Assuntos
Infecções por Coronavirus/tratamento farmacológico , Coronavirus/efeitos dos fármacos , Cavidade Nasal/virologia , Lavagem Nasal , Faringe/virologia , Pneumonia Viral/tratamento farmacológico , Solução Salina Hipertônica/farmacologia , Irrigação Terapêutica/métodos , Administração Intranasal , Betacoronavirus , COVID-19 , Infecções por Coronavirus/epidemiologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Solução Salina Hipertônica/administração & dosagem , Solução Salina Hipertônica/uso terapêutico , Tratamento Farmacológico da COVID-19RESUMO
INTRODUCTION: Hyperosmotic agents are used to decrease intracranial pressure (ICP). We aim to compare the effect of euvolemic solutions of 3% hypertonic saline (HTS) and 20% mannitol on intraoperative brain relaxation in patients with clinical or radiological evidence of raised ICP undergoing surgery for supratentorial tumors. MATERIALS AND METHODS: A.prospective double-blind study was conducted on 30 patients randomized into two equal groups. Each patient was administered 5 ml/kg of either 20% mannitol or 3% HTS over 15 minutes (min) after skin incision. Hemodynamic data, brain relaxation and serum electrolyte levels were recorded. RESULTS: Intraoperative brain relaxation was comparable between the two groups. There was a statistically significant difference in the mean arterial pressures (MAPs) between the two groups after one minutes (min) with a greater degree of decrease in blood pressure recorded in the mannitol group (P = 0.041). MAP with mannitol was significantly lower than the preinduction value after 75 min of administration of drug (P = 0.003). Urine output was significantly higher in the mannitol group (P = 0.00). Administration of HTS was associated with a transient increase in serum sodium concentrations, which was statistically significant but returned to normal within 48 h (P < 0.001). CONCLUSIONS: Both mannitol and HTS provided adequate intraoperative brain relaxation. On the contrary, there was no statistically significant fall in blood pressure with HTS. Thus, we advocate the use of HTS over mannitol as it maintains better hemodynamic stability.
Assuntos
Encéfalo/cirurgia , Hipertensão Intracraniana/terapia , Manitol/uso terapêutico , Neoplasias Supratentoriais/cirurgia , Adulto , Feminino , Hemodinâmica/fisiologia , Humanos , Hipertensão Intracraniana/etiologia , Pressão Intracraniana , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Estudos Prospectivos , Solução Salina Hipertônica/farmacologia , Neoplasias Supratentoriais/complicaçõesRESUMO
OBJECTIVE: There are various protoscolicidal agents for inactivation of protoscoleces of hydatid cysts before and during surgical operation. The present study was aimed to evaluate the protoscolicidal effect of two concentrations of Eucalyptus globulus on protoscoleces of Echinococcus granulosus sensu lato under in vitro condition and to compare its efficacy with hypertonic saline, povidone iodine and silver nitrate. METHODS: Live protoscoleces obtained from the liver of naturally infected sheep were exposed to 0.5% and 1% of Eucalyptus globulus essential oil, 5% hypertonic saline, 10% povidone iodine and 0.5% silver nitrate for 1 and 3minutes. Phosphate buffered saline was used as a negative control. One percent eosin staining method was used to test the viability of protoscoleces in different groups. RESULTS: While the mean percentage of dead protoscoleces was 6.08% in the control group, the scolicidal power of 5% hypertonic saline was only 6.54% and 6.60% after 1 and 3min respectively. 0.5% E. globulus EO demonstrated 97.38% and 100% scolicidal activity after 1 and 3min respectively. The mean protoscolicidal power of 1% E. globulus EO, 10% povidone iodine and 0.5% silver nitrate was 100% after one minute. CONCLUSIONS: According to the results of this study, E. globulus EO demonstrated high scolicidal power in a short period of time. Hence, this herbal product could be considered as a potent natural scolicidal agent that could be used before and during surgery of hydatid disease.
