Effects of dexamethasone on the morphometry and biometry of immune organs of broiler chicken / Efectos de la dexametasona en la morfometría y biometría de los Órganos Inmunes del pollo de engorde

The study was conducted to examine the histological changes i.e. morphology and biometry of immune organs (thymus, spleen and bursa cloacalis or «Fabricius¼) of broilers in response to dietary dexamethasone (DEX). The day old chicks were obtained from the commercial hatchery and randomly divided into two groups i.e. control and experimental or treated group. The control group was reared on commercial broiler ration and the experimental group (n=25) was maintained on commercial broiler ration with corticosteroid (Dexamethasone-Decason, BP 0.5 mg, Opsonin @ 7 mg/kg feed). Samples (bursa cloacalis, spleen, and thymus) were collected from the ten control and ten experimental broilers at 14 and 28 days of experiment; then tissues were stained with Hematoxylin and Eosin. The biometric measurements of the samples were performed by the calibrated stage micrometer. Finally, the obtained data were analyzed using GraphPad Prism 8 software. In DEX treated group, the morphology of thymus, spleen and bursa cloacalis did not show any abnormal alterations. But their development rate was slower on visual inspection in DEX treated group. The length and width of bursal follicle of bursa cloacalis, thymic lobule of thymus and white pulp of spleen were statistically consisted but numerically decreased in DEX treated group than the control. The present findings suggested that DEX does not affect the histological architectures of immune organs except causing developmental arrest. Numerical decrease in the biometry of immune organs indicates that DEX causes apoptosis of immune cells in lymphoid organs of broiler.

El estudio se realizó para examinar los cambios histológicos, es decir, la morfología y la biometría de los órganos inmunes (timo, bazo y bolsa cloacal) de pollos de engorde en respuesta a la dexametasona en la dieta (DEX). Los pollitos de un día se obtuvieron de un criadero comercial y se dividieron aleatoriamente en dos grupos, control y experimental. El grupo control se crió con una ración comercial de pollos de engorde y el grupo experimental (n = 25) se mantuvo con una ración comercial de pollos de engorde con corticosteroides (DexamethasoneDecason, BP 0,5 mg, Opsonin @ 7 mg/kg). Se recogieron muestras (bolsa cloacal, bazo y timo) de los diez pollos del grupo control y diez del grupo de engorde experimental, a los 14 y 28 días de experimento. Luego, los tejidos se tiñeron con hematoxilina y eosina. Las mediciones biométricas de las muestras fueron realizadas con un micrómetro calibrado. Finalmente, los datos obtenidos se analizaron utilizando el software GraphPad Prism 8. En el grupo tratado con DEX, la morfología del timo, el bazo y la bolsa cloacal no mostraron alteraciones anormales. Pero su tasa de desarrollo fue más lenta en la inspección visual en el grupo tratado con DEX. La longitud y el ancho del folículo bursal de la bolsa cloacal, el lóbulo tímico del timo y la pulpa blanca del bazo fueron estadísticamente consistentes, pero disminuyeron numéricamente en el grupo tratado con DEX en relación al control. Los hallazgos actuales sugirieron que DEX no afecta la arquitectura histológica de los órganos inmunes, excepto que causa una detención del desarrollo. La disminución numérica en la biometría de los órganos inmunes indica que DEX provoca apoptosis de las células inmunes en los órganos linfoides de los pollos de engorde.

Effects on gastric mucosa induced by dental bleaching – an experimental study with 6% hydrogen peroxide in rats

The value of aesthetic dentistry has precipitated several developments in the investigation of dental materials related to this field. The free marketing of these products is a problem and it is subject to various interpretations regarding its legality. There are several techniques for tooth whitening, the most used one being the external bleaching. It is the later version of such technique that poses the greatest danger of ingesting the product. The present study analysed the systemic effect of these products when they are swallowed.Objective This experimental study aimed to observe the effects of a tooth whitening product, whose active agent is 6% hydrogen peroxide, on the gastric mucosa of healthy and non-tumour gastric pathology animals.Material and Methods Fifty Wistar-Han rats were used and then distributed into 5 groups, one for control and four test groups in which the bleaching product was administered in animals with and without non-tumour gastric pathology (induced by the administration of 1 sample of 50% ethanol and 5% of drinking water during 6 days) at different times of study by gavage. There was a decrease in body weight in animals of groups handled during the study period, which was most pronounced in IV and VA groups. Changes in spleen weight relative to body weight revealed no statistically significant changes. An analysis of the frequency was performed on the results of macroscopic observation of the gastric mucosa.Results The gastric mucosa revealed lesions in all manipulated groups, being more frequent in groups III and IV. It appears that there is a synergism when using hydrogen peroxide and 50% ethanol in the same group.Conclusion Therefore, it seems that there are some signs of toxicity 3 to 4 days after administration of 6% hydrogen peroxide. The prescription of these therapies must be controlled by the clinician and the risks must be minimized.

