Assessment of the acid phosphatase CP01850 from Corynebacterium pseudotuberculosis in DNA and subunit vaccine formulations against caseous lymphadenitis / Avaliação da fosfatase ácida recombinante CP01850 de Corynebacterium pseudotuberculosis em formulações vacinais de subunidade e de DNA contra a linfadenite caseosa

The target cp1002_RS01850 from Corynebacterium pseudotuberculosis was used to construct a DNA and recombinant subunit vaccine against caseous lymphadenitis. Recombinant protein rCP01850 was expressed in Escherichia coli using pAE vector, and DNA vaccine was engineered with pTARGET vector. BALB/c mice were divided in five groups containing eight animals each, inoculated with: pTARGET/cp01850 as DNA vaccine (G1); rCP01850 plus Al (OH)3 as recombinant subunit vaccine (G2); pTARGET/cp01850 and a boost with rCP01850 plus Al (OH)3 (G3); pTARGET (G4); or Al (OH)3 (G5). Mice were inoculated and blood samples were collected on days 0, 21, and 42 for the analysis of total IgG, IgG1 and IgG2a by ELISA. In each group, five animals were challenged with Mic-6 C. pseudotuberculosis strain, and three were used for cytokine quantification by qPCR. Although no group has been protected by vaccines against lethal challenge, G2 showed an increase in the survival rate after challenge. Significantly higher levels of IL-4, IL-12, IFN-γ, total IgG, IgG1 and IgG2a were also detected for G2, evidencing a mixed Th1/Th2 immunological profile. In conclusion, despite no protection level provided by different vaccinal strategies using cp1002_RS01850 from C. pseudotuberculosis, G2 developed a Th1/Th2 immune response with an increase in survival rate.(AU)

O alvo cp1002_RS01850 de Corynebacterium pseudotuberculosis foi utilizado para construir uma vacina recombinante de subunidade e de DNA contra a linfadenite caseosa. A proteína recombinante rCP01850 foi expressa em Escherichia coli usando o vetor pAE, e a vacina de DNA foi construída com o vetor pTARGET. Camundongos BALB/c foram divididos em grupos de oito animais, inoculados com: pTARGET/cp01850 como vacina de DNA (G1); rCP01850 e Al (OH)3 como vacina recombinante de subunidade (G2); pTARGET/cp01850 e um boost com rCP01850 e Al (OH)3 (G3); pTARGET (G4); ou Al (OH)3 (G5). Os animais foram inoculados e amostras de sangue foram coletadas nos dias 0, 21, e 42 do experimento para a análise de IgG total, IgG1 e IgG2a por ELISA. De cada grupo, cinco animais foram desafiados com a cepa Mic-6 de C. pseudotuberculosis, e três foram usados para a quantificação de citocinas por qPCR. Apesar de nenhum grupo ter sido protegido pelas vacinas testadas contra o desafio letal, G2 apresentou taxa de sobrevida e níveis de IL-4, IL-12, IFN-γ, IgG total, IgG1 e IgG2a significativamente mais altos, evidenciando um perfil imunológico misto Th1/Th2. Conclui-se que apesar das diferentes estratégias vacinais utilizando cp1002_RS01850 de C. pseudotuberculosis não terem sido capazes de gerar proteção, G2 desenvolveu uma resposta Th1/Th2 e elevou a taxa de sobrevida.(AU)

Condiciones de adsorción de un candidato vacunal basado en vesículas de membrana externa derivada de Salmonella Paratyphi A en adyuvantes de aluminio / Adsorption conditions of a vacunal candidate based on outer membrane vesicles of Salmonella Paratyphi A in aluminum adjuvants

