Effects of excess nicotinamide administration on the urinary excretion of nicotinamide N-oxide and nicotinuric acid by rats

We investigated a useful chemical index for an excessive nicotinamide intake and how this excessive nicotinamide intake affects the tryptophan-nicotinamide metabolism in rats. Weaning rats were fed on a tryptophan-limited and nicotinic acid-free diet containing no, 0.003%, 0.1%, 0.2%, or 0.3% nicotinamide for 21 days. Urine samples were collected on the last day and analyzed the intermediates and metabolites on the tryptophan-nicotinamide pathway. Nicotinamide N-oxide, nicotinic acid and nicotinuric acid, metabolites of nicotinamide, were detected when nicotinamide at more than 0.1% had been taken. An intake of nicotinamide of more than 0.1% increased the urinary excretion of quinolinic acid, an intermediate on the pathway. Nicotinamide N-oxide and nicotinuric acid increased with increasing dietary concentration of nicotinamide. These results show that the measurements of nicotinamide N-oxide and nicotinuric acid in urine would be useful indices for an excessive nicotinamide intake.     

A mutant with constitutive sexual organ development in<Emphasis Type="Italic"> Marchantia polymorpha</Emphasis> L.

In lower land plants, genes controlling the transition from vegetative growth to sexual reproduction have not yet been identified. In the dioecious liverwort Marchantia polymorpha, the transition to sexual reproduction accompanied by the formation of sexual organs on the gametophytic thallus is initiated under long-day conditions. By particle bombardment-mediated mutagenesis, we generated a mutant of M. polymorpha that constitutively forms sexual organs. This mutant is fully fertile, showing that the mutation does not affect formation of male or female sexual organs per se. Genetic analysis reveals that this phenotype is caused by mutation of a single autosomal locus, suggesting that this mutation defines or controls a gene regulating the transition to sexual reproduction in M. polymorpha.     

Histochemical,ultrastructural, and three-dimensional observation of smooth muscle cells in human gastric mucosa

The present study was undertaken to clarify the histochemical and ultrastructural properties and the three-dimensional distribution of the smooth muscle cells (SMCs) located in the lamina propria (LP) of the human gastric mucosa. Standard paraffin sections obtained from stomachs surgically resected for gastric cancer were immunostained for alpha-smooth muscle actin (alpha-SMA), vimentin, desmin, laminin, and type IV collagen. In addition, 100-m-thick sections were fluorostained for alpha-SMA and CD34, while three-dimensional images were prepared by confocal laser scanning microscope. Ultrastructural studies were carried out using normal gastric biopsy specimens. The results indicated that SMCs in the LP differed between the upper and lower regions, SMCs in the lower LP being fairly typical SMCs, whereas those in the upper LP had apparently lost reactivity for desmin but gained that for vimentin. The basal lamina became sparser, but a fibronexus was occasionally seen in SMCs in the upper LP. Three-dimensional images revealed bundles of SMCs in the upper LP encircling several foveolae to form acinus-like structures and, in the upper LP, SMCs branching into fine fibrils with a brush-like (corpus) or besom-like (i.e., a twiggy witchs broom) appearance (antrum).     

Antibacterial activity of hydrolyzable tannins derived from medicinal plants against Helicobacter pylori

Helicobacter pylori is a major etiological agent in gastroduodenal disorders. In this study, we isolated 36 polyphenols and 4 terpenoids from medicinal plants, and investigated their antibacterial activity against H. pylori in vitro. All hydrolyzable tannins tested demonstrated promising antibacterial activity against H. pylori. Monomeric hydrolyzable tannins revealed especially strong activity. Other compounds demonstrated minimal antibacterial activity with a few exceptions. A monomeric hydrolyzable tannin, Tellimagrandin I demonstrated time- and dose-dependent bactericidal activity against H. pylori in vitro. On the other hand, hydrolyzable tannins did not affect the viability of MKN-28 cells derived from human gastric epithelium. Hydrolyzable tannins, therefore, have potential as new and safe therapeutic regimens against H. pylori infection. Furthermore, we investigated effects of hydrolyzable tannins on lipid bilayer membranes. All the hydrolyzable tannins tested demonstrated dose-dependent membrane-damaging activity. However, it remains to be elucidated whether their membrane-damaging activity directly contributes to their antibacterial action.     

