In vitro cytotoxic and anti-cancer effects of body wall for sea cucumber (Holothuria leucospilota)

In recent years efforts to find bioactive compounds from live organisms especially marine animals have been increased. In the present study, the anticancer and cytotoxic effects of sea cucumber body walls (Holothuria leucospilota) were investigated. For this purpose, sea cucumbers were collected from Larak Island at depths of 10 to 30 m and extraction process was done with methanol and diethyl ether solvent which then concentrated by rotary evaporator (40℃) following lyophilization with vacuum freeze dryer. XTT method was used to investigate anticancer and cytotoxic effects of body wall extracts. The results showed that the methanolic extract could prevent proliferation of human oral epidermoid carcinoma cells (KB) at concentrations of 100 and 500 μg/ml. The diethyl etheric extract also could prevent proliferation of KB at 500 μg/ml concentration. Overall result showed that sea cucumber body wall had a strong cytotoxic effect on normal cell line (Human embryonic kidney cell [HEK]) which can be used as potent cytotoxic material. However these extracts did not show significant therapeutic value against KB cells

Surficial and vertical distribution of heavy metals in marine and intertidal sediments in the Iranian sector of Gowatr bay

In order to identify natural and anthropogenic pollution in Gowatr bay (also gowadar bay), the distribution of heavy metals in the surface and different depths of marine and intertidal sediments was studied. For this purpose, 17 surficial sediment samples, and 5 sediment cores were collected, and compared with local background concentration. The results of surficial distribution of heavy metals indicate that maximum concentration of Copper and Zinc, Lead, and Nickel is related to Pasabandar harbor, sandy coast, and mudflats of Mangrove jungle, respectively. Calculated correlation coefficients indicate good positive correlation between Iron, clay fraction and potentially toxic metals, especially; Cu, Zn, Pb and Ni. Heavy metals distribution at depth was determined in five sediment cores. Sixty percent of sediment cores display surficial Pb enrichment, while Ni and Co are concentrated at depth. According to geo-accumulation factor (Igeo), zinc and copper show heavy contamination in Pasabandar harbor. Maximum PLI and RI are also related to Pasabandar harbor. Marine traffic, and ship yards activity at and close to Pasabandar harbor and mangrove jungle, along with weathering of ophiolites are apparently responsible for the observed elevated concentration of heavy metals in Gowatr bay

Global prostate cancer incidence and mortality rates according to the human development index

Background: Prostate cancer (PC) is one of the leading causes of death, especially in developed countries. The human development index (HDI) and its dimensions seem correlated with incidence and mortality rates of PC. This study aimed to assess the association of the specific components of HDI (life expectancy at birth, education, gross national income per 1000 capita, health, and living standards) with burden indicators of PC worldwide. Materials and Methods: Information of the incidence and mortality rates of PC was obtained from the GLOBOCAN cancer project in year 2012 and data about the HDI 2013 were obtained from the World Bank database. The correlation between incidence, mortality rates, and the HDI parameters were assessed using STATA software. Results: A significant inequality of PC incidence rates was observed according to concentration indexes=0.25 with 95 CI (0.22, 0.34) and a negative mortality concentration index of -0.04 with 95 CI (-0.09, 0.01) was observed. Conclusions: A positive significant correlation was detected between the incidence rates of PC and the HDI and its dimensions including life expectancy at birth, education, income, urbanization level and obesity. However, there was a negative significant correlation between the standardized mortality rates and the life expectancy, income and HDI

Characterization of the stress response in 17a-hydroxylase deficient common carp (Cyprinus carpio L.)

