Nitric oxide inhalation reduces brain damage, prevents mortality, and improves neurological outcome after subarachnoid hemorrhage by resolving early pial microvasospasms.

Subarachnoid hemorrhage is a stroke subtype with particularly bad outcome. Recent findings suggest that constrictions of pial arterioles occurring early after hemorrhage may be responsible for cerebral ischemia and - subsequently - unfavorable outcome after subarachnoid hemorrhage. Since we recently hypothesized that the lack of nitric oxide may cause post-hemorrhagic microvasospasms, our aim was to investigate whether inhaled nitric oxide, a treatment paradigm selectively delivering nitric oxide to ischemic microvessels, is able to dilate post-hemorrhagic microvasospasms; thereby improving outcome after experimental subarachnoid hemorrhage. C57BL/6 mice were subjected to experimental SAH. Three hours after subarachnoid hemorrhage pial artery spasms were quantified by intravital microscopy, then mice received inhaled nitric oxide or vehicle. For induction of large artery spasms mice received an intracisternal injection of autologous blood. Inhaled nitric oxide significantly reduced number and severity of subarachnoid hemorrhage-induced post-hemorrhage microvasospasms while only having limited effect on large artery spasms. This resulted in less brain-edema-formation, less hippocampal neuronal loss, lack of mortality, and significantly improved neurological outcome after subarachnoid hemorrhage. This suggests that spasms of pial arterioles play a major role for the outcome after subarachnoid hemorrhage and that lack of nitric oxide is an important mechanism of post-hemorrhagic microvascular dysfunction. Reversing microvascular dysfunction by inhaled nitric oxide might be a promising treatment strategy for subarachnoid hemorrhage.

Erratum to: Vascular endothelial growth factor induces contralesional corticobulbar plasticity and functional neurological recovery in the ischemic brain.

Erratum to: Acta Neuropathol (2012) 123:273–284. DOI 10.1007/s00401‑011‑0914‑z. The authors would like to correct Fig. 3 of the original manuscript, since the image in Fig. 3b does not correspond to a VEGF treated animal. Corrected Fig. 3 is shown below. We apologize for this mistake.

Cellular hyper-excitability caused by mutations that alter the activation process of voltage-gated sodium channels.

Voltage-gated sodium channels (Nav) are widely expressed as macro-molecular complexes in both excitable and non-excitable tissues. In excitable tissues, the upstroke of the action potential is the result of the passage of a large and rapid influx of sodium ions through these channels. NaV dysfunction has been associated with an increasingly wide range of neurological, muscular and cardiac disorders. The purpose of this review is to summarize the recently identified sodium channel mutations that are linked to hyper-excitability phenotypes and associated with the alteration of the activation process of voltage gated sodium channels. Indeed, several clinical manifestations that demonstrate an alteration of tissue excitability were recently shown to be strongly associated with the presence of mutations that affect the activation process of the Nav. These emerging genotype-phenotype correlations have expanded the clinical spectrum of sodium channelopathies to include disorders which feature a hyper-excitability phenotype that may or may not be associated with a cardiomyopathy. The p.I141V mutation in SCN4A and SCN5A, as well as its homologous p.I136V mutation in SCN9A, are interesting examples of mutations that have been linked to inherited hyperexcitability myotonia, exercise-induced polymorphic ventricular arrhythmias and erythromelalgia, respectively. Regardless of which sodium channel isoform is investigated, the substitution of the isoleucine to valine in the locus 141 induces similar modifications in the biophysical properties of the Nav by shifting the voltage-dependence of steady state activation toward more negative potentials.

