ABSTRACT
BACKGROUND: Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated whether changes occur in brain structures. METHODS: Three groups of gerbils were used: control (1), orogastrically inoculated on day 3 after birth with trophozoites of two isolates of Giardia intestinalis (HGINV/WB) group (2 and 3). Estimates were made at five ages covering: establishment of infection, Giardia population growth, natural parasite clearance and a post-infection age. QuantiChrome zinc assay kit, cresyl violet staining and TUNEL technique were used. RESULTS: A significant decrease (p<0.01) in tissue zinc was observed and persisted after infection. Cytoarchitectural changes were observed in 75% of gerbils in the HGINV or WB groups. Ectopic pyramidal neurons were found in the cornus ammonis (CA1-CA3). At 60 and 90 days of age loss of lamination was clearly visible in CA1. In the dentate gyrus (DG), thinning of the dorsal lamina and abnormal thickening of the ventral lamina were observed from 30 days of age. In the cerebellum, we found an increase (p<0.01) in the thickness of the external granular layer (EGL) at 14 days of age that persisted until day 21 (C 3 ± 0.3 µm; HGINV 37 ± 5 µm; WB 28 ± 3 µm); Purkinje cell population estimation showed a significant decrease; a large number of apoptotic somas were observed scattered in the molecular layer; in 60 and 90 days old gerbils we found granular cell heterotopia and Purkinje cell ectopia. The pattern of apoptosis was different in the cerebellum and hippocampus of parasitized gerbils. CONCLUSION: The morphological changes found suggest that neuronal migration is affected by zinc depletion caused by giardiasis in early postnatal life; for the first time, the link between giardiasis-zinc depletion and damaged brain structures is shown. This damage may explain the psychomotor/cognitive delay associated with giardiasis. These findings are alarming. Alterations in zinc metabolism and signalling are known to be involved in many brain disorders, including autism.
Subject(s)
Cerebellum , Gerbillinae , Giardia lamblia , Giardiasis , Hippocampus , Zinc , Animals , Gerbillinae/parasitology , Zinc/deficiency , Zinc/metabolism , Giardiasis/parasitology , Giardiasis/pathology , Cerebellum/pathology , Cerebellum/parasitology , Hippocampus/pathology , Hippocampus/parasitology , Giardia lamblia/growth & development , Male , Disease Models, AnimalABSTRACT
Oleic acid (OA) is a monounsaturated compound with many health-benefitting properties such as obesity prevention, increased insulin sensitivity, antihypertensive and immune-boosting properties, etc. The aim of this study was to analyze the effect of oleic acid (OA) and some anticancer drugs against oxidative damage induced by nitropropionic acid (NPA) in rat brain. Six groups of Wistar rats were treated as follows: Group 1, (control); group 2, OA; group 3, NPA + OA; group 4, cyclophosphamide (CPP) + OA; group 5, daunorubicin (DRB) + OA; and group 6, dexrazoxane (DXZ) + OA. All compounds were administered intraperitoneally route, every 24 h for 5 days. Their brains were extracted to measure lipoperoxidation (TBARS), H2O2, Ca+2, Mg+2 ATPase activity, glutathione (GSH) and dopamine. Glucose, hemoglobin and triglycerides were measured in blood. In cortex GSH increased in all groups, except in group 2, the group 4 showed the highest increase of this biomarker. TBARS decrease, and dopamine increase in all regions of groups 4, 5 and 6. H2O2 increased only in cerebellum/medulla oblongata of group 5 and 6. ATPase expression decreased in striatum of group 4. Glucose increased in group 6, and hemoglobin increased in groups 4 and 5. These results suggest that the increase of dopamine and the antioxidant effect of oleic acid administration during treatment with oncologic agents could result in less brain injury.
