Structural and functional analogies and differences between histidine decarboxylase and aromatic L-amino acid decarboxylase molecular networks: Biomedical implications.

Pharmacol Res. 2016 Oct 18;:

Authors: Sanchez-Jiménez F, Pino-Ángeles A, Rodríguez-López R, Morales M, Urdiales JL

Abstract
Human histidine decarboxylase (HDC) and dopa decarboxilase (DDC) are highly homologous enzymes responsible for the synthesis of biogenic amines (BA) like histamine, and serotonin and dopamine, respectively. The enzymes share many structural and functional analogies, while their product metabolisms also follow similar patterns that are confluent in some metabolic steps. They are involved in common physiological functions, such as neurotransmission, gastrointestinal track function, immunity, cell growth and cell differentiation. As a consequence, metabolic elements of both BA subfamilies are also co-participants in a long list of human diseases. This review summarizes the analogies and differences in their origin (HDC and DDC) as well as their common pathophysiological scenarios. The major gaps of information are also underlined, as they delay the possibility of holistic approaches that would help personalized medicine and pharmacological iniciatives for prevalent and rare diseases.

PMID: 27769832 [PubMed - as supplied by publisher]

Brain metabolite alterations in infants born preterm with intrauterine growth restriction: association with structural changes and neurodevelopmental outcome.

Am J Obstet Gynecol. 2016 Sep 22;:

Authors: Simões RV, Muñoz-Moreno E, Cruz-Lemini M, Eixarch E, Bargalló N, Sanz-Cortes M, Gratacós E

Abstract
BACKGROUND: Intrauterine growth restriction and premature birth represent 2 independent problems that may occur simultaneously and contribute to impaired neurodevelopment.
OBJECTIVE: The objective of the study was to assess changes in the frontal lobe metabolic profiles of 1 year old intrauterine growth restriction infants born prematurely and adequate-for-gestational-age controls, both premature and term adequate for gestational age and their association with brain structural and biophysical parameters and neurodevelopmental outcome at 2 years.
STUDY DESIGN: A total of 26 prematurely born intrauterine growth restriction infants (birthweight <10th centile for gestational age), 22 prematurely born but adequate for gestational age controls, and 26 term adequate-for-gestational-age infants underwent brain magnetic resonance imaging and magnetic resonance spectroscopy at 1 year of age during natural sleep, on a 3 Tesla scanner. All brain T1-weighted and diffusion-weighted images were acquired along with short echo time single-voxel proton spectra from the frontal lobe. Magnetic resonance imaging/magnetic resonance spectroscopy data were processed to derive structural, biophysical, and metabolic information, respectively. Neurodevelopment was evaluated at 2 years of age using the Bayley Scales 3rd edition, assessing cognitive, language, motor, socioemotional, and adaptive behavior.
RESULTS: Prematurely born intrauterine growth restriction infants had slightly smaller brain volumes and increased frontal lobe white matter mean diffusivity compared with both prematurely born but adequate for gestational age and term adequate for gestational age controls. Frontal lobe N-acetylaspartate levels were significantly lower in prematurely born intrauterine growth restriction than in prematurely born but adequate for gestational age infants but increased in prematurely born but adequate for gestational age compared with term adequate-for-gestational-age infants. The prematurely born intrauterine growth restriction group also showed slightly lower choline compounds, borderline decrements of estimated glutathione levels, and increased myoinositol to choline ratios, compared with prematurely born but adequate for gestational age controls. These specific metabolite changes were locally correlated to lower gray matter content and increased mean diffusivity and reduced white matter fraction and fractional anisotropy. Prematurely born intrauterine growth restriction infants also showed a tendency for poorer neurodevelopmental outcome at 2 years, associated with lower levels of frontal lobe N-acetylaspartate at 1 year within the preterm subset.
CONCLUSIONS: Preterm intrauterine growth restriction infants showed altered brain metabolite profiles during a critical stage of brain maturation, which correlate with brain structural and biophysical parameters and neurodevelopmental outcome. Our results suggest altered neurodevelopmental trajectories in preterm intrauterine growth restriction and adequate-for-gestational-age infants, compared with term adequate-for-gestational-age infants, which require further characterization.

