Development, Histological, and Ultrastructural Evaluation of Sheep Hyperimmune Serum Therapy for COVID-19 / Desarrollo, Evaluación Histológica y Ultraestructural de la Terapia con Suero Hiperinmune de Oveja para COVID-19

SUMMARY: In response to the threat posed by new variants of SARS-CoV-2 and the urgent need for effective treatments in the absence of vaccines, the aim of this study was to develop a rapid and cost-effective hyperimmune serum (HS) derived from sheep and assess its efficacy. The utilization of a halal-certified, easily maintained in certain geographic regions, easy-to-handle animal such as sheep could provide a viable alternative to the expensive option of horses. Sheep were immunized with a whole inactivated SARS-CoV- 2 antigen to produce HS, which was evaluated for neutralizing potency using the PRNT50 assay. K18-hACE2 transgenic mice (n=35) were divided into three groups: control, SARS-CoV-2 exposure through inhalation, and SARS-CoV-2 exposed mice treated with HS. HS efficacy was assessed through serum proinflammatory cytokine levels, qRT-PCR analysis, histopathological examination of lungs and hearts, and transmission electron microscopy. Purified HS exhibited significant neutralizing activity (1/24,576). The SARS-CoV-2+HS group showed lower levels of TNF-α, IL-10, and IL-6 (P<0.01) and relatively lower levels of MCP-1 compared to the SARS-CoV-2 group. HS prevented death, reduced viral RNA levels in the lungs and hearts, protected against severe interstitial pneumonia, preserved lung tissue integrity, and prevented myocyte damage, while the SARS-CoV-2 group exhibited viral presence in the lungs. This study successfully developed a sheep-derived HS against the entire SARS-CoV-2 virus, resulting in a significant reduction in infection severity, inflammation, and systemic cytokine production. The findings hold promise for treating severe COVID-19 cases, including emerging viral variants, and immunocompromised patients.

En respuesta a la amenaza que suponen las nuevas variantes del SARS-CoV-2 y la urgente necesidad de tratamientos eficaces en ausencia de vacunas, el objetivo de este estudio fue desarrollar un suero hiperinmune (HS) rápido y rentable derivado de ovejas. y evaluar su eficacia. La utilización de un animal con certificación halal, de fácil mantenimiento en determinadas regiones geográficas y de fácil manejo, como las ovejas, podría proporcionar una alternativa viable a la costosa opción de los caballos. Las ovejas fueron inmunizadas con un antígeno de SARS-CoV-2 completamente inactivado para producir HS, cuya potencia neutralizante se evaluó mediante el ensayo PRNT50. Los ratones transgénicos K18-hACE2 (n = 35) se dividieron en tres grupos: control, exposición al SARS-CoV-2 mediante inhalación y ratones expuestos al SARS-CoV-2 tratados con HS. La eficacia de HS se evaluó mediante niveles de citoquinas proinflamatorias en suero, análisis qRT-PCR, examen histopatológico de pulmones y corazones y microscopía electrónica de transmisión. El HS purificado exhibió una actividad neutralizante significativa (1/24,576). El grupo SARS-CoV-2+HS mostró niveles más bajos de TNF-α, IL-10 e IL-6 (P<0,01) y niveles relativamente más bajos de MCP-1 en comparación con el grupo SARS-CoV-2. HS evitó la muerte, redujo los niveles de ARN viral en los pulmones y el corazón, protegió contra la neumonía intersticial grave, preservó la integridad del tejido pulmonar y evitó el daño de los miocitos, mientras que el grupo SARS-CoV-2 exhibió presencia viral en los pulmones. Este estudio desarrolló con éxito un HS derivado de ovejas contra todo el virus SARS-CoV-2, lo que resultó en una reducción significativa de la gravedad de la infección, la inflamación y la producción sistémica de citocinas. Los hallazgos son prometedores para el tratamiento de casos graves de COVID- 19, incluidas las variantes virales emergentes y los pacientes inmunocomprometidos.

Morphological Effects of Cigarette Smoking on Respiratory System and Related Functions Based on AQPs Expression

SUMMARY: A great deal of attention of air pollution on respiratory health is increasing, particularly in relation to haze days. It is that exposure to cigarette smoke augments the toxicity of common air contaminants, thereby increasing the complexity of respiratory diseases. Although there are various mechanisms involved to respiratory diseases caused or worsen by cigarette smoking, in which the role of AQPs in the lung with regard to fluid homeostasis still remains elusive. In this paper, we copied the rat models based on smoke generator, and investigated the morphological changes of mucosa and related functions depending on the balance of lining liquid of alveoli via AQPs expression. Compared with normal group, weak labelling of AQP1 and AQP5 protein abundance were clearly detected in the corresponding part of smoke exposure groups compared with normal group. Hence, it is suggested that the contribution of AQPs in the lung is diminished, thereby causing perturbed balancing between resorptive and secretory fluid homeostasis under cigarette smoking.

