Metabolism of (−)-deprenyl and PF-(−)-deprenyl in brain after central and peripheral administration

We examined the cerebral metabolism of L-deprenyl and its fluoro-derivative pF-deprenyl, assaying the parent compounds, their metabolites desmethyl deprenyl, L-amphetamine, and L-methamphetamine, and the fluoro analogs of these metabolites. We compared the levels of the metabolites after subcutaneous injection with those after intracerebral administration (via microdialysis) of the parent compounds. The assay of the parent compounds and their metabolites was by GC-MS measurement of the components of brain microdialysate samples. After their subcutaneous administration, deprenyl and F-deprenyl rapidly entered the brain and then their concentration decreased, with an approximate half-life of 4.5 h. After the intracerebral administration the diffusion from the site of administration was minor. A small fraction (a few percent) of the intracerebrally administered deprenyl was metabolized in situ in the brain possibly by a nonenzymatic process. Metabolism of pF-deprenyl was somewhat more rapid. The higher cerebral levels of metabolites after the subcutaneous administration indicate their exogenous origin—metabolism of parent compounds in the periphery and penetration of the brain by the metabolites.     

Legg-Calvé-Perthes disease in a rhesus macaque (Macaca mulatta)

A juvenile rhesus macaque presented with atrophy of the musculature of its left leg. Physical examination localized the problem to the coxofemoral joint. Radiography revealed changes consistent with Legg-Calvé-Perthes (LCP) disease. Femoral head ostectomy was performed, and the femoral head was submitted for histologic examination, results of which confirmed a diagnosis of LCP.     

Inhibition of dopamine β-hydroxylase by bidentate chelating agents

1-2H-Phthalazine hydrazone (hydralazine; HYD), 2-1H-pyridinone hydrazone (2-hydrazinopyridine; HP), 2-quinoline-car☐ylic acid (QCA), 1-isoquinolinecar☐ylic acid (IQCA), 2,2′-bi-1H-imidazole (2,2′-biimidazole; BI), and 1H-imidazole-4-acetic acid (imidazole-4-acetic acid; IAA) directly and reversibly inhibit homogeneous soluble bovine dopamine β-hydroxylase (3,4-dihydroxyphenethylamine, ascorbate:oxygen oxidoreductase (β-hydroxylating), EC 1.14.17.1). HYD, QCA and IAA show competitive allosteric inhibition of dopamine β-hydroxylase with respect to ascorbate (K_is = 5.7(±0.9) μM, 0.14(±0.03) mM, 0.80(±0.20) mM; n_H= 1.4(±0.1), 1.8(±0.4), 2.8(±0.6), respectively). HYD and IAA show slope and intercept mixed-type allosteric inhibition of dopamine β-hydroxylase with respect to tyramine. QCA shows allosteric uncompetitive inhibition of dopamine β-hydroxylase with respect to tyramine. HP, BI and IQCA all show linear competitive inhibition (K_is = 1.9(±0.3) μM, 21(±6) μM, and 0.9(±0.3) μM, respectively) with respect to ascorbate. HP and BI show linear mixed-type while IQCA shows linear uncompetitive inhibition of dopamine β-hydroxylase with respect to tyramine. In the presence of HP, HYD or IAA intersecting double-reciprocal plots of the initial velocity as a function of tyramine concentration at differing fixed levels of ascorbate are observed. These findings are consistent with a uni-uni-ping-pong-ter-bi kinetic mechanism for dopamine β-hydroxylase that involves a ternary enzyme-ascorbate-tyramine-oxygen complex. The results for HYD, QCA and IAA are the first examples of allosteric inhibitor interactions with dopamine β-hydroxylase.     

‘Agonistic buffering’ in the wild barbary macaque,Macaca sylvana L.

Barbary apes are known to exhibit male care of babies at various locations, but only in the Middle Atlas mountains of Morocco has it been reported that a baby may be used in male-male interactions, apparently reducing the likelihood of aggression. The present study was made in order to discover if the behavior was characteristic of other groups reproductively isolated from the Atlas population. Male-male interactions involving a baby were observed in two groups and are described in detail; their friendly nature supports the hypothesis that the presence of a baby reduces the likelihood of aggression. We did not, however, see the active use of babies in this context which has been described for the Atlas population.     