Subject(s)
Antineoplastic Agents , Brain , Glutathione , Oleic Acid , Oxidative Stress , Rats, Wistar , Animals , Oxidative Stress/drug effects , Oleic Acid/pharmacology , Brain/drug effects , Brain/metabolism , Rats , Male , Glutathione/metabolism , Antineoplastic Agents/pharmacology , Hydrogen Peroxide/metabolism , Nitro Compounds/pharmacology , Dopamine/metabolism , Propionates/pharmacology , Cyclophosphamide , Lipid Peroxidation/drug effects , Daunorubicin/pharmacology , Thiobarbituric Acid Reactive Substances/metabolism , Adenosine Triphosphatases/metabolism , Antioxidants/pharmacologyABSTRACT
INTRODUCTION: Tuberculosis (TB) is an infectious, transmissible and immune disease caused by the Mycobacterium tuberculosis-complex (MTBC). Although osteoarticular tuberculosis (OATB) has been widely described, the ribcage variety remains a rare form. CASE REPORT: A thirteen-month-old male and a twenty-month-old female, both with pain and increased volume of anterolateral left rib cage were described. Physical examination revealed the presence of a soft consistent mass at the level of the 9th and 5th costal arches in the male and female patients respectively. Upon clinical evaluation, tuberculosis was suspected, which was confirmed by X-ray and histopathological studies. After confirmation, the management, based on anti-tuberculosis therapy was started as follows: nine months of anti-tuberculosis therapy for the male patient and fourteen months for the female. The outcomes were favorable for both patients. However, further interventions, consisting of abscess drainage in the male patient and excisional biopsy in the female patient were necessary. With these therapeutic interventions, to date, the patients are without any evidence of active TB.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Antitubercular Agents/therapeutic use , Drainage , Female , Humans , Infant , Male , Rib Cage , Tuberculosis/drug therapyABSTRACT
Tuberculosis (TB) remains a global problem and a diagnostic challenge, especially in pediatrics. The aim of this study was to describe the clinical, microbiological, radiological, and histopathological data of TB in children. A 7-year retrospective and descriptive cohort study that included 127 patients under 18 years of age with diagnosis of active TB was conducted from 2011 to 2018 in a pediatric hospital. Tuberculosis was microbiologically confirmed using Ziehl-Neelsen (ZN) staining, culture or polymerase chain reaction (PCR) in a total of 94 (74%) cases. Thirty-three cases were defined as probable TB based on tuberculin skin test result and epidemiological evaluation. The TB forms found were lymph node (39.3%), bone (15.7%), lung (13.6%), and meningeal TB (8.6%). The most common symptoms were fever (48.8%) and adenopathy (45.6%). History of contact was established in 34.6%. Positive ZN staining (sensitivity 30%) and culture (sensitivity 37%) were found in 29% and 37.7% of subjects, respectively. About 64.5% depicted abnormal chest X-ray. Xpert MTB/RIF® (PCR) was positive in 9.4% and biopsy was compatible in 52.7% of these samples. It is fundamental to have laboratory and epidemiological evaluation that support the diagnosis of the disease in children and thus, define its management; since, in most cases, early microbiologic confirmation is lacking.
Subject(s)
Hospitals, Pediatric , Tuberculosis , Adolescent , Child , Child, Preschool , Cohort Studies , Coloring Agents , Female , Humans , Male , Mexico/epidemiology , Mycobacterium tuberculosis/isolation & purification , Pathology, Molecular , Retrospective Studies , Sensitivity and Specificity , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis/pathology , Tuberculosis, Lymph Node/diagnosis , Tuberculosis, Lymph Node/epidemiology , Tuberculosis, Lymph Node/pathology , Tuberculosis, Meningeal/diagnosis , Tuberculosis, Meningeal/epidemiology , Tuberculosis, Meningeal/pathology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/pathologyABSTRACT
The aim of the present study was to determine the effect of sildenafil on dopamine, 5-hydroxyindol acetic acid (5-HIAA) and selected biomarkers of oxidative stress in the brain of hypoglycemic rats. The animals were treated intraperitoneally as follows: group 1 (control), saline solution; group 2, insulin (10 U per rat or 50 U kg-1); group 3, insulin + single dose of sildenafil (50 U kg-1 + 50 mg kg-1); group 4, insulin + three doses of sildenafil every 24 hours (50 U kg-1 + 50 mg kg-1). In groups 2, 3 and 4, insulin was administered every 24 hours for 10 days. Blood glucose was measured after the last treatment. On the last day of the treatment, the animals´ brains were extracted to measure the levels of oxidative stress markers [H2O2, Ca2+,Mg2+-ATPase, glutathione and lipid peroxidation (TBARS)], dopamine and 5-HIAA in the cortex, striatum and cerebellum/medulla oblongata by validated methods. The results suggest that administration of insulin in combination with sildenafil induces hypoglycemia and hypotension, enhances oxidative damage and provokes changes in the brain metabolism of biogenic amines. Administration of insulin and sildenafil promotes biometabolic responses in glucose control, namely, it induces hypoglycemia and hypotension. It also enhances oxidative damage and provokes changes in the brain metabolism of biogenic amines.