PMID: 27667762 [PubMed - as supplied by publisher]

[Erdheim-Chester disease, an incredible simulator. Cases reports and review of literature].

Neurocirugia (Astur). 2016 Nov - Dec;27(6):296-303

Authors: Rascón-Ramírez FJ, Avecillas-Chasín JM, Rodríguez-Boto G, Subhi-Issa I, Salazar A OA, Sallabanda D K

Abstract
Erdheim-Chester disease is a non-Langerhans histiocytosis. Until 2014 at least 550 cases have been reported. According to European Rare Disease Organization and National Organization for Rare Disorders it is a rare disease. The most common symptom is bone pain in the lower extremities and it usually appears between the 5th and 7th decades of life. The diagnostic is based on immunohistochemical results: S100(+/-), CD68(+), and CD1a(-), the latter 2 are mandatory. The best treatment nowadays is alpha-interferon or pegylated alpha-2. The overall survival is 96% at one year and 68% at 5 years. Central nervous system involvement is associated with a worse outcome. Two cases are presentedwith central nervous system lesions in the absence of lesions in other organs on their onset. Very few cases have been reported with this kind of presentation. We also noted that these patients had recurrences or new lesions at 8 months. A follow-up is proposed with brain MRI and thoraco-abdominal PET every 3-4 months.

PMID: 27091228 [PubMed - in process]

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/10/22

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

25 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

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These pubmed results were generated on 2016/10/21

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/10/19

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/10/18

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Parental Reflections on the Diagnostic Process for Duchenne Muscular Dystrophy: A Qualitative Study.

J Pediatr Health Care. 2016 Oct 12;:

Authors: Bendixen RM, Houtrow A

Abstract
PURPOSE: Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease with no known cure. We sought to update over 30 years of research reporting on the diagnostic delays in DMD.
METHODS: Through personal interviews, this study qualitatively explored parents' experiences regarding receipt of the DMD diagnosis and the guidance for care provided. Thematic analysis identified themes and provided answers to the research questions being addressed.
RESULTS: Four themes emerged: (a) Dismissive illustrates little consideration of parent concern in the diagnostic process; (b) Limited Knowledge describes misunderstandings about clinical signs, recommended screenings, and testing to achieve a diagnosis of DMD; (c) Careless Delivery reports on the manner in which the diagnosis was given; and (d) Lack of Guidance describes the follow-up that occurred after the diagnosis.
CONCLUSION: Despite marked medical progress over the past several decades, substantial barriers to arriving at the diagnosis of DMD and the provision of care guidance remain.

PMID: 27743907 [PubMed - as supplied by publisher]

Lupus anticoagulant-hypoprothrombinemia syndrome presenting with co-existing cerebral venous thrombosis and subdural hemorrhage.

J Mal Vasc. 2016 Oct 12;:

Authors: Bel Feki N, Zayet S, Ben Ghorbel I, Houman MH

Abstract
The lupus anticoagulant-hypoprothrombinemia syndrome (LA-HPS) - the association of acquired factor II deficiency and lupus anticoagulant - is a rare disease that may cause a predisposition not only to thrombosis but also to severe bleeding. We are reporting on a 36-year-old female patient presenting with co-existing cerebral venous thrombosis and subdural hemorrhage. The coagulation screening showed a prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), and a normal fibrinogen level and platelet count. Evaluation of the clotting factors revealed decreased levels of factors II (37%). Factors V, VIII, IX and XI were normal. Lupus anticoagulant (LA) was demonstrated by the Dilute Russell's Viper Venom Test (DRVVT). Immunological work-up was positive for IgG type anticardiolipines antibodies (aCL). Successful management consisted first of oral prednisone (60mg/d). Thus, anticoagulation was introduced once factor II had stabilized.