La capacidad inmunoestimuladora de la mayoría de las vacunas es potenciada mediante la adsorción en adyuvantes que contienen aluminio. Variando las condiciones de adsorción (pH, tiempo de adsorción) cambia la cantidad de antígeno adsorbida y por lo tanto la capacidad de estimulación del sistema inmune. El Instituto Finlay de Vacunas investiga un nuevo candidato vacunal basado en vesículas de membrana externa de Salmonella Paratyphi A (VME-SPA). El objetivo de este trabajo fue determinar las condiciones de adsorción de las VME-SPA en dos adyuvantes de sales de aluminio (Al(OH)3 y AlPO4). Para ello, las VME-SPA fueron adsorbidas en ambos adyuvantes bajo diferentes condiciones de pH y tiempo. Mediante la construcción de una Isoterma de Langmuir se determinaron parámetros como la capacidad adsortiva (qm) y el coeficiente de adsorción (Kd). El lote de VME-SPA empleado estaba formado por poblaciones de nanoestructuras con un tamaño de partículas entre 60 y 100 nm. La adsorción de las VME-SPA en ambos adyuvantes, mostró valores ≥95 por ciento a pH neutro (6,5-7,0). Las VME-SPA en presencia de AlPO4 alcanzaron el estado de equilibrio en menor tiempo (99 por ciento a partir de 30 min) en comparación con Al(OH)3 (95 por ciento a partir de 3 h). Las isotermas evaluadas para ambos adyuvantes cumplieron con el modelo de Langmuir (R2≥0,99), con valores de qm y Kd diferentes entre los sistemas de adsorción. El estudio demostró que las VME-SPA se adsorbieron satisfactoriamente en ambos geles, proceso en el que están involucrados diferentes mecanismos de adsorción(AU)

The immunostimulation capacity of most vaccines is enhanced through antigen adsorption on aluminum adjuvants. The changes in adsorption conditions (pH, adsorption time), could change the amount of antigen adsorbed and therefore the ability to stimulate the immune system. The Finlay Institute of Vaccine researches a new vaccine candidate based on outer membrane vesicle from Salmonella Paratyphi A (OMV-SPA). The study aim was to determine adsorption condition of OMV-SPA with two aluminium adjuvants (Al(OH)3 and AlPO4). OMV-SPA was adsorbed in both adjuvants under differences conditions of pH and time. Parameters as adsorptive capacity (qm) and adsorption coefficient (Kd) were determined by construction of Langmuir Isotherm. The lot of OMV-SPA used is composed by population of nanostructure with a particle size between 60 and 100 nm. Adsorption of OMV-SPA in both adjuvants showed values ≥95 percent in neutral pH (6.5-7.0). OMV-SPA with AlPO4 got equilibrium state in less time (99 percent from 30 min) compared with Al(OH)3 (95 percent from 3 h). Isotherms from both adjuvants described Langmuir model (R2≥0.99), with qm and Kd values very different between adsorption systems. As conclusion, the study showed that OMV-SPA was adsorbed satisfactorily in both aluminium adjuvants, process in which are involved different adsorption mechanism(AU)

Effects of nanoparticles of hydroxy-aluminum phthalocyanine on markers of liver injury and glucose metabolism in diabetic mice

Photodynamic therapy, by reducing pain and inflammation and promoting the proliferation of healthy cells, can be used to treat recurrent lesions, such as diabetic foot ulcers. Studies using the photosensitizer phthalocyanine, together with the nanostructured copolymeric matrix of Pluronic® and Carbopol® for the treatment of diabetic foot ulcers and leishmaniosis lesions, are showing promising outcomes. Despite their topical or subcutaneous administration, these molecules are absorbed and their systemic effects are unknown. Therefore, we investigated the effect of the subcutaneous administration of the hydroxy-aluminum phthalocyanine hydrogel without illumination on systemic parameters, markers of liver injury, and liver energy metabolism in type 1 diabetic Swiss mice. Both the hydrogel and the different doses of phthalocyanine changed the levels of injury markers and the liver glucose release, sometimes aggravating the alterations caused by the diabetic condition itself. However, the dose of 2.23 µg/mL caused less marked plasmatic and metabolic changes and did not change glucose tolerance or insulin sensitivity of the diabetic mice. These results are indicative that the use of hydroxy-aluminum phthalocyanine hydrogel for the treatment of cutaneous ulcers in diabetic patients is systemically safe.

Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin

BACKGROUND The B subunit of Escherichia coli heat-labile enterotoxin (LTB) is a potent mucosal immune adjuvant. However, there is little information about LTB's potential as a parenteral adjuvant. OBJECTIVES We aimed at evaluating and better understanding rLTB's potential as a parenteral adjuvant using the fused R1 repeat of Mycoplasma hyopneumoniae P97 adhesin as an antigen to characterise the humoral immune response induced by this construct and comparing it to that generated when aluminium hydroxide is used as adjuvant instead. METHODS BALB/c mice were immunised intraperitoneally with either rLTBR1 or recombinant R1 adsorbed onto aluminium hydroxide. The levels of systemic anti-rR1 antibodies (total Ig, IgG1, IgG2a, and IgA) were assessed by enzyme-linked immunosorbent assay (ELISA). The ratio of IgG1 and IgG2a was used to characterise a Th1, Th2, or mixed Th1/Th2 immune response. FINDINGS Western blot confirmed rR1, either alone or fused to LTB, remained antigenic; anti-cholera toxin ELISA confirmed that LTB retained its activity when expressed in a heterologous system. Mice immunised with the rLTBR1 fusion protein produced approximately twice as much anti-rR1 immunoglobulins as mice vaccinated with rR1 adsorbed onto aluminium hydroxide. Animals vaccinated with either rLTBR1 or rR1 adsorbed onto aluminium hydroxide presented a mixed Th1/Th2 immune response. We speculate this might be a result of rR1 immune modulation rather than adjuvant modulation. Mice immunised with rLTBR1 produced approximately 1.5-fold more serum IgA than animals immunised with rR1 and aluminium hydroxide. MAIN CONCLUSIONS The results suggest that rLTB is a more powerful parenteral adjuvant than aluminium hydroxide when administered intraperitoneally as it induced higher antibody titres. Therefore, we recommend that rLTB be considered an alternative adjuvant, even if different administration routes are employed.

Subcutaneous Immunotherapy for Allergic Asthma in a Single Center of Korea: Efficacy, Safety, and Clinical Response Predictors

Allergen-specific immunotherapy is the only causal treatment for allergic diseases. However, the efficacy of immunotherapy may vary around the world due to differences in climate, the nature of aero-allergens and their distribution. The aim of this study was to describe the effects of subcutaneous immunotherapy (SCIT) in Korean adults with allergic asthma (AA). As a retrospective cohort study, we reviewed medical records for 627 patients with AA in Korea who were sensitized to house dust mite (HDM) and/or pollens and who underwent SCIT with aluminum hydroxide adsorbed allergen extract from 2000 to 2012. Rates of remission, defined as no further requirement of maintenance medication, over time were determined by means of life tables and extension of survival analysis. Herein, 627 asthmatic patients achieved remission within a mean of 4.7 ± 0.2 years. The cumulative incidence rates of remission from AA were 86.9% upon treatment with SCIT. Baseline forced expiratory volume in the first second (FEV1) ≥ 80% (hazard ratio [HR], 3.10; 95% confidence interval [CI], 1.79–5.39; P < 0.001), and maintenance of immunotherapy for more than 3 years (HR, 1.82; 95% CI, 1.21–2.72; P = 0.004) were significant predictors of asthma remission during SCIT. In 284 patients on SCIT with HDM alone, initial specific immunoglobulin E (IgE) levels to Dermatophagoides pteronyssinus and Dermatophagoides farinae did not show significant difference between remission and non-remission group after adjusting demographic variables. In conclusion, SCIT was effective and safe treatment modality for patients with AA. Initial FEV1 ≥ 80% and immunotherapy more than 3 years were found to be associated with favorable clinical responses to SCIT.

