Visual complications of mitral leaflet prolapse.

Four young women and six older men with mitral leaflet prolapse presented with visual disturbances consistent with embolism in the ophthalmic or posterior cerebral circulation. Cardiac arrhythmias were common, but these are rarely associated with focal ischaemia. The evidence that mitral leaflet prolapse caused the embolism in these patients is suggestive but not conclusive. Further studies are needed. All patients with acute cerebral or ocular ischaemia should undergo through cardiovascular assessment, which should include routine echocardiography.     

Heat shock induces chromosome loss in the yeast Candida albicans

Summary The heat shock protocol described in this paper causes mitotic instability in log phase Candida albicans cells. Such instability is induced in diploid, aneuploid and tetraploid strains. The strains analysed are multiple heterozygotes which facilitates the detection of mitotic instability as manifested by the formation of homozygotes. Strains previously shows to be carrying cis linked mutant alleles show coincident segregation of the linked alleles. Conversely, strains which carry unlinked mutant alleles display no such coincident segregation. This segregation of complete linkage groups suggests that heat shock is inducing chromosome some loss in C. albicans. The application of this protocol to the genetics of the imperfect fungus C. albicans has produced evidence of at least three chromosomes.     

SIRT3-SOD2-mROS-dependent autophagy in cadmium-induced hepatotoxicity and salvage by melatonin

Cadmium is one of the most toxic metal compounds found in the environment. It is well established that Cd induces hepatotoxicity in humans and multiple animal models. Melatonin, a major secretory product of the pineal gland, has been reported to protect against Cd-induced hepatotoxicity. However, the mechanism behind this protection remains to be elucidated. We exposed HepG2 cells to different concentrations of cadmium chloride (2.5, 5, and 10 μM) for 12 h. We found that Cd induced mitochondrial-derived superoxide anion-dependent autophagic cell death. Specifically, Cd decreased SIRT3 protein expression and activity and promoted the acetylation of SOD2, superoxide dismutase 2, mitochondrial, thus decreasing its activity, a key enzyme involved in mitochondrial ROS production, although Cd did not disrupt the interaction between SIRT3 and SOD2. These effects were ameliorated by overexpression of SIRT3. However, a catalytic mutant of SIRT3 (SIRT3^H248Y) lacking deacetylase activity lost the capacity to suppress Cd-induced autophagy. Notably, melatonin treatment enhanced the activity but not the expression of SIRT3, decreased the acetylation of SOD2, inhibited mitochondrial-derived O₂^•− production and suppressed the autophagy induced by 10 μM Cd. Moreover, 3-(1H-1,2,3-triazol-4-yl)pyridine, a confirmed selective SIRT3 inhibitor, blocked the melatonin-mediated suppression of autophagy by inhibiting SIRT3-SOD2 signaling. Importantly, melatonin suppressed Cd-induced autophagic cell death by enhancing SIRT3 activity in vivo. These results suggest that melatonin exerts a hepatoprotective effect on mitochondrial-derived O₂^•−-stimulated autophagic cell death that is dependent on the SIRT3/SOD2 pathway.     

A new balancing act: The many roles of melatonin and serotonin in plant growth and development

Melatonin and serotonin are indoleamines first identified as neurotransmitters in vertebrates; they have now been found to be ubiquitously present across all forms of life. Both melatonin and serotonin were discovered in plants several years after their discovery in mammals, but their presence has now been confirmed in almost all plant families. The mechanisms of action of melatonin and serotonin are still poorly defined. Melatonin and serotonin possess important roles in plant growth and development, including functions in chronoregulation and modulation of reproductive development, control of root and shoot organogenesis, maintenance of plant tissues, delay of senescence, and responses to biotic and abiotic stresses. This review focuses on the roles of melatonin and serotonin as a novel class of plant growth regulators. Their roles in reproductive and vegetative plant growth will be examined including an overview of current hypotheses and knowledge regarding their mechanisms of action in specific responses.     

