Advances in studies on steroidal alkaloids and their pharmacological activities in genus Veratrum / 中国中药杂志

Genus Veratrum plants contain a diversity of steroidal alkaloids, so far at least 184 steroidal alkaloids attributed to cevanine type(A-1～A-69), veratramine type(B-1～B-21), jervanine type(C-1～C-31), solanidine type(D-1～D-10) and verazine type(E-1～E-53), respectively, have been isolated and identified in the genus Veratrum. Their pharmacological activities mainly focused on decreasing blood pressure, anti-platelet aggregation and anti-thrombosis, anti-inflammatory and analgesic, and antitumor effect. This paper classified and summarized the 184 kind of steroidal alkaloids from the Veratrum plants and their major pharmalogical activities in order to provide the scientific basis for the further development and utilization of active alkaloids.

Neuralgias of the Head: Occipital Neuralgia

Occipital neuralgia is defined by the International Headache Society as paroxysmal shooting or stabbing pain in the dermatomes of the greater or lesser occipital nerve. Various treatment methods exist, from medical treatment to open surgical procedures. Local injection with corticosteroid can improve symptoms, though generally only temporarily. More invasive procedures can be considered for cases that do not respond adequately to medical therapies or repeated injections. Radiofrequency lesioning of the greater occipital nerve can relieve symptoms, but there is a tendency for the pain to recur during follow-up. There also remains a substantial group of intractable patients that do not benefit from local injections and conventional procedures. Moreover, treatment of occipital neuralgia is sometimes challenging. More invasive procedures, such as C2 gangliotomy, C2 ganglionectomy, C2 to C3 rhizotomy, C2 to C3 root decompression, neurectomy, and neurolysis with or without sectioning of the inferior oblique muscle, are now rarely performed for medically refractory patients. Recently, a few reports have described positive results following peripheral nerve stimulation of the greater or lesser occipital nerve. Although this procedure is less invasive, the significance of the results is hampered by the small sample size and the lack of long-term data. Clinicians should always remember that destructive procedures carry grave risks: once an anatomic structure is destroyed, it cannot be easily recovered, if at all, and with any destructive procedure there is always the risk of the development of painful neuroma or causalgia, conditions that may be even harder to control than the original complaint.

Efeito da tibolona na morfologia do músculo esquelético, nas enzimas hepáticas e no nível sérico de glicose em ratas castradas / Effect of tibolone on the morphology of skeletal muscle, liver enzymes and blood glucose level in castrated female rats

INTRODUÇÃO: O fígado é uma estrutura de elevada complexidade e é fundamental entender como determinadas substâncias podem afetar sua estrutura e suas funções. OBJETIVO: Analisar a influência da tibolona no metabolismo hepático por meio da avaliação de enzimas e metabólitos comumente utilizados em provas de função hepática. MÉTODOS: Foram utilizadas dez ratas Wistar, divididas em dois grupos: controle (n = 4) e tibolona (n = 6), em status de menopausa cirúrgica. A tibolona (1 mg) foi administrada diariamente por gavagem durante 20 semanas, com avaliação periódica do peso corporal. Após sedação, efetuou-se coleta de sangue para avaliação bioquímica de albumina (Alb) sérica, fosfatase alcalina (FA), transaminases (aspartato aminotransferase e alanina aminotransferase [AST/ALT]), gama-glutamiltranspeptidase (GGT) e glicose, mediante espectrofotometria. O músculo esquelético da coxa foi avaliado por histomorfometria em cortes histológicos corados com hematoxilina e eosina (HE). RESULTADOS: Os animais do grupo tibolona mostraram menor peso corporal, alterações musculares esqueléticas e discretas alterações bioquímicas. Além disso, AST e FA estavam diminuídas e GGT estava mais elevada, porém sem significância estatística. A histomorfometria do músculo revelou uma tendência de menor volume celular nesse grupo. CONCLUSÃO: A tibolona, administrada em alta dose e por tempo prolongado, não interfere de forma significativa nas funções metabólicas e de síntese hepáticas, bem como na permeabilidade da membrana celular, entretanto parece modular a expressão genômica da GGT. A tibolona apresenta influência sistêmica associada a menor peso e diminuição da massa muscular e aumento significativo no peso relativo do fígado, além de alteração da glicogenólise hepática e muscular, da gliconeogênese hepática e dos níveis de glicose circulante.

