Bioactive Neolignans and Other Compounds from Magnolia grandiflora L.: Isolation and Antiplasmodial Activity

Bioassay‐guided fractionation of a methanol extract of Magnolia grandiflora against Plasmodium falciparum yielded two new ( 1 and 2 ) and six known ( 3 – 8 ) bioactive compounds. The structures of the new compounds were assigned by mass spectrometric and 1D‐ and 2D‐NMR data. Known compounds were identified by comparison of ¹H‐NMR and MS data with literature data. The two known neolignans 3 and 4 showed moderate antiplasmodial activity with the IC₅₀ values of 2.8 ± 0.1 and 3.4 ± 0.1 μm , respectively. Weak antiplasmodial activity was recorded for compounds 1 , 2 , 5 , 6 , 7 , and 8 , with the IC₅₀ values of 38 ± 2, 23 ± 2, 16.5 ± 0.2, 86 ± 1, 44 ± 4, and 114 ± 9 μm , respectively.     

The Non-NMDA Glutamate Receptor Antagonists 6-Cyano-7-Nitroquinoxaline-2,3-dione and 2,3-Dihydroxy-6-Nitro-7-Sulfamoylbenzo(f)quinoxaline, but Not NMDA Antagonists, Block the Intrastriatal Neurotoxic Effect of MPP+

Altered glutamatergic neurotransmission appears to be central to the pathophysiology of Parkinson's disease; consequently, considerable effort has been made to elucidate neuroprotective mechanisms against such toxicity. In the present study, the possible neuroprotective effect of glutamate receptor antagonists against MPP+ neurotoxicity on dopaminergic terminals of rat striatum was investigated. Different doses of glutamate receptor antagonists were coinfused with 1.5 microg of MPP+ into the striatum; kynurenic acid, a nonselective antagonist of glutamate receptors (30 and 60 nmol), partially protected dopaminergic terminal degeneration in terms of rescue of dopamine levels and tyrosine hydroxylase immunohistochemistry. Dizocilpine, a channel blocker of the NMDA receptor (1, 4, and 8 nmol), and 7-chlorokynurenic acid, a selective antagonist at the glycine site of the NMDA receptor (1 and 10 nmol), failed to protect dopaminergic terminals from MPP+ toxicity. However, 6-cyano-7-nitroquinoxaline-2,3-dione (0.5 and 1 nmol) and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (1 nmol), two AMPA-kainate receptor antagonists, protected against MPP toxicity. Our findings suggest that the toxic effects of MPP+ on dopaminergic terminals are not mediated through a direct interaction with the NMDA subtype of glutamate receptor, but with the AMPA-kainate subtype.     

Environmental and genetic variation in the haematocrit of fledgling pied flycatchers Ficedula hypoleuca

We exposed females of a highly placentotrophic viviparous scincid lizard (Pseudemoia pagenstecheri) to various environmental factors during pregnancy, and quantified the effects of these treatments on their offspring. The clear result was that the phenotypes of neonatal lizards can be substantially modified by the environment that their mother experiences during gestation. Restricting prey availability to the females reduced the size of their offspring. Limiting the females' basking opportunities delayed their seasonal timing of parturition, and modified body proportions (tail length relative to snout-vent length) of the neonates. More surprisingly, female lizards that were regularly exposed to the scent of sympatric lizard-eating snakes gave birth to offspring that were heavier, had unusually long tails relative to body length, and were highly sensitive to the odour of those snakes (as measured by tongue-flick responses). The neonates' antipredator responses were also modified by the experimental treatment to which their mother was exposed. The modifications in body mass, tail length and response to snake scent plausibly reduce the offspring's vulnerability to predatory snakes, and hence may constitute adaptive maternal manipulations of the neonatal phenotype. Received: 6 July 1998 / Accepted: 5 December 1998     

Production of limonoate A-ring lactone by immobilized limonin D-ring lactone hydrolase

Summary Limonin D-ring lactone hydrolase, the enzyme catalysing the reversible lactonization/hydrolysis of D-ring in limonin, has been purified from Citrus seeds and immobilized on Q-Sepharose to produce homogeneous limonoate A-ring lactone solutions. The immobilized limonin D-ring lactone hydrolase showed a good operational stability and was stable after sixty-seventy operations and storing at 4°C for six months.     