Cada vez se presta más atención a la contaminación del aire en la salud respiratoria, particularmente, en relación con los días de neblina. En consecuencia la exposición al humo del cigarrillo aumenta la toxicidad de los contaminantes comunes del aire, lo que además aumenta la complejidad de las enfermedades respiratorias. Aunque existen varios mecanismos involucrados en las enfermedades respiratorias causadas o empeoradas por el tabaquismo, en las que el papel de las AQP en el pulmón respecto a la homeostasis de líquidos sigue siendo difícil de alcanzar. En este artículo, copiamos los modelos de rata basados en el generador de humo e investigamos los cambios morfológicos de la mucosa y las funciones relacionadas según el equilibrio del líquido de revestimiento de los alvéolos a través de la expresión de AQP. En comparación con el grupo normal, se detectó claramente un etiquetado débil de la abundancia de proteínas AQP1 y AQP5 en la parte correspondiente de los grupos de exposición al humo en comparación con el grupo control. Por lo tanto, se sugiere que la contribución de las AQP en el pulmón está disminuida, provocando así un equilibrio perturbado entre la homeostasis del líquido secretor y de reabsorción bajo el hábito de fumar cigarrillos.

Evidence-based anti-viral and immunomodulatory potential of Black cumin (Nigella sativa L) in COVID-19 / Potencial antivírico e inmunomodulador en COVID-19 del comino negro (Nigella sativa L) basado en la evidencia

Currently, the whole world is facing a life-threatening novel coronavirus 2019 (COVID-19) pandemic. Natural products are well-known for their potential role against viral disease, and some anti-viral agents have been developed to combat these diseases. Herein, the authors investigated the possible effects of this Holy plant Nigella sativa L. (NS), against coronavirus, using evidence-based and mechanistic approaches to conclude the immune-boosting and alleviation of respiratory systemeffects of NS. The pharmacological studies established a prominent role in treating various respiratory, immune systems, cardiovascular, skin, and gastrointestinal disorders. Literature supported the significant anti-viral role and showed an inhibitory role for NS against MHV-A59 CoV (mouse-hepatitis virus­A59) infected Hela, i.e., HeLaCEACAM1a (HeLa-epithelial carcinoembryonic antigen-related cell adhesion molecule 1a) cell. NS is a safe herbal product or dietary supplement and could be an effective and affordable community adjuvant treatment for coronavirus in the current scenario.

Actualmente, el mundo entero se enfrenta a una pandemia del nuevo coronavirus 2019 (COVID-19) que amenaza la vida. Los productos naturales son bien conocidos por su papel potencial contra las enfermedades virales, y se han desarrollado algunos agentes antivirales para combatir estas enfermedades. En este documento, los autores investigaron los posibles efectos de esta planta sagrada Nigella sativa L. (NS), contra el coronavirus, utilizando enfoques mecanicistas y basados en la evidencia para concluir el refuerzo inmunológico y el alivio de los efectos del SN en el sistema respiratorio. Los estudios farmacológicos establecieron un papel destacado en el tratamiento de diversos trastornos respiratorios, del sistema inmunológico, cardiovasculares, cutáneos y gastrointestinales. La literatura apoyó el importante papel antivírico y mostró un papel inhibidor de NS contra células Hela infectadas con MHV-A59 CoV (virus de la hepatitis de ratón-A59), es decir, HeLaCEACAM1a (molécula de adhesión celular 1a relacionada con el antígeno carcinoembrionario epitelial de HeLa). NS es un producto a base de hierbas o un suplemento dietético seguro y podría ser un tratamiento adyuvante comunitario eficaz y asequible para el coronavirus en el escenario actual.

Alteraciones morfológicas en el tracto respiratorio de ratas Wistar inducidas por vapores de la raíz de hierba del zorrillo (Petiveria alliacea) del suroeste de México / Morphologic alterations in the respiratory tract of Wistar rats induced by steams of the root of hierba del zorrillo (Petiveria alliacea) from southwest of Mexico