Subject(s)
Biogenic Amines/metabolism , Hypoglycemia/physiopathology , Oxidative Stress/drug effects , Sildenafil Citrate/toxicity , Animals , Blood Glucose/drug effects , Brain/drug effects , Brain/pathology , Dopamine/metabolism , Hydroxyindoleacetic Acid/metabolism , Insulin/administration & dosage , Insulin/pharmacology , Lipid Peroxidation/drug effects , Male , Rats , Rats, WistarABSTRACT
Las necesidades especiales en salud han sido definidas por la Asociación Americana de Odontopediatría como "toda condición o limitación física, del desarrollo, mental, sen- sorial, conductual, cognitiva o deterioro emocional que requiere tratamiento médico, intervención de atención de la salud, y/o el uso de servicios o programas especializados". Actualmente, los pacientes con necesidades especiales en salud presentan una mayor tasa de supervivencia y expectativas de vida mayores. Además, presentan una mayor preva- lencia y severidad de anomalías dento-maxilares que impactan negativamente su salud general y calidad de vida. La creciente preocupación de los padres y profesionales por el aspecto estético y funcional, ha llevado a un aumento en la demanda por tratamiento de ortodoncia, sin embargo, el acceso a él sigue siendo limitado. El objetivo de la presente revisión es describir según la literatura disponible, las consideraciones para el tratamiento ortodóncico en pacientes con necesidades especiales en salud. Se concluye que el tra- tamiento no debe ser denegado solo por presentar una discapacidad; no obstante, el compromiso de los padres y/o cuidadores con el tratamiento es crucial para el éxito. El tratamiento debe ser planificado en etapas, siendo la fase de adaptación a la atención de gran importancia. La longitud de tratamiento en estos pacientes, es similiar a la de individuos sanos, pero se requiere un mayor tiempo-sillón y los resultados obtenidos suelen ser inferiores. El tratamiento de ortodoncia puede mejorar la estética y función en pacientes con situación de discapacidad, facilitando su integración social e impactando positivamente en su calidad de vida
The American Academy of Pediatric Dentistry defines Special Health Care Needs as "any physical, developmental, mental, sensory, behavioral, cognitive, or emotional impair- ment condition or limitation that requires medical management, health care interven- tion, and/or the use of specialized services or programs". Currently, patients with special health needs present a higher survival rate and higher life expectancies. In addition, they present a higher prevalence and severity of malocclusion that negatively impact their general health and quality of life. The growing concern of parents and professionals for the aesthetic and functional aspect, has led to an increase in the demand for orthodontic treatment, however, the health care access still remains limited. A review of the availa- ble literature was performed aiming at describing the considerations in the orthodontic treatment of special health care needs patients. It is concluded that the treatment should not be denied just for presenting a disability. Notwithstanding, it is crucial for the treat- ment success parents and/or caregivers commitment. The treatment should be planned in stages, being of great importance the care adaptation phase. The overall treatment time is similar to those patients without special needs, but still requires longer armchair time and the results obtained are usually lower. Orthodontic treatment can improve aesthetics and function in patients with disabilities, facilitating their social integration and positively impact in their quality of life.
ABSTRACT
BACKGROUND & OBJECTIVE: The purpose of this study was to measure the effect on brain biomarkers after treatment with anticancer compounds - cytarabine (CT) and ferric carboxymaltose (FC) (Fe+3) in Wistar rats. METHODS: The Wistar rats were treated as follows: group 1 (control), NaCl 0.9%; group 2, CT (25 mg/k), group 3, FC(Fe+3) (50 mg/k) and group 4, CT + FC(Fe+3). The animals were sacrificed and their brains were obtained and used to measure lipoperoxidation (TBARS), H2O2, Na+, K+ ATPase, glutathione (GSH), serotonin metabolite (5-HIAA) and dopamine. The results indicated an enhancement of lipid peroxidation in the cortex and striatum of groups treated with FC(Fe+3) and CT, while GSH decreased in the cortex of group treated with CT + FC(Fe+3). Dopamine decreased in the cortex of the rats that received CT, while in the striatum, 5HIAA increased in all groups. RESULTS & CONCLUSION: These results suggest that the treatment with CT and FC(Fe+3) boosted oxidative stress and led to an alteration in momoamine concentrations in the brain.
