Protective Effects and Mechanisms of Huangqi Decoction Against Radiation-Induced Bystander Effects / Efectos Protectores y Mecanismos de la Decocción de Huangqi Contra los Efectos Secundarios Inducidos por la Radiación

SUMMARY: The 12C6+ heavy ion beam irradiation can cause bystander effects. The inflammatory cytokines, endocrine hormones and apoptotic proteins may be involved in 12C6+ irradiation-induced bystander effects. This study characterized the protective effects and mechanisms of Huangqi decoction (HQD) against 12C6+ radiation induced bystander effects. Wistar rats were randomly divided into control, 12C6+ heavy ion irradiation model, and high-dose/medium-dose/low-dose HQD groups. HE staining assessed the pathological changes of brain and kidney. Peripheral blood chemical indicators as well as inflammatory factors and endocrine hormones were detected. Apoptosis was measured with TUNEL. Proliferating cell nuclear antigen (PCNA) expression was determined with real-time PCR and Western blot.Irradiation induced pathological damage to the brain and kidney tissues. After irradiation, the numbers of white blood cells (WBC) and monocyte, and the expression of interleukin (IL)-2, corticotropin-releasing hormone (CRH) and PCNA decreased. The damage was accompanied by increased expression of IL-1β, IL-6, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) as well as increased neuronal apoptosis. These effects were indicative of radiation-induced bystander effects. Administration of HQD attenuated the pathological damage to brain and kidney tissues, and increased the numbers of WBC, neutrophils, lymphocyte and monocytes, as well as the expression of IL-2, CRH and PCNA. It also decreased the expression of IL-1β, IL-6, CORT and ACTH as well as neuronal apoptosis. HQD exhibits protective effects against 12C6+ radiation-induced bystander effects. The underlying mechanism may involve the promotion of the production of peripheral blood cells, inhibition of inflammatory factors and apoptosis, and regulation of endocrine hormones.

La irradiación con haz de iones pesados 12C6+ puede provocar efectos secundarios. Las citoquinas inflamatorias, las hormonas endocrinas y las proteínas apoptóticas pueden estar involucradas en los efectos secundarios inducidos por la irradiación 12C6+. Este estudio caracterizó los efectos y mecanismos protectores de la decocción de Huangqi (HQD) contra los efectos externos inducidos por la radiación 12C6+. Las ratas Wistar se dividieron aleatoriamente en grupos control, modelo de irradiación de iones pesados 12C6+ y grupos de dosis alta/media/baja de HQD. La tinción con HE evaluó los cambios patológicos del cerebro y el riñón. Se detectaron indicadores químicos de sangre periférica, así como factores inflamatorios y hormonas endocrinas. La apoptosis se midió con TUNEL. La expresión del antígeno nuclear de células en proliferación (PCNA) se determinó mediante PCR en tiempo real y transferencia Western blot. La irradiación indujo daños patológicos en los tejidos cerebrales y renales. Después de la irradiación, disminuyó el número de glóbulos blancos (WBC) y monocitos, y la expresión de interleucina (IL)-2, hormona liberadora de corticotropina (CRH) y PCNA. El daño estuvo acompañado por una mayor expresión de IL-1β, IL-6, corticosterona (CORT) y hormona adrenocorticotrópica (ACTH), así como un aumento de la apoptosis neuronal. Estas alteraciones fueron indicativas de efectos inducidos por la radiación. La administración de HQD atenuó el daño patológico a los tejidos cerebrales y renales, y aumentó el número de leucocitos y monocitos, así como la expresión de IL-2, CRH y PCNA. También disminuyó la expresión de IL-1β, IL-6, CORT y ACTH, así como la apoptosis neuronal. HQD exhibe mecanismos protectores contra los efectos externos inducidos por la radiación 12C6+. El mecanismo subyacente puede implicar la promoción de la producción de células sanguíneas periféricas, la inhibición de factores inflamatorios y la apoptosis y la regulación de hormonas endocrinas.

Efectos de los opioides en endocrinología / Opioids effects in endocrinology

El uso de opioides ha aumentado en forma significativa en las últimas décadas, lo que nos ha permitido conocer sus diversos efectos en el sistema endocrino. Estos efectos están sub diagnosticados, en parte porque los síntomas se confunden con los de la misma enfermedad que lleva al uso de opioides y porque no los buscamos de forma dirigida. El hipogonadismo y la insuficiencia suprarrenal son sus efectos más establecidos, sin embargo, otros efectos como los provocados en el tejido óseo requieren de especial atención. La evaluación de los ejes gonadotropo, adrenal y de la salud ósea debe tenerse en consideración en los usuarios crónicos de opioides, particularmente frente a la presencia de síntomas. La suspensión o reducción del uso de opioides es el primer tratamiento del compromiso endocrinológico.

