THERAPEUTIC STRATEGIES FOR THE INHIBITION OF INDUCIBLE NITRIC OXIDE SYNTHASE—POTENTIAL FOR A NOVEL CLASS OF ANTI-INFLAMMATORY AGENTS

In recent years, NO, a gas previously considered a potentially toxic chemical, has become established as a diffusible universal messenger mediating cell—cell communication throughout the body. In mammals, NO is a recognized mediator of blood vessel relaxation that helps to maintain blood pressure. In the central nervous system NO acts as a non-conventional neurotransmitter and participates in the establishment of long-term plasticity required for memory formation. In addition, NO is responsible for some parts of the host response to sepsis and inflammation and contributes to certain disease states. A number of strategies have emerged with regard to a pharmacological control of pathological NO overproductions. This review will discuss these novel therapeutic approaches that may provide new means for clinical medicine.     

Effects of L-cysteine on lead acetate induced neurotoxicity in albino mice

Lead is a toxic heavy metal that adversely affects nervous tissues; it often occurs as an environmental pollutant. We investigated histological changes in the cerebral cortex, hippocampus and cerebellum of adult albino mice following exposure to lead acetate. We also studied the possible ameliorative effect of the chelating agent, L-cysteine, on lead-induced neurotoxicity. We divided albino mice into six groups: 1) vehicle-only control, 2) L-cysteine control, 3 and 4) treated for 7 days with 20 and 40 mg/kg lead acetate, respectively, and 5 and 6) treated for 7 days with 20 and 40 mg/kg lead acetate, respectively, followed by 50 mg/kg L-cysteine for 7 days. Lead acetate administration caused disorganization of cell layers, neuronal loss and degeneration, and neuropil vacuolization. Brain sections from lead-intoxicated mice treated with L-cysteine showed fewer pathological changes; the neuropil showed less vacuolization and the neurons appeared less damaged. L-cysteine at the dose we used only marginally alleviated lead-induced toxicity.     

Localization of calcium in roots and microsomal membranes of corn by direct pyroantimonate precipitation

Many cell membrane systems, including microsomal vesicles of corn, are able to regulate calcium levels both in vivo and in vitro, often in an ATP-dependent, calmodulin-stimulated fashion. The purpose of this study was to determine calcium distribution in meristematic cells of intact tissue and microsomal vesicles from corn roots using direct pyroantimonate-osmium fixation. In root cells, precipitates were localized in mitochondria, plastids, the nucleus, endoplasmic reticulum, Golgi apparatus, and along the plasma membrane. Plasma membrane-enriched microsomal vesicles isolated from corn roots incubated in media to permit calcium transport before pyroantimonate-osmium fixation show internal precipitates associated with the membrane and in the lumen of the vesicles. De-staining of the sections with 1 mM EDTA or EGTA removed precipitate from the sections, confirming the presence of calcium in the antimonate precipitates. These data support biochemical data that this same membrane preparation exhibited ATP-dependent calcium sequestration that was stimulated by calmodulin, as measured by retention of 45Ca. This provides evidence that these membranes are responsible for ATP-requiring, calmodulin-stimulated calcium transport in the intact cell.     

Photosynthetic acclimation and water-use efficiency of three species of understory herbaceous bamboo (Gramineae) in Panama

Summary To assess the role of photosynthetic acclimation in the response of tropical understory herbs to treefall light gaps, photosynthetic response curves were determined for three species of herbaceous bamboo growing in treatments of sun and shade at Barro Calorado Island, Panama. Increased maximum photosynthetic capacity did not always accompany higher ramet production in the sun treatment. Pharus latifolius reproduced abundantly in both treatments, and produced more ramets and developed higher maximum photosynthetic capacity under higher irradiance. Streptochaeta spicata also produced a high percentage of reproductive ramets in both treatments and produced more ramets in the sun, did not show any significant differences in photosynthetic parameters between treatments. Streptochaeta sodiroana did not change maximum photosynthetic capacity in the sun, and had higher photosynthetic efficiency and lower mortality in the shade. Stable carbon isotope composition of leaves indicated that all three species developed higher water-use efficiency under higher irradiance. Photosynthetic flexibility may contribute to the ability of P. latifolius to reproduce in treefall gaps, whereas S. spicata and S. sodiroana may maintain the ability to fix carbon efficiently in low irradiance even when growing or persisting in gaps.     

Molecular evolution of mammalian lactate dehydrogenase-A genes and pseudogenes: association of a mouse processed pseudogene with a B1 repetitive sequence

A mouse genomic clone containing a lactate dehydrogenase-A (LDH-A) processed pseudogene and a B1 repetitive element was isolated, and a nucleotide sequence of approximately 3 kb was determined. The pseudogene and B1 element are flanked by perfect 13-bp repeats, and the B1 sequence starts at 14 nucleotides 3' to the presumptive polyadenylation signal of the pseudogene. The nucleotide sequences of the LDH-A genes and processed pseudogenes from mouse, rat, and human were compared, and a phylogenetic tree was constructed. The rate and pattern of nucleotide substitutions in the LDH-A pseudogenes are similar to previously reported results (Li et al. 1984). The average rate of nucleotide substitutions in the LDH-A pseudogenes is 4.3 X 10(- 9)/site/year. The substitutions of C----T and G----A are most frequent, and A----G substitutions are relatively high. The rate of synonymous substitutions in the LDH-A genes is 5.3 X 10(-9), which is not significantly higher than the average rate of 4.7 X 10(-9) for 35 mammalian genes. The rate of nonsynonymous substitutions in the LDH-A genes is 0.20 X 10(-9), which is considerably lower than the average rate of 0.88 X 10(-9) for 35 mammalian genes. Thus, the mammalian LDH-A gene appears to be highly conserved in evolution.      