Subject(s)
Brain/drug effects , Cytarabine/pharmacology , Ferric Compounds/pharmacology , Lipid Peroxidation/drug effects , Maltose/analogs & derivatives , Oxidative Stress/drug effects , Animals , Brain/metabolism , Dopamine/metabolism , Hydrogen Peroxide/pharmacology , Maltose/pharmacology , Oxidation-Reduction/drug effects , Rats, Wistar , Serotonin/metabolismABSTRACT
La fisura labio-palatina es la malformación congénita más común entre las anomalías craneofaciales y causa una serie de alteraciones a nivel funcional, fisiológico, estético y social. Una de las características comúnmente asociada a estos pacientes, es la hipoplasia maxilar severa producto de la gran resistencia opuesta por los tejidos cicatrizales de labio y paladar, como consecuencia de la cirugía primaria. Tradicionalmente, el tratamiento ha sido la cirugía ortognática convencional al término del crecimiento, sin embargo, este enfoque ha demostrado tener ciertas limitaciones. La distracción osteogénica mediante un distractor rígido externo ha resultado ser una buena alternativa para el manejo de estos pacientes, ya que permite la distracción gradual del maxilar y de los tejidos asociados, mejorando los resultados a corto y largo plazo. Se realizó una revisión de la literatura actual disponible con el objetivo de describir el alcance del tratamiento de la distracción osteogénica maxilar con distractor rígido externo en los pacientes con fisura labio-pala-tina e hipoplasia maxilar severa. Se concluye que la distracción osteogénica maxilar con distractor rígido externo es un procedimiento efectivo, confiable y relativamente estable, con mínimas complicaciones asociadas y que podría superar a la cirugía convencional en el manejo de pacientes que requieran un avance maxilar severo. Palabras clave: Osteogénesis por distracción; Labio leporino; Fisura del paladar; Maxilar (fuente: DeCS BIREME).
The cleft lip and palate is the most common congenital malformation among craniofacial anomalies and causes a series of functional, physiological, aesthetic and social altera-tions. One commonly characteristic associated with these patients is a severe maxillary hypoplasia as a result of the great resistance opposed by scar lip and palate tissue from a primary surgery. Traditionally, the suggested treatment has been conventional orthogna-thic surgery at the end of skeletal maturity. However, this approach has revealed certain limitations. Distraction osteogenesis using a rigid external distractor has shown to be a good alternative for these patients' treatment, since it allows the gradual distraction of the maxilla and the associated tissues, thereby improving the short and long term results. A review of the available literature was performed to describe the maxillary distraction os-teogenesis treatment scope using a rigid external distractor in cleft lip and palate patients with severe maxillary hypoplasia. It was concluded that maxillary distraction osteogenesis using a rigid external distractor is an effective, reliable and relatively stable procedure, with minimal associated complications. This could be a better alternative compared to conventional surgery for patients' care having severe maxillary hypoplasia. Keywords: Distraction osteogenesis; Cleft lip; Cleft palate; Maxilla (source: MeSH NLM).
ABSTRACT
OBJECTIVES: The purpose of this study was to measure the effect of oseltamivir and indomethacin on dopamine and 5-HIAA levels and some oxidative biomarkers in brain and stomach of young rats in conditions of infection. METHODS: Female Sprague Dawley rats in absence or presence of a live culture of Salmonella typhimurium (S.Typh), were treated as follows: PBS, group 1 (control); oseltamivir (100 mg/kg), group 2; indomethacin (67 µg/kg) group 3; oseltamivir (100 mg/kg) + indomethacin (67 µg/kg), group 4. The drugs were administered intraperitoneally every 24 hr for 5 days while S. Typh was give orally in the first and third day. C-reactive proteins was measured in blood on sacrifice, and from brain extract, dopamine and 5-HIAA levels as well as GSH, calcium, and H2O2 and total ATPase activity were measured by validated methods. RESULTS: Dopamine increased significantly in cortex and cerebellum/medulla oblongata of groups that received indomethacin and oseltamivir. 5-HIAA increased significantly in all groups that received S.Typh. H2O2 decreased significantly in cortex regions of animals that received oseltamivir and indomethacin in presence of S.Typh. Total ATPase increased significantly in cortex and hemispheres of groups that received oseltamivir as well as in cerebellum/medulla oblongata and stomach of animals that received oseltamivir and indomethacin combined with S.Typh. GSH increased and calcium decreased significantly in stomach of animals that received oseltamivir or indomethacin alone or combined with S.Typh. CONCLUSION: These results demonstrate the association between inflammatory response, oxidative stress, dopaminergic, and serotonergic metabolism in an experimental inflammatory animal model.