Petiveria alliacea, es conocida con diferentes nombres según el lugar donde se le encuentre. Estudios con hojas, tallo, raíz o extractos describen múltiples usos medicinales. Sin embargo, son pocos los que describen efectos tóxicos. En este estudio se evaluó el efecto morfológico de los vapores de la raíz de P. alliacea sobre el tracto respiratorio de ratas Wistar. Se emplearon 15 ratas divididas en 5 grupos (n=3): control absoluto, 0, 5, 15 y 30 minutos post-exposición (grupos I-V, respectivamente). Las ratas se sacrificaron y se colectaron muestras representativas del tracto respiratorio que posteriormente se procesaron por la técnica histológica convencional, hasta su inclusión en bloques de parafina. Los cortes histológicos se tiñeron con H-E, tricrómico de Masson y azul de toluidina. En tráquea, bronquiolos y pulmón de las ratas de los grupos I y II se observó una histología normal. En la tráquea de los grupos III, IV y V se identificaron áreas variables de hiperplasia en el epitelio, zonas desprovistas de cilios, signos de aumento en la secreción de las células caliciformes y áreas desprovistas de epitelio que se incrementaron con el tiempo. En la lámina propia se observó congestión vascular e infiltrado mononuclear que incrementó con el tiempo. En los bronquiolos de los grupos III y IV se observó activación de las células de Clara, áreas desprovistas de epitelio, y células mononucleares en la luz bronquiolar. En el grupo V se observaron características histológicas normales. En pulmón de los grupos III y IV se identificó engrosamiento de tabiques alveolares, incremento de las fibras de colágena, congestión y extravasación capilar, además de exudado intralveolar. En el grupo V se observó aparente reversión de algunas alteraciones morfológicas de los grupos previos, aunque otras alteraciones persisten. No se observaron diferencias en el número de las células cebadas.

Petiveria alliacea, is known with different names depending of the place where it is found. Studies with leaves, stem, root or extracts, describe multiple medicinal uses. However, there are few reports that describe toxic effects. This study assessed the morphologic effect induced by steams of the root of P. alliacea on the respiratory tract of Wistar rats. We used 15 rats divided in 5 groups (n= 3): absolute control, 0, 5, 15 and 30 minutes post-exposure (I-V groups, respectively). The rats were sacrificed; representative samples of the respiratory tract were collected, and were processed by conventional histological technique until their inclusion in paraffin blocks. Histological sections were stained with H & E, Masson trichrome and toluidine blue stain. A normal histology was observed in trachea, bronchioles and lungs of rats in groups I and II. In trachea in groups III, IV and V, areas with variable hyperplasia in the epithelium, cells without cilia, increase in the secretion of goblet cells, and areas without epithelium were observed. These morphologic alterations were increased with time. In the lamina propia vascular congestion and mononuclear infiltrate were observed, also increasing with time. In bronchioles in groups III and IV, it was noted activation of Clara cells, areas without epithelium, and mononuclear cells in the bronchiolar light. In group V normal histology was observed. In lung in groups III and IV thickening of interalveolar septa, increase of collagen fibers, capillary congestion, extravasation, and exudates were present. Also was observed an apparent reversion of morphologic alterations of previous groups, but other alterations persist. No difference in mast cells number was observed.

Efeito da obstrução de vias aéreas nas variações das propriedades resistivas e elásticas do sistema respiratório de asmáticos, mediadas pelo uso de salbutamol / Effects of airway obstruction on albuterol-mediated variations in the resistive and elastic properties of the respiratory system of patients with asthma

OBJETIVO: Investigar os efeitos da obstrução de vias aéreas nas variações das propriedades resistivas e elásticas do sistema respiratório de asmáticos adultos mediadas pelo uso de salbutamol. MÉTODOS: Foram analisados 24 indivíduos controles e 69 asmáticos, todos não tabagistas, divididos em três grupos segundo o nível de obstrução de vias aéreas (leve, moderada e acentuada). Cada grupo foi dividido em dois subgrupos de acordo com a resposta broncodilatadora: resposta broncodilatadora positiva (RB+) ou negativa (RB-). A espirometria foi utilizada para a avaliação da obstrução, e a técnica de oscilações forçadas, para a análise das propriedades resistivas e elásticas, sendo realizadas antes e após a utilização de 300 µg de salbutamol. RESULTADOS: A resistência no intercepto (R0) apresentou maior redução nos grupos com maior obstrução. Essa redução foi mais evidente nos subgrupos RB+ do que nos RB- (p < 0,02 e p < 0,03, respectivamente). Houve diferença significativa entre o grupo controle e a o subgrupo com obstrução acentuada RB+ (p < 0,002). As reduções na elastância dinâmica (Edyn) se acentuaram significativamente com a obstrução, tanto para os subgrupos RB- (p < 0,03), quanto para os RB+ (p < 0,003). As reduções da Edyn foram significativamente maiores nos subgrupos com obstrução moderada RB- (p < 0,008) e com obstrução acentuada RB+ (p < 0,0005) do que no grupo controle. CONCLUSÕES: Em asmáticos, o aumento da obstrução de vias aéreas resulta na elevação das variações em R0 e Edyn com o uso de salbutamol. Pacientes com RB+ apresentam variações mais elevadas que indivíduos com RB-.