The use of opioids has increased significantly in recent decades, which has allowed us to understand its effects on the endocrine system. These effects are underdiagnosed, the symptoms are confused with those of the same disease that leads to the use of opioids and we do not look for them in a targeted way. Hypogonadism and adrenal insufficiency are its most established effects, however, other effects such as the ones caused on bone tissue require special attention. Evaluation of gonadotropic and adrenal axes as well as bone health should be taken into consideration in chronic opioid users, particularly in the presence of symptoms. Stopping or reducing opioid use is the first treatment for endocrine compromise.

Expression analysis of vasa in Asian paddle crab (Charybdis japónica) exposed to Bisphenol A

Background: Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) with a weak estrogen-like activity in fish that is found ubiquitously in aquatic environments. However, there has been little study about BPA on the endocrine disrupting effects of crab. In the present study, cDNA of vasa was cloned and characterized in the Charybdis japonica. Histological structures of testis and expression patterns of vasa gene in the testis of C. japonica after treatment with BPA were investigated. Results: The cDNA of vasa is composed of 3051 bp with a 2166 bp open reading frame encoding 721 AA. The deduced amino acid sequence contained eight conserved domains of the DEAD-box protein family. The tissue distribution showed that vasa mRNA was specifically expressed in ovary and testis. Histologically, the sperm cells were decreased in number and an acellular zone was seen in the testis. The transcript level of vasa gradually increased with a significant difference between the experimental and control groups. After BPA exposure with 0.50 and 1.00 mg/L for 1,3, 6 and 9 d, the expression levels of vasa increased. Conclusion: These findings suggest that BPA can increase the expression level of vasa mRNA and influence the development of the testis in C. japonica.

Effect of etomidate and propofol induction on hemodynamic and endocrine response in patients undergoing coronary artery bypass grafting/mitral valve and aortic valve replacement surgery on cardiopulmonary bypass.

Introduction: The concerns for induction of anaesthesia in patients undergoing cardiac surgery include hemodynamic stability, attenuation of stress response and maintenance of balance between myocardial oxygen demand and supply. Various Intravenous anaesthetic agents like Thiopentone, Etomidate, Propofol, Midazolam, and Ketamine have been used for anesthetizing patients for cardiac surgeries. However, many authors have expressed concerns regarding induction with thiopentone, midazolam and ketamine. Hence, Propofol and Etomidate are preferred for induction in these patients. However, these two drugs have different characteristics. Etomidate is preferred for patients with poor left ventricular (LV) function as it provides stable cardiovascular profile. But there are concerns about reduction in adrenal suppression and serum cortisol levels. Propofol, on the other hand may cause a reduction in systemic vascular resistance and subsequent hypotension. Thus, this study was conducted to compare induction with these two agents in cardiac surgeries. Methods: Baseline categorical and continuous variables were compared using Fisher’s exact test and student’s t test respectively. Hemodynamic variables were compared using student’s t test for independent samples. The primary outcome (serum cortisol and blood sugar) of the study was compared using Wilcoxon Rank Sum test. The P value less than 0.05 was considered significant. Results: Etomidate provides more stable hemodynamic parameters as compared to Propofol. Propofol causes vasodilation and may result in drop of systematic BP. Etomidate can therefore be safely used for induction in patients with good LV function for CABG/MVR/AVR on CPB without serious cortisol suppression lasting more than twenty-four hours.

Vitamina D y cáncer: acción antineoplásica de la 1α, 25(OH)2 -vitamina D3 / Vitamin D and cancer: antineoplastic effects of 1α,25(OH)2-vitamin D3

La forma hormonalmente activa de la vitamina D, 1α,25(OH)2-vitamina D3 (1α,25(OH)2D3), además de desempeñar un rol crucial en el mantenimiento de la homeostasis de calcio en el cuerpo, también regula el crecimiento y la diferenciación de diferentes tipos celulares, incluyendo células cancerosas. Actualmente hay numerosos estudios que investigan los efectos de la hormona en estas células, debido al interés en el uso terapéutico del 1α,25(OH)2D3 y de análogos con menor actividad calcémica para el tratamiento o prevención del cáncer. En este trabajo de revisión se describe el sistema endocrino de la vitamina D, su mecanismo de acción, su acción antineoplásica y se provee información sobre los últimos avances en el estudio de nuevos análogos de la hormona con menos actividad calcémica para el tratamiento del cáncer.