Subject(s)
Dopamine/metabolism , Hydroxyindoleacetic Acid/metabolism , Indomethacin/pharmacology , Oseltamivir/pharmacology , Oxidative Stress , Animals , Brain/microbiology , Disease Models, Animal , Female , Hydrogen Peroxide , Rats , Rats, Sprague-Dawley , Rats, Wistar , Salmonella typhimurium , Stomach/microbiology , Typhoid FeverABSTRACT
A number of drugs, like sibutramine, which are used clinically in weight control, act on serotonergic metabolism. However, their relation with zinc and free radical (FR) production in central nervous system remains unknown. This study aimed to evaluate the effect of sibutramine and zinc on FR production. Female Wistar rats (about 250 g) were used in this study. The animals received 400 µg/kg of zinc and 10 mg/kg of sibutramine intraperitoneally every 36 hr for 15 days. At the end of the study, the rats were killed and their brains used for the measurement of lipid peroxidation thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH), hydrogen peroxide (H(2) O(2) ), calcium and 5-hydroxyindole acetic acid (5-HIAA) levels, all by means of validated methods. Corporal weight and food consumption were found to be decreased in the zinc/sibutramine group. TBARS decreased in cortex, hemispheres and medulla oblongata. GSH decreased in cortex, hemispheres and cerebellum in the sibutramine group. Zinc given alone and in combination with sibutramine decreased H(2) O(2) concentration in cortex, hemispheres and cerebellum but increased calcium and 5-HIAA concentration in all brain regions. Our results suggest that sibutramine and zinc are associated with weight loss, an effect that was more pronounced in the group treated with both drugs. Reduction in oxidative stress may be involved in these effects.
Subject(s)
Appetite Depressants/pharmacology , Brain/metabolism , Cyclobutanes/pharmacology , Hydroxyindoleacetic Acid/metabolism , Lipid Peroxidation/drug effects , Zinc/pharmacology , Animals , Biomarkers/metabolism , Body Weight/drug effects , Calcium/metabolism , Energy Intake/drug effects , Female , Free Radicals/metabolism , Hydrogen Peroxide/metabolism , Oxidative Stress , Rats , Rats, Wistar , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
Introducción: Los variados cuadros clínicos que cursan con dolor orofacial, así como las repercusiones en la calidad de vida y la economía, tanto de los pacientes como de los organismos de atención de salud, hace que éstos requieran de un manejo multidisciplinario. Objetivo: Determinar la prevalencia de dolor orofacial como motivo de consulta maxilofacial en el Centro Médico San Joaquín de la Pontificia Universidad Católica de Chile. Material y método: Estudio descriptivo-retrospectivo del total de primeras consultas de Cirugía Maxilofacial entre los años 2007 y 2010. Se obtuvieron características demográficas y clínicas, generales y específicas para dolor orofacial. Resultados: De un total de 818 pacientes, 245 consultas (30 por ciento) fueron por dolor orofacial, de las cuales 174 (71 por ciento) correspondieron a dolor orofacial músculoesquelético. Conclusiones: La prevalencia de dolor orofacial en nuestro estudio fue de un 30 por ciento, cifra que se encuentra dentro de lo estimado en la literatura (1 por ciento a 55 por ciento), destacando el dolor músculoesquelético como el más prevalente. Un enfoque multidisciplinario se hace necesario dada la complejidad de estos pacientes.
