CT-guided stereotactic aspiration of intracerebral hematoma--result of a hematoma-lysis method using urokinase

CT-guided stereotactic aspiration was performed in the CT room on 97 patients with hypertensive intracerebral hematomas, using a standard ventricular cannula. Residual hematomas were liquefied by urokinase and aspirated through the drainage tube. Major and minor rebleeding were seen in 7 cases. Two out of the 4 major rebleeding cases were followed by craniotomy, while the other cases were treated conservatively. More than 80% of the hematomas were aspirated in 68 cases, 50-70% in 19 cases and 30-40% in 6 cases. Operation in the CT room and hematoma lysis with urokinase is very useful for the aspiration of intracerebral hematomas.     

The mechanism of the stimulation of LH production by synthetic LH-releasing hormone (LH-RH) in tissue culture

Synthetic LH-RH was found to stimulate production of LH by human female adenohypophysis in monolayer culture. This effect occurs at 0.30 μg/2 ml LH-RH. New messenger-RNA synthesis does not have to occur to stimulate the production of LH by the action of synthetic LH-RH in cultures of under 4 days. In cultures of over 4 days, this synthesis must occur in order for LH to be produced by the action of LH-RH. However, new DNA synthesis does not have to occur to stimulate the production of LH by the action of synthetic LH-RH.     

Environmental perturbations influence telomere dynamics in long-lived birds in their natural habitat

Telomeres are regarded as markers of biological or cellular ageing because they shorten with the degree of stress exposure. Accordingly, telomere lengths should show different rates of change when animals are faced with different intensities of environmental challenges. However, a relationship between telomere length and the environment has not yet been tested within a natural setting. Here, we report longitudinal telomere dynamics in free-living, black-tailed gulls (Larus crassirostris) through the recapture of birds of a known age over 2–5 consecutive years. The rate of change in telomere lengths differed with respect to year but not sex or age. The years when gulls showed stable telomere lengths or increases in telomere lengths (from 2009 to 2010) and decreases in telomere lengths (from 2010 to 2011) were characterized by El Niño and the Great Japan Earthquake, respectively. Both events are suspected to have had long-lasting effects on food availability and/or weather conditions. Thus, our findings that telomere dynamics in long-lived birds are influenced by dramatic changes in environmental conditions highlight the importance of environmental fluctuations in affecting stress and lifespan.     

Stroke and glide of wing-propelled divers: deep diving seabirds adjust surge frequency to buoyancy change with depth

In order to increase locomotor efficiency, breath-holding divers are expected to adjust their forward thrusts in relation to changes of buoyancy with depth. Wing propulsion during deep diving by Brünnich's guillemots (Uria lomvia) was measured in the wild by high-speed (32 Hz) sampling of surge (tail-to-head) and heave (ventral-to-dorsal) accelerations with bird-borne data loggers. At the start of descent, the birds produced frequent surges (3.2 Hz) during both the upstroke and the downstroke against buoyancy to attain a mean speed of 1.2-1.8 m s(-1) that was close to the expected optimal swim speed. As they descended deeper, the birds decreased the frequency of surges to 2.4 Hz, relaying only on the downstroke. During their ascent, they stopped stroking at 18 m depth, after which the swim speed increased to 2.3 m s(-1), possibly because of increasing buoyancy as air volumes expanded. This smooth change of surge frequency was achieved while maintaining a constant stroke duration (0.4-0.5 s), presumably allowing efficient muscle contraction.     

Brünnich's guillemots (Uria lomvia) maintain high temperature in the body core during dives

A major challenge for diving birds, reptiles, and mammals is regulating body temperature while conserving oxygen through a reduction in metabolic processes. To gain insight into how these needs are met, we measured dive depth and body temperatures at the core or periphery between the skin and abdominal muscles simultaneously in freely diving Brünnich's guillemots (Uria lomvia), an arctic seabird, using an implantable data logger (16-mm diameter, 50-mm length, 14-g mass, Little Leonardo Ltd., Tokyo). Guillemots exhibited increased body core temperatures, but decreased peripheral temperatures, during diving. Heat conservation within the body core appeared to result from the combined effect of peripheral vasoconstriction and a high wing beat frequency that generates heat. Conversely, the observed tissue hypothermia in the periphery should reduce metabolic processes as well as heat loss to the water. These physiological effects are likely one of the key physiological adaptations that makes guillemots to perform as an efficient predator in arctic waters.     

Studies on the structure-activity relationship of 2',6'-dimethyl-l-tyrosine (Dmt) derivatives: bioactivity profile of H-Dmt-NH-CH(3)

The 2',6'-dimethyl-l-tyrosine (Dmt) enhances receptor affinity, functional bioactivity and in vivo analgesia of opioid peptides. To further investigate its direct influence on these opioid parameters, we developed a series of compounds (H-Dmt-NH-X). Among them, H-Dmt-NH-CH(3) showed the highest affinity (K(i)mu=7.45 nM) equal to that of morphine, partial mu-opioid agonism (E(max)=66.6%) in vitro and a moderate antinociception in mice.     