Epidemiology of leishmaniasis in Ecuador: current status of knowledge -- a review

Although leishmaniasis is regarded as a significant health problem in Ecuador by the Ministry of Health, and the incidence has increased over the last years, an official map on the geographic distribution of disease and sand fly vectors or a control strategy do not exist yet. This article reviews the current situation based on published information to improve our knowledge and understand the epidemiological situation of leishmaniasis in Ecuador in order to help future research and to develop a national control strategy. The disease is endemic in most provinces throughout Pacific coastal region, Amazonian lowlands, and some inter-Andean valleys with a total 21,805 cases reported during 1990-2003. Whereas cutaneous leishmaniasis (CL) is found throughout Ecuador, mucocutaneous leishmaniasis (MCL) appears to be restricted to the Amazon region; one, parasitologically unconfirmed case of visceral form was reported in 1949. Most human infections are caused by Leishmania (Viannia) spp., which is distributed in the subtropical and tropical lowlands; infections due to L. (Leishmania) spp. are found in the Andean highlands and in the Pacific lowlands as well. The proven vectors are Lutzomyia trapidoi and Lu. ayacuchensis. Canis familiaris, Sciurus vulgaris, Potos flavus, and Tamandua tetradactyla have been found infected with Leishmania spp. It is estimated that around 3000-4500 people may be infected every year, and that 3.1 to 4.5 millions people are estimated to be at risk of contracting leishmaniasis.     

Sequence boundary and related sedimentary and diagenetic facies formed on Middle Permian mid-oceanic carbonate platform: Core observation of Akiyoshi Limestone,Southwest Japan

Detailed core observation of the Akiyoshi Limestone, Southwest Japan, reveals a sequence boundary and related sedimentary and diagenetic facies formed on a late Murgabian (Middle Permian) mid-oceanic carbonate platform. The sequence boundary lies upon karstified bioclastic grainstone and is overlain by peritidal lime- and dolo-mudstone. The karstified bioclastic grainstone, which had been affected by subaerial exposure and early diagenetic processes, is characterized by crystal silts, prismatic, bladed and dogtooth cements, blackened limestone features, and alveolar textures. The overlying peritidal lime- and dolo-mudstone is 8 m thick and exhibits fenestrae, fissures, laminations, black pebbles, and low-diversity biota composed exclusively of ostracodes and calcispherids. The sequence boundary almost coincides with a major fusulinoidean biostratigraphic boundary. A sea-level fall in the late Murgabian resulted in a biotic turnover and formed the sequence boundary and the karst textures. The following relatively slow transgression resulted in the deposition of the thick transgressive peritidal unit.     

Inhibition of sphingomyelinase activity helps to prevent neuron death caused by ischemic stress

Magnesium-dependent neutral sphingomyelinase (N-SMase) present in plasma membranes is an enzyme that can be activated by stress in the form of inflammatory cytokines, serum deprivation, and hypoxia. The design of small molecule N-SMase inhibitors may offer new therapies for the treatment of inflammation, ischemic injury, and cerebral infarction. Recently, we synthesized a series of difluoromethylene analogues (SMAs) of sphingomyelin. We report here the effects of SMAs on the serum/glucose deprivation-induced death of neuronally differentiated pheochromocytoma (PC-12) cells and on cerebral infarction in mice. SMAs inhibited the enhanced N-SMase activity in the serum/glucose-deprived PC-12 cells, and thereby suppressed the apoptotic sequence: ceramide formation, c-Jun N-terminal kinase phosphorylation, caspase-3 activation, and DNA fragmentation in the nuclei. Administration of SMA-7 (10 mg/kg i.v.) with IC50= 3.3 microM to mice whose middle cerebral arteries were occluded reduced significantly the size of the cerebral infarcts, compared to the control mice. These results suggest that N-SMase is a key component of the signaling pathways in cytokine- and other stress-induced cellular responses, and that inhibiting or stopping N-SMase activity is an important strategy to prevent neuron death from ischemia.     

