, but the role of this receptor has not been yet clarified. Therefore, we decided to examine the expression of both FGFR-2 isoform, FGFR-2-IIIb and FGFR-2-IIIc, in different histological thyroid variants such as hyperplasia, follicular adenoma and papillary carcinoma. Immunohistochemistry and quantitative Real-Time PCR analyses were performed on samples of hyperplasia, follicular adenoma and papillary carcinoma, compared with normal thyroid tissue. Thyroid hyperplasia did not show statistically significant reduction in FGFR-2 protein and mRNA levels. Interestingly, in both follicular adenoma and papillary carcinoma samples we observed a strongly reduced expression of both FGFR-2 isoforms. We speculate that FGFR-2 down-modulation might be an early event in thyroid carcinogenesis. Furthermore, we suggest the potential use of FGFR-2 as an early marker for thyroid cancer diagnosis