Tree species composition, growing stock and biomass carbon dynamics of the major timber species in Hindu Kush regions of Pakistan / Composição de espécies de árvores, estoque em crescimento e dinâmica de biomassa de carbono das principais espécies madeireiras nas regiões de Indocuche no Paquistão

Using inventory data, this study evaluates the species composition, growing stock volume (GSV), and biomass carbon (BMC) of the five major timber species in the sub-tropical, and temperate/sub-alpine regions of Pakistan. It was found that the stem density varies between 50 and 221 trees ha -1, with a mean of 142 trees ha-1 (13.68 million trees for entire forest area). Among the species, Pinus wallichiana showed a high species composition (27.80%) followed by Picea smithiana (24.64%). The GSV was found in the range of 67.81 to 425.94 m3 ha-1, with a total GSV value of 20.68 million m3 for the entire region. Similarly, The BMC ranged from 27.04 to 169.86 Mg ha-1, with a mean BMC value of 86.80 Mg ha-1. The total amount of stored carbon was found at 8.69 million tons for a total of 95842 ha of commercially managed forest. Furthermore, the correlation analysis between the basal area (BA) and GSV and BMC showed that BA is the best predictor of GSV and BMC. The findings provide insights to the policy makers and forest managers regarding the sustainable commercial forest management as well as forest carbon management in the recent global carbon management for climate change mitigation.

Usando dados de inventário, este estudo avaliou a composição de espécies, volume de estoque crescente (GSV) e carbono de biomassa (BMC) das cinco principais espécies madeireiras nas regiões subtropicais e temperadas/subalpinas do Paquistão. Constatou-se que a densidade do caule variou entre 50 e 221 árvores ha-1, com média de 142 árvores ha-1 (13,68 milhões de árvores para toda a área florestal). Entre as espécies, Pinus wallichiana apresentou alta composição de espécies (27,80%), seguida de Picea smithiana (24,64%). O GSV foi encontrado na faixa de 67,81 a 425,94 m3 ha-1, com um valor total de 20,68 milhões de m3 para toda a região. Da mesma forma, o BMC variou de 27,04 a 169,86 mg ha-1, com valor médio de 86,80 mg ha-1. A quantidade total de carbono armazenado foi de 8,69 milhões de toneladas para um total de 95.842 ha de floresta manejada comercialmente. Além disso, a análise de correlação entre área basal (BA), GSV e BMC mostrou que BA é o melhor preditor de GSV e BMC. As descobertas fornecem insights para os formuladores de políticas e gestores florestais sobre o manejo florestal comercial sustentável, bem como o manejo florestal de carbono no recente gerenciamento global de carbono para a mitigação das mudanças climáticas.

Tree species composition, growing stock and biomass carbon dynamics of the major timber species in Hindu Kush regions of Pakistan

Abstract Using inventory data, this study evaluates the species composition, growing stock volume (GSV), and biomass carbon (BMC) of the five major timber species in the sub-tropical, and temperate/sub-alpine regions of Pakistan. It was found that the stem density varies between 50 and 221 trees ha -1, with a mean of 142 trees ha-1 (13.68 million trees for entire forest area). Among the species, Pinus wallichiana showed a high species composition (27.80%) followed by Picea smithiana (24.64%). The GSV was found in the range of 67.81 to 425.94 m3 ha-1, with a total GSV value of 20.68 million m3 for the entire region. Similarly, The BMC ranged from 27.04 to 169.86 Mg ha-1, with a mean BMC value of 86.80 Mg ha-1. The total amount of stored carbon was found at 8.69 million tons for a total of 95842 ha of commercially managed forest. Furthermore, the correlation analysis between the basal area (BA) and GSV and BMC showed that BA is the best predictor of GSV and BMC. The findings provide insights to the policy makers and forest managers regarding the sustainable commercial forest management as well as forest carbon management in the recent global carbon management for climate change mitigation.