PMID: 27743753 [PubMed - as supplied by publisher]

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/10/16

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

11 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/10/14

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

11 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/10/13

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/10/12

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/10/11

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Dysregulation of the endocannabinoid signaling system in the cerebellum and brainstem in a transgenic mouse model of spinocerebellar ataxia type-3.

Neuroscience. 2016 Oct 4;:

Authors: Rodríguez-Cueto C, Hernández-Gálvez M, Hillard CJ, Maciel P, García-García L, Valdeolivas S, Pozo MA, Ramos JA, Gómez-Ruiz M, Fernández-Ruiz J

Abstract
Spinocerebellar ataxia type-3 (SCA-3) is a rare disease but it is the most frequent type within the autosomal dominant inherited ataxias. The disease lacks an effective treatment to alleviate major symptoms and to modify disease progression. Our recent findings that endocannabinoid receptors and enzymes are significantly altered in the post-mortem cerebellum of patients affected by autosomal-dominant hereditary ataxias suggest that targeting the endocannabinoid signaling system may be a promising therapeutic option. Our goal was to investigate the status of the endocannabinoid signaling system in a transgenic mouse model of SCA-3, in the two CNS structures most affected in this disease -cerebellum and brainstem-. These animals exhibited progressive motor incoordination, imbalance, abnormal gait, muscle weakness, and dystonia, in parallel to reduced in vivo brain glucose metabolism, deterioration of specific neuron subsets located in the dentate nucleus and pontine nuclei, small changes in microglial morphology, and reduction in glial glutamate transporters. Concerning the endocannabinoid signaling, our data indicated no changes in CB2 receptors. By contrast, CB1 receptors increased in the Purkinje cell layer, in particular in terminals of basket cells, but they were reduced in the dentate nucleus. We also measured the levels of endocannabinoid lipids and found reductions in anandamide and oleoylethanolamide in the brainstem. These changes correlated with an increase in the FAAH enzyme in the brainstem, which also occurred in some cerebellar areas, whereas other endocannabinoid-related enzymes were not altered. Collectively, our results in SCA-3 mutant mice confirm a possible dysregulation in the endocannabinoid system in the most important brain structures affected in this type of ataxia, suggesting that a pharmacological manipulation addressed to correct these changes could be a promising option in SCA-3.

PMID: 27717809 [PubMed - as supplied by publisher]

Tandem Mass Spectrometry of Sphingolipids: Applications for Diagnosis of Sphingolipidoses.

Adv Clin Chem. 2016;77:177-219

Authors: Kuchař L, Asfaw B, Rybová J, Ledvinová J

Abstract
In recent years, mass spectrometry (MS) has become the dominant technology in lipidomic analysis. It is widely used in diagnosis and research of lipid metabolism disorders including those characterized by impairment of lysosomal functions and storage of nondegraded-degraded substrates. These rare diseases, which include sphingolipidoses, have severe and often fatal clinical consequences. Modern MS methods have contributed significantly to achieve a definitive diagnosis, which is essential in clinical practice to begin properly targeted patient care. Here we summarize MS and tandem MS methods used for qualitative and quantitative analysis of sphingolipids (SL) relative to the diagnostic process for sphingolipidoses and studies focusing on alterations in cell functions due to these disorders. This review covers the following topics: Tandem MS is sensitive and robust in determining the composition of sphingolipid classes in various biological materials. Its ability to establish SL metabolomic profiles using MS bench-top analyzers, significantly benefits the first stages of a diagnosis as well as metabolic studies of these disorders. It can thus contribute to a better understanding of the biological significance of SL.

PMID: 27717417 [PubMed - in process]

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/10/08

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/10/07

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Performance of a third trimester combined screening model for the prediction of adverse perinatal outcome.