Assuntos
Anticestoides/farmacologia , Equinococose/cirurgia , Echinococcus granulosus/efeitos dos fármacos , Óleo de Eucalipto/farmacologia , Fígado/parasitologia , Óleos Voláteis/farmacologia , Animais , Anti-Infecciosos Locais/farmacologia , Avaliação Pré-Clínica de Medicamentos , Óleo de Eucalipto/química , Técnicas In Vitro , Povidona-Iodo/farmacologia , Solução Salina Hipertônica/farmacologia , Ovinos , Nitrato de Prata/farmacologia , Fatores de TempoRESUMO
There are no antivirals to treat viral upper respiratory tract infection (URTI). Since numerous viruses cause URTI, antiviral therapy is impractical. As we have evidence of chloride-ion dependent innate antiviral response in epithelial cells, we conducted a pilot, non-blinded, randomised controlled trial of hypertonic saline nasal irrigation and gargling (HSNIG) vs standard care on healthy adults within 48 hours of URTI onset to assess recruitment (primary outcome). Acceptability, symptom duration and viral shedding were secondary outcomes. Participants maintained a symptom diary until well for two days or a maximum of 14 days and collected 5 sequential mid-turbinate swabs to measure viral shedding. The intervention arm prepared hypertonic saline and performed HSNIG. We recruited 68 participants (2.6 participants/week; November 2014-March 2015). A participant declined after randomisation. Another was on antibiotics and hence removed (Intervention:32, Control:34). Follow up data was available from 61 (Intervention:30, Control:31). 87% found HSNIG acceptable, 93% thought HSNIG made a difference to their symptoms. In the intervention arm, duration of illness was lower by 1.9 days (p = 0.01), over-the-counter medications (OTCM) use by 36% (p = 0.004), transmission within household contacts by 35% (p = 0.006) and viral shedding by ≥0.5 log10/day (p = 0.04). We hence need a larger trial to confirm our findings.
Assuntos
Resfriado Comum/terapia , Lavagem Nasal , Solução Salina Hipertônica/farmacologia , Adulto , Resfriado Comum/virologia , Retroalimentação , Feminino , Humanos , Masculino , Projetos Piloto , Eliminação de Partículas Virais/efeitos dos fármacosRESUMO
BACKGROUND: Ischemic stroke is a major disease that threatens human health in ageing population. Increasing evidence has shown that neuroinflammatory mediators play crucial roles in the pathophysiology of cerebral ischemia injury. Notch signaling is recognized as the cell fate signaling but recent evidence indicates that it may be involved in the inflammatory response in activated microglia in cerebral ischemia. Previous report in our group demonstrated hypertonic saline (HS) could reduce the release of interleukin-1 beta and tumor necrosis factor-alpha in activated microglia, but the underlying molecular and cellular mechanisms have remained uncertain. This study was aimed to explore whether HS would partake in regulating production of proinflammatory mediators through Notch signaling. RESULTS: HS markedly attenuated the expression of Notch-1, NICD, RBP-JK and Hes-1 in activated microglia both in vivo and in vitro. Remarkably, HS also reduced the expression of iNOS in vivo, while the in vitro levels of inflammatory mediators Phos-NF-κB, iNOS and ROS were reduced by HS as well. CONCLUSION: Our results suggest that HS may suppress of inflammatory mediators following ischemia/hypoxic through the Notch signaling which operates synergistically with NF-κB pathway in activated microglia. Our study has provided the morphological and biochemical evidence that HS can attenuate inflammation reaction and can be neuroprotective in cerebral ischemia, thus supporting the use of hypertonic saline by clinicians in patients with an ischemia stroke.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Hipóxia Celular/efeitos dos fármacos , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Receptores Notch/metabolismo , Solução Salina Hipertônica/farmacologia , Animais , Isquemia Encefálica/imunologia , Isquemia Encefálica/patologia , Hipóxia Celular/fisiologia , Linhagem Celular , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Masculino , Camundongos , Microglia/imunologia , Microglia/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Increases in plasma osmolality activates the paraventricular nucleus of the hypothalamus (PVN) which in turn mounts a physiological response by increasing the release of arginine vasopressin and sympathetic nerve activity to end organs such as the kidney. The PVN expresses an abundance of purinergic receptors including P2X2 receptors. In the present study, we sought to determine (1) whether P2X2-expressing PVN neurons are activated by hypertonic saline or hypertonic mannitol and (2) what effects P2X receptor blockade has on sympathetic nerve activation mediated by a hyperosmotic stimulus. Male Wistar rats were randomly assigned to three groups and intravenously infused with either isotonic saline (0.154M, 0.5mL), hypertonic saline (3M, 0.5mL) or hypertonic mannitol (10% w/v, 0.5mL). Significantly greater numbers of Fos-positive cells were observed in the hypertonic saline (393±29)- and hypertonic mannitol (141±11)-infused rats compared with control, saline-treated, rats (47±2 neurons/PVN section). Furthermore, there was a significant increase in the number of activated (Fos-positive) P2X2 expressing PVN neurons in the hypertonic saline (65±7) and hypertonic mannitol (37±7)-treated rats compared with controls (16±2). Microinjection of a P2X receptor antagonist, PPADS, within the PVN significantly attenuated sympathetic nerve activation driven by a hyperosmotic stimulus. The hyperosmotically induced increase in lumbar sympathetic nerve activity was significantly blunted after PPADS pre-treatment. Collectively, our findings indicate that hyperosmotic stimulation activates a subset of P2X2 expressing PVN neurons that might facilitate increased sympathetic drive.