Resumo Usando dados de inventário, este estudo avaliou a composição de espécies, volume de estoque crescente (GSV) e carbono de biomassa (BMC) das cinco principais espécies madeireiras nas regiões subtropicais e temperadas/subalpinas do Paquistão. Constatou-se que a densidade do caule variou entre 50 e 221 árvores ha-1, com média de 142 árvores ha-1 (13,68 milhões de árvores para toda a área florestal). Entre as espécies, Pinus wallichiana apresentou alta composição de espécies (27,80%), seguida de Picea smithiana (24,64%). O GSV foi encontrado na faixa de 67,81 a 425,94 m3 ha-1, com um valor total de 20,68 milhões de m3 para toda a região. Da mesma forma, o BMC variou de 27,04 a 169,86 mg ha-1, com valor médio de 86,80 mg ha-1. A quantidade total de carbono armazenado foi de 8,69 milhões de toneladas para um total de 95.842 ha de floresta manejada comercialmente. Além disso, a análise de correlação entre área basal (BA), GSV e BMC mostrou que BA é o melhor preditor de GSV e BMC. As descobertas fornecem insights para os formuladores de políticas e gestores florestais sobre o manejo florestal comercial sustentável, bem como o manejo florestal de carbono no recente gerenciamento global de carbono para a mitigação das mudanças climáticas.

Autophagic-Related anticancer effect of grapes extract and tomatoes extract: Ex-Vivo study

Cells undergo autophagy to save themselves from injury, but progressive autophagy can cause cell death. This study characterized and compared the effect of grape (resveratrol) and tomato (lycopene) extracts and their combination on modulating autophagy-related miRNA and its target gene in squamous cell carcinoma cell line. Docking analysis for extracts and selected genes was performed. Methyl Thiazol Tetrazolium assays were used to assess the cytotoxicity of extracts and their combination toward HEp-2 cells. qRT-PCR was used to quantify changes in gene expression. Data were statistically analyzed. miRNA-20a was identified as a potential effector in laryngeal cancer, and sequestosome-1 (SQSTM1) was its target gene. Docking analysis showed that resveratrol interacted with miRNA-20a and showed less affinity toward SQSTM1. Hydrogen bonds and hydrophobic interactions were predicted. In contrast, lycopene showed less affinity toward miRNA-20a than resveratrol. Increasing doses of resveratrol, lycopene, and their combination induced a statistically significant reduction in mean percent viability and mean fold changes of miRNA-20a and SQSTM1 expression in treated HEp-2 cells. Pearson's correlation showed a statistically significant positive correlation between miRNA-20a and SQSTM1 (R=0.812, p≤0.001). Grape and tomato extracts and their combination display promising cytotoxicity against HEp-2 cells in a dose- and time-dependent fashion. Both extracts reduce the expression of miRNA-20a and SQSTM1 with subsequent inhibition autophagy and promotion of apoptosis in HEp-2 cells.

Las células se someten a autofagia para salvarse de lesiones, pero la autofagia progresiva puede provocar la muerte celular. Este estudio caracterizó y comparó el efecto de los extractos de uva (resveratrol) y tomate (licopeno) y su combinación en la modulación de miARN relacionado con la autofagia y su gen diana en la línea celular de carcinoma de células escamosas. Se realizó análisis de acoplamiento para extractos y genes seleccionados. Se utilizaron ensayos de metil tiazol tetrazolio para evaluar la citotoxicidad de los extractos y su combinación frente a las células HEp-2. qRT-PCR se utilizó para cuantificar los cambios en la expresión génica. Los datos fueron analizados estadísticamente. El miARN-20a se identificó como un efector potencial en el cáncer de laringe y el secuenciasoma-1 (SQSTM1) fue su gen diana. El análisis de acoplamiento mostró que el resveratrol interactuaba con miRNA-20a y mostraba menos afinidad hacia SQSTM1. Se predijeron enlaces de hidrógeno e interacciones hidrofóbicas. Por el contrario, el licopeno mostró menos afinidad hacia el miARN-20a que el resveratrol. El aumento de las dosis de resveratrol, licopeno y su combinación indujo una reducción estadísticamente significativa en el porcentaje medio de viabilidad y los cambios medios en la expresión de miRNA- 20a y SQSTM1 en las células HEp-2 tratadas. La correlación de Pearson mostró una correlación positiva estadísticamente significativa entre miRNA-20a y SQSTM1 (R=0,812, p≤0,001). Los extractos de uva y tomate y su combinación muestran una citotoxicidad prometedora contra las células HEp-2 de forma dependiente de la dosis y el tiempo. Ambos extractos reducen la expresión de miRNA-20a y SQSTM1 con la posterior inhibición de la autofagia y promoción de la apoptosis en células HEp-2.