INTRODUCTION: The liver is a highly complex structure and it is essential to understand how certain substances may affect its structure and functions. OBJECTIVE: Analyze the influence of tibolone on hepatic metabolism by assessing metabolites and enzymes commonly used in liver function tests. METHODS: Ten Wistar rats in surgical menopausal status were divided into two groups: control (n = 4) and tibolone (n = 6). Tibolone (1 mg) was administered by gavage daily for 20 weeks and body weight was periodically assessed. After sedation, blood sampling was performed for biochemical evaluation of serum albumin (Alb), alkaline phosphatase (ALP), transaminases (aspartat aminotranferase and alanine aminotranferase [AST/ALT]), gamma glutamyltranspeptidase (GGT) and glucose by spectrophotometry. Hematoxylin and eosin-stained histological sections of the skeletal thigh muscle were assessed by histomorphometry. RESULTS: The animals in the tibolone group showed lower body weight, skeletal muscle alterations and slight biochemical changes. In the tibolone group, AST and ALP were decreased GGT was higher, but without a statistically significant difference. The muscle histomorphometry showed that the tibolone group tended to present a lower cell volume. CONCLUSION: Tibolone administered in high doses and for a prolonged period does not interfere significantly neither with liver metabolic functions nor liver synthesis, nor with cell membrane permeability. However, it seems to modulate the genomic expression of GGT. Tibolone has systemic influence on lower body weight, reduced muscle mass, and significant increase in relative liver weight. Additionally, liver and muscular glycogenolysis, liver gluconeogenesis and circulating glucose levels are altered.

Avaliação descritiva sobre o uso de esteroides anabolizantes e seu efeito sobre as variáveis bioquímicas e neuroendócrinas em indivíduos que praticam exercício resistido / Descriptive assessment on the use of anabolic steroids and their effect on the biochemical and neuroendocrine variables in practitioners of resisted exercise

O uso dos esteroides anabolizantes vem se tornando um problema de saúde pública ao longo dos últimos anos. No bojo do uso abusivo, muitos efeitos deletérios são observados, na sua totalidade por disfunções dos vários sistemas fisiológicos. Sendo assim, o objetivo do estudo foi o de avaliar o eixo hipófise-gonadal, a função hormonal, as transaminases hepáticas e o perfil de hemograma de 61 voluntários distribuídos em três grupos: 20 usuários de esteroides anabolizantes praticantes de exercício físico resistido, 21 praticantes de exercício resistido sem uso de esteroides anabolizantes e 20 sedentários. Foi observada elevação do nível de creatina quinase nos dois grupos de indivíduos que se exercitavam de maneira resistida, em relação ao grupo de sedentários (p < 0,001). Redução das gonadotrofinas LH e FSH do grupo de usuários de esteroides anabolizantes e elevação do nível de estradiol, em comparação ao grupo sedentário e treinado que não usa esteroides anabolizantes (p < 0,001). Ainda, foi observada redução da fração HDL do colesterol, em relação aos dois grupos estudados (p < 0,001). Desta maneira, o uso dos esteroides anabolizantes causa alterações bioquímicas que podem levar a instalação de efeitos colaterais.

The use of anabolic asteroids has become a public health problem over the last years. Concerning their abusive use, many deleterious effects caused in their totality by dysfunction of the various physiological systems can be observed. Therefore, the aim of the present study was to assess the hypophyseal-gonadal axis, hormone function, hepatic transaminases and hemogram profile of 61 volunteers distributed in three groups: 20 anabolic steroid users, practitioners of resisted physical exercise; 21 practitioners of resisted physical exercise with no use of anabolic steroids and 20 sedentary subjects. Increase of the creatine kinase level was observed in the two exercised groups in comparison to the sedentary group (p < 0.001). Reduction of the LH and FSH gonadotrpins of the steroid users group and increase in the estradiol level were observed in comparison to the sedentary and with no steroid use groups (p < 0.001). Moreover, reduction of the HDL cholesterol fraction was observed in comparison to the two studied groups (p < 0.001). Thus, the use of anabolic steroids causes biochemical alterations which can lead to the installation of collateral effects.