Assuntos
Hipotálamo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Receptores Purinérgicos P2/metabolismo , Solução Salina Hipertônica/farmacologia , Animais , Arginina Vasopressina/metabolismo , Hipotálamo/metabolismo , Masculino , Neurônios/metabolismo , Ratos WistarRESUMO
OBJECTIVE: This study aimed to investigate the effects of pre-treatment with nimodipine and 7.5% hypertonic saline (HS) on postoperative cognitive dysfunction (POCD) in aged rats. METHODS: Healthy Sprague-Dawley aged rats were randomly assigned into 4 groups: POCD group, nimodipine group, HS group, and nimodipine+HS group. Rats in POCD group received normal saline injection and then splenectomy 30min later under 1.8% isoflurane inhalation for 2h. In remaining groups, rats received injection of 1mg/kg nimodipine (i.p) and/or 4ml/kg 7.5% HS (i.v) and then splenectomy. Morris water maze test was performed before and after surgery. The hippocampus was harvested for the detection of neuronal apoptosis rate (AR), cytoplasmic calcium ([Ca2+]i), Bcl-2 and Bax mRNA expression and hippocampal neuronal ultrastructure. RESULTS: When compared with POCD group, the latency to escape, neuronal AR, [Ca2+]i, Bax mRNA expression and Bax/Bcl-2 ratio reduced dramatically, but the times of crossing the platform and Bcl-2 mRNA expression increased significantly (P<0.05) in nimodipine group, NS group and nimodipine+HS group. In addition, the latency to escape, neuronal AR, [Ca2+]i, Bax mRNA expression and Bax/Bcl-2 ratio reduced markedly, but the times of crossing the platform and Bcl-2 mRNA expression increased significantly in nimodipine+HS group as compared to nimodipine group and NS group (P<0.05). Hippocampal neuronal ultrastructure damage was observed in all 4 groups, but it was the mildest in nimodipine+HS group. CONCLUSION: Pre-treatment with both nimodipine and 7.5% HS exerts better protective effects, which is related to the inhibition of hippocampal neuronal apoptosis.
Assuntos
Transtornos Cognitivos/prevenção & controle , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Nimodipina/farmacologia , Complicações Pós-Operatórias/prevenção & controle , Solução Salina Hipertônica/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Transtornos Cognitivos/fisiopatologia , Modelos Animais de Doenças , Quimioterapia Combinada , Hipocampo/patologia , Hipocampo/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Neurônios/fisiologia , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/fisiopatologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Esplenectomia , Fatores de Tempo , Proteína X Associada a bcl-2/metabolismoRESUMO
Normothermic intraperitoneal perfusion (IPEP) and hyperthermic intraperitoneal perfusion (HIPEP) were performed in 44 Wistar female rats with transplanted ascites tumor of the ovary. Opportunities of intraoperative hyperthermic perfusion application in treatment of peritoneal carcinomatosis. Antineoplastic affects were evaluated according to increase of animals' survival. IPEP and HIPEP increase median survival time by 78% (p=0.307) and 150% (p=0.005) respectively in comparison with conventional intraperitoneal introduction of physiological solution. Thus HIPEP has statistically more significant antineoplastic affect in vase of peritoneal carcinomatosis.
Assuntos
Temperatura Alta/uso terapêutico , Hipertermia Induzida , Cuidados Intraoperatórios/métodos , Laparotomia/métodos , Lavagem Peritoneal , Neoplasias Peritoneais/terapia , Animais , Feminino , Hipertermia Induzida/efeitos adversos , Hipertermia Induzida/métodos , Hipertermia Induzida/mortalidade , Lavagem Peritoneal/efeitos adversos , Lavagem Peritoneal/métodos , Lavagem Peritoneal/mortalidade , Ratos , Ratos Wistar , Solução Salina Hipertônica/farmacologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We recently reported that the latency to begin drinking water during slow, intravenous infusion of a concentrated NaCl solution was shorter in estradiol-treated ovariectomized rats compared to oil vehicle-treated rats, despite comparably elevated plasma osmolality. To test the hypothesis that the decreased latency to begin drinking is attributable to enhanced detection of increased plasma osmolality by osmoreceptors located in the CNS, the present study used immunocytochemical methods to label fos, a marker of neural activation. Increased plasma osmolality did not activate the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), or the nucleus of the solitary tract (NTS) in either oil vehicle-treated rats or estradiol-treated rats. In contrast, hyperosmolality increased fos labeling in the area postrema (AP), the paraventricular nucleus of the hypothalamus (PVN) and the rostral ventrolateral medulla (RVLM) in both groups; however, the increase was blunted in estradiol-treated rats. These results suggest that estradiol has selective effects on the sensitivity of a population of osmo-/Na(+)-receptors located in the AP, which, in turn, alters activity in other central areas associated with responses to increased osmolality. In conjunction with previous reports that hyperosmolality increases blood pressure and that elevated blood pressure inhibits drinking, the current findings of reduced activation in AP, PVN, and RVLM-areas involved in sympathetic nerve activity-raise the possibility that estradiol blunts HS-induced blood pressure changes. Thus, estradiol may eliminate or reduce the initial inhibition of water intake that occurs during increased osmolality, and facilitate a more rapid behavioral response, as we observed in our recent study.