Toxicological effects of thimerosal on rat kidney: a histological and biochemical study / Efeitos toxicológicos do timerosal no rim de rato: um estudo histológico e bioquímico

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.(AU)

O timerosal é um composto organomercurial, utilizado na preparação de imunoglobulina intramuscular, antivenenos, tintas de tatuagem, antígenos de teste cutâneo, produtos nasais, gotas oftálmicas e vacinas como conservante. Na maioria das espécies animais e nos humanos, o rim é um dos principais locais de deposição de compostos de mercúrio e órgãos-alvo de toxicidade. Assim, a presente pesquisa teve como objetivo avaliar a nefrotoxicidade induzida pelo timerosal em ratos machos. Vinte e quatro ratos albinos machos adultos foram categorizados em quatro grupos. O primeiro grupo era um grupo de controle. Ratos do Grupo II, Grupo III e Grupo IV receberam 0,5µg / kg, 10µg / kg e 50µg / kg de timerosal uma vez ao dia, respectivamente. A administração de timerosal diminuiu significativamente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa redutase (GR), glutationa (GSH) e conteúdo de proteína, enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e peróxido de hidrogênio (H2O2) níveis dependentes da dose. Os níveis de nitrogênio ureico no sangue (BUN), creatinina, urobilinogênio, proteínas urinárias, molécula de lesão renal-1 (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina urinária e a depuração da creatinina foram reduzidas de forma dependente da dose nos grupos tratados com timerosal. Os resultados demonstraram que o timerosal aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappaB (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), níveis de interleucina-6 (IL-6) e atividades da ciclooxigenase-2 (COX-2), DNA e danos histopatológicos dependentes da dose. Portanto, os presentes achados verificaram que o timerosal exerceu nefrotoxicidade em ratos albinos machos.(AU)

Toxicological effects of thimerosal on rat kidney: a histological and biochemical study / Efeitos toxicológicos do timerosal no rim de rato: um estudo histológico e bioquímico

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

O timerosal é um composto organomercurial, utilizado na preparação de imunoglobulina intramuscular, antivenenos, tintas de tatuagem, antígenos de teste cutâneo, produtos nasais, gotas oftálmicas e vacinas como conservante. Na maioria das espécies animais e nos humanos, o rim é um dos principais locais de deposição de compostos de mercúrio e órgãos-alvo de toxicidade. Assim, a presente pesquisa teve como objetivo avaliar a nefrotoxicidade induzida pelo timerosal em ratos machos. Vinte e quatro ratos albinos machos adultos foram categorizados em quatro grupos. O primeiro grupo era um grupo de controle. Ratos do Grupo II, Grupo III e Grupo IV receberam 0,5µg / kg, 10µg / kg e 50µg / kg de timerosal uma vez ao dia, respectivamente. A administração de timerosal diminuiu significativamente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa redutase (GR), glutationa (GSH) e conteúdo de proteína, enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e peróxido de hidrogênio (H2O2) níveis dependentes da dose. Os níveis de nitrogênio ureico no sangue (BUN), creatinina, urobilinogênio, proteínas urinárias, molécula de lesão renal-1 (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina urinária e a depuração da creatinina foram reduzidas de forma dependente da dose nos grupos tratados com timerosal. Os resultados demonstraram que o timerosal aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappaB (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), níveis de interleucina-6 (IL-6) e atividades da ciclooxigenase-2 (COX-2), DNA e danos histopatológicos dependentes da dose. Portanto, os presentes achados verificaram que o timerosal exerceu nefrotoxicidade em ratos albinos machos.