Ultrasound Obstet Gynecol. 2016 Oct 5;:

Authors: Miranda J, Triunfo S, Rodriguez-Lopez M, Sairanen M, Kouru H, Parra-Saavedra M, Crovetto F, Figueras F, Crispi F, Gratacos E

Abstract
OBJECTIVE: To explore the potential value of a third trimester combined screening for the prediction of adverse perinatal outcome (APO) in the general population and among small-for-gestational age (SGA) neonates.
METHODS: Nested case-control study within a prospective cohort of 1,590 singleton gestations referred for third-trimester evaluation (32(0) -36(6) weeks of gestation). Maternal baseline characteristics, mean arterial blood pressure, fetoplacental ultrasound and circulating biochemical markers [placental growth factor (PlGF), lipocalin-2, unconjugated estriol and inhibin A] were assessed in all women who subsequently presented an APO (n = 148) and in a control group without perinatal complications (n = 902). APO were defined by the occurrence of stillbirth, umbilical artery cord blood pH<7.15, 5 minutes Apgar score <7 or emergency operative delivery for fetal distress. Logistic regression predictive models were developed for the prediction of APO in the general population and among SGA cases (defined as customized birth weight < 10(th) centile).
RESULTS: The prevalence of APO was 9.3% in the general population and 27.4% among SGA cases. In the general population, a combined screening model including a priori risk (maternal characteristics), estimated fetal weight centile (EFW), umbilical artery pulsatility index (UA-PI), estriol and PlGF, achieves a detection rate of 26% (AUC 0.59, 95% CI 0.53-0.64) for APO, at a 10% false positive rate (FPR). Among SGA cases, the model included a priori risk, EFWc, UA-PI, cerebroplacental ratio, estriol and PlGF predicting 62% of APO [AUC 0.86 (95% CI 0.80-0.92)] at a 10% FPR.
CONCLUSIONS: The use of fetal ultrasound and maternal biochemical markers at 32-36 weeks of gestation provides a poor prediction for APO in the general population. Although continue to be limited, the performance of the screening model is improved when is applied to fetuses with suboptimal fetal growth.

PMID: 27706856 [PubMed - as supplied by publisher]

Primary immunodeficiencies : Report of 33 Pediatric Tunisian cases.

Tunis Med. 2016 Apr;94(4):320-325

Authors: Halioui-Louhaichi S, Azzabi O, Mattoussi N, Labiadh H, Bousseta K, Tebib N, Gargah T, Ben Becher S, Barbouch MR, Bejaoui M, Maherzi A

Abstract
Background Primary immunodeficiencies (PID) are a group of heterogeneous and relatively rare diseases. Aim to determine the clinical characteristics, outcome and genetic data of primary immunodeficiencies in pediatrics patients. Methods A retrospective, descriptive and multicentered study, enrolling 33 children presenting a PID in Tunis, during a period of 22 years (1991-2012). Resultats a masculine predominance has been noticed with a sex ratio at 2,3. Consanguinity was found in 71% of family cases. History of early infant deaths was found in 42% of cases. The media age of diagnosis was of 1 year 2 months. The median diagnosis delay was of 11 months and 1/2. Most frenquently observed PID were combined immunodeficiency (36%), mostly severe combined immunodeficiency (SCID) (21%), followed by congenial defects of phagocyte function (33%), mostly chronic granulomatosis disease (21%). Antibody defects were found in 21% of cases. Most frequently observed out comes were lung infections (66%) recurrent oral thrush (57%) and diarrhea (42%). Most important complications were severe infections and bronchiectasis. 30% of patients were dead by the end of the study. A molecular characterization was performed in 33% of patients, and an antenatal diagnosis was performed in 10% of cases. Conclusion The PID are a group of disease with variable expressions and etiologies. Their frequency remains understimated in Tunisia, and their management, difficult and insufficient. We suggest the establishment of systematic genetic consulting visit, the creation of a national registry and developing bone marrow transplantation in children in Tunisia.

PMID: 27704518 [PubMed - in process]