Antibody response in silver catfish (Rhamdia quelen) immunized with a model antigen associated with different adjuvants

Adjuvants are essential to boost the immune response to inoculated antigen and play a central role in vaccine development. In this study, we investigated the efficacy of several adjuvants in the production of anti-bovine serum albumin (BSA) antibodies in silver catfish. Two hundred and seventy juvenile silver catfish (60–80 g) of both sexes were intraperitoneally vaccinated with BSA (200 µg/fish) alone or mixed to the following adjuvants: Freund’s complete adjuvant (FCA), Freund’s incomplete adjuvant (FIA), aluminum hydroxide (AlOH), Montanide, four types of cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs) and three concentrations of β-glucan, and the immune enhancing property was evaluated by measuring anti-BSA antibodies in blood samples at biweekly intervals. Our results demonstrated that CpGs ODNs and β-glucan were as effective as classical adjuvants (FCA, FIA, AlOH and Montanide) in promoting anti-BSA antibodies and that the kinetics of antibody production induced by all adjuvants used in our study had a similar trend to that observed in other fish species, with a peak at 28 days post-vaccination. These results may be useful for the selection of adjuvants for vaccine formulation intended for silver catfish and for the development of vaccine and vaccination strategies to other fish species.

Principles and Application of Mouse Model of Allergic Rhinitis / 대한이비인후과학회지

Allergic rhinitis is a one of the most prevalent disease and its prevalence has been increasing these days. Many researchers have used the mouse models to study the mechanism of allergic rhinitis and development of anti-allergic medications. In the fields of allergic disease, several models such as allergic asthma, allergic contact dermatitis, and allergic rhinitis etc are introduced and several modifications are used. In case of mouse models of allergic rhinitis, it has been developed and modified from allergic asthma model. Most commonly used allergic rhinitis models are acute models and chronic models are used less. Ovalbumin, house dust mite and fungus are most commonly used allergens. Usually, mouse are sensitized with allergen and adjuvant such as aluminum hydroxide gel or Freund adjuvant for 2-3 weeks (once/week) then are challenged with allergen intranasally every day for 1 week. Mouse are sacrificed within 24 hours after final challenge and several parameters of allergic rhinitis are evaluated. They include nasal rubbing and sneezing count, eosinophil count in the nasal mucosa, total and allergen specific immunoglobulin E, nasal cytokine level and splenic cytokine level by splenocyte culture. By revealing those parameters, researchers could identify the allergic status of the mouse. However, there are many variables in mouse model of allergic rhinitis such as mouse strain, type of allergen, sensitization time, adjuvant, acute or chronic type, and allergen administration route etc. In this review, several variables and protocols of mouse model of AR will be discussed in detail.

Polyionic vaccine adjuvants: another look at aluminum salts and polyelectrolytes

Adjuvants improve the adaptive immune response to a vaccine antigen by modulating innate immunity or facilitating transport and presentation. The selection of an appropriate adjuvant has become vital as new vaccines trend toward narrower composition, expanded application, and improved safety. Functionally, adjuvants act directly or indirectly on antigen presenting cells (APCs) including dendritic cells (DCs) and are perceived as having molecular patterns associated either with pathogen invasion or endogenous cell damage (known as pathogen associated molecular patterns [PAMPs] and damage associated molecular patterns [DAMPs]), thereby initiating sensing and response pathways. PAMP-type adjuvants are ligands for toll-like receptors (TLRs) and can directly affect DCs to alter the strength, potency, speed, duration, bias, breadth, and scope of adaptive immunity. DAMP-type adjuvants signal via proinflammatory pathways and promote immune cell infiltration, antigen presentation, and effector cell maturation. This class of adjuvants includes mineral salts, oil emulsions, nanoparticles, and polyelectrolytes and comprises colloids and molecular assemblies exhibiting complex, heterogeneous structures. Today innovation in adjuvant technology is driven by rapidly expanding knowledge in immunology, cross-fertilization from other areas including systems biology and materials sciences, and regulatory requirements for quality, safety, efficacy and understanding as part of the vaccine product. Standardizations will aid efforts to better define and compare the structure, function and safety of adjuvants. This article briefly surveys the genesis of adjuvant technology and then re-examines polyionic macromolecules and polyelectrolyte materials, adjuvants currently not known to employ TLR. Specific updates are provided for aluminum-based formulations and polyelectrolytes as examples of improvements to the oldest and emerging classes of vaccine adjuvants in use.