Mycoplasma-induced minimally conscious state

Mycoplasma pneumoniae (M. pneumoniae) frequently causes community-acquired respiratory tract infection and often presents as atypical pneumonia. Following airborne infection and a long incubation period, affected patients mostly suffer from mild or even asymptomatic and self-limiting disease. In particular in school-aged children, M. pneumoniae is associated with a wide range of extrapulmonary manifestations including central nervous system (CNS) disease. In contrast to children, severe CNS manifestations are rarely observed in adults. We report a case of a 37 year-old previously healthy immunocompetent adult with fulminant M. pneumoniae-induced progressive encephalomyelitis who was initially able to walk to the emergency department. A few hours later, she required controlled mechanical ventilation for ascending transverse spinal cord syndrome, including complete lower extremity paraplegia. Severe M. pneumoniae-induced encephalomyelitis was postulated, and antimicrobial, anti-inflammatory and immunosuppressive therapy was applied on the intensive care unit. Despite early and targeted therapy using four different immunosuppressive strategies, clinical success was limited. In our patient, locked-in syndrome developed followed by persistent minimally conscious state. The neurological status was unchanged until day 230 of follow-up. Our case underlines that severe M. pneumoniae- related encephalomyelitis must not only be considered in children, but also in adults. Moreover, it can be fulminant and fatal in adults. Our case enhances the debate for an optimal antimicrobial agent with activity beyond the blood-brain barrier. Furthermore, it may underline the difficulty in clinical decision making regarding early antimicrobial treatment in M. pneumoniae disease, which is commonly self-limited.

Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis: a 10-year longitudinal study from the EUSTAR database.

OBJECTIVES To longitudinally map the onset and identify risk factors for skin sclerosis and digital ulcers (DUs) in patients with systemic sclerosis (SSc) from an early time point after the onset of Raynaud's phenomenon (RP) in the European Scleroderma Trials and Research (EUSTAR) cohort. METHODS 695 patients with SSc with a baseline visit within 1 year after RP onset were followed in the prospective multinational EUSTAR database. During the 10-year observation period, cumulative probabilities of cutaneous lesions were assessed with the Kaplan-Meier method. Cox proportional hazards regression analysis was used to evaluate risk factors. RESULTS The median modified Rodnan skin score (mRSS) peaked 1 year after RP onset, and was 15 points. The 1-year probability to develop an mRSS ≥2 in at least one area of the arms and legs was 69% and 25%, respectively. Twenty-five per cent of patients developed diffuse cutaneous involvement in the first year after RP onset. This probability increased to 36% during the subsequent 2 years. Only 6% of patients developed diffuse cutaneous SSc thereafter. The probability to develop DUs increased to a maximum of 70% at the end of the 10-year observation. The main factors associated with diffuse cutaneous SSc were the presence of anti-RNA polymerase III autoantibodies, followed by antitopoisomerase autoantibodies and male sex. The main factor associated with incident DUs was the presence of antitopoisomerase autoantibodies. CONCLUSION Early after RP onset, cutaneous manifestations exhibit rapid kinetics in SSc. This should be accounted for in clinical trials aiming to prevent skin worsening.

DNA incisions stimulate genetic instability of triplet repeat sequences related to human hereditary neurological diseases

The molecular mechanisms responsible for the expansion and deletion of trinucleotide repeat sequences (TRS) are the focus of our studies. Several hereditary neurological diseases including Huntington's disease, myotonic dystrophy, and fragile X syndrome are associated with the instability of TRS. Using the well defined and controllable model system of Escherichia coli, the influences of three types of DNA incisions on genetic instability of CTG•CAG repeats were studied: DNA double-strand breaks (DSB), single-strand nicks, and single-strand gaps. The DNA incisions were generated in pUC19 derivatives by in vitro cleavage with restriction endonucleases. The cleaved DNA was then transformed into E. coli parental and mutant strains. Double-strand breaks induced deletions throughout the TRS region in an orientation dependent manner relative to the origin of replication. The extent of instability was enhanced by the repeat length and sequence (CTG•CAG vs. CGG•CCG). Mutations in recA and recBC increased deletions, mutations in recF stabilized the TRS, whereas mutations in ruvA had no effect. DSB were repaired by intramolecular recombination, versus an intermolecular gene conversion or crossover mechanism. 30 nt gaps formed a distinct 30 nt deletion product, whereas single strand nicks and gaps of 15 nts did not induce expansions or deletions. Formation of this deletion product required the CTG•CAG repeats to be present in the single-stranded region and was stimulated by E. coli DNA ligase, but was not dependent upon the RecFOR pathway. Models are presented to explain the DSB induced instabilities and formation of the 30 nucleotide deletion product. In addition to the in vitro creation of DSBs, several attempts to generate this incision in vivo with the use of EcoR I restriction modification systems were conducted. ^