Messenger-dependent action of guanylylimidodiphosphate and translation inhibitors on rat brain polypeptide synthesis

The effects of the Guanosine 5'-triphosphate analog guanylylimidodiphosphate and several antibiotics on protein synthesis in a cell-free system from rat brain were investigated as a function of the template used. Polypeptide chain elongation was promoted by the analog only in the system coded by the endogenous template but not when coded by polyuridylic acid. The effects of the antibiotics were also dependent on the template used. This suggest that the template conditioned the ribosomal conformation which determine the inhibitory effect of the antibiotics.     

Developmental regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes.

Cell death is a prominent feature of B cell development. For example, a large population of B cells dies at the pre-B cell stage presumably due to the failure to express a functional immunoglobulin receptor. In addition, developing B cells expressing antigen receptors for self are selectively eliminated at the immature B cell stage. The molecular signals that control B cell survival are largely unknown. The product of the bcl-2 proto-oncogene may be involved as its overexpression inhibits apoptotic cell death in a variety of biological systems. However, the physiological role of the endogenous Bcl-2 protein during B cell development is undetermined. Here we show a striking developmental regulation of the Bcl-2 protein in B lymphocytes. Bcl-2 is highly expressed in CD43+ B cell precursors (pro-B cells) and mature B cells but downregulated at the pre-B and immature B cell stages of development. We found that Bcl-2 expressed by B cells is a long-lived protein with a half-life of approximately 10 h. Importantly, susceptibility to apoptosis mediated by the glucocorticoid hormone dexamethasone is stage-dependent in developing B cells and correlates with the levels of Bcl-2 protein. Furthermore, expression of a bcl-2 transgene rescued pre-B and immature B cells from dexamethasone-induced cell death, indicating that Bcl-2 can inhibit the apoptotic cell death of progenitors and early B cells. Taken together, these findings argue that Bcl-2 is a physiological signal controlling cell death during B cell development.     

Ozone oxidative preconditioning: a protection against cellular damage by free radicals.

There is some anecdotal evidence that oxygen-ozone therapy may be beneficial in some human diseases. However so far only a few biochemical and pharmacodynamic mechanisms have been elucidated. On the basis of preliminary data we postulated that controlled ozone administration would promote an oxidative preconditioning preventing the hepatocellular damage mediated by free radicals. Six groups of rats were classified as follows: (1) negative control, using intraperitoneal sunflower oil; (2) positive control using carbon tetrachloride (CCl4) as an oxidative challenge; (3) oxygen-ozone, pretreatment via rectal insufflation (15 sessions) and after it, CCl4; (4) oxygen, as group 3 but using oxygen only; (5) control oxygen-ozone, as group 3, but without CCl4; group (6) control oxygen, as group 5, but using oxygen only. We have evaluated critical biochemical parameters such as levels of transaminase, cholinesterase, superoxide dismutase, catalase, phospholipase A, calcium dependent ATPase, reduced glutathione, glucose 6 phosphate dehydrogenase and lipid peroxidation. Interestingly, in spite of CCl4 administration, group 3 did not differ from group 1, while groups 2 and 4 showed significant differences from groups 1 and 3 and displayed hepatic damage. To our knowledge these are the first experimental results showing that repeated administration of ozone in atoxic doses is able to induce an adaptation to oxidative stress thus enabling the animals to maintain hepatocellular integrity after CCl4 poisoning.     

Spirometric parameters of the working population of young non-smoking males of the Murcia area

A prospective study on dynamic spirometric parameters on 195 healthy non-smoking men-workers, representing the non-smoking labor population from 16 to 40 years of age, in the Murcia Region (Spain), has been carried out. Men were selected upon two criteria: age and height. Lower normality limits, have been estimated with 95% reliability by developing regression equations for the following spirometric parameters: forced vital capacity, forced expiratory volume (timed and relative), peak flow and forced mid-expiratory flow.