Evaluación del sistema de medición en la fabricación de gel de hidróxido de aluminio / Evaluation of the measurement system analysis in the aluminum hydroxide gel production

Introducción: el estudio de repetibilidad y reproducibilidad se basa en la cuantificación experimental de la contribución del sistema de medición a la variabilidad total observada, y determina si este es aceptable o no. Objetivo: evaluar el sistema de medición en la fabricación de gel de hidróxido de aluminio mediante el estudio de repetibilidad y reproducibilidad. Métodos: el estudio de repetibilidad y reproducibilidad se desarrolló a través de un experimento factorial balanceado de efecto aleatorio. Se tomaron 10 muestras (partes) del producto terminado, de un lote de producción, las que se midieron dos veces por tres operadores seleccionados aleatoriamente. Las mediciones se realizaron en el Laboratorio de Investigación de Medilip (nivel de confianza: α= 0,05; 95 por ciento). Se aplicó el método ANOVA cruzado. El procesamiento de los datos se realizó utilizando el paquete estadístico Minitab 16. Resultados: según los índices Cg y Cgk (estudio tipo I), se comprobó que el sistema de medición fue aceptable. Con el estudio de repetibilidad y reproducibilidad se determinó que el factor que contribuye en mayor cuantía resultó el denominado partes (96,85 por ciento) y que la contribución de la variabilidad del sistema de medición (3,15 por ciento) fue aceptable, así como el porcentaje de la varianza del estudio con respecto a la varianza total (17,75 por ciento). Conclusiones: el estudio de repetibilidad y reproducibilidad identifica al factor parte como el de mayor contribución a la variabilidad total y que el sistema de medición es adecuado, lo cual está avalado por los índices reconocidos internacionalmente, por lo que se recomenda tomar acciones para mejorar el desempeño(AU)

Introduction: the repeatability and reproducibility study is based on experimental quantitation of the measurement system contribution to the total observed variability, and is aimed at determining whether this system is acceptable. Objective: to evaluate the measurement system in aluminum hydroxide gel production process through the repeatability and reproducibility study. Methods: this study was carried out through a balanced factorial experiment of random effect. Ten finished product samples from a production batch were measured twice by three randomly selected operators. The measurements were made in the Medilip research laboratory (Cross ANOVA method. Confidence level α= 0.05; 95 percent). The statistical package Minitab 16 served to process relevant data. Results: according to Cg and Cgk (type I Study) indexes, the measurement system was acceptable. The repeatability and reproducibility study determined that the main contributing factor was parts (98.85 percent) and that the measurement system variability (3.15) was also allowable as well as the percentage of the study variance with regard to the total variance (17.75 percent). Conclusions: the repeatability and reproducibility study identifies the factor called parts as the one largely contributing to the total variability and determines that the measurement system is adequate, which is endorsed by international set standards, so it is recommended to take actions to improve its performance(AU)