Assuntos
Área Postrema/fisiologia , Estradiol/farmacologia , Bulbo/fisiologia , Concentração Osmolar , Núcleo Hipotalâmico Paraventricular/fisiologia , Solução Salina Hipertônica/farmacologia , Animais , Área Postrema/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Terapia de Reposição de Estrogênios/métodos , Feminino , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiologia , Infusões Intravenosas , Bulbo/efeitos dos fármacos , Imagem Molecular/métodos , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Ovariectomia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Plasma/metabolismo , Ratos , Ratos Sprague-Dawley , Solução Salina Hipertônica/administração & dosagem , Núcleo Solitário/efeitos dos fármacos , Núcleo Solitário/fisiologia , Órgão Subfornical/efeitos dos fármacos , Órgão Subfornical/fisiologiaRESUMO
During heat waves many elderly individuals die as a consequence of dehydration. This is partially due to deficits in mechanisms controlling thirst. Reduced thirst following dipsogenic stimuli is well documented in aged humans and rodents. Low in vivo long-chain omega-3 fatty acid levels, as can occur in aging, have been shown to alter body fluid and sodium homeostasis. Therefore, the effect of dietary omega-3 fatty acid supplementation on drinking responses in aged rats was examined. Omega-3 fatty acids reversed thirst deficits in aged rats following dehydration and hypertonic stimuli; angiotensin (ANG) II induced drinking was unaffected in aged rats. Plasma atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) were altered with age, but not affected by diet. Aged omega-3 fatty acid deficient animals displayed increased hypothalamic cytosolic phospholipase A(2) (cPLA(2)), cyclooxygenase (COX)-2, and prostaglandin E (PGE) synthase messenger (m)RNA expression, compared with animals that received omega-3 fatty acids. The aged low omega-3 fatty acid fed animals had significantly elevated hypothalamic PGE(2) compared with all other groups. Hypothalamic PGE(2) was negatively correlated with drinking induced by both dehydration and hypertonicity. The results indicate that PGE(2) may be the underlying mechanism of the reduced thirst observed in aging.
Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Sede/efeitos dos fármacos , Fatores Etários , Angiotensina II/farmacologia , Animais , Arginina Vasopressina/sangue , Fator Natriurético Atrial/sangue , Ciclo-Oxigenase 2/biossíntese , Desidratação/tratamento farmacológico , Desidratação/fisiopatologia , Dinoprostona/análise , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Líquidos/fisiologia , Hipotálamo/química , Hipotálamo/enzimologia , Oxirredutases Intramoleculares/biossíntese , Masculino , Fosfolipases A2 Citosólicas/biossíntese , Prostaglandina-E Sintases , Ratos , Solução Salina Hipertônica/farmacologia , Sede/fisiologiaRESUMO
We evaluated the effect of plasma hyperosmolality on behavioral thermoregulation in mice, using a new experimental system. The system consisted of Plexiglas box (dimensions: 50×12×19 cm) with five computer-controlled Peltier boards (dimensions: 10×10 cm) at the bottom. Experiments were conducted in two different settings of the system. An operant behavior setting: each board was first set to 39°C, and the right-end board was changed to 20°C for 1 min when a mouse moved to a specific position. A temperature mosaic setting: each board was randomly set to 15°C, 22°C, 28°C, 35°C, or 39°C with a 6-min interval, but each board temperature was different from the others at a given time point. Mice were injected subcutaneous (s.c.) isotonic or hypertonic saline (154 mM (IS group) or 2,500 mM (HS group), 10 ml/kg body wt), and exposed to either setting for 90 min. In the operant setting, the HS group showed fewer operant behavior counts than the IS group (11±5 and 25±4 counts, respectively; P<0.05) with greater increase in body temperature (1.6±0.4°C vs. 0.0±0.2°C, respectively; P<0.05). In the mosaic setting, the HS group selected the board temperature of 35°C more frequently than the other temperatures (P<0.05) with the same increase in body temperature. These results may suggest that plasma hyperosmolality modulates behavioral thermoregulatory response to heat and induce regulated hyperthermia.