Effect of Solanum nudum steroids on uninfected and Plasmodium falciparum-infected erythrocytes

Steroids from Solanum nudum (SNs) have demonstrated antiplasmodial activity against erythrocytic stages of the Plasmodium falciparum strain FCB-2. It is well known that steroids can alter the membrane function of erythrocytes. Thus, we assessed alterations in the membranes of uninfected red blood cells, the parasite invasiveness and the solute-induced lysis of parasitised red blood cells (pRBCs). induced by SNs. We found that most merozoites were unable to invade SN-treated erythrocytes. However, transmission electron microscopy revealed no effect on the morphology of uninfected erythrocytes treated with either SN2 or diosgenone and neither SN induced haemolysis of uninfected erythrocytes. SN2 and SN4 inhibited isosmotic sorbitol and alanine-induced haemolysis of pRBCs. In contrast, diosgenone and SN1 did not inhibit solute-induced haemolysis. The inhibition of solute-induced lysis of parasitised erythrocytes by SN2 and SN4 suggest an action of these SNs on new permeability pathways of pRBCs.

Sexualidade e hormônios na transição menopausal e na pós-menopausa / Sexuality and hormones in menopausal transition and after the menopause

A síntese dos esteróides segue seqüência consagrada. Dois sistemas enzimáticos são importantes para a biotransformação das diversas substâncias: hidrogenases e citocromo P450. Tanto os estrogênios como os androgênios são relevantes para o desenvolvimento e manutenção da troficidade das estruturas genitais, além de muitas outras ações metabólicas em todo o organismo. Há queda na síntese dos androgênios a partir da terceira década da vida da mulher, podendo agravar-se em situações especiais. Algumas mulheres têm manifestações clínicas, impondo-se a suplementação terapêutica. É também inegável a ação dos esteróides sexuais no sistema nervoso central. Experiências em aves e animais comprovaram essas influências. Malgrado outros estímulos na atividade sexual - olfato, visão, tato - e de várias substâncias - vasopressina, ocitocina, dopamina, é inegável o fator preponderante dos esteróides sexuais. A insuficiência androgênica (IA) pode manifestar-se com sinais e sintomas peculiares. A reposição androgênica poderá melhorar tanto a sexualidade quanto o bem-estar das pacientes.

The steroid biosynthesis follows a time-honored sequence. Two enzymatic groups are important in this action: hydrogenases and cytochrome P450. Both estrogens and androgens act on the development and trophicity of genital organs besides other metabolic actions. Female androgen secretion declines, starting in the thirties, with aggravation in particular clinical situations needing therapeutic supplementation. The action of sexual steroids on the Central Nervous System is well established. Experiments with birds and animals prove this action. Despite the influence of smell, vision, tact and substances such as vasopressin, oxytocin, and dopamine, it is indisputable that the sexual steroids play the major role in sexual activity. Androgen insufficiency (AI) may exhibit signs and symptoms in particular clinical situations. Replacement therapy (androgens) may improve well-being and sexual activity.

Incidence of anaphylaxis in the emergency department: a 1-year study in a university hospital.

The aim of this study was to estimate the incidence of anaphylaxis in an emergency department, identify rate and risk factors of recurrent anaphylaxis, and describe its clinical features and management. A retrospective study of patients who attended the emergency department at Thammasat University Hospital was conducted during 2003-2004 with anaphylactically related ICD-9 and ICD-10 terms. There were 64 patients who experienced 65 anaphylactic episodes during the 1-year period. The anaphylaxis occurrence rate was 223 per 100,000 patients per year. The most common manifestations were cutaneous symptoms and signs, followed by respiratory expression. Food allergy was the most common cause of anaphylaxis. Eighty-five percent of admitted cases had monophasic anaphylaxis. Patients with and without biphasic reactions did not differ significantly in terms of epinephrine and steroid usage. In conclusion, anaphylaxis is not rare. Epinephrine and steroid usage did not prevent biphasic reactions.

