Treatment of neuromyelitis optica: state-of-the-art and emerging therapies.

Neuromyelitis optica (NMO) is an autoimmune disease of the CNS that is characterized by inflammatory demyelinating lesions in the spinal cord and optic nerve, potentially leading to paralysis and blindness. NMO can usually be distinguished from multiple sclerosis (MS) on the basis of seropositivity for IgG antibodies against the astrocytic water channel aquaporin-4 (AQP4). Differentiation from MS is crucial, because some MS treatments can exacerbate NMO. NMO pathogenesis involves AQP4-IgG antibody binding to astrocytic AQP4, which causes complement-dependent cytotoxicity and secondary inflammation with granulocyte and macrophage infiltration, blood-brain barrier disruption and oligodendrocyte injury. Current NMO treatments include general immunosuppressive agents, B-cell depletion, and plasma exchange. Therapeutic strategies targeting complement proteins, the IL-6 receptor, neutrophils, eosinophils and CD19--all initially developed for other indications--are under clinical evaluation for repurposing for NMO. Therapies in the preclinical phase include AQP4-blocking antibodies and AQP4-IgG enzymatic inactivation. Additional, albeit currently theoretical, treatment options include reduction of AQP4 expression, disruption of AQP4 orthogonal arrays, enhancement of complement inhibitor expression, restoration of the blood-brain barrier, and induction of immune tolerance. Despite the many therapeutic options in NMO, no controlled clinical trials in patients with this condition have been conducted to date

Generation of standard gaseous mixtures using pneumatic generator

W pracy przedstawiono konstrukcję pneumatycznego generatora wzorcowych mieszanin gazowych przeznaczonych do kalibracji różnych analizatorów gazów. Pneumatyczny generator wzorcowych mieszanin gazowych może być również wykorzystywany do wytwarzania mieszanin oddechowych dla nurków pracujących na różnych głębokościach. Błąd bezwzględny wykonania mieszanin dwuskładnikowych i trójskładnikowych za pomocą skonstruowanego generatora nie przekracza 2%.The paper presents the construction of pneumatic generator for obtaining standard gaseous mixtures used for calibration of different gas analyzers. The system consists of gas cylinders with appropriate valves, electromagnetic valves, pneumatic containers, mixer and pulse suppressor. The generator is operated by programmed controller. The operator adjusts only the initial parameters, i.e. time of opening of inlet and outlet valves, pressure values, number of gas rations and composition of the desired gas mixture (two or three components). The developed program is responsible for automatic preparation of the desired mixture after pushing button "Start". The results are displayed on a screen enabling correction of initial parameters. The pneumatic generator of standard gaseous mixtures may be also applied for generating of breathing mixtures for divers working at different depths. The maximum error for binary and ternary gaseous mixtures generation does not exceeds 2%. The correctness of the desired mixture composition strongly depends on the leak tightness of the whole system. Filling and emptying times of pneumatic volumes also influences on the final results

Lower weight gain after vaping cessation than after smoking quitting

Background. Smoking is frequently a way to control appetite and weight. The data concerning the body mass gain after quitting among the users of electronic cigarettes who have no prior history of smoking traditional cigarettes is inconsistent. Objective. In our study we have compared smoking and vaping impact on weight gain and glycaemia. Material and methods. 3 groups of rats were used. The group A was exposed to vapour and group B were exposed to smoke. Rats in the group C constituted the control group without nicotine exposition. Results. During 6 weeks of experiment weight gain of rats in the A and B groups was comparable, while animals from group C had gained signifi0cantly more. During 2 weeks after cessation of exposition to nicotine animals from group B gained more weight than rats of A and C group. Blood glucose was higher in group B than in groups A and C 24 h after last exposure to nicotine and 2 weeks after nicotine exposure cessation. Conclusion. Effects of vaping on weight increase is similar to smoking, but after vaping cassation weight gain is lower and comparable with nicotine nonusers.Wprowadzenie. Palenie papierosów jest często stosowaną metodą utrzymywania niskiej masy ciała i kontroli apetytu. Badania dotyczące przyrostu masy ciała wśród osób, które nigdy nie paliły tradycyjnych papierosów i zaprzestały stosowania papierosów elektronicznych są niejednoznaczne. Cel badań. W naszym badaniu porównaliśmy wpływ papierosów tradycyjnych i elektronicznych na przyrost masy ciała i poziom cukru we krwi. Materiał i metody. Do badania użyto 3 grupy szczurów. Grupa A była eksponowana na parę z podgrzania płynu papierosa elektronicznego, grupa B została poddana działaniu dymu tytoniowego. Zwierzęta grupy C stanowiły grupę kontrolną bez narażenia na nikotynę. Wyniki. W trakcie 6 tygodni trwania eksperymentu przyrost masy ciała szczurów z grupy A i B był porównywalny, natomiast zwierzęta z grupy C przybrały istotnie więcej. Podczas 2 tygodni następujących po zaprzestaniu ekspozycji zwierzęta z grupy B przybrały więcej niż szczury z grypy A i C. Glikemia była najwyższa w grupie B zarówno bezpośrednio po zakończeniu ekspozycji, jak i po 2 tygodniowej przerwie w narażeniu na nikotynę. Wnioski. Wpływ stosowania papierosów elektronicznych na przyrost masy ciała jest porównywalny do palenia papierosów tradycyjnych w trakcie ekspozycji. Natomiast po zakończeniu narażenia na pary liquidu przyrost masy ciała jest mniejszy, podobnie jak w grupie kontrolnej