The hormonal form of vitamin D, 1α,25(OH)2-vitamin D3 (1α,25(OH)2D3), in addition of playing a central role in the control of calcium homeostasis in the body, regulates the growth and differentiation of different cell types, including cancer cells. At present several epidemiologic and clinical studies investigate the effect of the hormone in these cells due to the interest in the therapeutic use of 1α,25(OH)2D3 and analogues with less calcemic activity for prevention or treatment of cancer. This review describes vitamin D endocrine system, its mechanism of action, its antineoplastic activity and provides information about the latest advances in the study of new hormone analogues with less calcemic activity for cancer treatment.

The effects of 4-nonylphenol contamination on livers of Tilapia fish (Oreochromus spilurs) in Jeddah

Alkylphenol polyethoxylates is a group of estrogenic compounds. Natural or synthetic types of these compounds react with the endocrine system by binding hormone receptors, resulting in interference with their action, which is why they are called endocrine disrupting chemicals. Among their hydrolytic products are nonylphenols (NP), which are considered pollutants of aquatic environments. The objective of this study was to evaluate the pathological alterations on liver tissue of fish exposed to these compounds for long durations, starting from beginning of life and during the period of sexual maturity. Tilapia fish were obtained from Abhur fish farms, reared in the laboratory in special basins, and divided into two groups. The first maternal group was untreated and their larvae were divided into three sub-groups: control; exposed to 15μg/L; and exposed to 30 μg/L. The second maternal group was divided into 2 sub-groups: with larvae exposed to 15μg/L; and with their larvae exposed to 30 μg/L. Larvae and mother exposed to different concentrations of NP (15 and 30 μg/L) showed an increased accumulation of NP in both livers and muscles compared to the control group due to bioaccumulation. Tissue section examinations of the treated group (15 μg NP /L) showed disruption of liver architecture, with lyses, loss of nuclei, necrosis, and fatty infiltration. The changes were more marked in tissues exposed to (30 μg NP /L). Although this pollution was not lethal, its effect may be reflected in vital activities and in the economy.

Endophenotypes and serotonergic polymorphisms associated with treatment response in obsessive-compulsive disorder

OBJECTIVES: Approximately 40-60% of obsessive-compulsive disorder patients are nonresponsive to serotonin reuptake inhibitors. Genetic markers associated with treatment response remain largely unknown. We aimed (1) to investigate a possible association of serotonergic polymorphisms in obsessive-compulsive disorder patients and therapeutic response to selective serotonin reuptake inhibitors and (2) to examine the relationship between these polymorphisms and endocrine response to intravenous citalopram challenge in responders and non-responders to serotonin reuptake inhibitors and in healthy volunteers. METHODS: Patients with obsessive-compulsive disorder were classified as either responders or non-responders after long-term treatment with serotonin reuptake inhibitors, and both groups were compared with a control group of healthy volunteers. The investigated genetic markers were the G861C polymorphism of the serotonin receptor 1Dβ gene and the T102C and C516T polymorphisms of the serotonin receptor subtype 2A gene. RESULTS: The T allele of the serotonin receptor subtype 2A T102C polymorphism was more frequent among obsessive-compulsive disorder patients (responders and non-responders) than in the controls (p<0.01). The CC genotype of the serotonin receptor subtype 2A C516T polymorphism was more frequent among the non-responders than in the responders (p<0.01). The CC genotype of the serotonin receptor subtype 1Dβ G681C polymorphism was associated with higher cortisol and prolactin responses to citalopram (p<0.01 and p<0.001, respectively) and with a higher platelet-rich plasma serotonin concentration among the controls (p<0.05). However, this pattern was not observed in the non-responders with the same CC genotype after chronic treatment with serotonin reuptake inhibitors. This CC homozygosity was not observed in the responders.

Triorganotin as a compound with potential reproductive toxicity in mammals

Organotin compounds are typical environmental contaminants and suspected endocrine-disrupting substances, which cause irreversible sexual abnormality in female mollusks, called "imposex". However, little is known about the capability of triorganotin compounds, such as tributyltin and triphenyltin, to cause disorders in the sexual development and reproductive functions of mammals, including humans and rodents. Moreover, these compounds can act as potential competitive inhibitors of aromatase enzyme and other steroidogenic enzymes, affecting the reproductive capacity of male and female mammals. In this review, we discuss the cellular, biochemical, and molecular mechanisms by which triorganotin compounds induce adverse effects in the mammalian reproductive function.