Fiebre amarilla: la enfermedad recurrente: a propósito de un caso / Yellow fever: the recurrent disease: a purpose of a case

La fiebre amarilla es una enfermedad infecciosa producida por arbovirus que origina compromisos hepático, hemorrágico y renal, frecuentemente fatales. Tiene dos patrones de transmisión, el urbano, generalmente epidémico y el selvático de presentación esporádica o pequeños brotes. Esta enfermedad es una de las grandes plagas de la historia de la humanidad; durante siglos azotó a los habitantes y colonizadores del Africa y la América tropical. A mediados de este siglo la enfermedad disminuyó su incidencia con las campañas de erradiación del vector y la introducción de la vacunación en 1934. Actualmente se informan entre 1000 y 3000 casos anuales, un 10 por ciento de los cuales tiene lugar en Centro y Sudamérica. No existen antivirales efectivos disponibles para esta enfermedad. La fiebre amarilla es difícil de identificar durante las etapas tempranas, ya que puede confundirse fácilmente con malaria, fiebre tifoidea, fiebre viral hemorrágica, leptospirosis y hepatitis viral. El tratamiento es sintomático y de sostén. La fiebre amarilla puede prevenirse con la vacunación. El caso que se presenta a continuación es un paciente masculino de 19 años que consulta por presentar fiebre, evacuaciones líquidas, cefalea y epistaxis, teniendo antecedentes apidemiológicos y familiares importantes, el cual fue tratado desde el comienzo de su ingreso como un Síndrome Icterohemorrágico, al no tener un diagnóstico bien establecido, el cual se obtuvo al egresado el paciente mediante resultados serológicos positivos para fiebre amarilla (1,2).

Effects of steroid hormones on total brain Na(+)-k+ ATPase activity in Oreochromis mossambicus.

The effects of administration of cortisol, corticosterone, testosterone, progesterone and a synthetic estrogen. diethylstilbestrol (DES) on total brain Na(+)-K+- ATPase were investigated in tilapia, O. mossambicus. Exogenous administration of 0.125 and 0.25 microg/g body weight of glucocorticoids and 0.125, 0.25 and 0.5 microg/g body weight of DES for 5 days significantly stimulated Na+(-) K+ ATPase activity by 14-41% in the brain, while 0.5 microg/g body weight of glucocorticoids did not evoke any response on the activity of the enzyme. Progesterone (0.125 and 0.25 microg/g body weight) administration significantly decreased the enzyme activity by 21-36% and high dose (0.5 microg/g body weight) was ineffective. Testosterone exhibited a biphasic effect on Na(+)-K+ ATPase activity--a low dose stimulated by 14% while middle and high doses inhibited it by 19-24%. The results seem to be the first report on the effect of steroids on brain ATPase activity in a teleost. When 0.25microg/g body weight of actinomycin D or puromycin was administered prior to the treatment of similar doses of hormones, the inhibitors significantly inhibited the effect of the hormones by 24-52%. This clearly shows that the effect of the hormones was sensitive to the action of inhibitors suggesting a possible genomic mode of action under long-term treatment. The results suggest that cortisol, corticosterone and DES may possibly stimulate the co-transport of glucose and excitation of membrane potential while progesterone and testosterone inhibit them in the brain of O. mossambicus by regulating the activity of Na(+)-K+ ATPase.

Steroid resistant nephrotic syndrome.

Steroid Resistant-Nephrotic Syndrome (NS) is a chronic, progressive disorder affecting upto 10% of all children with NS. It causes morbidity and mortality due to persistent edema, hypertension, hyperlipidemia, thrombosis and infection. Progression to renal failure was thought to be inevitable in survivors. Recent insights into the pathogenesis of the disease has identified several responsible genes and proteins. Studies have shown that long term aggressive therapy with combinations of steroids, alkylating agents and cyclosporine, cause complete or partial remission in 20-80% patients. The use of nonspecific renal protective agents such as the angiotensin converting enzyme inhibitors, angiotensin 2 receptor blockers, and anti-lipid agents retard disease progression. Although these are indications of significant improvement in outcome, further multicentre controlled studies are required to determine the optimum drugs and regimens to be used.