Gravity-Induced Polar Transport of Calcium across Root Tips of Maize

Calcium movement across primary roots of maize (Zea mays, L.) was determined by application of ⁴⁵Ca²⁺ to one side of the root and collection of radioactivity in an agar receiver block on the opposite side. Ca movement across the root tip was found to be at least 20 times greater than movement across the elongation zone. The rapid movement of Ca across the tip was severely inhibited in roots from which the root cap had been removed. Ca movement across the tip was also strongly retarded in roots pretreated with 2,4-dinitrophenol or potassium cyanide. Orientation of roots horizontally had no effect on Ca movement across the elongation zone but caused a strong asymmetry in the pattern of Ca movement across the tip. In gravistimulated roots, the movement of Ca from top to bottom increased while movement from bottom to top decreased. The data indicate that gravistimulation induces polar movement of Ca toward the lower side of the root cap. An earlier report (Lee, Mulkey, Evans 1983 Science 220: 1375-1376) from this laboratory showed that artificial establishment of calcium gradients at the root tip can cause gravitropic-like curvature. Together, the two studies indicate that Ca plays a key role in linking gravistimulation to the gravitropic growth response in roots.     

Comparative life history and physiology of two understory Neotropical herbs

Summary Demography and physiology of two broad-leaved understory tropical herbs (Marantaceae) were studied in gaps and shaded understory in large-scale irrigated and control treatments during the dry season at Barro Colorado Island (BCI), Panama. Because photosynthetic acclimation potential may not predict light environments where tropical species are found, we studied a suite of physiological features to determine if they uniquely reflect the distribution of each species. Calathea inocephala and Pleiostachya pruinosa grow and reproduce in gaps, persist in shade, and have equivalent rates of leaf production. Calathea leaves survived 2 to 3 times as long as leaves of Pleiostachya and plants of Pleiostachya were 6 to 8 times more likely to die as plants of Calathea during 3.5 years of study. Pleiostachya had lowest survival in shade and when not irrigated during the dry season, while Calathea survived well in both habitats and both treatments. Pleiostachya had higher photosynthetic capacity and stomatal conductance than Calathea and acclimated to gaps by producing leaves with higher photosynthetic capacity. Calathea had lower mesophyll CO₂ concentrations than Pleiostachya. Both species had similar dark respiration rates and light compensation points, and water-use and nitrogen-use efficiencies were inversely related between species. Species showed no differences in leaf osmotic potentials at full turgor. Calathea roots were deeper and had tuberous swellings.Leaf-level assimilation and potential water loss are consistent with where these species are found, but photosynthetic acclimation to high light does not reflect both species' abilities to grow and reproduce in gaps. Pleiostachya's gap-dependent, rapid growth and reproduction require high rates of carbon gain in short-lived leaves, which can amortize their cost quickly. High rates of water loss are associated with reduced longevity during drought. Calathea's roots may confer greater capacitance, while its leaves are durable, long-lived and have lower water loss, permitting persistence long after gap closure.     

Phylogenetic screening of the human genome: identification of differentially hybridizing repetitive sequence families

The phi-screen, a method of phylogenetic screening, can be employed to detect repetitive sequence families that differentially hybridize between closely related species. Such differences may involve sequence divergence or variations in copy number, including total presence versus absence of a family of repeated DNA. We present the results of a phi-screen comparing the human genome to that of the prosimian, Galago crassicaudatus. Three human repetitive families that are divergent or not present in galago have been detected. One of these families is described in detail; it is similar among the anthropoids but is present in a lower copy number and/or divergent form in prosimians. The family is clearly related to the transposon-like human element (THE) described by Paulson et al. (1985). THEs have long terminal repeats reminiscent of retroviruses but are unique in that they have no sequence similarity to known mammalian retroviruses. The sequence of a solo long terminal repeat, found unassociated with THE internal sequence, is presented. This family member, THE p2, is bordered by a 5-bp target-site repeat and is interrupted by the insertion of an Alu element. A solo THE element sequenced by Wiginton et al. (1986) contains an insertion of Alu at precisely the same position as does THE p2.      

Evaluation of the prevalence and economic burden of adverse drug reactions presenting to the medical emergency department of a tertiary referral centre: a prospective study

Background  

Adverse drug reactions (ADRs) are now recognized as an important cause of hospital admissions, with a proportion ranging from 0.9–7.9%. They also constitute a significant economic burden. We thus aimed at determining the prevalence and the economic burden of ADRs presenting to Medical Emergency Department (ED) of a tertiary referral center in India