Sickle cell disease: Its signs, symptoms and varied manifestations

Seventy-five sickle cell patients, age 3-36 years from Houston, Texas, participated in the research study to investigate sickle cell manifestations, conducted between November 1989 and August 1990. All the participants were blacks. There were 35 females and 39 males among the participants in this research study. One of the participants did not document the gender.^ The sickle cell history questionnaire was administered to the participants. Data collected from this study were statistically analyzed using frequencies, percentages, crosstabulations and chi-squares.^ Regular source of health care influences the time of diagnosis of sickle cell disease. Early diagnosis of sickle cell disease with proper care and management will reduce the morbidity and mortality rate of the disease.^ Fevers, bacterial infection, pneumoniae, anemiae, pains, ulcers and cardiovascular problems are common causes of hospitalizations. The average length of stay in the hospital on admission were higher among the sickle cell patients than their family members who themselves did not have sickle cell disease. ^

Average contents of chemical elements in different types of hydrothermal manifestations within 16°38'N hydrothermal field, MAR

An additional ore field in the central part of the MARhas been discovered. Together with previously discovered Logachev (14°45'N) and Ashadze (12°58'N) ore fields, the new ore field constitutes a cluster with preliminarily estimated total ore reserve of >10 Mt, which is comparable with large continental massive sulfide deposits.

Perfil clínico y social del paciente adicto hospitalizado

Objetivos: Determinar las características clínicas y morbilidad de los pacientes (pac.) adictos ingresados a un Servicio de Clínica Médica. Material y métodos: Estudio protocolizado, observacional, descriptivo y transversal. Criterio de inclusión: pac. adicto con consumo de sustancias ilícitas. Informe preliminar: Periodo: 24 meses. Datos analizados en Epi info 6.4 Resultados: Se incluyeron 40 pac. Prevalencia: 0.2/1000 egresos. El 82.5% eran hombres. Edad media: 31.5 años (DS±9.65). Permanencia media: 11 días (DS±13.98) vs 7.12 (DS±10.1) del Servicio (p=0.016). Consumían cocaína el 82.5% (IC95%67.22-92.66) marihuana el 77.5% (IC95% 61.65- 89.16), tolueno el 10% (IC95%2.79-23.66), floripondio y hachis el 2.5% (IC95% 0.06-13.16) cada uno. En el 2.5% la vía de administración era endovenosa y el 60% eran poliadictos. Solo el 10% recibió tratamiento para abandonar la adicción (100% tratamiento psicológico y 5.13% farmacológico). De clase social pobre el 75%. El 62.5% de los pac. estaban desocupados, tenían antecedentes judiciales el 10% y el 7.5% había estado en prisión. El 92.5% (IC95% 76.34-97.21) era heterosexual, 2.5% hombres que tenían sexo con hombres y bisexuales 5% (IC95% 0.61-16.92). Solo el 10% tenían secundaria completa. El 80% ingreso por Emergencias y por causa infecciosa el 45%. El 12.5% ingreso por complicaciones de la adicción. Las manifestaciones relacionadas con la adicción fueron: manifestaciones del sistema nervioso central: 12.5% (IC95%4.19-26.80); síndrome de abstinencia y temblor 7.5% cada uno y excitación psicomotriz, delirium, signo de foco neurológico y rigidez 5% cada uno. El 100% presentaba alguna comórbida; tabaquismo 80%, depresión 12.8% Y alcoholismo 57.5%, entre otras. Presentaban enfermedades de transmisión sexual 5 pac. (4 HIV, 2 VHC y 1 pediculus pubis). No hubo mortalidad hospitalaria. Conclusión: El paciente adicto internado se caracteriza por ser joven, pertenecer a un grupo social desprotegido, sin trabajo y sin educación, tener poliadicción, con alta carga de comórbidas y de internación, principalmente por complicaciones infecciosas.