Morphometric alterations induced by the toxicity of variable sizes of silver nanoparticles / Alteraciones morfométricas inducidas por la toxicidad de diferentes tamaños de nanopartículas de plata

Silver nanoprticles (SNPs) are invested in medical, industrial and environmental applications. Little if any, is known about the morphometric alterations induced by the toxicity of SNPs. The aim of the present work is to find out the effect of variable size of SNPs on different morphometric parameters. Adult healthy male mice (BAL/C) were subjected to (10 nm, 20 nm, 40 nm 60 nm and 100 nm) SNPs for 35 days. Silver NPs caused non-significant decline on the average weight, significant decline in food consumption, increase in water intake, unilateral blindness, tanning fur color and cholestasis together with a decrease in the relative ratio of the liver, kidney and spleen weight to body weight. Mice subjected to 10 nm and 20 nm were more affected than mice receiving larger nanoparticles. These findings may indicate that SNPs could induce morphometric alterations that are size related wheresmaller SNPs have more impact than the larger ones.

Poco se sabe acerca de las alteraciones morfométricas inducidas por la toxicidad de las nanopartículas de plata (NPP). El objetivo fue investigar el efecto del tamaño variable de las NPP en diferentes parámetros morfométricos. Ratones machos adultos sanos (BAL/C) fueron sometidos a diferentes NPP de diferentes tamaños durante 35 días (10 nm, 20 nm, 40 nm 60 nm y 100 nm, respectivamente). Las NPP causaron una disminución no significativa del peso promedio, una disminución significativa en el consumo de alimentos, un aumento de la ingesta de agua, ceguera unilateral, cambios en el color de piel y colestasis junto con una disminución en el tamaño promedio del hígado, riñón y el peso del bazo, en relación al peso corporal. Los ratones sometidos a 10 nm y 20 nm fueron más afectados que los ratones que recibieron las nanopartículas más grandes. Estos resultados pueden indicar que las NPP podrían inducir alteraciones morfométricas que están relacionadas con el tamaño, en las cuales las NPP más pequeñas tienen un mayor impacto que las más grandes.

Assessment of nursing care using indicators generated by software / Avaliação da assistência de enfermagem utilizando indicadores gerados por um software / Evaluación de la asistencia de enfermería utilizando indicadores generados por un software

OBJECTIVE: to analyze the efficacy of the Nursing Process in an Intensive Care Unit using indicators generated by software. METHOD: cross-sectional study using data collected for four months. RNs and students daily registered patients, took history (at admission), performed physical assessments, and established nursing diagnoses, nursing plans/prescriptions, and assessed care delivered to 17 patients using software. Indicators concerning the incidence and prevalence of nursing diagnoses, rate of effectiveness, risk diagnoses, and rate of effective prevention of complications were computed. RESULTS: the Risk for imbalanced body temperature was the most frequent diagnosis (23.53%), while the least frequent was Risk for constipation (0%). The Risk for Impaired skin integrity was prevalent in 100% of the patients, while Risk for acute confusion was the least prevalent (11.76%). Risk for constipation and Risk for impaired skin integrity obtained a rate of risk diagnostic effectiveness of 100%. The rate of effective prevention of acute confusion and falls was 100%. CONCLUSION: the efficacy of the Nursing Process using indicators was analyzed because these indicators reveal how nurses have identified patients' risks and conditions, and planned care in a systematized manner. .