OBJECTIVE: To investigate the effects of airway obstruction on albuterol-mediated variations in the resistive and elastic properties of the respiratory system of adult patients with asthma. METHODS: This study comprised 24 healthy controls and 69 patients with asthma, all of whom were nonsmokers. The patients were divided into three groups according to the severity of airway obstruction (mild, moderate or severe). Each of the three groups was divided into two subgroups according to the bronchodilator response (BR): positive (BR+) or negative (BR-). Airway obstruction was determined by means of spirometry, and the resistive and elastic properties were determined by means of the forced oscillation technique. These measurements were conducted before and after albuterol use (300 µg). RESULTS: The resistance at the intercept (R0) presented greater reductions in the groups with higher obstruction. This reduction was more evident in the BR+ subgroups than in the BR- subgroups (p < 0.02 and p < 0.03, respectively). There was a significant difference between the control group and the BR+ subgroup with severe obstruction (p < 0.002). The reductions in dynamic elastance (Edyn) were significantly greater in proportion to the degree of obstruction, in the BR- subgroups (p < 0.03), and in the BR+ subgroups (p < 0.003). The reductions in Edyn were significantly greater in the BR- subgroup with moderate obstruction (p < 0.008) and in the BR+ subgroup with severe obstruction (p < 0.0005) than in the control group. CONCLUSIONS: In patients with asthma, increased airway obstruction results in greater reductions in R0 and Edyn after albuterol use. These reductions are greater among BR+ patients than among BR- patients.

Antileukotrienes in the treatment of asthma and allergic rhinitis

OBJETIVO: Comparar os antagonistas de leucotrienos (ARLT) aos outros grupos de medicamentos utilizados para tratar a asma e a rinite alérgica. FONTES DOS DADOS: MEDLINE, LILACS e Biblioteca Cochrane. Palavras chaves: leucotrienos, antileucotrienos, tratamento da asma, tratamento da rinite alérgica, asma e rinite alérgica. Procurou-se agrupar os principais trabalhos e revisões sobre o assunto. SíNTESE DOS DADOS: Os ARLT são mais eficazes do que placebo e potencializam os efeitos dos corticosteróides inalados. A associação de corticosteróides inalados com agentes beta2 agonistas de longa duração (LABA) é mais eficaz do que a associação de cortiscoteróides inalados + ARLT. Embora pareça racional o uso de ARLT na crise aguda de asma e rinite alérgica, mais estudos são necessários para comprovar esse benefício. Os ARLT promovem redução no tempo de hospitalização e no número de crises de sibilância em lactentes com bronquiolite viral aguda pelo vírus respiratório sincicial e na sibilância recorrente após bronquiolite viral aguda. Os ARLT são menos eficazes que os corticosteróides intranasais no manejo da rinite alérgica. Os ARLT são eficazes na asma induzida por exercício (AIE), embora não constituam a primeira linha de tratamento. CONCLUSÃO: Estudos controlados e randomizados mostram que os corticosteróides inalados são as drogas de escolha para o tratamento da asma persistente e rinite alérgica. :Não existem evidências suficientes para recomendar o uso de ARLT como medicamento de primeira linha (monoterapia) em crianças com asma (nível I). Nas crianças que não podem usar corticosteróides inalados, os ARLT podem ser uma alternativa (nível II).

OBJECTIVE: To compare leukotriene antagonists (LTA) to other groups of drugs used in asthma and allergic rhinitis treatment. SOURCES: MEDLINE, LILACS and Cochrane Library. Keywords: leukotrienes, antileukotrienes, asthma treatment, allergic rhinitis treatment, asthma and allergic rhinitis. An attempt was made to group the main studies and reviews about this topic. SUMMARY OF THE FINDINGS: LTA are more efficient than placebo and enhance the effects of inhaled corticosteroids. The association of inhaled corticosteroids with long-acting beta2-agonists is more efficient than the association of inhaled corticosteroids + LTA. Although use of LTA in acute asthma attacks and allergic rhinitis seems reasonable, more studies are needed to confirm this benefit. LTA reduce hospitalization time and the number of wheezing attacks in infants with acute viral bronchiolitis caused by respiratory syncytial virus, as well as recurrent wheezing after acute viral bronchiolitis. LTA are less efficient than intranasal corticosteroids for allergic rhinitis management. LTA are efficient in exercise-induced asthma, although they are not the first-line treatment. CONCLUSIONS: Controlled and randomized studies show that inhaled corticosteroids are the drugs of choice to treat persistent asthma and allergic rhinitis. There is not enough evidence to recommend the use of LTA as first-line drug (monotherapy) in children with asthma (level I). For children who cannot use inhaled corticosteroids, LTA may be a good alternative (level II).

