Academic literature on the topic 'NNAVA'

In nonsedated newborn lambs, nasal pressure support ventilation (nPSV) can lead to an active glottal closure in early inspiration, which can limit lung ventilation and divert air into the digestive system, with potentially deleterious consequences. During volume control ventilation (nVC), glottal closure is delayed to the end of inspiration, suggesting that it is reflexly linked to the maximum value of inspiratory pressure. Accordingly, the aim of the present study was to test whether inspiratory glottal closure develops at the end of inspiration during nasal neurally adjusted ventilatory assist (nNAVA), an increasingly used ventilatory mode where maximal pressure is also reached at the end of inspiration. Polysomnographic recordings were performed in eight nonsedated, chronically instrumented lambs, which were ventilated with progressively increasing levels of nPSV and nNAVA in random order. States of alertness, diaphragm, and glottal muscle electrical activity, tracheal pressure, Spo2, tracheal PetCO2, and respiratory inductive plethysmography were continuously recorded. Although phasic inspiratory glottal constrictor electrical activity appeared during nPSV in 5 of 8 lambs, it was never observed at any nNAVA level in any lamb, even at maximal achievable nNAVA levels. In addition, a decrease in Pco2 was neither necessary nor sufficient for the development of inspiratory glottal constrictor activity. In conclusion, nNAVA does not induce active inspiratory glottal closure, in contrast to nPSV and nVC. We hypothesize that this absence of inspiratory activity is related to the more physiological airway pressurization during nNAVA, which tightly follows diaphragm electrical activity throughout inspiration.

Recent evidence suggests that neuronal Na+ channels (nNavs) contribute to catecholamine-promoted delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardia (CPVT). The newly identified overlap between CPVT and long QT (LQT) phenotypes has stoked interest in the cross-talk between aberrant Na+ and Ca2+ handling and its contribution to early afterdepolarizations (EADs) and DADs. Here, we used Ca2+ imaging and electrophysiology to investigate the role of Na+ and Ca2+ handling in DADs and EADs in wild-type and cardiac calsequestrin (CASQ2)-null mice. In experiments, repolarization was impaired using 4-aminopyridine (4AP), whereas the L-type Ca2+ and late Na+ currents were augmented using Bay K 8644 (BayK) and anemone toxin II (ATX-II), respectively. The combination of 4AP and isoproterenol prolonged action potential duration (APD) and promoted aberrant Ca2+ release, EADs, and DADs in wild-type cardiomyocytes. Similarly, BayK in the absence of isoproterenol induced the same effects in CASQ2-null cardiomyocytes. In vivo, it prolonged the QT interval and, upon catecholamine challenge, precipitated wide QRS polymorphic ventricular tachycardia that resembled human torsades de pointes. Treatment with ATX-II produced similar effects at both the cellular level and in vivo. Importantly, nNav inhibition with riluzole or 4,9-anhydro-tetrodotoxin reduced the incidence of ATX-II–, BayK-, or 4AP-induced EADs, DADs, aberrant Ca2+ release, and VT despite only modestly mitigating APD prolongation. These data reveal the contribution of nNaVs to triggered arrhythmias in murine models of LQT and CPVT-LQT overlap phenotypes. We also demonstrate the antiarrhythmic impact of nNaV inhibition, independent of action potential and QT interval duration, and provide a basis for a mechanistically driven antiarrhythmic strategy.

Previous studies reported thatNaja naja atravenom (NNAV) inhibited inflammation and adjuvant arthritis. Here we investigated the role of NNAV in regulation of immune responses in mice. Oral administration of NNAV to normal mice showed significant increase in natural killer cell activity, B lymphocyte proliferation stimulated by lipopolysaccharides, and antibody production in response to sheep red blood cells. Meanwhile, NNAV markedly decreased T lymphocyte proliferation stimulated by concanavalin A, arrested the cell cycle at G0/G1phase, and suppressed CD4 and CD8 T cell divisions. Furthermore, NNAV inhibited the dinitrofluorobenzene-induced delayed-type hypersensitivity reaction. This modulation of immune responses may be partly attributed to the selective increase in Th1 and Th2 cytokines (IFN-γ, IL-4) secretion and inhibition of Th17 cytokine (IL-17) production. In dexamethasone-induced immunosuppressed mice, NNAV restored the concentration of serum IgG and IgM, while decreasing the percentage of CD4 and CD8 T-cell subsets. These results indicate that NNAV enhances the innate and humoral immune responses while inhibiting CD4 Th17 and CD8 T cell actions, suggesting that NNAV could be a potential therapeutic agent for autoimmune diseases.