OBJETIVO: analisar a eficácia do Processo de Enfermagem em uma Unidade de Terapia Intensiva, utilizando indicadores gerados por um software. MÉTODO: estudo transversal, cujos dados foram coletados durante quatro meses. Enfermeiros e acadêmicos realizaram, diariamente, cadastro e anamnese (na admissão), exame físico, diagnósticos de enfermagem, planejamento/prescrição de enfermagem e avaliação da assistência de 17 pacientes, utilizando um software. Calculou-se os indicadores incidência e prevalência de diagnósticos de enfermagem, taxa de efetividade diagnóstica de risco e taxa de efetividade na prevenção de complicações. RESULTADOS: o Risco de desequilíbrio na temperatura corporal foi o diagnóstico mais incidente (23,53%) e o menos incidente foi o Risco de constipação (0%). O Risco de integridade da pele prejudicada foi prevalente em 100% dos pacientes, enquanto o Risco de confusão aguda foi o menos prevalente (11,76%). Risco de constipação e Risco de integridade da pele prejudicada obtiveram taxa de efetividade diagnóstica de risco de 100%. A taxa de efetividade na prevenção de confusão aguda e de queda foi de 100%. CONCLUSÃO: analisou-se a eficácia do Processo de Enfermagem utilizando indicadores, pois retratam como o enfermeiro tem identificado os problemas e riscos do paciente, e planejado a assistência de forma sistematizada. .

OBJETIVO: analizar la eficacia del Proceso de Enfermería en una Unidad de Terapia Intensiva, utilizando indicadores generados por un software. MÉTODO: estudio transversal, cuyos datos fueron recolectados durante cuatro meses. Enfermeros y académicos realizaron, diariamente, registro y anamnesis (en la admisión), examen físico, diagnósticos de enfermería, planificación/prescripción de enfermería y evaluación de la asistencia en 17 pacientes, utilizando un software. Se calculó los indicadores incidencia y prevalencia de diagnósticos de enfermería, la tasa de efectividad diagnóstica de riesgo y la tasa de efectividad en la prevención de complicaciones. RESULTADOS: el Riesgo de desequilibrio en la temperatura corporal fue el diagnóstico más prevalente (23,53%) y el menos prevalente fue el Riesgo de constipación (0%). El Riesgo de integridad de la piel perjudicada fue prevalente en 100% de los pacientes, en cuanto el Riesgo de confusión aguda fue el menos prevalente (11,76%). El Riesgo de constipación y el Riesgo de integridad de la piel perjudicada obtuvieron una tasa de efectividad diagnóstica de riesgo de 100%. La tasa de efectividad en la prevención de confusión aguda y de caída fue de 100%. CONCLUSIÓN: se analizó la eficacia del Proceso de Enfermería utilizando indicadores, ya que retratan cómo el enfermero ha identificado los problemas y riesgos del paciente, y planificado la asistencia de forma sistematizada. .

Evaluation of role of Glibenclamide and Aphanizomenon flos-aquae extract on Lymph Node and Spleen of Diabetic rats

Background: diabetes mellitus is a metabolic disorder in the endocrine system with a common biochemical manifestation, thus hyper-glycemia is a disturbed carbohydrate metabolism. This work aimed to evaluate the role of antidiabetic and hypoglycemic drug glibenclamide as a chemical agent and Aphanizomenon flos- aquae extract as a natural agent on lymphoid organs such as lymph nodes and spleen in the diabetic [type-2] white male albino rats

Material and methods: Fifty male albino rats were used and categorized into five groups; group 1: control [C], group 2: Alloxan induced diabetic rats [D] [150 mg/kg b .wt]; group 3: diabetic rats treated with daonil [D+Do][daonil 5 mg/kg b.wt/day]; group 4: Aphanizomenon flos-aquae extract [AFA][94.5mg/kg b.wt/day] and group 5: diabetic rats treated with Aphanizomenon flos -aquae extract[94.5mg/kg b.wt/day] [AFA+D]. All groups were dissected after 30 days of treatment. Lymph nodes and spleen samples were taken for histological and histochemical studies. Blood samples were taken for measurement of serum glucose and serum insulin level

Results: Diabetic male rats showed very highly significant increase in the serum glucose level, while non significant increase was recorded in the other treated groups in comparison with the control group.Diabetic male rats showed highly significant decrease in the serum insulin level as compared to the control group. Conversely, treatment of diabetic rats with daonil showed a significant increase in the levels of serum insulin. On the other hand non significant increase in the serum insulin was observed in AFA or AFA+D groups in comparison with the control group. Many histopathological and histochemical changes were observed in the lymph nodes and spleen of the diabetic rats, but using AFA extract succeeded to minimize the drastic changes which were observed in the lymph nodes and spleen of the diabetic rats more than that observed with glibenclamide

Conclusion: glibenclamide [daonil] as asynthetic drug and Aphanizomenon flos-aquae extract as a natural product ameliorated biochemical, histopathological and histochemical changes in the lymph nodes and splenic tissues of the diabetic rats.Aphanizomenon flos-aquae extract proved to be antidiabetic agent better than daonil drug and its antidiabetic action may be due to its anti-inflammatory, antioxidant and hypoglycemic action

Prenatal and developmental toxicity study of meclizine and caffeine combination in female albino wistar rats.

