The effect of DL-propranolol on γ-aminolevulinic acid synthetase activity and urinary excretion of porphyrins in allylisopropylacetamide-induced experimental porphyria

Experimental porphyria was induced in rats by allylisopropylacetamide. DL-Propranolol, a β-adrenergic-receptor blocking agent, significantly reduced the elevated urinary excretion of δ-aminolevulinic acid, porphobilinogen and total porphyrins. DL-Propranolol also partially prevented the increased activity of δ-aminolevulinic acid synthesis in liver homogenates of allylisopropylacetamide-treated rats. It had no effect on the above parameters in normal rats. These findings support the hypothesis that δ-aminolevulinic acid exists in two forms, a constitutive and an inducible one.In order to examine whether the action of the drug was caused by its membrane effect. D-propranolol and quinidine sulphate were used in similar sets of experiments. These drugs had no effect on the abnormal porphyrin metabolism of allylisoprpyl-acetamide-treated rats, indicating that the results obtained with DL-propranolol were not due to its membrane action.     

Ancient dominance of the Quercus calliprinos - Pistacia palaestina association in mediterranean Israel

Abstract. The natural Mediterranean maquis and forest vegetation of Israel is commonly considered to be composed mainly of four, roughly equal components: Pinus halepensis, deciduous oak, evergreen oak, and Ceratonia - Pistacia communities. They represent the past climax and subclimax of this region. Evidence accumulated from pollen analysis and wood remnant research in geological and archaeological excavations, as well as from written historical sources, shows that this view is wrong: the ancient vegetation in this area was dominated by Quercus calliprinos.     

Mechanism of aluminium-induced porphyrin synthesis in bacteria

In previous studies, aluminium was found to retard bacterial growth and enhance porphyrin formation in Arthrobacter aurescens RS-2. The aim of this study was to establish the mechanism of action of aluminium which leads to increased porphyrin production. Cultures of Arthrobacter aurescens RS-2 were incubated in the absence and presence of 0.74 mm aluminium. After 6 and 24 h of incubation, various parameters of the haem biosynthetic pathway were determined. After 6 h of incubation with aluminium, the activities of the enzymes aminolevulinate synthase (ALAS), aminolevulinate dehydratase (ALAD), porphobilinogen deaminase (PBGD) and uroporphyrinogen decarboxylase (UROD) were increased by 120, 170, 190 and 203%, respectively, while that of ferrochelatase (FC) was found to be unchanged. However, after 24 h of incubation, no change in the activities of ALAS and ALAD was noted, while an about 2-fold increase in PBGD and UROD activities were observed. FC activity was decreased by 63%. It was concluded that aluminium exerts its effect by inducing the enzymes PBGD and UROD rather than by a direct or indirect effect on ALAS. Its effect on the final step in the haem biosynthetic pathway is discussed.     

Transcriptional Heterogeneity of Beta Cells in the Intact Pancreas

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Regulatory proteins alter nucleotide binding to acto-myosin of sliding filaments in motility assays

The sliding speed of unregulated thin filaments in motility assays is only about half that of the unloaded shortening velocity of muscle fibers. The addition of regulatory proteins, troponin and tropomyosin, is known to increase the sliding speed of thin filaments in the in vitro motility assay. To learn if this effect is related to the rate of MgADP dissociation from the acto-S1 cross-bridge head, the effects of regulatory proteins on nucleotide binding and release in motility assays were measured in the presence and absence of regulatory proteins. The apparent affinity of acto-heavy meromyosin (acto-HMM) for MgATP was reduced by the presence of regulatory proteins. Similarly, the regulatory proteins increase the concentration of MgADP required to inhibit sliding. These results suggest that regulatory proteins either accelerate the rate of MgADP release from acto-HMM-MgADP or slow its binding to acto-HMM. The reduction of temperature also altered the relationship between thin filament sliding speed and the regulatory proteins. At lower temperatures, the regulatory proteins lost their ability to increase thin filament sliding speed above that of unregulated thin filaments. It is hypothesized that structural changes in the actin portion of the acto-myosin interface are induced by regulatory protein binding to actin.     

Comparison of the Four Proposed Apgar Scoring Systems in the Assessment of Birth Asphyxia and Adverse Early Neurologic Outcomes

Objectives

To compare the Conventional, Specified, Expanded and Combined Apgar scoring systems in predicting birth asphyxia and the adverse early neurologic outcomes.

Methods

This prospective cohort study was conducted on 464 admitted neonates. In the delivery room, after delivery the umbilical cord was double clamped and a blood samples was obtained from the umbilical artery for blood gas analysis, meanwhile on the 1- , 5- and 10- minutes Conventional, Specified, Expanded, and Combined Apgar scores were recorded. Then the neonates were followed and intracranial ultrasound imaging was performed, and the following information were recorded: the occurrence of birth asphyxia, hypoxic Ischemic Encephalopathy (HIE), intraventricular hemorrhage (IVH), and neonatal seizure.

Results

The Combined-Apgar score had the highest sensitivity (97%) and specificity (99%) in predicting birth asphyxia, followed by the Specified-Apgar score that was also highly sensitive (95%) and specific (97%). The Expanded-Apgar score was highly specific (95%) but not sensitive (67%) and the Conventional-Apgar score had the lowest sensitivity (81%) and low specificity (81%) in predicting birth asphyxia. When adjusted for gestational age, only the low 5-minute Combined-Apgar score was independently associated with the occurrence of HIE (B = 1.61, P = 0.02) and IVH (B = 2.8, P = 0.01).

Conclusions

The newly proposed Combined-Apgar score is highly sensitive and specific in predicting birth asphyxia and also is a good predictor of the occurrence of HIE and IVH in asphyxiated neonates.     

Gene expression of rat alveolar type II cells during hyperoxia exposure and early recovery

Alveolar epithelial cell (AEC) injury and repair during hyperoxia exposure and recovery have been investigated for decades, but the molecular mechanisms of these processes are not clear. To identify potentially important genes involved in lung injury and repair, we studied the gene expression profiles of isolated AEC II from control, 48-h hyperoxia-exposed (>95% O(2)), and 1-7 day recovering rats using a DNA microarray containing 10,000 genes. Fifty genes showed significant differential expression between two or more time points (P<0.05, fold change >2). These genes can be classified into 8 unique gene expression patterns. Real-time PCR verified 14 selected genes in three patterns related to hyperoxia exposure and early recovery. The change in the protein level for two of the selected genes, bmp-4 and retnla, paralleled that of the mRNA level. Many of these genes were found to be involved in cell proliferation and differentiation. In an in vitro AEC trans-differentiation culture model using AEC II isolated from control and 48-h hyperoxia-exposed rats, the expressions of the cell proliferation and differentiation genes identified above were consistent with their predicted roles in the trans-differentiation of AEC. These data indicate that a coordinated mechanism may control AEC differentiation during in vivo hyperoxia exposure and recovery as well as during in vitro AEC culture.