Adverse effects of systemic isotretinoin therapy: a study of 78 patients

Isotretinoin is an effective treatment for severe forms of acne refractory to other therapies, but it is a teratogen and can cause serious side effects. The side effects, in addition to the constitutional features are related to skin, mucosae, eyes, sexual organs, central nervous system, respiratory system and gastrointestinal tract. Deranged biochemical profile may also be seen in few patients. The current study was aimed to determine the frequency of side effects of systemic isotretinoin therapy in patients treated for acne, thereby assessing its safety. During the calendar year 2004, all the acne patients attending the outpatient department of dermatology, Ziauddin Medical University, KDLB campus, Karachi, fulfilling the inclusion criteria, managed on systemic isotretinoin were enrolled. All were taking isotretinoin at a dose of 0.5mg/kg body weight daily. Baseline investigations were performed in all the patients i.e. liver function tests, lipid profile, complete blood picture and renal function tests. They were followed up for any side effects and clinical improvement. The baseline investigations were repeated monthly to see any biochemical and hematological derangements. 78 patients, 42 females [53.8%] and 36 males [46.2%], with ages ranging from 18 to 24 years, were enrolled. 72 patients [92.2%, p<0.001] developed side effects with a variable frequency of at least one feature in each of these subjects. The side effects, in addition to the constitutional features, observed were related to skin [87.2%], mucosae [10.3%], central nervous system [5.2%], eyes [3.8%], reproductive organs [2.6%], respiratory system [1.3%] and gastrointestinal tract [1.3%]. Deranged biochemical profile was also a feature in few patients [6.3%]. The majority of the patients on systemic isotretinoin have side effects, the most common being cutaneous and mucosal but are trivial. Side effects pertaining to the other systems are less frequent

General pharmacological profiles of bee venom and its water soluble fractions in rodent models

Recently, the antinociceptive and anti-inflammatory efficacy of bee venom (BV, Apis mellifera) has been confirmed in rodent models of inflammation and arthritis. Interestingly, the antinociceptive and anti-inflammatory effect of whole BV can be reproduced by two water-soluble fractions of BV (>20 kDa:BVAF1 and<10 kDa: BVAF3). Based on these scientific findings, BV and its effective water-soluble fractions have been proposed as potential anti-inflammatory and antinociceptive pharmaceuticals. While BV's anti-inflammatory and antinociceptive properties have been well documented, there have been no careful studies of potential, side effects of BV and its fractions when administered in the therapeutic range (BV, 5 microgram/kg; BVAF1, 0.2 microgram/kg: BVAF3, 3 microgram/kg; subcutaneous or intradermal). Such information is critical for future clinical use of BV in humans. Because of this paucity of information, the present study was designed to determine the general pharmacological/physiological effects of BV and its fractions administration on the rodent central nervous, cardiovascular, respiratory and gastrointestinal system. Subcutaneous BV and its fractions treatment did not produce any significant effects on general physiological functions at the highest dose tested (200-fold and 100-fold doses higher than that used clinically, respectively) except writhing test. These results demonstrate that doses of BV or BV subfractions in the therapeutic range or higher can be used as safe antinociceptive and anti-inflammatory agents.

In vitro lethal efficacy of leaf extract of Cannabis sativa Linn on the larvae of Chironomous samoensis Edward: an insect of public health concern.

Leaf extract of C. sativa causes paralysis leading to death in larvae of C. samoensis. The extract brought a drastic change in the morphology of sensilla trichoidea and the general body cuticle. The larvae exposed to the leaf extract also showed a significant reduction in the concentration of Mg and Fe, while Mn showed only slight average increase. Since the sensilla trichoidea has nerve connection, it is expected that the toxic principle of the leaf extract has affected the central nervous system. The significant reduction of the level of Fe indicates that the extract could cause the reduction in oxygen binding capacity of the haemolymph, thereby acting as a respiratory poison in addition to its known role as a neurotoxic substance.

Effects of formaldehyde on the frog's mucociliary epithelium as a surrogate to evaluate air pollution effects on the respiratory epithelium

The increasing use of alcohol as an alternative fuel to gasoline or diesel can increase emission of formaldehyde, an organic gas that is irritant to the mucous membranes. The respiratory system is the major target of air pollutants and its major defense mechanism depends on the continuous activity of the cilia and the resulting constant transportation of mucous secretion. The present study was designed to evaluate the effects of formaldehyde on the ciliated epithelium through a relative large dose range around the threshold limit value adopted by the Brazilian legislation, namely 1.6 ppm (1.25 to 5 ppm). For this purpose, the isolated frog palate preparation was used as the target of toxic injury. Four groups of frog palates were exposed to diluted Ringer solution (control, N = 8) and formaldehyde diluted in Ringer solution at three different concentrations (1.25, 2.5 and 5.0 ppm, N = 10 for each group). Mucociliary clearance and ciliary beat frequency decreased significantly in contact with formaldehyde at the concentrations of 2.5 and 5.0 ppm after 60 min of exposure (P<0.05). We conclude that relatively low concentrations of formaldehyde, which is even below the Brazilian threshold limit value, are sufficient to cause short-term mucociliary impairment

Remifentanil: por que precisamos de outro opióide? / Remifentanil: do we need any other opioid?