Meclizine and caffeine combination is used for the treatment of morning sickness. Both compounds are teratogenic and caffeine is known to possess anti-fertility activity also. The present study was undertaken to evaluate the reproductive toxic effect of meclizine and caffeine combination. Three doses were taken for the study; low dose (LD; meclizine 3.7 mg/kg and caffeine 3 mg/kg) was selected from commercially available formulation, middle dose (MD; meclizine 37 mg/kg and caffeine 30 mg/kg) and high dose (HD; meclizine 370 mg/kg and caffeine 300 mg/kg). The mixture was administered 1-7 days and 8-14 days for fertility and embryotoxic studies respectively. Laparotomy was done on 10th day of gestation period. Number of implants and corpora lutea were counted, pre and post-implantation losses were determined. In embryo toxicity study fetuses were evaluated for external, skeletal and visceral examination. High dose was removed from both fertility and embryotoxicity studies due to its severe toxicity to the dam. Significant anti-fertility activity was observed at middle dose. Embryotoxicity study showed significant reduction in fetal body weight, body length and body mass index, dam body weight gain on gestation day 14. Absolute kidney weight in MD and absolute and relative spleen weight in both LD and MD were significantly reduced. There was no increase in external or internal congenital anomalies at both LD and MD. The, results suggest that prescription of meclizine and caffeine for morning sickness in early pregnancy should be reviewed carefully.

Distribution and expression of visfatin-positive cells in the spleen of lipopolysaccharide-stimulated piglets / Distribución y expresión de células visfatin positivas en el bazo de lechones estimulados con lipopolisacáridos

The histological changes in the spleen and the immunohistochemical expression of visfatin in lipopolysaccharide-stimulated piglets are reported to examine the relation between visfatin and inflammation. The results are as follows: (1) After LPS treated, the spleen displayed thicker capsules and trabecula, the thinner periarterial lymphatic sheath, and the more expandable splenic sinusoid, with an increase in the number of splenic nodules, lymphocytes, ellipsoids of the marginal zone, red blood cells and macrophagocytes. (2) Visfatin-positive cells were mainly distributed in the red pulp of the spleen, with less in splenic nodules and periarterial lymphatic sheath. In the LPS-treated group, the signal intensity and quantity of the visfatin-positive cells were significantly higher in the red pulp and the ellipsoids of the spleen (P<0.01), whereas lower in the periarterial lymphatic sheath. These results indicate that LPS stimulation induces inflammation, causing the histological changes of the piglet spleen and activating humoral immune response. Moreover, variation of visfatin in the spleen suggests that lymphocytes and macrophages are the potent source of visfatin which participates in the humoral immune response in the inflammation.

Se presentan los cambios histológicos en el bazo y la expresión inmunohistoquímica de visfatin en lechones estimulados mediante lipopolisacáridos (LPS) con el objetivo de estudiar la relación entre visfatin e inflamación. Los resultados fueron los siguientes: (1) Después del tratamiento por LPS se observaron en el bazo cápsulas más gruesas y trabéculas, una vaina linfática periarterial más delgada, y más sinusoides esplénicos expandible, con un aumento en el número de nódulos esplénicos, linfocitos, elipsoides de la zona marginal, como también un aumento de las células rojas de la sangre y los macrofagocitos. (2) Las células visfatina-positivas se distribuyeron principalmente en la pulpa roja del bazo, con una cantidad menor en los nódulos esplénicos y la vaina linfática periarterial. En el grupo tratado con LPS, la intensidad de la señal y número de células positivas fueron significativamente mayor en la pulpa roja y los elipsoides del bazo (P<0,01), mientras que estas fueron menores en la vaina linfática periarterial. Estos resultados indican que la estimulación con LPS induce la inflamación provocando cambios histológicos del bazo de los lechones y la activación de la respuesta inmune humoral. Por otra parte, la variación de visfatin en el bazo sugiere que los linfocitos y los macrófagos son una fuente potente de visfatin en la respuesta inmune humoral de la inflamación.