Cross-protection between experimental anti-leptospirosis bacterins

We investigated the existence of cross-protection between two anti-leptospirosis monovalent experimental bacterins produced with two strains of Leptospira serogroup Pomona: Fromm strain of serovar Kennewicky, isolated from pigs in the United States, and strain GR6 of serovar Pomona isolated from pigs in Brazil. Both were added of aluminum hydroxide as an adjuvant. Experimental bacterins were tested with the hamster potency test in order to assess protection provided against the disease and against the establishment of kidney infection. Controls were polyvalent commercial vaccine produced with Leptospira strains isolated outside Brazil, which included a representative of Pomona serovar, or Sorensen solution added of aluminum hydroxide adjuvant. The challenge was performed with cross-strains of serogroup Pomona tested in accordance with international standards established for the potency test. After 21 days of the challenge, survivors were killed to evaluate the condition of Leptospira renal carrier. Experimental bacterins protected hamsters against homologous and heterologous strains, demonstrating the existence of cross-protection. The commercial vaccine protected the hamsters challenged with both strains, but there was a high proportion of animals diagnosed as renal carriers when the challenge was performed with strain GR6, isolated from pigs in Brazil.

Influence of aluminum hydroxide adjuvant on a murine model of allergic rhinitis / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the influence of aluminum hydroxide adjuvant on a murine model of allergic rhinitis (AR) and to confirm an appropriate method of establishing a mouse model of AR.@*METHOD@#Establishing two types of BALB/c mice models of AR, one was identified as Local group which was characterized through intranasal sensitization and challenge using ovalbumin (OVA), and the other Systemic group which was made by intraperitoneal sensitization with OVA plus aluminum hydroxide and intranasal challenge through OVA. Then the numbers of sneezing and nasal rubbing were counted after the last challenge and the eosinophils in the nasal mucosa of mice models were observed and counted though Luna stain. Furthermore, morphological hyperplasia was examined in intraepithelial goblet cells and submucosal glands with HE stain. In addition, interlukin (IL) -4, IL-5, OVA specific IgE (sIgE) and interferon (IFN)-gamma in nasal lavage fluid (NLF) and serum of mice were examined u sing enzyme linked immunosorbent assay (ELISA).@*RESULT@#The counts of sneezing and nasal rubbing in local group were more than those in systemic group and eosinophilia in the nasal mucosa of former group was greater than that in the latter one. Morphological hyperplasia was stronger in intraepithelial goblet cells and submucosal glands in local group compared with that in systemic group. Furthermore, the contents of IL-4, IL-5 and sIgE increased in the NLF and serum of mice of local group compared to those of systemic one. However, the production of IFN-gamma of mice in local group decreased when compared with that in Systemic group.@*CONCLUSION@#OVA plus aluminum hydroxide adjuvant may promote Th1 type immune response as well as Th2 response. OVA intranasal sensitization and challenge locally is an appropriate way in the establishment of AR mice models.

Assessment of mOMV adjuvant efficacy in the pathogenic H1N1 influenza virus vaccine

PURPOSE: Since the pandemic (H1N1) 2009 virus has been a seasonal flu which still poses great human health concerns worldwide, vaccination would be considered as the most effective strategy to control the influenza virus spreading. Here, we assessed adjuvant efficacy of modified outer membrane vesicle (mOMV) towards the pandemic H1N1 split antigen. MATERIALS AND METHODS: For this study, mice were vaccinated twice with various amount of antigen (0.05, 0.1, and 0.5 microg/dose hemagglutinin [HA]) that were mixed with mOMV, aluminum hydroxide (alum), and MF59, as well as the combined adjuvant comprising the mOMV plus alum. RESULTS: We found that all the adjuvanted vaccines of A/California/04/09 (CA04, H1N1) containing HA antigen more than 0.1 microg/dose protected effectively from lethal challenge (maCA04, H1N1) virus, compared to the antigen only group. Furthermore, vaccinated mice received as low as 0.05 microg/dose of the split vaccine containing the combined adjuvant (10 microg of mOMV plus alum) showed a full protection against lethal challenge with H1N1 virus. Taken together, these results suggest that mOMV can exert not only the self-adjuvanticity but also a synergy effect for the vaccine efficacy when combined with alum. CONCLUSION: Our results indicate that mOMV could be a promising vaccine adjuvant by itself and it could be used as a vaccine platform for development of various vaccine formulations to prepare future influenza pandemic.