Justifiactiva e objetivos - O remifentanil é o mais recente opióide em uso clínico. Apresenta rápido início de açäo e depuraçäo, sendo metabolizado por esterases plasmáticas e teciduais inespecíficas. O objetivo desta revisäo é apresentar as características farmacocinéticas e farmacodinâmicas do remifentanil, o seu emprego clínico em diversas cirurgias. Conteúdo - Säo apresentadas as características farmacocinéticas e farmacodinâmicas do remifentanil, comparando-as com a de outros opióides. Säo comentados resultados de trabalhos em cirurgias abdominais, torácicas, ortopédicas e cardíacas. Conclusöes - O remifentanil tem perfil adequado para cirurgias de curta duraçäo, em regime de infusäo contínua em anestesia venosa ou ainda, como analgésico, em anestesias balanceadas em que necessita de proteçäo aos estímulos nociceptivos e despertar precoce

Efecto de los extractos acuosos de Sesamum indicum L. Pedaliacea (Ajonjolí), en el aparato respiratorio en animales de experimentación / Effect of aquos extracts of Sesamun indicum L. Pedaliacea (Ajonjolí), on the respiratory tract of experimental animals

En algunos países caribeños se usa el Ajonjolí o Worwoli para el tratamiento del llamado pecho apretado o neumopatía y en el tratamiento de la conjuntivitis . Las semillas de Sesamum indicum L. Pedaliacea, contienen globulinas, aniones, cationes, arginina, ácidos grasos, carbohidratos, flavonoides, llignanos y otras sustancias con diferentes acciones farmacológicas: inmunológicas, bactericidas, inhibidoras de prostaglandina sintetasa y lipoxigenasa, corticoesteroidea, antiagregante plaquetaria, antidisminorréicas, antiespasmódicas, hipoglicemiante y otras. La investigación inicial sobre los efectos del extracto acuoso de semillas de Sesamum indicum L. Pediaceae (Ajonjolí) en ratas anestesiadas revelan efectos estimuladores de la frecuencia respiratoria a dosis de 12.5 y 25 mg/kg I.g. (intragástrica) seguidos de inhibición, comienza a invertirse las respuestas a los 50 mg/kg I.g. y deprimen la frecuencia respiratoria a dosis de 100 mg/kg I.g. en forma estadísticamente significativa. La amplitud de los movimientos respiratorios es disminuido en casi todas las dosis ensayadas 12.5, 25, 50 y 100 mg/kg I.g. En las primeras dos dosis ocasionalmente se observan respuestas estimuladoras. En el ensayo Hipócratico de Malone realizado en ratas, dosis de 100,500 y 750 mg/kg I.g. redujeron significativamente la frecuencia respiratoria en delta porcentaje de -39.2, -45.6 y -40.9 respectivamente. La administración del extractoo de semillas de Sesamum indicum L. Pedaliaceae en conejos anestesiados, incrementó: el flujo respiratorio y el volumen ventilatorio, la frecuencia respiratoria y el volumen ventilatorio, la frecuencia respiratoria y el volumen respiratorio minuto a dosis menores de 200 mg/kg I.g. del extracto de Sesamum indicum L. Pedaliceae, la frecuencia cardíaca prácticamente no se modificó. Este hallazgo se había observado en las ratas. Podemos concluír que los efectos del ajonjoli se pueden clasificar en el grupo "D" de Cámbar P. que son los extractos que disminuyen la resistencia pulmonar y aumentan la adaptabilidad pulmonar. Se puede asumir que esta planta es broncodilatodora y aumenta la "elasticidad" pulmonar. Los mecanismos precisos de estos cambios permanecerían por dilucidar

Comparison of respiratory sensations induced by J receptor stimulation with lobeline in left handers & right handers.

We examined the hypothesis that right handers and left handers may differ in sensory perceptions and respiratory responses to J receptor stimulation with intravenous injections of lobeline HCl in incremental doses. The comparison was made between 6 right handers and 9 left handers (all males) for (i) the dose of lobeline required to produce sensory threshold (viz., first appearance of respiratory sensations) and cough threshold (first appearance of cough); and (ii) latency and duration of sensations for sensory and cough threshold. All these comparisons were not found to be significant statistically. The sensation of breathlessness, and feelings of drowsiness, giddiness and headache were perceived in 3 of the 9 left handers, and in none of the right handers, but the difference was not significant. Reflex bradycardia was recorded only in left handers (5 of 9). The time (sec) for cough threshold was negatively correlated to threshold dose of lobeline (r = -0.5, and P < 0.05). The left handers perceived cough at the threshold as more distressing as compared with right handers (VAS P < 0.05). In conclusion, handedness did not influence J receptor responses to i.v. lobeline.

Biochemical and histopathological changes in respiratory system of rats following exposure to diesel exhaust.