Cáncer oral en Santiago de Cali, Colombia: análisis poblacional de la tendencia de incidencia y mortalidad / Oral cancer in Cali, Colombia: a population-based analysis of incidence and mortality trends

Objetivo. Describir la tendencia de las tasas de incidencia y mortalidad por cáncer oral (CaO) en Cali, Colombia durante el periodo 1962-2007. Material y métodos. Se obtuvieron las tasas estandarizadas por edad (población mundial) de incidencia (TIEE) y mortalidad (TMEE) por CaO con información del Registro Poblacional de Cáncer en Cali-Colombia (RPCC) y de la Secretaría de Salud Pública Municipal de Cali (SSPM), respectivamente. Se utilizó el porcentaje de cambio anual (APC) para describir la tendencia de las mismas. Resultados. Se registraron 1637 casos nuevos de CaO y la edad promedio al diagnóstico fue de 60 años. Las TIEE disminuyeron entre 1962-2007 en hombres APC= -1.3 (IC95%:-2.0; -0.6) y mujeres, APC= -1.0 (IC95%: -1.7; -0.4). Las TMEE disminuyeron entre 1984-2001 sólo en los hombres, APC= -2.8 (IC95%: -4.1; -1.5). Conclusión. La morbilidad y mortalidad por CaO ha disminuido de manera significativa en Cali, Colombia. El tipo de tumor asociado con estos cambios fue el carcinoma de células escamosas.

Objective. To describe the time trends of the incidence and mortality rates of oral cancer (OC) in Cali, Colombia between 1962-2007. Materials and methods. Age-standardized (Segi's world population) incidence (ASIR) and mortality (ASMR) rates for oral cancer were estimated using data from the Population-based Cancer Registry of Cali, Colombia and from the database of the Municipal Secretary of Public Health (MSPH) respectively. Annual percentage change (APC) was used to measure the changes in rates over time. Results. 1637 new cases of oral cancer were registered in the CPCR and the mean age upon diagnosis was 60 years. The ASIR decreased from 1962-2007 in men APC= 1.3 (IC95%:-2.0; -0.6) and women APC= -1.0 (IC95%: -1.7; -0.4).The ASMR decreased from 1984-2001 only in men, APC=2.8 (IC95%: -4.1; -1.5). Conclusions. There was a significant decrease in the incidence and mortality rates for OC in Cali, Colombia. The type of tumor associated to these changes was the squamous cell carcinoma.

In vivo redox effects of Aspidosperma quebracho-blanco Schltdl., Lantana grisebachii Stuck and Ilex paraguariensis A. St.-Hil. on blood, thymus and spleen of mice.

Argentinian native plants Aspidosperma quebracho-blanco, Lantana grisebachii and Ilex paraguariensis are known to have antiinflammatory and antioxidant properties. We demonstrated it in vivo by the redox changes in murine hemolymphatic tissues after infusive extract intake of these plants as revealed in organic trophism, tissue phenolics, hydroperoxides, superoxide, nitrites and γ-glutamyltranspeptidase in thymus, blood and spleen. A. quebracho-blanco reduced hydroperoxidation in blood and spleen of both sexes, with γ-glutamyltranspeptidase negativization in lymphatic organs and thymic nitrosative up-regulation. Males have shown increased phenolic content in blood after treatment. L. grisebachii and I. paraguariensis treatment exhibited incomplete antioxidation and oxidative induction in the studied tissues. Different results according to sex were found in redox response to phenolics and their kinetics, with males showing antioxidant effects, whereas females showed oxidative susceptibility. A. quebracho-blanco exhibited protection of murine tissues against oxidation in both sexes and modulation of their trophism, supporting its therapeutic uses in inflammatory diseases. Also, gender had significant influence in phenolic biodistribution and redox response.

Effect of gold nanoparticles on superoxide dismutase and indoleamine 2, 3-dioxygenase in various rat tissues.