In this thesis we describe interrenal hyperplasia in a teleost fish, the common carp, Cyprinus carpio L, caused by 17α-hydroxylase deficiency. Two homozygous, XX male inbred strains, “E5” and “E7”, consistently show 5-10 fold less plasma cortisol in response to net confinement compared to normal male and female carp strains. Both E5 and E7 fish have enlarged head kidneys, which is caused by an increase in size and number of interrenal cells. The experiments and results described in this thesis aim to provide further insight into the genetic background of the 17α-hydroxylase deficiency, and the expression of genes involved in the stress response in P450c17 deficient common carp during and after stress. First, we describe the sequencing of the 17α-hydroxylase/17, 20 lyase gene, CYP17a1, in a normal, standard strain (“STD”) and one of the 17α-hydroxylase deficient strains (E5) of common carp. Two variants of the CYP17a1 gene were found. The nucleotide coding region of the CYP17a1.I variant contained 8 exons and 7 introns which is identical to the human CYP17. In total 3122 base pairs of the nucleotide sequence were determined. Variant I showed no differences between STD and E5, while variant II is missing exon 7 and part of exon 8 and contains a 3 bp insertion and 8 homozygous SNP’s downstream of exon 6. Next, we describe the stress response and gene expression in 17α-hydroxylase deficient E5 and normal STD common carp. The results show a significant increase of corticosterone levels in E5 carp in response to stress. Normal STD carp produce only small amounts of corticosterone. STD carp show a correlation between cortisol production and 11β-HSD2 mRNA expression during the stress response. In contrast, 11β-HSD2 expression is significantly lower in E5 fish and stays at a constant level during confinement. Real-time PCR analysis of StAR and 3β-HSD show a significantly higher expression of these enzymes in E5 during and after net confinement, but P450c21 not, suggesting that transcription of P450c21 is not a limiting step in corticosterone production. Messenger RNA levels in P450c17a1.I are quite variable with a trend towards lower expression levels in E5, suggesting a dysfunction at the transcriptional level. In the last part of this thesis, we investigate the inheritance of interrenal hyperplasia and low cortisol response using backcross and gynogenetic progeny of heterozygote carriers of common carp. Six-month old backcross (BC5 and BC7) and double haploid (DH) progenies were sacrificed after one hour net-confinement, blood sampled, and dissected to determine sex and head kidney-somatic index. Values for cortisol and head kidney index showed a continuous distribution in BC and DH progeny. Values for corticosterone, on the other hand showed a very clear segregation pattern in high and low responders, consistent with a single gene model. There was a significant difference in mean cortisol level between high (H) and low (L) corticosterone responders in BC and DH progeny groups. Surprisingely, H responders were predominantly male, while L responders were female or intersex. These results confirm that 17α-hydroxylase deficiency is inherited as a recessive mutation, and that 17α-deficiency and sex reversal are either caused by the same mutation (pleiotropy) or by closely linked genes. <br/

Transcript levels of five enzymes involved in cortisol synthesis and regulation during the stress response in common carp: Relationship with cortisol

In this study the expression of five genes involved in cortisol synthesis and regulation in the head kidneys of common carp (Cyprinus carpio L.) has been investigated in response to 3 h net confinement stress, followed by 22 h recovery. Cortisol, glucose, lactate and free fatty acid levels were measured in blood plasma. StAR, P450c17a2, 3ßHSD, P450c21 and 11ßHSD2 transcript sequences were identified based on Cyprinidae homologs and quantified by real-time PCR. Results showed that the plasma cortisol level reached a peak at one hour post-stress (85-fold higher than in control) and quickly returned to normal after 4 h recovery. 11ßHSD2 transcripts were for the first time identified in interrenals. Changes in cortisol levels during and after confinement were correlated in a time-delayed relationship with increase and decrease in mRNA levels of 11ßHSD2, respectively. These results suggest that cortisol may be involved in the control or activation of 11ßHSD2. StAR and P450c21 mRNA levels did not change during net confinement stress and recovery, but P450c17a2 levels were significantly increased 4 and 22 h after recovery. Since plasma cortisol levels increased by 68-fold within 5 min net confinement stress, it seems that transcriptional activation of this enzyme is not directly involved in acute cortisol production

Transcript levels of five enzymes involved in cortisol synthesis and regulation during the stress response in common carp: Relationship with cortisol