Toxicological effects of thimerosal on rat kidney: a histological and biochemical study

Abstract Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-B), tumor necrosis factor- (TNF-), Interleukin-1 (IL-1), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

Resumo O timerosal é um composto organomercurial, utilizado na preparação de imunoglobulina intramuscular, antivenenos, tintas de tatuagem, antígenos de teste cutâneo, produtos nasais, gotas oftálmicas e vacinas como conservante. Na maioria das espécies animais e nos humanos, o rim é um dos principais locais de deposição de compostos de mercúrio e órgãos-alvo de toxicidade. Assim, a presente pesquisa teve como objetivo avaliar a nefrotoxicidade induzida pelo timerosal em ratos machos. Vinte e quatro ratos albinos machos adultos foram categorizados em quatro grupos. O primeiro grupo era um grupo de controle. Ratos do Grupo II, Grupo III e Grupo IV receberam 0,5µg / kg, 10µg / kg e 50µg / kg de timerosal uma vez ao dia, respectivamente. A administração de timerosal diminuiu significativamente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa redutase (GR), glutationa (GSH) e conteúdo de proteína, enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e peróxido de hidrogênio (H2O2) níveis dependentes da dose. Os níveis de nitrogênio ureico no sangue (BUN), creatinina, urobilinogênio, proteínas urinárias, molécula de lesão renal-1 (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina urinária e a depuração da creatinina foram reduzidas de forma dependente da dose nos grupos tratados com timerosal. Os resultados demonstraram que o timerosal aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappaB (NF-B), fator de necrose tumoral- (TNF-), interleucina-1 (IL-1), níveis de interleucina-6 (IL-6) e atividades da ciclooxigenase-2 (COX-2), DNA e danos histopatológicos dependentes da dose. Portanto, os presentes achados verificaram que o timerosal exerceu nefrotoxicidade em ratos albinos machos.

Tree species composition, growing stock and biomass carbon dynamics of the major timber species in Hindu Kush regions of Pakistan.

Using inventory data, this study evaluates the species composition, growing stock volume (GSV), and biomass carbon (BMC) of the five major timber species in the sub-tropical, and temperate/sub-alpine regions of Pakistan. It was found that the stem density varies between 50 and 221 trees ha -1, with a mean of 142 trees ha-1 (13.68 million trees for entire forest area). Among the species, Pinus wallichiana showed a high species composition (27.80%) followed by Picea smithiana (24.64%). The GSV was found in the range of 67.81 to 425.94 m3 ha-1, with a total GSV value of 20.68 million m3 for the entire region. Similarly, The BMC ranged from 27.04 to 169.86 Mg ha-1, with a mean BMC value of 86.80 Mg ha-1. The total amount of stored carbon was found at 8.69 million tons for a total of 95842 ha of commercially managed forest. Furthermore, the correlation analysis between the basal area (BA) and GSV and BMC showed that BA is the best predictor of GSV and BMC. The findings provide insights to the policy makers and forest managers regarding the sustainable commercial forest management as well as forest carbon management in the recent global carbon management for climate change mitigation.

Toxicological effects of thimerosal on rat kidney: a histological and biochemical study.

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

Conus vexillum venom induces oxidative stress in Ehrlich's ascites carcinoma cells: an insight into the mechanism of induction.

BACKGROUND: It is estimated that venoms of marine cone snails (genus Conus) contain more than 100,000 different small peptides with a wide range of pharmacological and biological actions. Some of these peptides were developed into potential therapeutic agents and as molecular tools to understand biological functions of nervous and cardiovascular systems. In this study we examined the cytotoxic and anticancer properties of the marine vermivorous cone snail Conus vexillum (collected from Hurgada and Sharm El-Shaikh, Red Sea, Egypt) and suggest the possible mechanisms involved. The in vitro cytotoxic effects of Conus venom were assessed against Ehrlich's ascites carcinoma (EAC) cells. RESULTS: Conus venom treatment resulted in concentration-dependent cytotoxicity as indicated by a lactate dehydrogenase leakage assay. Apoptotic effects were measured in vivo by measuring levels of reactive oxygen species and oxidative defense agents in albino mice injected with EAC cells. Conus venom (1.25 mg/kg) induced a significant increase (p < 0.05) in several oxidative stress biomarkers (lipid peroxidation, protein carbonyl content and reactive nitrogen intermediates) of EAC cells after 3, 6, 9 and 12 hours of venom injection. Conus venom significantly reduced (p < 0.05) the activities of oxidative defense enzymes (catalase and superoxide dismutase) as well as the total antioxidant capacity of EAC cells, as evidenced by lowered levels of reduced glutathione. CONCLUSIONS: These results demonstrate the cytotoxic potential of C. vexillum venom by inducing oxidative stress mediated mechanisms in tumor cells and suggest that the venom contains novel molecules with potential anticancer activity.