Effect of exposure to diesel exhaust (DE) for different durations was evaluated using histopathological and biochemical parameters in respiratory system of the rats. Animals were exposed to 1 part DE diluted with 5 parts of clean air in a simulation chamber for 15 min/day for 1, 7, 14 and 21 days. After completion of various exposures, biochemical parameters including elastase inhibitory capacity (EIC) and protein content of the bronchial airway lavage (BAL) and histopathological changes along with lung/body weight ratio were assessed. The elastase inhibitory capacity (an index of the protection against destruction of elastin, a lung connective tissue) was maximum at 1 week indicating thereby that the body renders protection against injury by increasing EIC levels in the initial phase. However, protein content in the BALF increased after 1 week and reached maximum at 2 weeks. Histopathological changes followed similar time course of pattern with accumulation of macrophages and protein exudation. Prolonged exposure up to 3 weeks, however was accompanied by chronic inflammatory changes and thickening of alveolar septa and blood vessels. Changes in lung/body weight ratio and suspended particulate matter (SPM) deposited on filters (simulation chamber) correlated well with EIC, protein content in BALF and histopathological changes. The biochemical findings accompanied with chronic structural changes in the lungs of rats following exposure to DE could be relevant to the clinical observation of increased incidence of chronic lung diseases after continued DE exposure.

Sedación trasoperatoria y analgesia postquirúrgica del paciente crítico / Transoperatory sedation and analgesia after surgery in the critically ill patient

Introducción. La sedación y la analgesia se usan ampliamente en el paciente en estado crítico durante y después de la cirugía. Objetivo. Evaluar el efecto de dos fármacos sobre la sedación en pacientes sometidos a procedimientos quirúrgicos, y analizar la utilidad de la analgesia epidural después de la cirugía. Pacientes y métodos. Tratamos 27 pacientes durante la cirugía con dos fármacos: a) propofol (n = 19) y b) midazolam (n = 8). Se les infundió en forma continua con bomba de infusión 910 mL de solución salina al 0.9 por ciento + bupivacaína al 0.5 por ciento 450 mg y buprenorfina 2.7 mg en el espacio epidural a través de un catéter insertado previamente, después de la cirugía por 72 horas. El nivel de analgesia se evaluó mediante la escala visual análoga. Resultados. El nivel de sadación no tuvo cambios en los dos grupos de pacientes, pero la recuperación fue mejor en el grupo b. El nivel de analgesia fue de 1.26 ñ 0.46 en todos los pacientes. Conclusión. La analgesia epidural después de la cirugía, es una buena elección en el tratamiento del dolor del paciente crítico

Hipóxia decorrente de sedaçåo com midazolam durante anestesia peridural / Hypoxia following sedation with midazolam during epidural anesthesia

Justificativa e objetivos - Os benzodiazepínicos possuem açäo sedativa por excelência e säo habitualmente escolhidos para a sedaçäo de pacientes submetidos a bloqueios raquídeos. O midazolam entretanto, deprime a ventilaçäo por açäo central e promove variados graus de obstruçäo respiratória por seu efeito relaxante sobre a musculatura da orofaringe. Considerando-se que a hipóxia está na gênese de um grande número de acidntes durante anestesias e pode agravar os efeitos tóxicos dos anestésicos locais sobre o miocárdio, o objetivo deste trabalho foi estudar os efeitos de doses sedativas de midazolam sobre a saturaçäo da hemoglobina pelo oxigênio (SpO2) em pacientes a anestesia peridural. Método - Participaram do estudo oitenta pacientes do sexo feminino, com idades entre 38 e 46 anos, estado físico ASA I, aleatoriamente divididas em dois grupos A e B, escaladas para abdominoplastias estéticas. As pacientes näo receberam medicaçåo pré-anestésica e foram submetidas à anestesia peridural lombar, através de punçäo única em L1L2, com bupivacaína a 0,5 por cento em volume fixo de 25 ml. As pacientes foram sedadas com midazolam na dose de 0,1 mg.kg -1, por via venosa, após a instalaçäo do bloqueio sensitivo cujo nível foi registrado. Nas integrantes do grupo A, colocou-se máscara com fluxo de oxigênio, 3L. min -1). Nas pacientes do grupo B a máscara, com fluxo idêntico, só foi colocada quando a SPO2 atingiu 90 por cento. As pacientes foram monitorizadas com: eletrocardiopatia contínua (D11), pressåo arterial sistólica e diastólica por esfigmomanometria e SpO2 contínua. Os valores obtidos foram anotados na sequência: antes da punçäo peridural, após a instalaçäo do bloqueio e a cada minuto após a injeçäo do midazolam por cerca de quinze minutos. Para efeitos de cálculos foram utilizadas as médias dos valores de antes da punçäo, após o bloqueio e no quinto...