Localization of breast cancer resistance protein (Bcrp) in endocrine organs and inhibition of its transport activity by steroid hormones

Breast cancer resistance protein (BCRP) is known for its protective function against the toxic effects of exogenous compounds. In addition to this, a role in the transport of endogenous compounds has been described. Since BCRP in the plasma membrane was shown to be regulated by sex steroids, we investigated the presence and possible role of BCRP in steroid hormone-producing organs. Therefore, the presence and localization of Bcrp was investigated in endocrine organs of wild-type mice. Furthermore, the interaction of various steroid hormones with human BCRP activity was studied. Quantitative PCR revealed Bcrp mRNA in the pituitary and adrenal glands, pancreas, ovary, testis and adipose tissue. Immunohistochemistry revealed the presence of Bcrp in the cortex of the adrenal gland and in plasma membranes of adipocytes. In the pituitary gland, pancreas, ovary and testis, Bcrp was mainly located in the capillaries. The interaction between BCRP and 12 steroid hormones was studied using membrane vesicles of HEK293-BCRP cells. Estradiol, testosterone, progesterone and androstenedione inhibited BCRP-mediated uptake of (3)H-estrone sulphate (E(1)S) most potently, with calculated inhibitory constant (Ki) values of 5.0?±?0.2, 36?±?14, 14.7?±?1.3 and 217?±?13?μM, respectively. BCRP function was attenuated non-competitively, which implies an allosteric inhibition of BCRP-mediated E(1)S transport by these steroids. In conclusion, localization of Bcrp in endocrine organs together with the efficient allosteric inhibition of the efflux pump by steroid hormones are suggestive for a role for BCRP in steroid hormone regulation.     

A possible role of perinatal light in mood disorders and internal cancers: reconciliation of instability and latitude concepts

Thought-provoking experimental evidence suggests that perinatal light exposure may imprint circadian clocks with lasting effects on the alignment and the stability of circadian rhythms later in life. Assuming that exposure to light early in life could determine the stability of an individual's circadian system later in life, the present hypothesis proposes that time of year and location of birth (i.e., season and latitude) and thus differential Zeitgeber strengths may be key contributors to a person's susceptibility of developing mood disorders like seasonal affective disorder (SAD) and common internal cancers such as those of breast and prostate. Consequently, when and where people are born might critically predispose them to both mood disorders and internal cancers, and may affect the onset and course of such illnesses. This paper develops a causal framework and presents suggestions for rigorous tests of the associated corollary and predictions. It does not escape our attention that links between the perinatal Zeitgeber strength of light and its effects on the stability of circadian systems later in life could have a role to play in affecting long-term health beyond cancer and mood disorders - mostly in adults but also in children.     

Adrenalectomy or Superior Cervical Ganglionectomy Modifies the Nocturnal Increase in Rat Pineal Type II Thyroxine 5′-Deiodinase

We studied the response of type II thyroxine 5′-deiodinase (5′-D) activity to superior cervical ganglionectomy (SCGX) or adrenalectomy (ADX) in the rat pineal gland and other tissues. The results show that no difference was found between controls and SCGX animals during the day, but at night, SCGX modified the day-night cycle of 5′-D activity in the pineal gland. In the same way, ADX did not modify the enzyme activity during the day in pineal gland, harderian gland, hypophysis, or brain frontal cortex (BFC). However, in brown adipose tissue (BAT), where thyroid hormone metabolism is extremely dependent on α₁-adren-ergic stimulation by blood circulating catecholamines, 5′-D activity is significantly decreased. At the time point of maximal pineal 5′-D activity in controls (02:00 h), ADX animals did not exhibit the nocturnal increase of the enzyme activity that occurs with control rats. Moreover, at 04:00 h ADX did not show any effect on pineal 5′-D activity. These results seem to suggest that the presence of catecholamines in blood is necessary for the pineal 5′-D activity nocturnal increase, although it does not participate in regulating the basal enzyme activity during the day.     

Breeding biology,diet and vocalization of the Helmet Vanga,Euryceros prevostii,on the Masoala Peninsula,Madagascar

La Morco, G. & Thorstrom, R. 2000. Breeding biology, diet and vocalization of the Helmet Vanga Euryceros prevostii on the Masoala Peninsula, Madagascar. Ostrich 71 (3&4): 400-403. The endemic Helmet Vanga, Euryceros prevostii, was studied from October to December 1997, with incidental observations from October to December 1993-1997, on the Masoala Peninsula, northeastern Madagascar. Three types of vocalizations of this species were associated with territorial, alarm and contact calls, respectively. Nests were open cups placed in the forks of trees or at the apex of small trees. Nests were composed of interlaced grasses in the nest bawl, woven plant fibres supporting the centre of the nest and lichen/moss on the exterior portion of the nest. Average clutch size was 2.7 (n = 6 nests). During incubation, either adult was on the nest 99% of the time. The reproductive output was 1.8 young fledged per nest (n = 4 nests) with 75% nest success (3/4). Of the 106 prey items recorded, 91% were invertebrates and 9% verte-brates. Cockroaches, butterflies, moths, crickets, katydids and beetles represented the most numerous insect prey taken, representing 73% of the identified prey. [A French translation of the abstract is provided on p. 403.]     

