Prenatal diagnosis of Caudal Regression Syndrome : a case report

BACKGROUND: Caudal regression is a rare syndrome which has a spectrum of congenital malformations ranging from simple anal atresia to absence of sacral, lumbar and possibly lower thoracic vertebrae, to the most severe form which is known as sirenomelia. Maternal diabetes, genetic predisposition and vascular hypoperfusion have been suggested as possible causative factors. CASE PRESENTATION: We report a case of caudal regression syndrome diagnosed in utero at 22 weeks' of gestation. Prenatal ultrasound examination revealed a sudden interruption of the spine and "frog-like" position of lower limbs. Termination of pregnancy and autopsy findings confirmed the diagnosis. CONCLUSION: Prenatal ultrasonographic diagnosis of caudal regression syndrome is possible at 22 weeks' of gestation by ultrasound examination

Gene expression markers of tendon fibroblasts in normal and diseased tissue compared to monolayer and three dimensional culture systems

<p>Abstract</p> <p>Background</p> <p>There is a paucity of data regarding molecular markers that identify the phenotype of the tendon cell. This study aims to quantify gene expression markers that distinguish between tendon fibroblasts and other mesenchymal cells which may be used to investigate tenogenesis.</p> <p>Methods</p> <p>Expression levels for 12 genes representative of musculoskeletal tissues, including the proposed tendon progenitor marker scleraxis, relative to validated reference genes, were evaluated in matched samples of equine tendon (harvested from the superficial digital flexor tendon), cartilage and bone using quantitative PCR (qPCR). Expression levels of genes associated with tendon phenotype were then evaluated in healthy, including developmental, and diseased equine tendon tissue and in tendon fibroblasts maintained in both monolayer culture and in three dimensional (3D) collagen gels.</p> <p>Results</p> <p>Significantly increased expression of scleraxis was found in tendon compared with bone (P = 0.002) but not compared to cartilage. High levels of COL1A2 and scleraxis and low levels of tenascin-C were found to be most representative of adult tensional tendon phenotype. While, relative expression of scleraxis in developing mid-gestational tendon or in acute or chronically diseased tendon did not differ significantly from normal adult tendon, tenascin-C message was significantly upregulated in acutely injured equine tendon (P = 0.001). Relative scleraxis gene expression levels in tendon cell monolayer and 3D cultures were significantly lower than in normal adult tendon (P = 0.002, P = 0.02 respectively).</p> <p>Conclusion</p> <p>The findings of this study indicate that high expression of both COL1A2 and scleraxis, and low expression of tenascin-C is representative of a tensional tendon phenotype. The <it>in vitro </it>culture methods used in these experiments however, may not recapitulate the phenotype of normal tensional tendon fibroblasts in tissues as evidenced by gene expression.</p

TIG3 Tumor Suppressor-Dependent Organelle Redistribution and Apoptosis in Skin Cancer Cells

TIG3 is a tumor suppressor protein that limits keratinocyte survival during normal differentiation. It is also important in cancer, as TIG3 level is reduced in tumors and in skin cancer cell lines, suggesting that loss of expression may be required for cancer cell survival. An important goal is identifying how TIG3 limits cell survival. In the present study we show that TIG3 expression in epidermal squamous cell carcinoma SCC-13 cells reduces cell proliferation and promotes morphological and biochemical apoptosis. To identify the mechanism that drives these changes, we demonstrate that TIG3 localizes near the centrosome and that pericentrosomal accumulation of TIG3 alters microtubule and microfilament organization and organelle distribution. Organelle accumulation at the centrosome is a hallmark of apoptosis and we demonstrate that TIG3 promotes pericentrosomal organelle accumulation. These changes are associated with reduced cyclin D1, cyclin E and cyclin A, and increased p21 level. In addition, Bax level is increased and Bcl-XL level is reduced, and cleavage of procaspase 3, procaspase 9 and PARP is enhanced. We propose that pericentrosomal localization of TIG3 is a key event that results in microtubule and microfilament redistribution and pericentrosomal organelle clustering and that leads to cancer cell apoptosis

Carbon Nanotubes in Tissue Engineering

For their peculiar features carbon nanotubes (CNTs) are emerging in many areas of nanotechnology applications. CNT-based technology has been increasingly proposed for biomedical applications, to develop biomolecule nanocarriers, bionanosensors and smart material for tissue engineering purposes. In the following chapter this latter application will be explored, describing why CNTs can be considered an ideal material able to support and boost the growth and the proliferation of many kind of tissues