Systemic lupus erythematosus (SLE) is an autoimmune disease and effective therapy for this pathology is currently unavailable. We previously reported that oral administration ofNaja naja atravenom (NNAV) had anti-inflammatory and immune regulatory actions. We speculated that NNAV may have therapeutic effects in MRL/lpr SLE mice. Twelve-week-old MRL/lpr mice received oral administration of NNAV (20, 40, and 80 μg/kg) orTripterygium wilfordii polyglycosidium(10 mg/kg) daily for 16 weeks. The effects of NNAV on SLE manifestations, including skin erythema, proteinuria, and anxiety-like behaviors, were assessed with visual inspection and Multistix 8 SG strips and open field test, respectively. The pathology of spleen and kidney was examined with H&E staining. The changes in autoimmune antibodies and cytokines were determined with ELISA kits. The results showed that NNAV protected against the manifestation of SLE, including skin erythema and proteinuria. In addition, although no apparent histological change was found in liver and heart in MRL/lpr SLE mice, NNAV reduced the levels of glutamate pyruvate transaminase and creatine kinase. Furthermore, NNAV increased serum C3 and reduced concentrations of circulating globulin, anti-dsDNA antibody, and inflammatory cytokines IL-6 and TNF-α. NNAV also reduced lymphadenopathy and renal injury. These results suggest that NNAV may have therapeutic values in the treatment of SLE by inhibiting autoimmune responses.

To investigate the antinociceptive and anti-inflammatory activities of the denatured Naja Naja atra venom (NNAV) in rheumatoid arthritis-associated models, the denatured NNAV (heat treated; 30, 90, 270 μg/kg), the native NNAV (untreated with heat; 90 μg/kg), and Tripterygium wilfordii polyglycoside (TWP, 15 mg/kg) were administrated orally either prophylactically or therapeutically. We measured time of licking the affected paw in formaldehyde-induced inflammatory model, paw volume in egg-white-induced inflammation, and granuloma weight in formalin-soaked filter paper-induced granuloma. For adjuvant-induced arthritis (AIA) rats, paw edema, mechanical withdrawal threshold, serum levels of TNF-αand IL-10, and histopathological changes of the affected paw were assessed. We found that the denatured NNAV (90, 270 μg/kg) significantly reduced time of licking paw, paw volume, and granuloma weight in above inflammatory models and also attenuated paw edema, mechanical hyperalgesia, and histopathology changes in AIA rats. Additionally, the increase in serum TNF-αand the decrease in serum IL-10 in AIA rats were reversed by the denatured NNAV. Although the native NNAV and TWP rendered the similar pharmacological actions on the above four models with less potency than that of the denatured NNAV, these findings demonstrate that oral administration of the denatured NNAV produces antinociceptive and anti-inflammatory activities on rheumatoid arthritis.

This study investigated the effects ofNaja naja atravenom (NNAV) on acute and chronic nephropathy in rats. Rats received 6 mg/kg adriamycin (ADR) once to evoke the chronic nephropathy or 8 ml/kg 50% v/v glycerol to produce acute renal failure (ARF). The NNAV was given orally once a day starting five days prior to ADR or glycerol injection and continued to the end of experiments. The animals were placed in metabolic cages for 24 h for urine collection for urinary protein determination. The kidney function-related biochemical changes and index of oxidative stress were determined with automatic biochemistry analyzer or colorimetric enzyme assay kits. The pathomorphological changes were observed using light and transmission electron microcopies. The levels of inflammatory cytokines and NF-κB activation were determined using ELISA kits, Western blot analysis, or immunofluorescence. The results showed that NNAV relieved ADR-induced chronic nephropathy and glycerol-triggered acute renal failure syndromes including proteinuria, hypoalbuminemia, hyperlipidemia, serum electrolyte unbalance, renal oxidative stress, and pathological damages. NNAV reduced kidney levels of TNF-αand IL-1β, but it increased the levels of IκB-αand inhibited NF-κB p65 nuclear localization. These findings suggest that NNAV may be a valuable therapeutic drug for acute and chronic kidney diseases.