Secuelas Endocrinológicas del Tratamiento de las Enfermedades Oncológicas en la Infancia y Adolescencia / Endocrinological schools of the Treatment of Oncological Diseases in Childhood and Adolescence

Los avances en el tratamiento de las enfermedades oncológicas en la infancia y adolescencia han permitido que la tasa de sobrevida en niños tratados por cáncer aumente progresivamente. Alrededor del 70% de los pacientes pediátricos tratados por tumores del SNC, el 80% por leucemias linfoblásticas agudas y más del 90% por linfoma de Hodgkin sobreviven a los mismos. Los trastornos endocrinos de los diferentes ejes se observan en un alto porcentaje de los sobrevivientes, debido a afecciones producidas por la enfermedad de base, el tratamiento o intercurrencias. Muchas de estas anomalías pueden sobrevenir años o décadas luego del tratamiento. La terapéutica de estas enfermedades comprende diferentes esquemas incluyendo cirugía, quimioterapia y radioterapia. Estos intensos esquemas de tratamiento pueden tener como consecuencia la aparición de diversas secuelas; 40% de los pacientes tratados por enfermedades oncológicas en la infancia va a tener alguna secuela endocrina relacionada con la enfermedad de base, la cirugía, la radio y/o quimioterapia; dependiente de la edad al inicio de la enfermedad y/o tratamiento, el género y el tiempo transcurrido desde la finalización del tratamiento. Postradioterapia craneal el orden de alteración de los ejes es 1) eje somatotrófico, 2) eje gonadotrófico, 3) eje adrenocorticotrófico y 4) eje tiroideo. La radio y quimioterapia pueden producir daño gonadal primario siendo el epitelio germinal del varón el más susceptible. La recuperación a medida que se aleja de la finalización del tratamiento es infrecuente, pero posible. Es de suma importancia conocer las posibles alteraciones con el objeto de realizar un adecuado control de los pacientes, durante su infancia y adolescencia y en la vida adulta. Con este fin se recomienda: • Una observación semestral del crecimiento y desarrollo puberal, en todos los niños tratados por neoplasia maligna, hasta que alcancen su estatura adulta y completen su desarrollo sexual. Se deberá prestar especial atención al inicio precoz de los signos puberales y a la falta de aparición de los mismos dentro del rango de edad esperado. • Un control anual de la función tiroidea, que incluya los valores de TSH y hormonas tiroideas, examen clínico con palpación de la glándula y ecografía. • El nivel de cortisol matinal debe ser determinado anualmente por un período de hasta 15 años luego de la finalización del tratamiento oncológico.

Most children diagnosed with a malignancy may now be expected to become long term survivors. The overall survival rate for childhood cancers is greater than 70% for pediatric central nervous system tumors, 80% for acute lymphoblastic leukemia and exceeds 90% for those diagnosed with Hodgkin´s disease. Endocrine sequelae, ranging from 20 to 50%, have been documented in these children, related to the underlying condition, the nature and dosage of cytotoxic chemotherapy and the amount and schedule of irradiation. Long term effects affecting the endocrine system represent a frequent complication of treatment and many of these endocrine disturbances could develop several years after the completion of treatment schedules. Several factors as age at which treatment was initiated, the length of time since treatment and gender modified these long term late effects. There is a strong association between the total radiation doses and pituitary hormone deficiencies. The growth hormone axis is the most sensitive followed by the gonadotropic and thyrotropic axes. Radio and chemotherapy cause male and female gonadal dysfunction Patients at risk of developing endocrinologic sequelae must be identified and monitored closely to assess the magnitude of any late effects in order to prevent associated morbidity. The following are the recommendations of the Children´s Oncology Group for the surveillance of these group of patients: • Semi-annual screening of growth in all children. Pubertal onset and tempo should be assessed to detect precocious, early, late puberty or gonadal failure. • Annual screening including clinical examination and levels of T4 and TSH. • Serum cortisol levels should be obtained yearly until 15 years off therapy.

A treatise on hazards of endocrine disruptors and tool to evaluate them.