Role of arginine in protein refolding, solubilization, and purification

Recombinant proteins are often expressed in the form of insoluble inclusion bodies in bacteria. To facilitate refolding of recombinant proteins obtained from inclusion bodies, 0.1 to 1 M arginine is customarily included in solvents used for refolding the proteins by dialysis or dilution. In addition, arginine at higher concentrations, e.g., 0.5-2 M, can be used to extract active, folded proteins from insoluble pellets obtained after lysing Escherichia coli cells. Moreover, arginine increases the yield of proteins secreted to the periplasm, enhances elution of antibodies from Protein-A columns, and stabilizes proteins during storage. All these arginine effects are apparently due to suppression of protein aggregation. Little is known, however, about the mechanism. Various effects of solvent additives on proteins have been attributed to their preferential interaction with the protein, effects on surface tension, or effects on amino acid solubility. The suppression of protein aggregation by arginine cannot be readily explained by either surface tension effects or preferential interactions. In this review we show that interactions between the guanidinium group of arginine and tryptophan side chains may be responsible for suppression of protein aggregation by arginine.     

Physiological and subjective responses in the elderly when using floor heating and air conditioning systems

The purpose of this study was to investigate the effects of a floor heating and air conditioning system on thermal responses of the elderly. Eight elderly men and eight university students sat for 90 minutes in a chair under the following 3 conditions: air conditioning system (A), floor heating system (F) and no heating system (C). The air temperature of sitting head height for condition A was 25 degrees C, and the maximum difference in vertical air temperature was 4 degrees C. The air and floor temperature for condition F were 21 and 29 degrees C, respectively. The air temperature for condition C was 15 degrees C. There were no significant differences in rectal temperature and mean skin temperature between condition A and F. Systolic blood pressure of the elderly men in condition C significantly increased compared to those in condition A and F. No significant differences in systolic blood pressure between condition A and F were found. The percentage of subjects who felt comfortable under condition F was higher than that of those under condition A in both age groups, though the differences between condition F and A was not significant. Relationships between thermal comfort and peripheral (e.g., instep, calf, hand) skin temperature, and the relationship between thermal comfort and leg thermal sensation were significant for both age groups. However, the back and chest skin temperature and back thermal sensation for the elderly, in contrast to that for the young, was not significantly related to thermal comfort. These findings suggested that thermal responses and physiological strain using the floor heating system did not significantly differ from that using the air conditioning system, regardless of the subject age and despite the fact that the air temperature with the floor heating system was lower. An increase in BP for elderly was observed under the condition in which the air temperature was 15 degrees C, and it was suggested that it was necessary for the elderly people to heat the room somehow in winter. Moreover, it is particularly important for elderly people to avoid a decrease in peripheral skin temperature, and maintain awareness of the warmth of peripheral areas, such as the leg, in order to ensure thermal comfort.     

BAC libraries and comparative genomics of aquatic chordate species

The bacterial artificial chromosome (BAC) system is useful for creating a representation of the genomes of target species. The system is advantageous in that it can accommodate exogenous inserts that are very large (>100 kilobases, kb), thereby allowing entire eukaryotic genes (including flanking regulatory regions) to be encompassed in a single clone. The interest in BACs has recently been spawned by vast improvements in high throughput genomic sequencing such that comparisons of orthologous regions from different genomes (comparative genomics) are being routinely investigated, and comprise a significant component, of all major sequencing centers. In this review, we discuss the general principles of BAC cloning, the resources that are currently available, and some of the applications of the technology. It is not intended to be an exhaustive treatise; rather our goal is to provide a primer of the BAC technology in order to make readers aware of these resources and how they may utilize them in their own research programs.