Conus vexillum venom induces oxidative stress in Ehrlich's ascites carcinoma cells: an insight into the mechanism of induction

It is estimated that venoms of marine cone snails (genus Conus) contain more than 100,000 different small peptides with a wide range of pharmacological and biological actions. Some of these peptides were developed into potential therapeutic agents and as molecular tools to understand biological functions of nervous and cardiovascular systems. In this study we examined the cytotoxic and anticancer properties of the marine vermivorous cone snail Conus vexillum (collected from Hurgada and Sharm El-Shaikh, Red Sea, Egypt) and suggest the possible mechanisms involved. The in vitro cytotoxic effects of Conus venom were assessed against Ehrlich’s ascites carcinoma (EAC) cells. Results Conus venom treatment resulted in concentration-dependent cytotoxicity as indicated by a lactate dehydrogenase leakage assay. Apoptotic effects were measured in vivo by measuring levels of reactive oxygen species and oxidative defense agents in albino mice injected with EAC cells. Conus venom (1.25 mg/kg) induced a significant increase ( p  < 0.05) in several oxidative stress biomarkers (lipid peroxidation, protein carbonyl content and reactive nitrogen intermediates) of EAC cells after 3, 6, 9 and 12 hours of venom injection. Conus venom significantly reduced ( p  < 0.05) the activities of oxidative defense enzymes (catalase and superoxide dismutase) as well as the total antioxidant capacity of EAC cells, as evidenced by lowered levels of reduced glutathione.Conclusions These results demonstrate the cytotoxic potential of C. vexillum venom by inducing oxidative stress mediated mechanisms in tumor cells and suggest that the venom contains novel.

Conus vexillum venom induces oxidative stress in Ehrlich's ascites carcinoma cells: an insight into the mechanism of induction

Background: It is estimated that venoms of marine cone snails (genus Conus) contain more than 100,000 different small peptides with a wide range of pharmacological and biological actions. Some of these peptides were developed into potential therapeutic agents and as molecular tools to understand biological functions of nervous and cardiovascular systems. In this study we examined the cytotoxic and anticancer properties of the marine vermivorous cone snail Conus vexillum (collected from Hurgada and Sharm El-Shaikh, Red Sea, Egypt) and suggest the possible mechanisms involved. The in vitro cytotoxic effects of Conus venom were assessed against Ehrlich's ascites carcinoma (EAC) cells. Results: Conus venom treatment resulted in concentration-dependent cytotoxicity as indicated by a lactate dehydrogenase leakage assay. Apoptotic effects were measured in vivo by measuring levels of reactive oxygen species and oxidative defense agents in albino mice injected with EAC cells. Conus venom (1.25 mg/kg) induced a significant increase (p < 0.05) in several oxidative stress biomarkers (lipid peroxidation, protein carbonyl content and reactive nitrogen intermediates) of EAC cells after 3, 6, 9 and 12 hours of venom injection. Conus venom significantly reduced (p < 0.05) the activities of oxidative defense enzymes (catalase and superoxide dismutase) as well as the total antioxidant capacity of EAC cells, as evidenced by lowered levels of reduced glutathione. Conclusions: These results demonstrate the cytotoxic potential of C. vexillum venom by inducing oxidative stress mediated mechanisms in tumor cells and suggest that the venom contains novel molecules with potential anticancer activity.(AU)

Conus vexillum venom induces oxidative stress in Ehrlich's ascites carcinoma cells: an insight into the mechanism of induction