Bioinformatic,phylogenetic and chemical analysis of the UV-absorbing compounds scytonemin and mycosporine-like amino acids from the microbial mat communities of Shark Bay,Australia

Shark Bay, Western Australia is a World Heritage area with extensive microbial mats and stromatolites. Microbial communities that comprise these mats have developed a range of mitigation strategies against changing levels of photosynthetically active and ultraviolet radiation, including the ability to biosynthesise the UV-absorbing natural products scytonemin and mycosporine-like amino acids (MAAs). To this end, the distribution of photoprotective pigments within Shark Bay microbial mats was delineated in the present study. This involved amplicon sequencing of bacterial 16S rDNA from communities at the surface and subsurface in three distinct mat types (smooth, pustular and tufted), and correlating this data with the chemical and molecular distribution of scytonemin and MAAs. Employing UV spectroscopy and MS/MS fragmentation, mycosporine-glycine, asterina and an unknown MAA were identified based on typical fragmentation patterns. Marker genes for scytonemin and MAA production (scyC and mysC) were amplified from microbial mat DNA and placed into phylogenetic context against a broad screen throughout 363 cyanobacterial genomes. Results indicate that occurrence of UV screening compounds is associated with the upper layer of Shark Bay microbial mats, and the occurrence of scytonemin is closely dependent on the abundance of cyanobacteria.     

Melatonin reduces oxidative damage and increases survival of mice infected with Schistosoma mansoni

The tropical parasite Schistosoma mansoni causes granulomatous inflammation after its eggs lodge in hepatic portal capillaries. In vitro studies indicate that the host's response involves the production of reactive oxygen species, although whether this occurs in vivo at the site of the infection is unknown. The role of oxidative processes in mice infected with S. mansoni was investigated in the current study using the antioxidant melatonin. In Experiment 1, the survival rate of infected mice with and without daily melatonin (10 mg/kg) administration was determined. After 56 d, 25 of 25 infected mice that were diluent treated had died. In contrast, 22 or 25 infected mice (88%) given melatonin were still alive at 56 d. Of these 22 surviving mice, melatonin injections were continued in 11 while the 11 others were switched to diluent. Within 10 d, 11 of 11 diluent-injected mice that were infected with S. mansoni were dead while 6 of 11 melatonin-treated mice survived. In Experiment 2, S. mansoni-infected mice were treated for 30 d with either melatonin or diluent. Uninfected, untreated mice served as controls. In these mice, the levels of lipid peroxidation (LPO) products, vitamin E, nitric oxide (NO), glutathione (GSH), and superoxide dismutase (SOD) activity in the liver, kidney, and spleen were measured. In the serum, cholesterol levels and liver damage (alkaline phosphatase (ALP), aspartate transaminases (AST), total protein, and albumin) were monitored. In addition, peroxynitrite anion (ONOO(-)) in the liver and kidney and inducible nitric oxide synthase (iNOS) in the spleen were immunocytochemically localized. Also, histopathological changes in the liver, kidney, and spleen were examined. The results documented increased LPO and NO levels and decreased vitamin E, GSH, and SOD activity in the liver, kidney, and spleen of S. mansoni-infected mice. Also, there was an increase in serum cholesterol and evidence of liver damage in the infected mice. Immunohistochemical results indicated positive staining of ONOO(-) in the liver and kidney and positive iNOS staining in the spleen of S. mansoni-infected mice. Histopathological observations revealed granuloma formation in the liver with eosinophil infiltration, a large number of megakaryocytes in the spleen, and degeneration with necrotic cells in some tubules of the kidney cortex in the infected mice. Melatonin administration after S. mansoni infection prevented most of the previously described changes. These results suggest that oxidative processes occur at the site of inflammation and are involved in the damaging effects of schistosomiasis and indicate that free radicals may be a major component of the disease. Likewise, melatonin, presumably due to its antioxidant and free radical scavenging activity, is highly protective against the pathological changes associated with schistosomiasis.