Gold nanoparticles have diverse applications and are being used in food and cosmetic industry, for drug delivery and in the diagnosis and treatment of cancer. However there is a need to study their biochemical mode of action. In this study, in vivo effect of gold nanoparticles on the activities of the two antioxidant enzymes — superoxide dismutase (SOD) and indoleamine 2,3-dioxygenase (IDO) was investigated in various tissues of rats. Rats were injected with 20 μg/kg body wt of 20 nm gold nanoparticles for three consecutive days through intraperitoneal route. The animals were sacrificed by CO2 asphyxiation 24 h after the last dose of gold nanoparticles. Results showed that treatment with gold nanoparticles caused no significant change in SOD activity in most of the tissues, except kidneys. In kidneys, gold nanoparticles caused a significant increase in SOD activity, when compared to the activity in control rats. However, treatment with gold nanoparticles altered the expression pattern of SOD activity in various tissues. For example, in control rats highest SOD activity was demonstrated in heart and least in kidneys and spleen. But, in gold nanoparticles treated rats, maximum SOD activity was observed in liver and the lowest in spleen. Gold nanoparticles caused no significant change in IDO activity in the studied tissues.

Histopathological alterations induced by diazinon in rainbow trout [oncorhynchus mykiss]

Diazinon is a moderately persistent organ phosphorus pesticide largely used in agriculture. The purpose of this study was to evaluate the histopathological damages induced by diazinon in gills, kidney, spleen, and intestine tissues of rainbow trout, Oncorhynchus mykiss. The fishes were exposed to sub-lethal concentrations of diazinon [0.1 and 0.2 mg/L] for a period of 28 days. Tissues analyzed by a microscope were normal in the control group. The histological alterations in gills were characterized by epithelial hyperplasia, necrosis of epithelial filament and lamellar fusion, edema and curling of secondary lamellae. Glomerular lesions, shrinking of the glomerulus and enlargement of space inside Bowman's capsule, dwindling of the tubular lumen, degeneration and necrosis of renal tubules were observed in the kidney tissue of the exposed fish. The spleen tissue showed disorder in ellipsoids cellular and deposition hemosiderin in melanomacrophage centers. Exfoliate of mucosal epithelium, lymphocyte infiltration to lamina propria, reduction of the elastic properties and capillary bleeding were seen in intestine tissue of fish exposed to diazinon. In conclusion, these results indicate the existence of a direct relationship between the pollution of ecosystems by organ phosphorus pesticides such as diazinon and histopathological disorders in different tissues of exposed fishes

Preclinical studies for pharmacokinetics and biodistribution of Ad-stTRAIL, an adenovirus delivering secretable trimeric TRAIL for gene therapy

Malignant glioma is the most frequent type in brain tumors. The prognosis of this tumor has not been significantly improved for the past decades and the average survival of patients is less than one year. Thus, an effective novel therapy is urgently needed. TNF-related apoptosis inducing ligand (TRAIL), known to have tumor cell-specific killing activity, has been investigated as a novel therapeutic for cancers. We have developed Ad-stTRAIL, an adenovirus delivering secretable trimeric TRAIL for gene therapy and demonstrated the potential to treat malignant gliomas. Currently, this Ad-stTRAIL gene therapy is under phase I clinical trial for malignant gliomas. Here, we report preclinical studies for Ad-stTRAIL carried out using rats. We delivered Ad-stTRAIL intracranially and determined its pharmacokinetics and biodistribution. Most Ad-stTRAIL remained in the delivered site and the relatively low number of viral genomes was detected in the opposite site of brain and cerebrospinal fluid. Similarly, only small portion of the viral particles injected was found in the blood plasma and major organs and tissues, probably due to the brain-blood barrier. Multiple administrations did not lead to accumulation of Ad-stTRAIL at the injection site and organs. Repeated delivery of Ad-stTRAIL did not show any serious side effects. Our data indicate that intracranially delivered Ad-stTRAIL is a safe approach, demonstrating the potential as a novel therapy for treating gliomas.

Preclinical studies for pharmacokinetics and biodistribution of Ad-stTRAIL, an adenovirus delivering secretable trimeric TRAIL for gene therapy