Assuntos
Comportamento Animal , Regulação da Temperatura Corporal/fisiologia , Temperatura Corporal/fisiologia , Plasma/metabolismo , Temperatura , Análise de Variância , Animais , Temperatura Corporal/efeitos dos fármacos , Regulação da Temperatura Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Comportamento de Escolha/efeitos dos fármacos , Condicionamento Operante/efeitos dos fármacos , Hipertermia Induzida/métodos , Hipotermia Induzida/métodos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Concentração Osmolar , Plasma/efeitos dos fármacos , Reprodutibilidade dos Testes , Solução Salina Hipertônica/farmacologia , Fatores de TempoRESUMO
Administration of hypertonic saline (HS) solution to rats with acute pancreatitis (AP) decreases mortality and systemic inflammation. We hypothesized that these effects are related not only to systemic inflammatory reduction, but also to a reduction of the pancreatic lesion. Acute pancreatitis was induced in Wistar rats by injection of 2.5% sodium taurocholate. Animals were divided in groups: without AP, not treated AP, AP treated with NaCl 0.9%, and AP treated with NaCl 7.5%. Trypsinogen activation peptides and amylase activity were increased in ascitic fluid and serum and were not affected by treatment with HS. Pancreatic inflammation was evaluated by increased myeloperoxidase activity, malondialdehyde formation, and histopathology for severity of pancreatic lesions. The HS did not affect these parameters. Expression of cyclooxygenase 2 and inducible nitric oxide synthase was markedly increased in the pancreas of the AP group and was reduced by treatment with HS. This treatment also reduced the levels of TNF-α and IL-6 but not of IL-10 in the pancreatic tissue. These results show that HS modulates cytokine production and expression of enzymes responsible for inflammatory mediator production in the pancreas without affecting the severity of the pancreatic lesions.
Assuntos
Pancreatite/tratamento farmacológico , Solução Salina Hipertônica/farmacologia , Doença Aguda , Amilases/sangue , Animais , Ascite/metabolismo , Ciclo-Oxigenase 2/análise , Avaliação Pré-Clínica de Medicamentos , Interleucina-10/análise , Interleucina-6/análise , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Neutrófilos/enzimologia , Óxido Nítrico Sintase Tipo II/análise , Oligopeptídeos/análise , Pancreatite/induzido quimicamente , Pancreatite/metabolismo , Pancreatite/patologia , Peroxidase/análise , Ratos , Ratos Wistar , Ácido Taurocólico/toxicidade , Fator de Necrose Tumoral alfa/análiseRESUMO
Panic disorder is a severe anxiety disorder characterized by recurrent panic attacks that can be consistently provoked with intravenous (i.v.) infusions of hypertonic (0.5 M) sodium lactate (NaLac), yet the mechanism/CNS site by which this stimulus triggers panic attacks is unclear. Chronic inhibition of GABAergic synthesis in the dorsomedial hypothalamus/perifornical region (DMH/PeF) of rats induces a vulnerability to panic-like responses after i.v. infusion of 0.5 M NaLac, providing an animal model of panic disorder. Using this panic model, we previously showed that inhibiting the anterior third ventricle region (A3Vr; containing the organum vasculosum lamina terminalis, the median preoptic nucleus, and anteroventral periventricular nucleus) attenuates cardiorespiratory and behavioral responses elicited by i.v. infusions of NaLac. In this study, we show that i.v. infusions of 0.5 M NaLac or sodium chloride, but not iso-osmolar D-mannitol, increased 'anxiety' (decreased social interaction) behaviors, heart rate, and blood pressure responses. Using whole-cell patch-clamp preparations, we also show that bath applications of NaLac (positive control), but not lactic acid (lactate stimulus) or D-mannitol (osmolar stimulus), increases the firing rates of neurons in the A3Vr, which are retrogradely labeled from the DMH/PeF and which are most likely glutamatergic based on a separate study using retrograde tracing from the DMH/PeF in combination with in situ hybridization for vesicular glutamate transporter 2. These data show that hypertonic sodium, but not hyper-osmolarity or changes in lactate, is the key stimulus that provokes panic attacks in panic disorder, and is consistent with human studies.