The neurogenic bladder: medical treatment

Neurogenic bladder sphincter dysfunction (NBSD) can cause severe and irreversible renal damage and bladder-wall destruction years before incontinence becomes an issue. Therefore, the first step in adequate management is to recognize early the bladder at risk for upper- and lower-tract deterioration and to start adequate medical treatment proactively. Clean intermittent catheterization combined with anticholinergics (oral or intravesical) is the standard therapy for NBSD. Early institution of such treatment can prevent both renal damage and secondary bladder-wall changes, thereby potentially improving long-term outcomes. In children with severe side effects or with insufficient suppression of detrusor overactivity despite maximal dosage of oral oxybutynin, intravesical instillation is an effective alternative. Intravesical instillation eliminates systemic side effects by reducing the first-pass metabolism and, compared with oral oxybutynin, intravesical oxybutynin is a more potent and long-acting detrusor suppressor. There is growing evidence that with early adequate treatment, kidneys are saved and normal bladder growth can be achieved in children so they will no longer need surgical bladder augmentation to achieve safe urinary continence in adolescence and adulthood

The HELLP syndrome: Clinical issues and management. A Review

<p>Abstract</p> <p>Background</p> <p>The HELLP syndrome is a serious complication in pregnancy characterized by haemolysis, elevated liver enzymes and low platelet count occurring in 0.5 to 0.9% of all pregnancies and in 10–20% of cases with severe preeclampsia. The present review highlights occurrence, diagnosis, complications, surveillance, corticosteroid treatment, mode of delivery and risk of recurrence.</p> <p>Methods</p> <p>Clinical reports and reviews published between 2000 and 2008 were screened using Pub Med and Cochrane databases.</p> <p>Results and conclusion</p> <p>About 70% of the cases develop before delivery, the majority between the 27th and 37th gestational weeks; the remainder within 48 hours after delivery. The HELLP syndrome may be complete or incomplete. In the Tennessee Classification System diagnostic criteria for HELLP are haemolysis with increased LDH (> 600 U/L), AST (≥ 70 U/L), and platelets < 100·10⁹/L. The Mississippi Triple-class HELLP System further classifies the disorder by the nadir platelet counts. The syndrome is a progressive condition and serious complications are frequent. Conservative treatment (≥ 48 hours) is controversial but may be considered in selected cases < 34 weeks' gestation. Delivery is indicated if the HELLP syndrome occurs after the 34th gestational week or the foetal and/or maternal conditions deteriorate. Vaginal delivery is preferable. If the cervix is unfavourable, it is reasonable to induce cervical ripening and then labour. In gestational ages between 24 and 34 weeks most authors prefer a single course of corticosteroid therapy for foetal lung maturation, either 2 doses of 12 mg betamethasone 24 hours apart or 6 mg or dexamethasone 12 hours apart before delivery. Standard corticosteroid treatment is, however, of uncertain clinical value in the maternal HELLP syndrome. High-dose treatment and repeated doses should be avoided for fear of long-term adverse effects on the foetal brain. Before 34 weeks' gestation, delivery should be performed if the maternal condition worsens or signs of intrauterine foetal distress occur. Blood pressure should be kept below 155/105 mmHg. Close surveillance of the mother should be continued for at least 48 hours after delivery.</p

Pregnancy-related pelvic girdle pain: an update

A large number of scientists from a wide range of medical and surgical disciplines have reported on the existence and characteristics of the clinical syndrome of pelvic girdle pain during or after pregnancy. This syndrome refers to a musculoskeletal type of persistent pain localised at the anterior and/or posterior aspect of the pelvic ring. The pain may radiate across the hip joint and the thigh bones. The symptoms may begin either during the first trimester of pregnancy, at labour or even during the postpartum period. The physiological processes characterising this clinical entity remain obscure. In this review, the definition and epidemiology, as well as a proposed diagnostic algorithm and treatment options, are presented. Ongoing research is desirable to establish clear management strategies that are based on the pathophysiologic mechanisms responsible for the escalation of the syndrome's symptoms to a fraction of the population of pregnant women

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field