Can Acid Pocket-targeting Alginate-antacid (Gaviscon Double Action) Relieve Upper Gastrointestinal Symptoms in Gastro-oesophageal Reflux Disease? / 대한소화기학회지

No abstract available.

The effect of aluminum adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the effect of aluminume adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine.</p><p><b>METHODS</b>Four batches of Sabin IPV were produced by different concentrations of type 1, 2, and 3 poliovirus and administrated on three-dose schedule at 0, 1, 2 months and 0, 2, 4 months on rats. Serum samples were collected one month after each dose and neutralizing antibody titers against three types poliovirus were determined by micro-neutralization assay.</p><p><b>RESULTS</b>The GMTs of neutralizing antibodies against three types poliovirus increased significantly and the seropositivity rates were 100% in all groups after 3 doses. There was no significant difference between two immunization schedules, and the 0, 2, 4 month schedule could induce higher level neutralizing antibody compared to the 0, 1, 2 month schedule. The groups with aluminum adjuvant could induce higher level neutralizing antibody compared to the groups without adjuvant.</p><p><b>CONCLUSION</b>Aluminum djuvant and immunization schedule could improve the immunogenicity of Sabin IPV.</p>

Effect of aluminum chloride on the hippocampus of adult rats and the possible protective role of Nigella sativa: a histological and immunohistochemical study

Aluminum is among the most abundant elements on earth and it is associated with the etiology of Alzheimer's disease. The hippocampus plays an important role in short-term memory and decision making. The Nigella sativa was reported to have anti-inflammatory and antioxidant properties. To investigate the histopathological effects of aluminum chloride on the hippocampus of adult male albino rat and the possible protective role of N. sativa. Twenty-five adult male albino rats were used in this study. They were divided into five groups [each group included five rats]: group I [control] received no treatment and group II [N. sativatreated] received N. sativa oil daily at a dose of 1 ml/kg orally for 8 weeks. Group III [aluminum chloride treated] received aluminum chloride daily at a dose of 320 mg/kg/l added to the drinking water for 8 weeks. Group IV [aluminum chloride + N. sativa] received N. sativaoil with aluminum for 8 weeks at the same dose as the two previous groups. Group V [withdrawal] received aluminum only without N. sativa oil at the same previous dose for 8 weeks and then the animals were left without treatment for another 4 weeks. Specimens from the hippocampus were processed for light and electron microscopical examination. Also, the immunohistochemical technique was used with glial fibrillary acidic protein [GFAP]. Group III showed apoptotic changes in many pyramidal cells. Moreover, there was a significant decrease in the number of pyramidal cells. These changes were accompanied by a significant increase in GFAP-positive astrocytes. In group IV, minimal apoptotic changes were detected in pyramidal cells, with a significant increase in their number. This was accompanied by a significant decrease in GFAP-positive astrocytes. In group V, many pyramidal cells still showed degenerative changes, with a significant decrease in their number. GFAP-positive cells showed a significant increase. Gliosis was marked in the pyramidal cell layer. One-month withdrawal of aluminum chloride was not sufficient to gain a normal histological appearance of the hippocampus. N. sativa could be used to protect the hippocampus against aluminum chloride-induced damage