Inhibition of monoamine oxidase–A activity in rat brain by synthetic hydrazines: Structure-activity relationship (SAR)

A series of hydrazine derivatives was synthesized in order to evaluate their monoamine oxidase A (MAO-A) inhibitory effects. MAO-A inhibitory activity of 4-tosyl benzoic acid carbohydrazide was quite potent, similarly to that of the corresponding 4-benzyloxy-benzoic acid carbohydrazide and its N-cyanoethylated derivative. Structural variations of these compounds, such as the replacement of the 4-substitutent, of the aromatic ring on which the carbohydrazide moiety is grafted, as well as cyclization of the hydrazide moiety in five- or six-membered rings caused either significant decline or complete loss of MAO inhibitory properties. The most active compound (4-tosyl benzoic acid carbohydrazide) was also subjected to the forced swim test, an animal model of depression, eliciting a marked reduction in immobility time in rats, without affecting the locomotor activity, implying that it possesses anti-depressant properties due to inhibition of MAO type-A.     

Inhibition of activity of the ethylene-forming enzyme by α(p-chlorophenoxy)isobutyric acid

(p-Chlorophenoxy)isobutyric acid (PCIB) inhibited indole-3-acetic acid (IAA)-induced ethylene production in etiolated mung bean hypocotyl sections. The endogenous level of 1-aminocyclopropane-1-carboxylic acid (ACC) was not significantly affected by PCIB, indicating that PCIB exerted its effect primarily by inhibiting the activity of the ethylene-forming enzyme (EFE). This conclusion was supported by the observations that PCIB inhibited the conversion of exogenously applied ACC to ethylene. The inhibitory effect of PCIB was already evident with 0.05 mM PCIB, and it increased with time after application of the inhibitor. PCIB also significantly inhibited ethylene production in apple fruit tissues, but it only slightly reduced the level of endogenous ACC. Similar to mung bean, EFE activity in apple tissue was significantly inhibited by PCIB. The possibility that PCIB also inhibits auxin-induced ACC synthase activity is discussed.     

Inhibition of RNA synthesis in the germinal cysts of the silkmoth by β-ecdysone

When the steroidal moulting hormone of insects, β-ecdysone, is injected into saturniid pupae, net RNA synthesis in the testis and testicular germinal cysts is inhibited. This inhibition does not appear to be due to a decrease in the size of the RNA precursor pool. On the other hand, β-ecdysone stimulates both the in vitro uptake and incorporation of [³H]leucine into protein. Inhibitor studies suggest the presence of stable pre-existing mRNA in the testes of chilled pupae. Analysis of the germinal cyst RNA revealed that most of the newly synthesized RNA from chilled pupae was in the nuclei and was heterodisperse with very little mature rRNA. It is suggested that the β-ecdysone inhibits net testicular RNA synthesis either directly by stimulating an RNAse or indirectly via other endocrine glands or factors as previously suggested.     

Biotransformation of (−)-epicatechin, (+)-epicatechin, (−)-catechin,and (+)-catechin by intestinal bacteria involved in isoflavone metabolism

Isoflavone-metabolizing bacteria, Adlercreutzia equolifaciens, Asaccharobacter celatus, Slackia equolifaciens, and Slackia isoflavoniconvertens catalyzed C-ring cleavage of (–)-epicatechin and (+)-catechin, (+)-epicatechin, and (–)-catechin in varying degrees. The cleaving abilities of (–)-epicatechin and (+)-catechin were enhanced by hydrogen, except (+)-catechin cleavage by S. equolifaciens, which was not accelerated. (?)-Catechin cleavage by Ad. equolifaciens was remarkably accelerated by hydrogen.     

Inhibition of metabolism by hydrostatic pressure: what limits microbial growth?

Summary Analysis of recent and older published data of many investigators indicates that in prokaryotic organisms normally found in environments at atmospheric pressure, the major biological process which is most sensitive to increased hydrostatic pressure is protein synthesis and its inhibition approximately parallels that for growth under the same physical conditions.     