In this study the expression of five genes involved in cortisol synthesis and regulation in the head kidneys of common carp (Cyprinus carpio L.) has been investigated in response to 3 h net confinement stress, followed by 22 h recovery. Cortisol, glucose, lactate and free fatty acid levels were measured in blood plasma. StAR, P450c17a2, 3ßHSD, P450c21 and 11ßHSD2 transcript sequences were identified based on Cyprinidae homologs and quantified by real-time PCR. Results showed that the plasma cortisol level reached a peak at one hour post-stress (85-fold higher than in control) and quickly returned to normal after 4 h recovery. 11ßHSD2 transcripts were for the first time identified in interrenals. Changes in cortisol levels during and after confinement were correlated in a time-delayed relationship with increase and decrease in mRNA levels of 11ßHSD2, respectively. These results suggest that cortisol may be involved in the control or activation of 11ßHSD2. StAR and P450c21 mRNA levels did not change during net confinement stress and recovery, but P450c17a2 levels were significantly increased 4 and 22 h after recovery. Since plasma cortisol levels increased by 68-fold within 5 min net confinement stress, it seems that transcriptional activation of this enzyme is not directly involved in acute cortisol production

High corticosterone and sex reversal in common carp (Cyprinus carpio L.) with adrenal hyperplasia caused by P450c17a2 deficiency

The aim of this study was to investigate the inheritance of adrenal hyperplasia, caused by 17a-hydroxylase deficiency, and its association with female to male sex reversal in common carp. Inbred strains used in this experiment were E4 (XX, female, normal), E5 (XX, male, adrenal hyperplasia) and E7 (XX, male, adrenal hyperplasia). F1 females (E4E5: XX, normal) were crossed to E5 and E7 males to produce backcross progeny (BC5 and BC7), or reproduced by gynogenesis to produce doubled haploid progeny (DH). Fish (age 6 months) were subjected to a net confinement stressor and sacrificed to collect blood plasma for analysis of cortisol and corticosterone, and to determine sex. Values for plasma corticosterone showed a clear segregation pattern, consistent with a single recessive gene model. There was a highly significant difference between high and low corticosterone responders in BC and DH progeny groups. Mean corticosterone values for high corticosterone responders in the three groups BC5, BC7 and DH were, respectively: 1706, 1760 and 1366 ng/ml. For low corticosterone responders values were 1.5, 1.1 and 0.6 ng/ml. High corticosterone responders had on average low levels of cortisol: 21.3, 24 and 17.3 ng/ml for BC5, BC7 and DH. Low corticosterone responders had normal levels (66.7, 105.1 and 65.2 ng/ml for BC5, BC7 and DH, respectively). Sex ratios were significantly different between high and low corticosterone responders. High corticosterone responders were predominantly male, while low corticosterone responders were female or intersex. High corticosterone responders had well developed testis and were fertile indicating that in the gonads, 17a-hydroxylase is not impaired. The observed effect on sex shows that 17a-hydroxylase deficiency most likely augments sex reversal in common carp, either directly through high levels of plasma corticosterone, or through paracrine effects of elevated ACTH production

Response to Stress in 17 alpha-hydroxylase Deficient Common Carp (Cyprinus carpio L.)

The aim of this study was to analyze the stress response during 3 hours net confinement stress and recovery period of 22 hours in normal (STD) and in 17 alpha-hydroxylase deficient common carp (E5). Fish were raised for 6 months and sampled at T-0 (control, unstressed), 5 minutes, 20 minutes, 1 hour and 3 hours of exposure to net confinement, and after 1 hour, 4 hours, and 22 hours of recovery. At every sampling time, blood was collected to determine cortisol, corticosterone, glucose, lactate and free fatty acids (FFA) levels (5 fish per strain). Fish and head kidney were weighed before and after dissection, respectively, to determine head kidney somatic Index (HKSI). Morphometric analysis of head kidney tissues indicated that the head kidney somatic index was significantly higher in E5 fish (0.076 +/- 0.021) compared with STD fish (0.045 +/- 0.015). Also, significant differences in cortisol and corticosterone as well as in glucose, lactate and FFA values were observed between the two strains of E5 and STD. Moreover, the pattern of changes of glucose and FFA during stress and afterward indicated a significant difference compared to the T-0. Results support the conclusion that the reduced capacity of ill fish to produce cortisol is caused by a deficiency in 17 alpha-hydroxylase activity. A reduced cortisol output leads to increased stimulation of adrenals by adrenocorticotropic Hormone (ACTH), resulting in increased outputs of corticosterone