Effect of persistent activation of phosphoinositide 3-kinase on heart

AimsInsulin/insulin-like growth factor-1 (IGF-1) signaling plays an important role in many biological processes. The class IA isoform of phosphoinositide 3-kinase (PI3K) is an important downstream effector of the insulin/IGF-1 signaling pathway. The aim of this study is to examine the effect of persistent activation of PI3K on gene expression and markers of cellular senescence in murine hearts.Main methodsTransgenic mice expressing a constitutively active PI3K in a heart-specific manner were analyzed at the ages of 3 and 20 months. Effects of persistent activation of PI3K on gene expression were comprehensively analyzed using microarrays.Key findingsUpon comprehensive gene expression profiling, the genes whose expression was increased included those for several heat shock chaperons. The amount and nuclear localization of a forkhead box O (FOXO) protein was increased. In addition, the gene expression of insulin receptor substrate-2 decreased, and that of phosphatase and tensin homolog deleted on chromosome ten (PTEN) increased, suggesting that the persistent activation of PI3K modified the expression of molecules of insulin/IGF-1 signaling. The expression of markers of cellular senescence, such as senescence-associated beta-galactosidase activity, cell cycle inhibitors, proinflammatory cytokines, and lipofuscin, did not differ between old wild-type and caPI3K mice.SignificanceThe persistent activation of PI3K modified the expression of molecules of insulin/IGF-1 signaling pathway in a transgenic mouse line. Markers of cellular senescence were not changed in the aged mutant mice.     

Benefits of mass reduction for commuting flight with heavy food load in Leach’s storm-petrel,Oceanodroma leucorhoa

When rearing chicks, Leach’s storm-petrels (Oceanodroma leucorhoa) commute between foraging areas and breeding colonies with heavy food loads. At this time they should maximize the size of energy-supplying organs in response to increased energy expenditure but minimize total body mass to decrease the energetic cost of flight. Nineteen storm-petrels were killed to examine the changes in body composition and the masses of energy-supplying organs in birds that were incubating and rearing chicks. Parents lost a mean of 7.95 g in body mass between the stages of incubation and chick-rearing mainly via a loss of skin including subcutaneous adipose tissue, and a small fraction of heart and digestive organs, which are considered energy-supplying organs. This mass loss actually enables them to decrease flight cost by 14.4%. The benefits of decreasing flight costs by reducing total body mass are greater than if the energy-supplying organs of birds are enlarged only.

     

Stress‐induced tRNA cleavage and tiRNA generation in rat neuronal PC12 cells

Transfer RNA (tRNA) plays a role in stress response programs involved in various pathological conditions including neurological diseases. Under cell stress conditions, intracellular tRNA is cleaved by a specific ribonuclease, angiogenin, generating tRNA‐derived fragments or tRNA‐derived stress‐induced RNA (tiRNA). Generated tiRNA contributes to the cell stress response and has potential cell protective effects. However, tiRNA generation under stress conditions in neuronal cells has not been fully elucidated. To examine angiogenin‐mediated tiRNA generation in neuronal cells, we used the rat neuronal cell line, PC12, in combination with analysis of SYBR staining and immuno‐northern blotting using anti‐1‐methyladenosine antibody, which specifically and sensitively detects tiRNA. Oxidative stress induced by arsenite and hydrogen peroxide caused tRNA cleavage and tiRNA generation in PC12 cells. We also demonstrated that oxygen‐glucose deprivation, which is an in vitro model of ischemic–reperfusion injury, induced tRNA cleavage and tiRNA generation. In these stress conditions, the amount of generated tiRNA was associated with the degree of morphological cell damage. Time course analysis indicated that generation of tiRNA was prior to severe cell damage and cell death. Angiogenin over‐expression did not influence the amount of tiRNA in normal culture conditions; however, it significantly increased tiRNA generation induced by cell stress conditions. Our findings show that angiogenin‐mediated tiRNA generation can be induced in neuronal cells by different cell stressors, including ischemia–reperfusion. Additionally, detection of tiRNA could be used as a potential cell damage marker in neuronal cells.

Cover Image for this issue: doi: 10.1111/jnc.14191 .

     

Synthesis and biological activities of a pH-dependently activated water-soluble prodrug of a novel hexacyclic camptothecin analog

CH0793076 (1) is a novel hexacyclic camptothecin analog showing potent antitumor activity in various human caner xenograft models. To improve the water solubility of 1, water-soluble prodrugs were designed to generate an active drug 1 nonenzymatically, thus expected to show less interpatient PK variability than CPT-11. Among the prodrugs synthesized, 4c (TP300, hydrochloride) having a glycylsarcosyl ester at the C-20 position of 1 is highly water-soluble (>10 mg/ml), stable below pH 4 and rapidly generates 1 at physiological pH in vitro. The rapid (ca. <1 min) generation of 1 after incubation of TP300 with plasma (mouse, rat, dog and monkey) was also demonstrated. TP300 showed a broader antitumor spectrum and more potent antitumor activity than CPT-11 in various human cancer xenograft models.