Evaluación de acciones colaterales del anticonvulsionante DL-4 hidroxi, 4-etil, 4-fenil butiramida (HEPB) sobre los sistemas cardiovascular y respiratorio / Evaluation of the collateral actions of the anticonvulsant DL-4-hydroxy, 4-ethyl, 4-phenyl butyramide (HEPB) on the cardiovascular and respiratory systems

Para llevar a cabo una evaluación de la seguridad farmacológica de la HEPB como anticonvulsionante, determinamos los efectos de la administración aguda de este fármaco (5, 25, 50, 100 y 125 mg/kg-1 ip) sobre los sistemas cardiovasculares y respiratorios de la rata. Mientras que en animales anestesiados con pentobarbital HEPB no modificó la frecuencia cardiaca, este anticonvulsionante indujo cambios significativos sobre la presión arterial media (PAM) y la frecuencia respiratoria (FR) a dosis mayores de 50 mg/kg-1 resultando en una inhibición del 37.18 por ciento de la PAM y del 49.5 por ciento de la FR después de la administración de 125 mg/kg-1 de HEPB. En animales no anestesiados, HEPB no alteró la presión arterial sistólica ni la frecuencia cardiaca a ninguna de las dosis probadas. Nuestros datos indican que dentro del intervalo de dosis encontradas para la acción anticonvulsionante de HEPB en diferentes modelos experimentales de epilepsia, este fármaco no ejerce acciones colaterales sobre los sistemas cardiovascular y respiratorio en la rata. Sin embargo, HEPB potencial las acciones depresivas de los barbitúricos sobre dichos sistemas

Predicting offensive-defensive potentials of an anticalmodulin versus Ca entry blockers on respiratory airways. an experimental study in non-sensitized and sensitized dogs

The experimental design comprised equally dividing 48 dogs into major groups: A non-sensitized and a sensitized [by becoming positive for Ascaris lumbricoids antigen extract]. Required estimates were conducted on day 28 in both groups, but after being antigenically challenged only in the sensitized subgroups. In the non-sensitized series, results revealed that calcium entry blockers [CEBs] increased significantly enzymatic antioxidant activities in tracheal mucosa. A concomitant significant decrease in neutrophil phagocytic function was encountered by all drugs and in total leukocytic count by trifluoperazine [TFP] > verapamil hydrochloride [V] in comparison to control [C]. While, in the sensitized series, leukocytosis observed in sensitized [S] did not revert to normal by any of the studied drugs when all were compared to [C]. The concomitant blood and tracheal histamine were significantly reduced by [S + TFP] > [S + V] and only little affected by [S + N], while the significant hypocapnia and alkalosis encountered in [S] reverted to normal by CEBs when data were compared to [C]

Efeitos cardiovasculares e respiratórios em cães anestesiados com diferentes concentrações de isoflurano / Cardiovascular and pulmonary effects of different isoflurane concentrations in dogs

No presente trabalho foram analisados os efeitos sobre os aparelhos cardiovascular e respiratório da anestesia inalatória com isoflurano em 3 (três) concentrações fixas (1, 1 ,5 e 2 CAM) no cão. Foram utilizados 6 (seis) cães machos, pesando 25 ± 2, 7 kg, com valores hematológicos e bioquímicas dentro da faixa de normalidade. Os parâmetros analisados foram: frequência cardíaca (FC), pressão arterial sistólica (PS), diastólica (PD) e média (PM), débito cardíaco (DC), índice cardíaco (IC), frequência respiratória (FR),volume corrente (VC) e volume minuto (VM). Observou-se que, baixas concentrações de isoflurano (1 e 1,5 CAM) produziram um aumento de FC. Com relação à pressão arterial, verificou-se um decréscimo dose-dependente, causado pela diminuição da resistência vascular periférica, o que explicaria a manutenção do DC e IC em baixas concentrações (1 e 1,5 CAM). A 2 CAM de concentração, o aumento da FC não foi capaz de compensar o menor volume de ejeção do coração. Devido a isso, observou-se queda do DC e IC. No sistema respiratório, encontrou-se diminuição da FR, VC e VM, dose-dependente.

Cardiovascular and pulmonary effexts of isoflurane anesthesia at 1, 1 ,5 and 2 minimum alveolar concentration (MAC) were studies in 6 male dogs, healty, weighting 25 ± 2.7 kg. Heart rate (HR), systolic arterial pressure (SAP), dyastolic arterial pressure rate (RR), tidal volume (TV) and minute ventilation (MV) were measured. Low isoflurane concentrations (1 and 1,5 MAC) increased the heart rate (HR). Arterial blood pressure decreased as the MAC increased, explaining the maintenance of the CO and the Cl at low concentrations of isoflurane (1 and 1,5 MAC). At 2 MAC the increase of the HR is not enough to compensate the low heart stroke volume, soa drop of CO an Cl was obseved. A dose-dependent decrease of the RR, TV and MV was also obseved.