Cardiotoxin (CTX) fromNaja naja atravenom (NNAV) reportedly had analgesic effect in animal models but its role in inflammation and arthritis was unknown. In this study, we investigated the analgesic, anti-inflammatory, and antiarthritic actions of orally administered CTX-IV isolated from NNAV on rodent models of inflammation and adjuvant arthritis. CTX had significant anti-inflammatory effects in models of egg white induced nonspecific inflammation, filter paper induced rat granuloma formation, and capillary osmosis tests. CTX significantly reduced the swelling of paw induced by egg white, the inflammatory exudation, and the formation of granulomas. CTX reduced the swelling of paw, the AA clinical scores, and pathological alterations of joint. CTX significantly decreased the number of the CD4 T cells and inhibited the expression of relevant proinflammatory cytokines IL-17 and IL-6. CTX significantly inhibited the secretion of proinflammatory cytokine IL-6 and reduced the level of p-STAT3 in FLS. These results suggest that CTX inhibits inflammation and inflammatory pain and adjuvant-induced arthritis. CTX may be a novel therapeutic drug for treatment of arthritis.

Previous studies reported the oral administration ofNaja naja atravenom (NNAV) reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin fromNaja naja atravenom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight) via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180 μg/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.

Penelitian ini berfokus pada proses produksi sapu di UMKM. Tujuan utama penelitian adalah mengidentifikasi waste yang terjadi dalam proses produksi sapu sehingga dapat dilakukan usulan peraikan untuk meningkatkan kualitas dan daya saing produk sapu di UD ini. Penelitian ini menggunakan lean manufacturing dalam mengeliminasi waste dengan menggunakan tool value stream mapping dan diagram Fishbone. Hasil dari analisa ini menunjukkan aktivitas non value added (NVA) sebesar 88,7%. Aktivitas value added (VA) sebesar 10,7% dan aktivitas necessary but non value adding (NNVA) memilik persentase paling rendah dari ketiga aktivitas lainnya yaitu 0,6%. Terdapat empat jenis waste yang terjadi, yakni pada waste of defects sebesar 21,95%, waste of overproduction sebesar 19,51%, waste of waiting 17,07%, danwaste of unnecessary inventory sebesar 17,07%.