Introduction: The varied clinical conditions that present with orofacial pain, and the impact on quality of life and economy of both the patients and health care agencies, make these require a multidisciplinary management. Objective: To determine the prevalence of orofacial pain as the reason for maxillofacial consultation to Centro Médico San Joaquín, Pontificia Universidad Católica de Chile. Material and Method: Retrospective descriptive study of all first consultations of Maxillofacial Surgery between 2007 and 2010. Clinic and demographic characteristics were obtained.Results: Of a total of 818 patients, 245 (30 per cent) consultations were for orofacial pain, of which 174 (71 per cent) were for musculoskeletal orofacial pain. Conclusions: The prevalence of orofacial pain found is similar to that reported in the literature. We found a high prevalence of neuropathic pain in this study. Specialized multidisciplinary approach is necessary for the management of this type of pathology, given the complexity in both the diagnosis and treatment.
Subject(s)
Humans , Male , Female , Adult , Facial Pain/epidemiology , Musculoskeletal Pain/epidemiology , Chile/epidemiology , Age and Sex Distribution , Retrospective Studies , Neuralgia/epidemiology , PrevalenceABSTRACT
There is increasing evidence that describes a histamine role in normal and cancer cell proliferation. To better understand the importance of histamine in breast cancer development, the expression of histamine H3 (H3R) and H4 (H4R) receptors and their association with proliferating cell nuclear antigen (PCNA), histidine decarboxylase (HDC) and histamine content were explored in mammary biopsies. Additionally, we investigated whether H3R and H4R were implicated in the biological responses triggered by histamine in MDA-MB-231 breast cancer cells. The expression levels of H3R, H4R, PCNA, HDC and histamine content were determined by immunohistochemistry in 40 benign and malignant lesions. MDA-MB-231 cells proliferation (clonogenic assay and BrdU incorporation) and cell cycle distribution (flow cytometry) were evaluated upon treatment with histamine, H3R and H4R agonists and antagonists. Apoptosis was determined by Annexin staining and TUNEL assay. Cell migration was assessed by transwell system. Results indicate that H3R was detected in 67% (10/15) of benign lesions and in almost all carcinomas (24/25), being the level of its expression significantly higher in carcinomas (p = 0.0016). The non-tumoral breast tissue surrounding carcinomas revealed a lower H3R expression compared to the tumor cells. Only 13% (2/15) of the benign lesions expressed H4R compared to 44% (11/25) of the carcinomas. Interestingly, H3R expression was correlated in carcinomas with the expression of HDC and PCNA (p < 0.0001), and also histamine content (p = 0.0229). Accordingly, histamine increased MDA-MB-231 cells proliferation and also migration via H3R. In contrast, activation of H4R inhibited proliferation and this effect was associated with an arrest in the G(0)/G(1) phase of the cell cycle and an induction of apoptosis. Present findings demonstrate the presence of H3R and H4R in human mammary tissue and suggest that H3R may be involved in the regulation of breast cancer growth and progression representing a novel molecular target for new therapeutic approach.
Subject(s)
Breast Neoplasms/etiology , Histamine/physiology , Receptors, G-Protein-Coupled/physiology , Receptors, Histamine H3/physiology , Receptors, Histamine/physiology , Adult , Aged , Breast/chemistry , Breast Neoplasms/drug therapy , Cell Movement/drug effects , Cell Proliferation/drug effects , Female , Histamine/analysis , Histidine Decarboxylase/analysis , Humans , Imidazoles/pharmacology , Middle Aged , Proliferating Cell Nuclear Antigen/analysis , Receptors, G-Protein-Coupled/analysis , Receptors, G-Protein-Coupled/drug effects , Receptors, Histamine/analysis , Receptors, Histamine/drug effects , Receptors, Histamine H3/analysis , Receptors, Histamine H3/drug effects , Receptors, Histamine H4 , Thiourea/analogs & derivatives , Thiourea/pharmacologyABSTRACT
The aim of this study was to evaluate the effect of 2,5-dihydroxybenzoic acid, a salicylate derived from Acetyl salicylic acid (ASA) and vitamin A (vit A) on Na(+), K(+) ATPase enzyme and GSH levels in brain of rats exposed to hyperoxia (Hyp) as oxidant protocol. Rats were treated as follow: group I (control), group II (Hyp), group III (Hyp, ASA), group IV (vit A), group V (Hyp, vit A), group VI (Hyp, vit A, ASA). Vit A was given 5 days before and during Hyp, aspirin at the end of Hyp. Na(+),K(+) ATPase and total ATPase activity was significantly increased in group V. Levels of GSH showed a significant increase in group III, besides, levels of 2,5-dihydroxybenzoic acid as salicylate in plasma were significantly increased in group II. These results elucidate differences in the biochemical response of animal towards intake of various types of antioxidant substances, with increased GSH and salicylate in hyperoxia.