It is estimated that venoms of marine cone snails (genus Conus) contain more than 100,000 different small peptides with a wide range of pharmacological and biological actions. Some of these peptides were developed into potential therapeutic agents and as molecular tools to understand biological functions of nervous and cardiovascular systems. In this study we examined the cytotoxic and anticancer properties of the marine vermivorous cone snail Conus vexillum (collected from Hurgada and Sharm El-Shaikh, Red Sea, Egypt) and suggest the possible mechanisms involved. The in vitro cytotoxic effects of Conus venom were assessed against Ehrlichs ascites carcinoma (EAC) cells. Results Conus venom treatment resulted in concentration-dependent cytotoxicity as indicated by a lactate dehydrogenase leakage assay. Apoptotic effects were measured in vivo by measuring levels of reactive oxygen species and oxidative defense agents in albino mice injected with EAC cells. Conus venom (1.25 mg/kg) induced a significant increase ( p  < 0.05) in several oxidative stress biomarkers (lipid peroxidation, protein carbonyl content and reactive nitrogen intermediates) of EAC cells after 3, 6, 9 and 12 hours of venom injection. Conus venom significantly reduced ( p  < 0.05) the activities of oxidative defense enzymes (catalase and superoxide dismutase) as well as the total antioxidant capacity of EAC cells, as evidenced by lowered levels of reduced glutathione.Conclusions These results demonstrate the cytotoxic potential of C. vexillum venom by inducing oxidative stress mediated mechanisms in tumor cells and suggest that the venom contains novel.(AU)

The trypanocidal activity of amidine compounds does not correlate with their binding affinity to Trypanosoma cruzi kinetoplast DNA.

Due to limited efficacy and considerable toxicity, the therapy for Chagas' disease is far from being ideal, and thus new compounds are desirable. Diamidines and related compounds such as arylimidamides have promising trypanocidal activity against Trypanosoma cruzi. To better understand the mechanism of action of these heterocyclic cations, we investigated the kinetoplast DNA (kDNA) binding properties and trypanocidal efficacy against T. cruzi of 13 compounds. Four diamidines (DB75, DB569, DB1345, and DB829), eight arylimidamides (DB766, DB749, DB889, DB709, DB613, DB1831, DB1852, and DB2002), and one guanylhydrazone (DB1080) were assayed in thermal denaturation (T(m)) and circular dichroism (CD) studies using whole purified T. cruzi kDNA and a conserved synthetic parasite sequence. The overall CD spectra using the whole kDNA were similar to those found for the conserved sequence and were indicative of minor groove binding. Our findings showed that some of the compounds that exhibited the highest trypanocidal activities (e.g., DB766) caused low or no change in the T(m) measurements. However, while some active compounds, such as DB766, induced profound alterations of kDNA topology, others, like DB1831, although effective, did not result in altered T(m) and CD measurements. Our data suggest that the strong affinity of amidines with kDNA per se is not sufficient to generate and trigger their trypanocidal activity. Cell uptake differences and possibly distinct cellular targets need to be considered in the final evaluation of the mechanisms of action of these compounds.

Trypanocidal activity and selectivity in vitro of aromatic amidine compounds upon bloodstream and intracellular forms of Trypanosoma cruzi.

Trypanosoma cruzi is the etiological agent of Chagas disease, an important neglected illness affecting about 12-14 million people in endemic areas of Latin America. The chemotherapy of Chagas disease is quite unsatisfactory mainly due to its poor efficacy especially during the later chronic phase and the considerable well-known side effects. These facts emphasize the need to search for find new drugs. Diamidines and related compounds are minor groove binders of DNA at AT-rich sites and present excellent anti-trypanosomal activity. In the present study, six novel aromatic amidine compounds (arylimidamides and diamidines) were tested in vitro to determine activity against the infective and intracellular stages of T. cruzi, which are responsible for sustaining the infection in the mammalian hosts. In addition, their selectivity and toxicity towards primary cultures of cardiomyocyte were evaluated since these cells represent important targets of infection and inflammation in vivo. The aromatic amidines were active against T. cruzi in vitro, the arylimidamide DB1470 was the most effective compound presenting a submicromolar LD(50) values, good selectivity index, and good activity at 4 °C in the presence of blood constituents. Our results further justify trypanocidal screening assays with these classes of compounds both in vitro and in vivo in experimental models of T. cruzi infection.

Biological, ultrastructural effect and subcellular localization of aromatic diamidines in Trypanosoma cruzi.