Hormones mediate a major part of our essential physiological functions. Both endogenous and exogenous compounds and their metabolites are known to act through hormone receptors leading to regulation of endocrine function. The endogenous ligands that control reproductive functions are generally steroids such as 17beta-estradiol, androgens, progesterone, pregnenolone and glucocorticoids. However, exogenous compounds that are structurally and functionally similar gain entry into animals including humans through the diet or by occupational exposures, causing endocrine disruption. In the recent decade, there is a lot of apprehension about the so-called "endocrine disruptors" which are wide spread in the environment, mainly due to unrestricted human activity. These compounds of anthropogenic or natural origin mimic the action of sex hormones and can interfere with the endocrine system. It has been hypothesized that environmental exposure to synthetic estrogenic chemicals and related endocrine active compounds may be responsible for malformations in the male reproductive tract, crytorchidism, hypospadias, decrease in sperm counts, decreased male reproductive capacity and even testicular cancers. The increasing concern in both public and scientific communities about these abnormalities have prompted the initiation of epidemiological studies to not only identify, but to also analyze the short and long term effects of endocrine disruptors. As a result, a number of assays have been developed and are undergoing validation aimed at high throughput screening of chemical agents that disrupt endocrine activity. This review consolidates the findings of epidemiological studies, particularly in relation to male reproductive disorders and brings to light the various types of in vitro and in vivo models that are available for tiered testing of suspected compounds.

Effects of medical therapy, alcohol, smoking, and endocrine disruptors on male infertility

A infertilidade afeta até 15% da população sexualmente ativa e em 50% dos casos, o fator masculino está envolvido, como problema primário ou em combinação com causas de origem feminina. Como muitas drogas comumente encontradas e medicações podem ter efeitos deletérios na infertilidade masculina, a avaliação médica deve incluir uma discussão sobre o uso de drogas recreacionais e ilícitas, medicamentos e outras substâncias podem prejudicar a fertilidade. Com o conhecimento de quais drogas e medicamentos podem ser prejudiciais à fertilidade talvez seja possível mudar os hábitos ou a posologia das medicações para diminuir os efeitos adversos na fertilidade e aumentar as chances de engravidar com sucesso. Preocupações referentes ao desenvolvimento sexual masculino e reprodução tem mudado para a pior nos últimos 30-50 anos. Embora alguns relatos não demonstrem modificações, outros sugerem que a concentração espermática esteja diminuindo e que a incidência de anormalidades do desenvolvimento como hipospádia e criptorquidia parecem estar aumentando, assim como a incidência de câncer de testículo. Estas preocupações sobre a possibilidade do ambiente estar contaminado com substâncias químicas - naturais ou sintéticas - que podem interagir com o sistema endócrino.

Behavioural and mdocrine response to melatonin and bromazepam in normal and ovariectommized rats

The behavioral and hormonal effects of melatonin [0.3 mg/kg] and bromazepam [0.3 mg/kg] were determined in normal and ovariectomized rats. The drugs were given orally twice daily for two weeks. Behavioral study was assessed using the open field test. Prolactin [Prl.], follicle stimulating hormone [FSH] and luteinizing hormone [LH] plasma levels were determined

Trastornos endocrinos en el paciente VIH+/SIDA / Endocrine disturbances in the HIV+/AIDS patient

En el paciente VIH+/Sida se producen diversas alteraciones en el sistema endocrino, siendo los mecanismos involucrados: infección por el VIH, neoplasias, infecciones oportunistas y el síndrome consuntivo general. Las alteraciones en general son subclínicas y sólo evidentes en estadios avanzados de la infección por el VIH. En esta revisión además se alerta al clínico respecto a medicamentos usados en estos pacientes y que pueden condicionar alteraciones en la esfera endocrinológica

Efectos endócrinos de la hipnosis con tiopental sódico en los perros / Endocrine effects of thiopental anaesthesia in dogs

se estudiaron los efectos endócrinos de la hipnosis con tiopental sódico (TPS) en perros con respiración espontánea (RE) y controlada mecánicamente (RC) durante tres horas. Se emplearon 18 perros divididos en tres grupos: 1-controles no anestesiados (CNA). 2-anestesiados con TPS y RE y 3-anestesiados con TPC y RC. Se controló la: tensión arterial media, frecuencia cardíaca, frecuencia respiratoria y temperatura rectal. Se efectuaron extracciones de sangre antes de la inducción y luego periódicamente para controlar la glucemia y los niveles de: ácidos grasos no esterificados ACTH, cortisol, catecolaminas, insulina, T3, T4 junto con las concentraciones plasmáticas de TPS. También se monitoreó el pH, gases en sangre, exceso de base y bicarbonato standard. La técnica anestésica descrita con RE y RC no modificó los niveles séricos y plasmáticos de insulina, T3 y catecolaminas, pero provocó una disminución importante en los ácidos grasos no esterificados séricos y en las concentraciones de T4, sin embargo, no logró suprimir totalmente la respuesta tardía del eje hipófiso-suprarrenal al stress anestésico.