Résumé : INTRODUCTION : Il a été démontré que la ventilation assistée nasale (AIn) provoque la fermeture laryngée active chez les agneaux nouveau-nés sans sédation. Ceci pourrait limiter la ventilation alvéolaire, entrainer l’air insufflé dans l’appareil digestif et provoquer des conséquences délétères graves. Le neuro-asservissement de la ventilation assistée nasale (NAVAn) et la ventilation nasale par oscillations à haute fréquence (VOHFn) sont des modes de ventilation attractifs. La NAVA semble être plus physiologique que l’AIn, car elle est synchronisée avec le contrôle neural. Cependant, la VOHF ne nécessite pas de synchronisation et diminue les lésions pulmonaires provoquées par la ventilation mécanique conventionnelle. Le but de mon projet est d’étudier l’effet de la NAVAn et de la VOHFn sur la dynamique laryngée chez les agneaux nouveau-nés sans sédation, en testant l’hypothèse que, contrairement à l’AIn, la fermeture laryngée active n’apparait pas durant la NAVAn et la VOHFn. MÉTHODES : deux groupes d’agneaux nés à terme (NAVAn : 8 agneaux ; et VOHFn : 7 agneaux) ont été instrumentés chirurgicalement à 2 jours de vie, afin de recueillir l’électromyogramme des muscles constricteur et dilatateur laryngés, du diaphragme, les pressions au masque, trachéale, pression de CO[indice inférieur 2] en fin d’expiration (P[indice inférieur ET]CO[indice inférieur 2]) et des gaz sanguins artériels. 48h suivant l’instrumentation, un enregistrement polysomnographique a été réalisé pour chaque groupe (AIn / VOHFn et AIn / NAVAn) dans un ordre randomisé. La pression inspiratoire (AIn & NAVAn) et la puissance des oscillations (VOHFn) ont été progressivement augmentées. RÉSULTATS : Les résultats démontrent que l’augmentation des niveaux de NAVAn et de la puissance de VOHFn n’entraine pas de fermeture laryngée active, contrairement à l’AIn. De plus, la diminution du PaCO[indice inférieur 2] provoquée par l’hyperventilation en AIn pourrait contribuer à la fermeture laryngée active. En VOHFn, la diminution progressive de la fréquence des oscillations jusqu’à 4 Hz induit des apnées centrales. En revanche, aucune fermeture laryngée active n’a été observée à 4 Hz. CONCLUSION : La NAVAn et la VOHFn ne provoquent pas la fermeture laryngée active chez l’agneau nouveau-né, et pourraient constituer des nouvelles alternatives dans le traitement des pathologies respiratoires en période néonatale. //Abstract : INTRODUCTION : We have previously shown that nasal pressure support ventilation (nPSV) can lead to an active laryngeal closure in non-sedated newborn lambs. This, in turn, can limit lung ventilation and divert air into the digestive system, with potentially deleterious consequences. Nasal neurally adjusted ventilator assist (nNAVA) and nasal high frequency oscillatory ventilation (nHFOV) are new attractive non-invasive ventilation modalities in newborns. Neurally adjusted ventilator assist (NAVA) seems to be a more physiological ventilator mode than PSV: it is more synchronized with neural control. However, HFOV is associated with less lung injury and does not require synchronization. Thus, the aim of the present study was to assess the effects of nNAVA and nHFOV on laryngeal dynamics in non-sedated newborn lambs, testing the hypothesis that active laryngeal closure does not develop during both nHFOV and nNAVA. METHODS : Polysomnographic recordings were performed in two groups of non-sedated chronically instrumented lambs (nHFOV, 7 lambs) and (nNAVA, 8 lambs), which were ventilated with progressively increased levels of nPSV and nHFOV or nNAVA, in random order. States of alertness, diaphragm and glottal muscle electrical activity, mask and tracheal pressure, tracheal end tidal CO[subscript 2] (P[subscript ET]CO[subscript 2]) and blood gases were continuously recorded in each group. RESULTS: While active laryngeal closure appeared with increasing levels of nPSV, it was never observed at any nHFOV power or nNAVA levels in any lamb. In addition, a decrease in PaCO[subscript 2] was neither necessary nor sufficient for the development of active laryngeal closure. nHFOV at 4Hz dramatically inhibited central respiratory drive. However, no active laryngeal closure was observed at 4 Hz. CONCLUSION: nHFOV and nNAVA does not induce active laryngeal closure in inspiration in non-sedated newborn lambs, in contrast to nPSV. nNAVA and nHFOV could be an alternatives in the treatment of neonatal respiratory disorders.