No vaccines or safe chemotherapy are available for Chagas disease. Pentamidine and related di-cations are DNA minor groove-binders with broad-spectrum anti-protozoal activity. Therefore our aim was to evaluate the in vitro efficacy of di-cationic compounds - DB1645, DB1582, DB1651, DB1646, DB1670 and DB1627 - against bloodstream trypomastigotes (BT) and intracellular forms of Trypanosoma cruzi. Cellular targets of these compounds in treated parasites were also analysed by fluorescence and transmission electron microscopy (TEM). DB1645, DB1582 and DB1651 were the most active against BT showing IC50 values ranging between 0.15 and 6.9 microm. All compounds displayed low toxicity towards mammalian cells and DB1645, DB1582 and DB1651 were also the most effective against intracellular parasites, with IC50 values ranging between 7.3 and 13.3 microm. All compounds localized in parasite nuclei and kDNA (with greater intensity in the latter structure), and DB1582 and DB1651 also concentrated in non-DNA-containing cytoplasmic organelles possibly acidocalcisomes. TEM revealed alterations in mitochondria and kinetoplasts, as well as important disorganization of microtubules. Our data provide further information regarding the activity of this class of compounds upon T. cruzi which should aid future design and synthesis of agents that could be used for Chagas disease therapy.

Enterotoxigenic Escherichia coli and diffusely adherent E. coli as likely causes of a proportion of pathogen-negative travelers' diarrhea--a PCR-based study.

BACKGROUND: Enteropathogens cannot be identified in 40% to 50% of subjects with travelers' diarrhea (TD). METHODS: We used polymerase chain reaction (PCR) methods to look for the presence of two bacterial causes of diarrhea in a large group of international travelers after failing to detect a pathogen by conventional tests. DNA was isolated from the diarrheal stool and subjected to PCR from 162 subjects from whom we earlier failed to identify a pathogen in a previous study and included 54 from Antigua, Guatemala, 39 from Guadalajara, Mexico, 29 from Kolkata, India, and 40 from Goa, India. Gene products for enterotoxigenic Escherichia coli (ETEC)--LT (heat-labile enterotoxin) and ST (heat-stable enterotoxin)--and diffusely adherent E. coli (DAEC), afa/dr (Afa fimbrial and Dr nonfimbrial family of adhesins), were used. RESULTS: At least one gene product was identified in diarrhea stool samples of 47 of 162 (29%) subjects. ETEC virulence genes (LT, ST) were found in 34 (21%) samples studied, with rates of occurrence ranging from 8% in Goa to 39% for the samples from Guatemala (p = 0.0006). A large number of ST-only strains explained the high ETEC rate in Guatemala. DAEC afa/dr family of adhesions was identified in between 8 and 14% of the samples. CONCLUSIONS: ETEC and DAEC were implicated in nearly one-third of the subjects initially diagnosed as pathogen negative. Direct PCR results from stools are consistent with the previous assumption that most undiagnosed TD is bacterial in nature and also highlights the potential value that PCR can add to studies designed to evaluate treatment and preventive interventions for TD, including vaccines.

Does Cleome droserifolia have anti-schistosomiasis mansoni activity?

The present study was undertaken to assess the effect of the crude extract of Cleome droserifolia (CD) leaves on experimentally infected mice with Schistosoma mansoni. Two groups of mice, showing a patent infection of S. mansoni, one of them was daily treated with an alcoholic extract of CD leaves (0.31 g kg-1 body weight, i.p.) for 21 days. The schistosomicidal activity of the CD extract was evaluated, three weeks post-treatment, on some parasitological and histopathological aspects including worm load, oogram pattern, faecal eggs releasing and granuloma formation. In addition, serum thyroid hormones levels (tri-iodothyronine; T3 and tetra-iodo-thyronine; T4), serum total protein contents and hepatic reduced glutathione (GSH) were evaluated. Treatment using CD extract resulted in a weak reduction in worm burden (32.46%) and affected the viability of both mature and immature eggs as indicated by the increase in the percentage of dead eggs and the decrease in the percentage of live ones. In addition, a week post-treatment, eggs elimination was observed in the stool of the infected-treated group which was low compared to the infected group. There was a suppressive effect of the extract on granuloma formation that could be due to the antioxidant effect of the extract. These data are confirmed by increasing hepatic GSH, serum total proteins and thyroid hormone levels in the infected-treated group as compared to the infected group. Treatment significantly enhanced b globulin fractions of the protein. Based on these assumptions, CD extract has beneficial effects on thyroid hormones status and anti-schistosomiasis activity. The beneficial effects of CD extract could be related to its direct effects on the parasite, and secondary to its effect on the antioxidant capacity of the host. The present study could emphasize the precise mechanism (s) of CD extract protection.