Evaluation of the analgesic effect of neurosteroids and their possible mechanism of action.

The present study investigates the effect of progesterone (P), a pregnane precursor of neurosteroids and 4-chlordiazepam (4-CD), a high affinity ligand for mitochondrial diazepam binding inhibitor receptor (MDR) that stimulates neurosteroid synthesis, in both acute, (tail flick latency test, TFL) and chronic, (formalin-induced pain response, FT), models. Both P and 4-CD showed an analgesic response in these models. The effect of P and 4-CD was antagonized by bicuculline on TEL but not in FT. However, naloxone attenuated the antinociceptive response of P and 4-CD in TFL as well as FT. Further, P and 4-CD pretreatment potentiated the analgesic effect of morphine and nimodipine in both the models of pain sensitivity. Thus, neurosteroids produce an antinociceptive effect which may be mediated by modulation of GABAergic and/or opiodergic mechanisms as well as voltage gated calcium channels.

Uso racional de los esteroides / A review about steroid use

Se hace una revisión sobre los esteroides, invitando al médico general a olvidar el mito de que los esteroides son "veneno" y que solo son de uso privativo de los especialistas. La mayoría de errores que se comenten en la práctica diaria son por la ignorancia sobre el manejo de estos medicamentos que a través de la historia siguen demostrando ser armas importantísimas en el manejo de muchas patologías sobre todo en aquellas que son de origen "autoinmune".

Neuroesteroides: neuromoduladores de la excitabilidad cerebral / Neurosteroids: neuromodulators of cerebral excitability

A los esteroides producidos por el cerebro se les denomina neuroesteroides (NE), los cuales pueden modular las neurotransmisiones; GABAérgica, glutametérgica, glicinérgica y colinérgica (receptor nicotínico). Estos efectos son de latencia y duración corta, y no implican al genoma celular. La interacción de estos NE con receptores membranales contribuye a la regulación de la escitabilidad neuronal, y su estudio ha permitido un mejor entendimiento de fenómenos cognoscitivos, hormonales, de la epilepsia, así como el desarrollo de nuevos fármacos con efectos ansiolíticos, antidepresivos, antestésicos y anti-epilépticos

Terapêutica de reposiçäo hormonal em pacientes com diabetes mellitus / Hormonal replacement therapy in diabetes mellitus patients

Säo indiscutíveis os benefícios da hormonioterapia de reposiçäo (TRH) em mulheres climatéricas. A abordagem de pacientes diabéticas candidatas a essa modalidade terapêutica reveste-se de importância, pela complexidade deste distúrbio metabólico. Os autores fazem revisäo da literatura e discutem as alteraçöes inerentes ao metabolismo dos carbohidratos, sua relaçäo com os esteróides sexuais e com os esquemas terapéuticos atualmente empregados na terapia de reposiçäo hormonal.

Animal models of anxiety an ethological perspective

In the field of anxiety research, animal models are used as screening tools in the search for compounds with therapeutic potential and as simulations for research on mechanisms underlying emotional behaviour. However, a solely pharmacological approach to the validation of such tests has resulted in distinct problems with their applicability to systems other than those involving the benzodiazepine/GABA(A) receptor complex. In this context, recent developments in our understanding of mammalian defensive behaviour have not only prompted the development of new models but also attempts to refine existing ones. The present review focuses on the application of ethological techniques to one of the most widely used animal models of anxiety, the elevated plus-maze paradigm. This fresh approach to an established test has revealed a hitherto unrecognized multidimensionality to plus-maze behaviour and, as it yields comprehensive behavioural profiles, has many advantages over conventional methodology. This assertion is supported by reference to recent work on the effects of diverse manipulations including psychosocial stress, benzodiazepines, GABA receptor ligands, neurosteroids, 5-HT(lA) receptor ligands, and panicolytic/panicogenic agents. On the basis of this review, it is suggested that other models of anxiety may well benefit from greater attention to behavioural detail.