Chemical composition of ferromanganese manifestations from the Sea of Okhotsk

New data on microstructures and mineral and chemical compositions of ferromanganese crusts sampled from the western slope of the Kuril Island Arc in the Sea of Okhotsk during cruises of R/V Vulkanolog are discussed. The study of the crusts using analytical electron microscopy methods revealed that their manganese phase is represented by vernadite, Fe-vernadite, todorokite, asbolane, and asbolane-buserite, while iron phase consists of hematite, hydrohematite, ferroxyhite, and magnetite. Lithic mineral assemblage includes apatite, quartz, epidote, and montmorillonite. According to chemical analysis most of the crusts contain significant part of volcanogenic and hydrothermal material. It is evident from elevated values of Mn/Fe and (Mn+Fe)/Ti ratios, low concentrations of some trace elements, and positive Eu anomaly.

Chemical composition of Fe-Mn manifestations from the Laptev Sea

In sediments of the Laptev Sea unknown earlier ferromanganese manifestations have been found. On the basis of structural-textural external signs they have been divided to five groups: 1) tube- and spindle-shaped pseudomorphs after and within invertebrates; 2) nuclear and non-nuclear nodules; 3) flagellum- and tube-like skeletons of polychaetes; 4) flat and flattened crustate nodules and crusts; 5) micronodules. All types of ferromanganese manifestations have been sorted in three main genetic series: eigenferrous formations of autochthonous (polychaetes, goethite micronodules) and allochthonous (nuclear nodules) nature; ferromanganese nodules formed under mild hydro-geodynamic conditions at the sediment-seawater geochemical barrier; and ferromanganese manifestations formed under conditions of the variable physico-chemical environment. Ferromanganese manifestations of allochthonous type have signs of littoral zones. They contain both ferrous and ferric iron and have low oxidation degree of manganese in comparison with the autochthonous type manifestations. Manganese minerals with moderate oxidation degree are represented by vernadite and buserite. Such features of iron and manganese indicate different conditions of their formation and occurrence. The main distinctive feature of ferromanganese mineralisation in the Laptev Sea is the redox barrier: the oxidized water layer enriched in oxygen and reduced sediments. This barrier provides favorable conditions for bacterial formation of ferromanganese ores. Understanding of the genesis of ferromanganese manifestations should be found in a study of organic matter reworking by bacteria.

Composition of sediments, hydrothermal manifestations, interstitial waters, and aeolian material from the TAG Hydrothermal Field and Central Atlantic

The book is devoted to regularities of spatial distribution, mineralogy and geochemistry of hydrothermal and hydrothermal-sedimentary manifestations of the Mid-Atlantic Ridge rift zone.

Composition of hydrothermal manifestations in the World Ocean

The monograph summarizes results of studies of hydrothermal fields on the ocean floor, hydrothermal plumes and metalliferous sediments. Hydrothermal ore manifestations formed in different geodynamic settings, with different character of volcanism in different facial conditions of deposition are described. Causes of non-uniformity of hydrothermal system functioning in different parts of the ocean and therefore variability of hydrothermal deposits are under consideration. On the base of found relationships of these irregularities with geodynamics, volcanism and sedimentation a new classification of hydrothermal processes and genetic models of hydrothermal ore formation in the ocean have been created. Regularities of hydrothermal sedimentary material dispersion in bottom waters are discussed.