The Effect of Obstructive Sleep Apnea on DNA Damage and Oxidative Stress

OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) is associated with repeated hypoxia and re-oxygenation. This characteristic of OSAS may cause oxidative stress and DNA damage. However, the link of OSAS with oxidative stress and DNA damage is still controversial. In the current study, we investigated whether OSAS causes DNA damage using alkaline single-cell gel electrophoresis (comet assay) and measuring oxidative stress by monitoring serum malondialdehyde (MDA) levels. METHODS: From March 2009 to August 2010, 51 patients who underwent polysomnography (PSG) during the night were enrolled in this study. We obtained serum from the patients at 6 AM. DNA damage and oxidative stress were evaluated using a comet assay and measuring serum MDA, respectively. We divided the patients into two groups according to the existence of comets appearing in the comet assay. Group 1 included 44 patients with negative assay results and group 2 consisted of seven patients with positive comet assay findings. We compared the age, gender proportion, PSG data (respiratory disturbance index [RDI], lowest O2 saturation level, and arousal index [AI]), time of disease onset, smoking habits, and serum MDA levels between the two groups. RESULTS: The average age and gender proportion of the two groups were not statistically different (P>0.05). The average of RDI for group 1 was 30.4+/-18.4 and 8.0+/-7.7 (P0.05). No relationship between positive comet assay results and OSAS severity was identified. CONCLUSION: Results of the current study showed that OSAS was not associated with DNA damage as measured by comet assays or oxidative stress according to serum MDA levels.

Assessment of Gastritis Using Operative Link for Gastritis Assessment System

Gastritis is an inflammatory condition of the gastric mucosa induced by Helicobacter pylori infection, autoimmunity and chemical agents. Although Sydney system was devised for semiquantitative methods of gastritis, most physicians and pathologists consider it to be too complex and bothersome to use for routine diagnosis. Moreover, Sydney system does not reflect the overall gastritis condition and it cannot directly predict increased gastric cancer risk. To overcome these limitations, a new gastritis staging method, called Operative Link for Gastritis Assessment (OLGA) system was designed by the international group of gastroenterologists and pathologists. This system may achieve simplification of reports for the gastritis condition and it can aid in predicting gastric cancer risk and planning patient surveillance. Herein, we reviewed the routine evaluation methods, clinical implication and advantage/limitations of the OLGA system.

Assessment of Gastritis Using Operative Link for Gastritis Assessment System

Gastritis is an inflammatory condition of the gastric mucosa induced by Helicobacter pylori infection, autoimmunity and chemical agents. Although Sydney system was devised for semiquantitative methods of gastritis, most physicians and pathologists consider it to be too complex and bothersome to use for routine diagnosis. Moreover, Sydney system does not reflect the overall gastritis condition and it cannot directly predict increased gastric cancer risk. To overcome these limitations, a new gastritis staging method, called Operative Link for Gastritis Assessment (OLGA) system was designed by the international group of gastroenterologists and pathologists. This system may achieve simplification of reports for the gastritis condition and it can aid in predicting gastric cancer risk and planning patient surveillance. Herein, we reviewed the routine evaluation methods, clinical implication and advantage/limitations of the OLGA system.

Cerebral Microbleeds: Their Associated Factors, Radiologic Findings, and Clinical Implications / 대한뇌졸중학회지

Cerebral microbleeds (CMBs) are tiny, round dark-signal lesions that are most often detected on gradient-echo MR images. CMBs consist of extravasations of blood components through fragile microvascular walls characterized by lipohyalinosis and surrounding macrophages. The prevalence of CMBs in elderly subjects with no history of cerebrovascular disease is around 5%, but is much higher in patients with ischemic or hemorrhagic stroke. Development of CMBs is closely related to various vascular risk factors; in particular, lobar CMBs are thought to be associated with cerebral amyloid angiopathy. The presence of CMBs has been hypothesized to reflect cerebral-hemorrhage-prone status in patients with hypertension or amyloid microangiopathy. Stroke survivors with CMBs have been consistently found to have an elevated risk of subsequent hemorrhagic stroke or an antithrombotic-related hemorrhagic complication, although studies have failed to establish a link between CMBs and hemorrhagic transformation after thrombolytic treatment. A large prospective study is required to clarify the clinical significance of CMBs and their utility in a decision-making index.