Abordaje posterior con descompresión circunferencial y reconstrucción en las metástasis de la columna torácica y lumbar / Posterior approach with descompression circumferential y reconstruction in the metastatic of thoracic and lumbar spine

Desde 1990 hasta 1994, cuarenta y ocho pacientes con tumor metastásico de la columna torácica y lumbar fueron tratados con abordaje posterior, descompresión circunferencial, vertebrectomía parcial y reconstrucción con cemento óseo. Para obtener la estabilidad de usó el Fijador Interno AO o el sistema Harrington-Luque. El tumor primario más frecuente fue el cáncer de mama (42 por ciento). De toda la serie estudiada, el 54 por ciento presentaba algún grado de déficit neurológico asociado con severo dolor, el cual se observó en el 92 por ciento de los casos. En el presente estudio, el 88 por ciento de los pacientes presentó una mejoría del déficit neurológico y en todos los casos se obtuvo el alivio del dolor, lo cual les permitió una movilización precoz

Uso de esteroides en niños asmáticos / Treatment with steroids in children with bronchial asthma

A partir del conocimiento de que la inflamación es la base de la fisiopatología del asma, el tratamiento con esteroides sistémicos e inhalados se considera de primera línea para el proceso inflamatorio en la fase aguda o crónica, y se recomienda su uso temprano para evitar la prolongación de los cuadros. En la época actual la disponibilidad de esteroides inhalados viene a cambiar la manera de enfrentar esta enfermedad, dada su gran potencia local, sus mínimos efectos colaterales y la disponibilidad de inhaladores de dosis medida

Uso de esteroides intravenosos como tratamiento de la lumbociática aguda / Intravenous steroids for treatmente of acute lumbosciatic pain

Se realizó un estudio prospectivo de marzo de 1992 a junio de 1993 en 25 pacientes adultos, de 24 a 45 años, con cuadro de lumbociatalgia aguda secundaria a radiculopatía por hernia de disco intervertebral lumbar, que se trataron en forma intra-hospitalaria con un succinato sódico de metil-prednisolona en dosis de 500 mg por vía intravenosa, a intervalos de 8 a 12 horas durante un periodo de tres a cinco días. De los 25 pacientes tratados, en 14 desapareció del dolor y en 10 de esos 14 desaparecieron las alternaciones neurológicas. De los 11 restantes en tres hubo mejoría significativa con fisioterapia y reposo. Finalmente ocho no mejoraron, de los cuales solamente cinco aceptaron someterse a cirugía. El porcentaje de pacientes que mejoró en forma primaria con este tratamiento fue de 56 por ciento, el cual se considera de valor clínico

Evaluación morfologia de las uniones intercellulares en el ovario del embrión de pollo: acción de hormonas esteroideas y gonadotroficas in vitro / Morphological evaluation of intercellular junctions in the ovary of chick embryos: action of steroid and gonadotropic hormones in vitro

Se determinaron las variaciones de las uniones intercelulares de las células germinales y epiteliales en el epitelio ovárico producidas por hormonas gonadotróficas y esteroideas sobrelos ovarios del embrión de pollo a los 7 días de desarollo. Se cultivaron explantos de ovarios derecho e izquierdo Sin (controles) y con adición de hormonas (experimental durante 4 días. Los cultivos fueron procesados para su estudio ultraestructural (MET). En ambos ovarios controles los complejos de unión eran similares a los identificados in ovo. En el ovario izquierdo se observó aumento y mayor desarollo de las uniones adherens y desmosomas; en el ovario derecho los mismos disminuyeron por acción de 17 Beta-estradiol. La respuesta del ovario izquierdo a la progesterona y testoterona fue similar a la obtida con estrógeno. En la gónada derecha no se observaron cambios. En ambos ovarios se produjo una dismunucíon de las uniones intercelulares por accíon de FSH. Los cambios producidos por LH y hCG fueron semejantes a los encontrados en el ovario izquierdo por efecto del estrógeno, consistentes en un incremento de los complejos de uníon, principalmente los de tipo adherens. Estos análisis indican que las hormonas esteroideas y gonadotróficas actúan modificando las uniones intercelulares y participarían en los procesos de crecimiento y atrofia que ocurren en los ovarios del embríon de pollo.