Malignant glioma is the most frequent type in brain tumors. The prognosis of this tumor has not been significantly improved for the past decades and the average survival of patients is less than one year. Thus, an effective novel therapy is urgently needed. TNF-related apoptosis inducing ligand (TRAIL), known to have tumor cell-specific killing activity, has been investigated as a novel therapeutic for cancers. We have developed Ad-stTRAIL, an adenovirus delivering secretable trimeric TRAIL for gene therapy and demonstrated the potential to treat malignant gliomas. Currently, this Ad-stTRAIL gene therapy is under phase I clinical trial for malignant gliomas. Here, we report preclinical studies for Ad-stTRAIL carried out using rats. We delivered Ad-stTRAIL intracranially and determined its pharmacokinetics and biodistribution. Most Ad-stTRAIL remained in the delivered site and the relatively low number of viral genomes was detected in the opposite site of brain and cerebrospinal fluid. Similarly, only small portion of the viral particles injected was found in the blood plasma and major organs and tissues, probably due to the brain-blood barrier. Multiple administrations did not lead to accumulation of Ad-stTRAIL at the injection site and organs. Repeated delivery of Ad-stTRAIL did not show any serious side effects. Our data indicate that intracranially delivered Ad-stTRAIL is a safe approach, demonstrating the potential as a novel therapy for treating gliomas.

Induction of oxidative stress and histopathological changes by sub-chronic doses of triazophos.

The effect of triazophos (O, O-diethyl O-1-phenyl-1 H-1, 2, 4-triazol-3-yl phosphorothioate), a widely used insecticide was studied on the induction of oxidative stress and histological alterations at sub-chronic doses in male albino rats. Oral administration of triazophos at concentrations of 1.64, 3.2 and 8.2 mg/kg body wt for 30 days produced dose as well as time-dependent increase in the lipid peroxidation (determined by malondialdehyde levels) and glutathione-S-transferase (GST) activity in serum with a concomitant decrease in ferric reducing ability of plasma (FRAP) and blood glutathione (GSH) content. Histopathological examination of liver of triazophos-treated rats showed significant and progressive degenerative changes as compared to control, which could be due to induction of oxidative stress. However, no significant histopathological changes were observed in spleen, kidney and brain at either dose of triazophos with respect to control. These results indicated that oral administration of triazophos was associated with enhanced lipid peroxidation and compromised antioxidant defence in rats in dose and time-dependent manner. Thus the present study demonstrated for the first time the role of oxidative stress as the important mechanism involved in the stimulation of hepatic histo-architectural alterations at sub-chronic doses of triazophos in rats.

effect of MS14 on body weight, spleen index and structures of kidney, liver, spleen, lung, lymph node and bone marrow histology in Balb/c mice

MS 14 is an Herbal-marine preparation that has been used in experimental studies for the management of Multiple sclerosis, [MS]. In this study the effect of MS 14 on body weight, spleen index and the histological picture of various organs was evaluated. Female Balb/C mice of 6-8 weeks age were divided into control and test groups. MS 14 was orally administrated at a dose of 100 mg/kg for five days to the experimental group and normal saline given to the control group. After euthanasia on day six, the body weight was measured, spleen index was calculated and representative pieces of tissues including kidney, liver, spleen, lung, lymph node and bone marrow were collected in 10% formalin solution and processed through a standard paraffin embedding method. Sections of 5 micrometer thickness were cut and stained with hematoxylin and eosin. MS 14 at 100 mg/kg did not affect body weight and spleen index, but in the test group, at least 50% of spleen and 90% of lymph node micro sections showed lymphoid hyperplasia: no reactive changes were observed in controls. In both groups, histological evaluation of kidney, liver, spleen, lung, lymph node and bone marrow micro sections showed no significant histological alterations in the normal architecture. According to result of this study, it seems that although MS 14 has no effect on body weight and spleen index, it may induce hyperplastic changes in spleen and lymph nodes, thus signaling activation of the immune system

Immunoprotective role of cyanocobalamin [vitamin B-12] in heat-induced splenic white pulp damage in rats: an immunohistological study

To evaluate the immunoproteetive role of Gyanocobalomin on detrimental effects of heat induced stress on splenic white pulp T-cells [cellular immunity]. This experimental study was conducted in the Anatomy Department, BMSI, JPMC, Karachi from March 2009 to May 2009. Thirty male albino rats weighing about 180-200 grams were used and divided into three groups labeled A, B and C. Group A served as control. Group C received heat and protection with Cyanocobalmin at an intrapesitoneal dose of 0.8 mg / kg body weight per day before heat-induction. After 6 weeks of treatment animals were sacrificed. The blood samples were collected and assayed for plasma ACTH concentration by ELISA method. For immunohistochemistry 4-micron thick-formalin fixed paraffin- embedded splenic sections were obtained on polysine coated slides. Antigens were retrieved by HIER technique and stained with immunomarker anti-CD3 for the evaluation of T-Lymphocytes. Five - micron thick hacmatoxylin-eosin sections were prepared for other morphological details. Control group A reveals normal architecture of splenic white pulp. Heat induced group B showed atrophic white pulp and hypocellularity in all compartments. Cellular loss was largely due to apoptosis. Most of the splenic periarteriolar lymphoid sheaths and marginal zones contain clumps of apoptotic cells engulfed by tangible body macrophages. Protective group C shows comparable architecture with control. Plasma ACTH concentration in group B [67.63 +/- 0.69 pg/ml] statistically increased [P<0.001] compared to control group [23.94 +/- 0.87 pg/ml] and significantly changed [P<0.001] when compared with group C [34.71 +/- 1.24 pg/ml] Present study concludes that cyanocobalamin has substantial immunopotentiating effects on immune organs and cells of cellular immunity [T-lymphocytes] and it may compensate the detrimental effect of heat-stress on both humans and animals