Subject(s)
Antioxidants , Brain Chemistry/drug effects , Gentisates/pharmacology , Hyperoxia/drug therapy , Vitamin A/pharmacology , Animals , Female , Free Radicals/metabolism , Glutathione/metabolism , Hyperoxia/metabolism , Oxidative Stress/drug effects , Oxidative Stress/physiology , Rats , Rats, Sprague-Dawley , Salicylates/blood , Sodium-Potassium-Exchanging ATPase/metabolismABSTRACT
Histamine is a biogenic amine responsible for multiple biological actions including regulation of physiological functions of mammary gland. It has been postulated that histamine plays a critical role in proliferation of normal and cancer cells. To investigate the biological responses that histamine exerts in malignant cells derived from human mammary gland, we evaluated in MDA-MB-231 line the expression of histamine receptors, histamine intracellular content, the capacity of histamine to influence proliferation, cell cycle progression, differentiation and apoptosis. We also studied histamine involvement in cellular response to ionizing radiation. HBL-100 cells were used as control of non-tumorigenic breast cells. Proliferation and surviving fraction were assessed by clonogenic assay. Cell cycle progression and lipid accumulation were determined by flow cytometry while apoptosis was studied by Annexin V and DNA fragmentation assays. Both cell lines expressed the four histamine receptors subtypes as evaluated by western blot and RT-PCR analyses, and present endogenous histamine. Histamine regulated proliferation of cancer cells in a dose-dependent way and 10 microM histamine reduced significantly proliferation to 23% inducing cell cycle arrest in G(2)/M phase, differentiation by 26% and a significant increase in the number of apoptotic cells (p < 0.01). These responses were not observed in HBL-100 cells. Furthermore, 10 microM histamine exclusively enhanced the radiosensitivity of MDA-MB-231 cells. These results represent the first report about the expression of H3 and H4 receptors in human breast cells. In addition, we conclude that histamine exerts different effects on biological responses of normal and cancer breast cells representing a promising target for the development of more specific and less toxic cancer therapies.
Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/physiopathology , Histamine/pharmacology , Signal Transduction/physiology , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Division/drug effects , Cell Line, Tumor , DNA Primers , Female , Humans , RNA, Neoplasm/genetics , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effectsABSTRACT
En el uso clínico de medicamentos, se ha observado con frecuencia ineficacia terapéutica o toxicidad farmacológica, las cuales pueden presentarse en algunos individuos quienes reciben tratamiento farmacológico. Debido a la presencia de algunas enzimas metabolizantes de fármacos, los medicamentos pueden participar como sustratos inhibidores o inductores de dichas enzimas, la actividad de éstas varía entre los individuos. Esta variabilidad enzimática puede ser determinada por el análisis del ADN recombinante como son: el análisis de restricción del ADN genómico Fragmentos de Restricción de Longitud Polimórfica (RFLP), y la amplificación enzimática del ADN por la Reacción en Cadena de la Polimerasa (PCR). Esta tecnología se ha empleado en estudios clínicos que permiten conocer los mecanismos de las variaciones heredadas en las respuestas a los fármacos las cuales son reguladas por los genes de cada individuo de las diferentes razas, donde estas diferencias enzimáticas también pueden estar influenciadas por hábitos nutricionales o factores ambientales. Con este trabajo pretendemos presentar la importancia que tiene el conocimiento del metabolismo de los fármacos aplicado al manejo terapéutico de individuos que presentan ineficacia terapéutica o toxicidad farmacológica.
Subject(s)
Pharmacogenetics/trends , Polymorphism, Genetic/physiology , Pharmaceutical Preparations/metabolismABSTRACT
La biología molecular constituye hoy en día la punta de lanza dentro de las perspectivas diagnósticas y terapéuticas para el próximo milenio. Ni el médico clínico ni el investigador biomédico pueden permanecer ajenos a dichos acontecimientos, es por ello que hemos considerado importante revisar los aspectos sobresalientes y prácticos de esta rama de la ciencia, a través de una serie de artículos que hagan más familiar su comprensión, fundamentalmente para aquellos quienes no tienen acceso a la información especializada