Assuntos
Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Transtorno de Pânico/induzido quimicamente , Solução Salina Hipertônica/farmacologia , Cloreto de Sódio/farmacologia , Terceiro Ventrículo/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Modelos Animais de Doenças , Núcleo Hipotalâmico Dorsomedial/efeitos dos fármacos , Núcleo Hipotalâmico Dorsomedial/metabolismo , Núcleo Hipotalâmico Dorsomedial/fisiopatologia , Hipotálamo/metabolismo , Hipotálamo/fisiopatologia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Técnicas de Cultura de Órgãos , Concentração Osmolar , Transtorno de Pânico/metabolismo , Transtorno de Pânico/fisiopatologia , Técnicas de Patch-Clamp , Área Pré-Óptica/efeitos dos fármacos , Área Pré-Óptica/metabolismo , Ratos , Ratos Sprague-Dawley , Lactato de Sódio/farmacologia , Terceiro Ventrículo/anatomia & histologia , Terceiro Ventrículo/fisiopatologia , Ácido gama-Aminobutírico/metabolismoRESUMO
Fluid loading is the first step, necessary to care for severe sepsis. Two main classes of solutions are currently available: crystalloids and colloids. The concept of small volume resuscitation with hypertonic saline has emerged these last years in the care of traumatic haemorrhagic shock. The main benefits are the restoration of intravascular volume, improvement of cardiac output and improvement of regional circulations. Many experiments highlight modulation of immune and inflammatory cascades. We report the mechanisms of action of hypertonic saline based on experimental human and animal studies, which advocate its use in septic shock.
Assuntos
Hidratação , Substitutos do Plasma/uso terapêutico , Soluções para Reidratação/uso terapêutico , Solução Salina Hipertônica/uso terapêutico , Choque Séptico/terapia , Animais , Adesão Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Edema/prevenção & controle , Endotélio Vascular/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Sistema Imunitário/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Leucócitos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/prevenção & controle , Substitutos do Plasma/administração & dosagem , Substitutos do Plasma/efeitos adversos , Substitutos do Plasma/farmacologia , Soluções para Reidratação/administração & dosagem , Soluções para Reidratação/efeitos adversos , Soluções para Reidratação/farmacologia , Ressuscitação/métodos , Solução Salina Hipertônica/administração & dosagem , Solução Salina Hipertônica/efeitos adversos , Solução Salina Hipertônica/farmacologia , Choque Séptico/complicações , Choque Séptico/fisiopatologia , SuínosRESUMO
The up-regulation in the expression of mRNA or protein encoded by the c-fos gene is widely used as a marker of neuronal activation elicited by various stimuli. To facilitate the detection of activated neurons, we generated transgenic rats expressing a fusion gene consisting of c-fos coding sequences in frame with monomeric red fluorescent protein 1 (mRFP1) under the control of c-fos gene regulatory sequences (c-fos-mRFP1 rats). In c-fos-mRFP1 transgenic rats, 90 min after hypertonic saline ip administration, nuclear mRFP1 fluorescence was observed abundantly in brain regions known to be osmosensitive, namely the median preoptic nucleus, organum vasculosum lamina terminalis, supraoptic nucleus, paraventricular nucleus, and subfornical organ. Immunohistochemistry for Fos protein confirmed that the distribution of Fos-like immunoreactivity in nontransgenic rats was similar to those of mRFP1 fluorescence after ip administration of hypertonic saline in the transgenic rats. Several double-transgenic rats were obtained from matings between transgenic rats expressing an arginine vasopressin-enhanced green fluorescent protein fusion gene (AVP-eGFP rats) and c-fos-mRFP1 rats. In these double-transgenic rats, almost all eGFP neurons in the supraoptic nucleus and PVN expressed nuclear mRFP1 fluorescence 90 min after hypertonic saline administration. The c-fos-mRFP1 rats are a powerful tool that enables the facile identification of activated neurons in the nervous system. Furthermore, when combined with transgenes expressing another fluorophore under the control of cell-specific regulatory sequences, activation of specific neuronal cell types in response to physiological cues can be readily detected.