Assessment of NADPH-diaphorase stained myenteric neurons of the jejunum of diabetic rats supplemented with ascorbic acid Avaliação dos neurônios NADPH-diaforase reativos do jejuno de raots diabéticos suplementados com ácido ascórbico

The relation between hyperglycemia and diabetic neuropathy has already been demonstrated in some studies. Among the theories proposed for its etiology the oxidative stress stands out. The performance of nitric oxide as a link between the metabolic and vascular neuropathogenic factors that triggers the diabetic neuropathy has already been put forward. This study aimed to assess the quantification and measurements of the cell body profile area (CBPA) of NADPH-diaphorase reactive (NADPH-dp) myenteric neurons of the jejunum of diabetic rats (induced by streptozotocin) supplemented with Ascorbic Acid (AA). These changes in the myenteric neurons seem to be related to the gastrointestinal disturbances observed in diabetes mellitus (DM). Twenty male Wistar rats (Rattus norvegicus) were distributed in 4 groups (n=5): controls (C), control supplemented (CS), diabetic (D), and diabetic suplemented (DS). DM was induced by estreptozotocin (50mg/kg body wt). One week after the induction and confirmation of the DM (glycemia exam), animals of the groups CS and DS received 50mg of AA three times a week by gavage. After 90 days of experiment, the animals were anesthetized with lethal thiopental dose (40mg/kg) and the collected jejunum processed for the histochemistry NADPH-diaphorase technique. Whole-mount preparations were obtained for quantitative and morphometric analysis of the myenteric neurons. A quantity of jejunum neurons in the Group D (96&plusmn;7.5) was not different (P>0.05) from Group DS (116&plusmn;8.08), C (92&plusmn;9.7), and CS (81&plusmn;5.4), but in Group DS the quantity was higher (P<0.05) than in Group C and CS. The CBPA of neurons from Group D (189.50&plusmn;2.68µm²) and DS (195.92&plusmn;3.75µm²) were lower (P<0.05) than from Group C (225.13&plusmn;4.37µm²) and CS (210.23&plusmn;3.15µm²). The streptozotocin-induced DM did not change the jejunum-ileum area, the jejunum myenteric plexus space organization and the density of NADPH-dp neurons. The 50g AA-supplementation, three times a week, during 90 days, did not decrease hyperglycemia; however, it had a neuroprotective effect on the myenteric neurons, minimizing the increase on the CBPA of NADPH-dp neurons and increasing the amount of NADPD-dp neurons.<br>A relação entre hiperglicemia e neuropatia diabética foi demonstrada em várias pesquisas. Entre as teorias propostas para sua etiologia destaca-se o estresse oxidativo. O papel do óxido nítrico como elo entre os fatores neuropatogênicos metabólico e vascular que ativam a neuropatia diabética tem sido ressaltado. Este estudo objetivou avaliar a quantificação e a morfometria da área do perfil do corpo celular (CBPA) de neurônios mioentéricos NADPH-diaforase reativos (NADPH-dp) do jejuno de ratos diabéticos e suplementados com Ácido Ascórbico (AA), uma vez que alterações nos neurônios mioentéricos parecem estar relacionadas aos distúrbios gastrointestinais observados no diabetes mellitus (DM). Vinte ratos machos da linhagem Wistar (Rattus norvergicus) foram distribuídos em 4 grupos (n=5): controle (C), controle suplementado (CS), diabético (D) e diabético suplementado (DS). O DM foi induzido através de injeção de estreptozootocina (50mg/kg de peso corporal). Uma semana depois da indução e confirmação do DM (glicemia), animais dos grupos CS e DS receberam, via gavagem, 50mg de AA três vezes por semana. Após 90 dias de período experimental, os animais foram anestesiados com dose letal de thiopental intravenosa (40mg/kg) e o jejuno foi retirado e processado para a técnica histoquímica da NADPH-diaforase. Preparados de membrana foram obtidos para análises quantitativa e morfométrica dos neurônios mioentéricos. A quantidade de neurônios do jejuno do Grupo D (96&plusmn;7,5) não diferiu (P>0,05) dos Grupos DS (116&plusmn;8,08), C (92&plusmn;9,7) e CS (81&plusmn;5,4), mas no Grupo DS o número de neurônios foi superior (P<0,05) aos Grupos C e CS. A CBPA de neurônios do Grupo D (189,50&plusmn;2,68µm²) e DS (195,92&plusmn;3,75µm²) foi menor (P<0,05) do que a dos Grupos C (225,13&plusmn;4,37µm²) e CS (210,23&plusmn;3,15µm²). O DM induzido por estreptozootocina não alterou a área do jejuno-íleo, a organização espacial do plexo mioentérico e a densidade de neurônios de NADPH-dp do jejuno. A suplementação de 50mg de AA, três vezes por semana, durante 90 dias, não diminuiu a hiperglicemia, porém teve efeito neuroprotetor nos neurônios mioentéricos, minimizando o aumento na CBPA dos neurônios NADPH-dp e aumentando a quantidade de neurônios reativos a NADPD-diaforase