Does Cleome droserifolia have anti-schistosomiasis mansoni activity? / Cleome droserifolia tem atividade anti-esquistossomose mansônica?

The present study was undertaken to assess the effect of the crude extract of Cleome droserifolia (CD) leaves on experimentally infected mice with Schistosoma mansoni. Two groups of mice, showing a patent infection of S. mansoni, one of them was daily treated with an alcoholic extract of CD leaves (0.31 g kg-1 body weight, i.p.) for 21 days. The schistosomicidal activity of the CD extract was evaluated, three weeks post-treatment, on some parasitological and histopathological aspects including worm load, oogram pattern, faecal eggs releasing and granuloma formation. In addition, serum thyroid hormones levels (tri-iodothyronine; T3 and tetra-iodo-thyronin; T4), serum total protein contents and hepatic reduced glutathione (GSH) were evaluated. Treatment using CD extract resulted in a weak reduction in worm burden (32.46 percent) and affected the viability of both mature and immature eggs as indicated by the increase in the percentage of dead eggs and the decrease in the percentage of live ones. In addition, a week post-treatment, eggs elimination was observed in the stool of the infected-treated group which was low compared to the infected group. There was a suppressive effect of the extract on granuloma formation that could be due to the antioxidant effect of the extract. These data are confirmed by increasing hepatic GSH, serum total proteins and thyroid hormone levels in the infected-treated group as compared to the infected group. Treatment significantly enhanced b globulin fractions of the protein. Based on these assumptions, CD extract has beneficial effects on thyroid hormones status and anti-schistosomiasis activity. The beneficial effects of CD extract could be related to its direct effects on the parasite, and secondary to its effect on the antioxidant capacity of the host. The present study could emphasize the precise mechanism (s) of CD extract protection.

O presente estudo foi realizado para verificar o efeito do extrato cru de folhas de Cleome droserifolia (CD) em camundongos experimentalmente infectados com Schistosoma mansoni. Em dois grupos de camundongos mostrando infecção patente por S. mansoni, um deles foi tratado diariamente com extrato alcoólico de folhas de CD (0.31g kg-1 por peso corporal, i.p.) por 21 dias. A atividade esquistossomicida do extrato de CD foi avaliada, três semanas após o tratamento, em alguns aspectos parasitológicos e histopatológicos incluindo carga parasitária, padrão de oograma, eliminação fecal de ovos e formação de granuloma. Além disto, níveis séricos de hormônio tireoideano (tri-iodotironina: T3 e tetra-iodotironina: T4), conteúdo sérico total de proteínas e glutatione hepático reduzido (GSH) foram avaliados. Tratamento usando extrato de CD resultou em fraca redução da carga de vermes (32,46 por cento) e afetou a viabilidade de ovos maduros ou não, como indicado pelo aumento na porcentagem de ovos mortos e o descrécimo na porcentagem de ovos viáveis. Além disso, uma semana após o tratamento, a eliminação de ovos foi observada nas fezes do grupo infectado-tratado que foi baixa comparada ao grupo infectado. Houve efeito supressivo do extrato sobre a formação de granuloma que poderia ser devido ao efeito antioxidante do extrato. Estes dados são confirmados pelo aumento do GSH hepático, soro total de proteínas e níveis dos hormônios tireoideanos no grupo infecto-tratado quando comparado com o grupo infectado. O tratamento aumentou significativamente as frações beta-globulina da proteína. Baseado nestas afirmativas o extrato de CD tem efeitos benéficos sobre o nível dos hormônios tireoideanos e da atividade anti-esquistossomica. Os efeitos benéficos do extrato de CD poderiam estar relacionados com seu efeito direto sobre o parasita, e secundariamente por seus efeitos na capacidade anti-oxidante do hospedeiro. O presente trabalho poderia enfatizar o(s) mecanismo(s) preciso(s) desta proteção do extrato de CD.