Assuntos
Arginina Vasopressina/metabolismo , Encéfalo/metabolismo , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Animais , Arginina Vasopressina/genética , Encéfalo/citologia , Feminino , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hipotálamo/citologia , Hipotálamo/metabolismo , Imuno-Histoquímica , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Microscopia de Fluorescência , Núcleo Hipotalâmico Paraventricular/citologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Ratos , Ratos Transgênicos , Ratos Wistar , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Sequências Reguladoras de Ácido Nucleico/genética , Solução Salina Hipertônica/administração & dosagem , Solução Salina Hipertônica/farmacologia , Órgão Subfornical/citologia , Órgão Subfornical/metabolismo , Núcleo Supraóptico/citologia , Núcleo Supraóptico/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteína Vermelha FluorescenteRESUMO
In spite of the use of protoscolocidal agents during hydatid cyst surgery, a notable rate of disease recurrence in postoperation patients is still observed. The question remains whether living protoscolices lead to recurrence or the recurrence is due to the remainder of the germinative layer in the peritoneal cavity. The aim of this study was in vivo evaluation of different chemical (protoscolicidal) solutions on the germinative layer of the hydatid cyst. The germinative layer of sheep hydatid cyst was separated under sterile condition, divided into 0.25-cm(2) parts, and exposed to 0.5% cetrimide, 0.5% silver nitrate, 20% hypertonic saline, 15% dextrose and 25% dextrose, and normal saline as negative control for 2 min. The exposed germinative layers were implanted into the peritoneal cavity of 90 Balb/C mice (15 mice in each group). After nine months, the peritoneum was evaluated macroscopically as well as microscopically for the presence of any hydatid cyst. No hydatid cyst was observed in the peritoneal cavity of the exposed mice. The role of the germinative layer for inducing hydatid cysts in mice is questionable. However, the present study showed that the germinative layer had no role in the induction of hydatid cyst in these laboratory animals.
Assuntos
Anti-Helmínticos/uso terapêutico , Equinococose/tratamento farmacológico , Animais , Cetrimônio , Compostos de Cetrimônio/farmacologia , Compostos de Cetrimônio/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Equinococose/parasitologia , Equinococose/patologia , Equinococose/veterinária , Feminino , Glucose/farmacologia , Glucose/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Cavidade Peritoneal , Recidiva , Solução Salina Hipertônica/farmacologia , Solução Salina Hipertônica/uso terapêutico , Ovinos , Doenças dos Ovinos/parasitologia , Nitrato de Prata/farmacologia , Nitrato de Prata/uso terapêuticoRESUMO
PURPOSE: To investigate hemodynamic response to volume replacement with saline solution and hypertonic hydroxyethyl starch in hypovolemic dogs. METHODS: Forty dogs under general anesthesia and hemodynamic monitoring, following measurements at baseline, were bled 20 ml x Kg(-1) and parameters were measured again after 10 minutes. The animals were randomly divided in two groups and volume replacement was performed with saline solution twice the volume removed or 4 ml x Kg(-1) of hypertonic hydroxyethyl starch. Hemodynamic data were again measured after 5, 15, 30, 45 and 60 minutes. RESULTS: With both solutions values returned to satisfactory hemodynamic levels. With saline solution, there was a greater amplitude in variations that tended to decrease progressively. With hypertonic hydroxyethyl starch, the parameters studied returned more rapidly to levels similar to those at baseline and varied less. CONCLUSION: Both solutions proved to be efficient at replacing volume in the short period studied, although hypertonic hydroxyethyl starch produced more stable results.
Assuntos
Hemodinâmica/efeitos dos fármacos , Derivados de Hidroxietil Amido/farmacologia , Hipovolemia/terapia , Substitutos do Plasma/farmacologia , Solução Salina Hipertônica/farmacologia , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Cães , Avaliação Pré-Clínica de Medicamentos , Feminino , Hidratação , Derivados de Hidroxietil Amido/uso terapêutico , Masculino , Substitutos do Plasma/uso terapêuticoRESUMO
In adult mammals, the CNS vasculature remains essentially quiescent, excepted for specific pathologies. In the seventies, it was reported that proliferation of astrocytes and endothelial cells occurs within the hypothalamic magnocellular nuclei when strong metabolic activation of the vasopressinergic and oxytocinergic neurons was induced by prolonged hyperosmotic stimulation. Using more appropriate techniques, we first demonstrated that in these nuclei, the proliferative response to osmotic stimulus is essentially associated with local angiogenesis. We then showed that hypothalamic magnocellular neurons express vascular endothelial growth factor (VEGF), a potent angiogenic factor, that plays a major rôle in the angiogenesis induced by osmotic stimuli. We then demonstrated a correlation between increased VEGF secretion and local hypoxia. In AVP-deficient Brattleboro rats, the dramatic activation of magnocellular hypothalamic neurons failed to induce hypoxia, VEGF expression or angiogenesis suggesting a major role of hypothalamic AVP. Lastly we showed that 1) hypoxia and angiogenesis were not observed in non-osmotically stimulated Wistar rats in which circulating AVP was increased by the prolonged infusion of exogenous AVP, 2) contractile arterioles afferent to the magnocellular nuclei were strongly constricted by the perivascular application of AVP via V1a receptors (V1a-R) stimulation, and 3) following the intracerebral administration of selective V1a-R antagonist to osmotically stimulated rats, hypothalamic hypoxia and angiogenesis were inhibited. Together, these data strongly suggest that the angiogenesis induced by osmotic stimulation relates to tissue hypoxia resulting from the constriction of local arterioles, via the stimulation of perivascular V1a-R by AVP locally released from dendrites.