Stress modulating antioxidant effect of Nardostachys jatamansi.

The rhizomes of Nardostachysjatamansi, the plant commonly known as Jatamansi have been described in Ayurveda for their soothing and sedative action on the central nervous system. In the present study, the anti-stress effect of hydroethanolic extract (70%) of N. jatamansi (NJE) was evaluated in reference to its antioxidant property. Wistar rats were divided into four groups: naive, stressed, and T-200 and T-500 stressed with oral pre-treatment of NJE 200 and 500 mg/kg, respectively. Restraint of rats in metallic chambers for 4 h at 4 degreesC was followed by sacrifice and assessment of stress-induced alterations in biochemical parameters, incidence and severity of ulcers. Lipid peroxidation (LPO) and NO levels in stomach and LPO, NO levels and catalase activity in brain, plasma corticosterone level and adrenal ascorbic acid were measured. In vitro antioxidant activity of NJE was studied by measuring the free radical scavenging activity. NJE showed potent antioxidant activity and significantly reversed the stress-induced elevation of LPO and NO levels and decrease in catalase activity in the brain. It inhibited the incidence of gastric ulcerations and reversed the alterations in biochemical parameters/markers of stress-induced gastric ulceration. NJE also significantly altered stress-induced increase in adrenal and spleen weights and decrease in level of ascorbic acid in adrenal gland. Elevation of plasma corticosterone level was negated dose- dependently. The findings suggest that the NJE possesses significant anti-stress activity, which may be due to its antioxidant activity.

Effects of zinc on morphology of erythrocytes and spleen in Carassius gibelio.

The influence of increased zinc concentrations (0.1, 0.5, 1.0, 1.5 and 2.0 mg(-1) ZnSO4 x 7H2O) on the total number and the morphology of the erythrocytes, as well as the processes related to their formation and destruction in the spleen of Carassius gibelio were investigated ex situ. It was found that zinc concentrations caused pathological alterations in the erythrocytes that were not identical in the different concentrations-poikilocytosis; ruptures in cell membranes in the concentrations of 0.5mg(-1) and 1.5 mg(-1); cells with double nuclei (symplasts); in the concentration of 1.0 mg(-1); in the highest concentrations (1.5 mg(-1) and 2.0 mg(-1)) presence of erythrocytes at initial stage of atypical mitotic division. Against the background of those various alterations, the total number of the erythrocytes in the peripheral blood increased simultaneously with the increase of zinc concentrations (p < 0.001). Morphological alterations in the spleen were also observed, indicating a compensational tendency against the toxic influence of zinc upon the fish erythrocytes-hyperplasia of the red pulp and lack of hemosiderin. These results show that the alterations in the total number and the morphology of the erythrocytes are connected with the relevant compensatory histopathological alterations in the spleen. The use of the ascertained alteration could be valuable in monitoring zinc-polluted waters.

Aspirin intake suppresses MMC-induced genotoxicity in mice.

The genotoxicity induced by mitomycin C (MMC) was found to be decreased by aspirin on alkaline single cell gel electrophoresis (SCG) assay in multiple organs of mice. Aspirin at doses of 0.5, 5 and 50 mg/kg and MMC at 2 mg/kg were administered and then liver, lung, kidney, spleen, colon and bone marrow were sampled after 3 h. Significant protective effects of aspirin against MMC-induced genotoxicity was observed in all but the bone marrow, where no change was evident. The results suggest that the radical scavenging ability of aspirin prevents danage by MMC-induced reactive oxygen species (ROS) in multiple organs.