Immunolocalization of exoglycoproteins (“ependymins”) in the goldfish brain

Exoglycoproteins (X-GPs) are a group of very abundant soluble glycoproteins in the goldfish, brain. Immunostaining with polyclonal antisera to X-GPs revealed consistent perinuclear staining in the cells of the inner and intermediate layers of the leptomeninx, which is homologous to the piaarachnoid. Immunolabelling was also prominent in the outer wall of capillaries, and in a variable population of 10–12 m granular cells that appeared mainly near the ventricles and occasionally within the ventricles or under the meninges. In some cases, small and medium-sized lymphocytes were immunostained. Lymphocytes were sometimes associated with the granular cells, which may be hematogenous cells in transit toward the ventricles. the choroid plexus, saccus dorsalis, the roof of the third ventricle and Reissner's fiber showed strong immunostaining. The localization of the X-GPs suggests that they may contribute to maintenance of the blood-brain barrier or to regulation of immune function within the brain.Special issue dedicated to Dr. Sidney Ochs.     

Kinetic Analysis of the Effect of (−)-Epigallocatechin Gallate on the DNA Scission Induced by Fe(II)

The DNA strand scission induced by Fe(II) in a citrate buffer solution and the effect of (?)-epigallocatechin gallate (EGCg) were kinetically analyzed. The rate of consumption of dissolved oxygen by Fe(II) in each of these solutions was measured and paralleled that DNA scission. Coordinated EGCg accelerated these reactions. Curves of the time-course characteristics of DNA scission were simulated by using the rate constant of oxygen consumption and by assuming that scission with the hydroxyl radical (OH), which was formed from the dissolved oxygen, proceeded competitively with the scavenging of OH by citrate, Cl^? ions and EGCg added. Free EGCg acted as a DNA scission inhibitor to scavenge OH, in contrast to the case of the coordinated one. This analysis is useful for estimating the rate constant of the reaction between an antioxidant and OH, and might provide a new method for measuring the OH-scavenging activity.     

Reversible protection of Cys-93(β) by PEG alters the structural and functional properties of the PEGylated hemoglobin

As a potential hemoglobin (Hb)-based oxygen carrier (HBOC), the PEGylated Hb has received much attention for its non-nephrotoxicity. However, PEGylation can adversely alter the structural and functional properties of Hb. The site of PEGylation is an important factor to determine the structure and function of the PEGylated Hb. Thus, protection of some sensitive residues of Hb from PEGylation is of great significance to develop the PEGylated Hb as HBOC. Here, Cys-93(β) of Hb was conjugated with 20 kDa polyethylene glycol (PEG20K) through hydrazone and disulfide bonds. Then, the conjugate was modified with PEG5K succinimidyl carbonate (PEG5K-SC) using acylation chemistry, followed by removal of PEG20K Hb with hydrazone hydrolysis and disulfide reduction. Reversible conjugation of PEG20K at Cys-93(β) can protect Lys-95(β), Val-1(α) and Lys-16(α) of Hb from PEGylation with PEG5K-SC. The autoxidation rate, oxygen affinity, structural perturbation and tetramer instability of the PEGylated Hb were significantly decreased upon protection with PEG20K. The present study is expected to improve the efficacy of the PEGylated Hb as an oxygen therapeutic.     

Is the scaling of swim speed in sharks driven by metabolism?

The movement rates of sharks are intrinsically linked to foraging ecology, predator–prey dynamics and wider ecosystem functioning in marine systems. During ram ventilation, however, shark movement rates are linked not only to ecological parameters, but also to physiology, as minimum speeds are required to provide sufficient water flow across the gills to maintain metabolism. We develop a geometric model predicting a positive scaling relationship between swim speeds in relation to body size and ultimately shark metabolism, taking into account estimates for the scaling of gill dimensions. Empirical data from 64 studies (26 species) were compiled to test our model while controlling for the influence of phylogenetic similarity between related species. Our model predictions were found to closely resemble the observed relationships from tracked sharks, providing a means to infer mobility in particularly intractable species.