Assuntos
Arginina Vasopressina/fisiologia , Hipotálamo/fisiologia , Neovascularização Fisiológica/fisiologia , Animais , Arginina Vasopressina/deficiência , Arginina Vasopressina/genética , Arteríolas/metabolismo , Astrócitos/citologia , Hipóxia Celular , Artérias Cerebrais/metabolismo , Dendritos/metabolismo , Endotélio Vascular/citologia , Hipotálamo/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Brattleboro , Ratos Wistar , Receptores de Vasopressinas/efeitos dos fármacos , Receptores de Vasopressinas/fisiologia , Solução Salina Hipertônica/administração & dosagem , Solução Salina Hipertônica/farmacologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética , Vasoconstrição/fisiologiaRESUMO
PURPOSE: To investigate hemodynamic response to volume replacement with saline solution and hypertonic hydroxyethyl starch in hypovolemic dogs. METHODS: Forty dogs under general anesthesia and hemodynamic monitoring, following measurements at baseline, were bled 20 ml.Kg-1 and parameters were measured again after 10 minutes. The animals were randomly divided in two groups and volume replacement was performed with saline solution twice the volume removed or 4 ml.Kg-1 of hypertonic hydroxyethyl starch. Hemodynamic data were again measured after 5, 15, 30, 45 and 60 minutes. RESULTS: With both solutions values returned to satisfactory hemodynamic levels. With saline solution, there was a greater amplitude in variations that tended to decrease progressively. With hypertonic hydroxyethyl starch, the parameters studied returned more rapidly to levels similar to those at baseline and varied less. CONCLUSION: Both solutions proved to be efficient at replacing volume in the short period studied, although hypertonic hydroxyethyl starch produced more stable results.
OBJETIVO: Avaliar em cães hipovolêmicos as respostas hemodinâmicas da reposição volêmica com solução salina e hidroxi-etil amido hipertônico. MÉTODOS: Quarenta cães sob anestesia geral e monitorização hemodinâmica, após medidas em repouso foram sangrados 20 ml.Kg-1 e tiveram os parâmetros novamente medidos após 10 minutos. Os animais foram aleatoriamente divididos em dois grupos nos quais foi realizada reposição volêmica com solução fisiológica duas vezes o volume retirado ou 4 ml.Kg-1 de hidroxi-etil amido hipertônico e os dados hemodinâmicos medidos novamente após 5, 15, 30, 45 e 60 minutos. RESULTADOS: A reposição volêmica com as duas soluções fez os valores retornarem a níveis hemodinâmicos satisfatórios, a amplitude das variações com solução fisiológica foi maior, mas tendeu a diminuir progressivamente, com o hidroxi-etil amido hipertônico os parâmetros estudados retornaram a semelhantes ao repouso mais rapidamente e variaram menos. CONCLUSÃO: Ambas soluções se mostraram eficientes na reposição volêmica, o hidroxi-etil amido hipertônico proporcionou resultados mais estáveis.
Assuntos
Animais , Cães , Feminino , Masculino , Hemodinâmica/efeitos dos fármacos , Derivados de Hidroxietil Amido/farmacologia , Hipovolemia/terapia , Substitutos do Plasma/farmacologia , Solução Salina Hipertônica/farmacologia , Pressão Sanguínea , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Hidratação , Derivados de Hidroxietil Amido/uso terapêutico , Substitutos do Plasma/uso terapêuticoRESUMO
The influence of some selected pharmacological compounds on the structure of human erythrocytes (red blood cells, RBCs) has been studied by means of an atomic force microscopy (AFM). The imaging has been done both in the air environment on the fixed cells, and in the liquid (physiological conditions). It was shown that RBCs are very sensitive to osmotic changes in the solution. Increased NaCl concentration in the solution to a value higher than 0.9% leads to the characteristic changes of the erythrocyte from a discoid-like shape to a very irregular one, the so-called "echinocyte", with a lot of ledges. After exposition on nifedipin the modification of the erythrocyte surface morphology was observed. Based on the contact and non-contact AFMs study the consecutive stages of RBCs surface modification were observed. Scanning electron microscopy pictures of erythrocytes were presented for comparison.