R??sum?? : INTRODUCTION : Il a ??t?? d??montr?? que la ventilation assist??e nasale (AIn) provoque la fermeture laryng??e active chez les agneaux nouveau-n??s sans s??dation. Ceci pourrait limiter la ventilation alv??olaire, entrainer l???air insuffl?? dans l???appareil digestif et provoquer des cons??quences d??l??t??res graves. Le neuro-asservissement de la ventilation assist??e nasale (NAVAn) et la ventilation nasale par oscillations ?? haute fr??quence (VOHFn) sont des modes de ventilation attractifs. La NAVA semble ??tre plus physiologique que l???AIn, car elle est synchronis??e avec le contr??le neural. Cependant, la VOHF ne n??cessite pas de synchronisation et diminue les l??sions pulmonaires provoqu??es par la ventilation m??canique conventionnelle. Le but de mon projet est d?????tudier l???effet de la NAVAn et de la VOHFn sur la dynamique laryng??e chez les agneaux nouveau-n??s sans s??dation, en testant l???hypoth??se que, contrairement ?? l???AIn, la fermeture laryng??e active n???apparait pas durant la NAVAn et la VOHFn. M??THODES : deux groupes d???agneaux n??s ?? terme (NAVAn : 8 agneaux ; et VOHFn : 7 agneaux) ont ??t?? instrument??s chirurgicalement ?? 2 jours de vie, afin de recueillir l?????lectromyogramme des muscles constricteur et dilatateur laryng??s, du diaphragme, les pressions au masque, trach??ale, pression de CO[indice inf??rieur 2] en fin d???expiration (P[indice inf??rieur ET]CO[indice inf??rieur 2]) et des gaz sanguins art??riels. 48h suivant l???instrumentation, un enregistrement polysomnographique a ??t?? r??alis?? pour chaque groupe (AIn / VOHFn et AIn / NAVAn) dans un ordre randomis??. La pression inspiratoire (AIn & NAVAn) et la puissance des oscillations (VOHFn) ont ??t?? progressivement augment??es. R??SULTATS : Les r??sultats d??montrent que l???augmentation des niveaux de NAVAn et de la puissance de VOHFn n???entraine pas de fermeture laryng??e active, contrairement ?? l???AIn. De plus, la diminution du PaCO[indice inf??rieur 2] provoqu??e par l???hyperventilation en AIn pourrait contribuer ?? la fermeture laryng??e active. En VOHFn, la diminution progressive de la fr??quence des oscillations jusqu????? 4 Hz induit des apn??es centrales. En revanche, aucune fermeture laryng??e active n???a ??t?? observ??e ?? 4 Hz. CONCLUSION : La NAVAn et la VOHFn ne provoquent pas la fermeture laryng??e active chez l???agneau nouveau-n??, et pourraient constituer des nouvelles alternatives dans le traitement des pathologies respiratoires en p??riode n??onatale. //Abstract : INTRODUCTION : We have previously shown that nasal pressure support ventilation (nPSV) can lead to an active laryngeal closure in non-sedated newborn lambs. This, in turn, can limit lung ventilation and divert air into the digestive system, with potentially deleterious consequences. Nasal neurally adjusted ventilator assist (nNAVA) and nasal high frequency oscillatory ventilation (nHFOV) are new attractive non-invasive ventilation modalities in newborns. Neurally adjusted ventilator assist (NAVA) seems to be a more physiological ventilator mode than PSV: it is more synchronized with neural control. However, HFOV is associated with less lung injury and does not require synchronization. Thus, the aim of the present study was to assess the effects of nNAVA and nHFOV on laryngeal dynamics in non-sedated newborn lambs, testing the hypothesis that active laryngeal closure does not develop during both nHFOV and nNAVA. METHODS : Polysomnographic recordings were performed in two groups of non-sedated chronically instrumented lambs (nHFOV, 7 lambs) and (nNAVA, 8 lambs), which were ventilated with progressively increased levels of nPSV and nHFOV or nNAVA, in random order. States of alertness, diaphragm and glottal muscle electrical activity, mask and tracheal pressure, tracheal end tidal CO[subscript 2] (P[subscript ET]CO[subscript 2]) and blood gases were continuously recorded in each group. RESULTS: While active laryngeal closure appeared with increasing levels of nPSV, it was never observed at any nHFOV power or nNAVA levels in any lamb. In addition, a decrease in PaCO[subscript 2] was neither necessary nor sufficient for the development of active laryngeal closure. nHFOV at 4Hz dramatically inhibited central respiratory drive. However, no active laryngeal closure was observed at 4 Hz. CONCLUSION: nHFOV and nNAVA does not induce active laryngeal closure in inspiration in non-sedated newborn lambs, in contrast to nPSV. nNAVA and nHFOV could be an alternatives in the treatment of neonatal respiratory disorders.