bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute and late effects on induction of allodynia by acromelic acid, a mushroom poison related structurally to kainic acid
Authors: Minami Toshiaki , Matsumura Shinji , Nishizawa Mikio , Sasaguri Yasuyuki , Hamanaka Nobuyuki , Ito Seiji 
Published: June 2004

Ingestion of a poisonous mushroom Clitocybe acromelalga is known to cause severe tactile pain (allodynia) in the extremities for a month and acromelic acid (ACRO), a kainate analogue isolated from the mushroom, produces selective damage of interneurons of the rat lower spinal cord when injected either systemically or intrathecally. Since ACRO has two isomers, ACRO‐A and ACRO‐B, here we examined their acute and late effects on induction of allodynia.
Intrathecal administration of ACRO‐A and ACRO‐B provoked marked allodynia by the first stimulus 5 min after injection, which lasted over the 50‐min experimental period. Dose‐dependency of the acute effect of ACRO‐A on induction of allodynia showed a bell‐shaped pattern from 50 ag kg−1 to 0.5 pg kg−1 and the maximum effect was observed at 50 fg kg−1. On the other hand, ACRO‐B induced allodynia in a dose‐dependent manner from 50 pg kg−1 to 50 ng kg−1.
N‐methyl‐D‐aspartate (NMDA) receptor antagonists and Joro spider toxin, a Ca2+‐permeable AMPA receptor antagonist, inhibited the allodynia induced by ACRO‐A, but not by ACRO‐B. However, other AMPA/kainate antagonists did not affect the allodynia induced by ACRO.
Whereas no neuronal damage was observed in the spinal cord in ACRO‐A‐treated mice, induction of allodynia by ACRO‐A (50 fg kg−1) and ACRO‐B (50 ng kg−1) was selectively lost 1 week after i.t. injection of a sublethal dose of ACRO‐A (50 ng kg−1) or ACRO‐B (250 ng kg−1). Higher doses of ACRO‐A, however, could evoke allodynia dose‐dependently from 50 pg kg−1 to 500 ng kg−1 in the ACRO‐A‐treated mice. The allodynia induced by ACRO‐A (500 ng kg−1) was not inhibited by Joro spider toxin or NMDA receptor antagonists. These properties of the late allodynia induced by ACRO‐A were quite similar to those of the acute allodynia induced by ACRO‐B.
ACRO‐A could increase [Ca2+]i in the deeper laminae, rather than in the superficial laminae, of the spinal cord. This increase was not blocked by the AMPA‐preferring antagonist GYKI52466 and Joro spider toxin.
Taken together, these results demonstrate the stereospecificity of ACRO for the induction of allodynia and suggest the presence of a receptor specific to ACRO.

British Journal of Pharmacology (2004) 142, 679–688. doi:10.1038/sj.bjp.0705834
Selectins and integrins but not platelet–endothelial cell adhesion molecule‐1 regulate opioid inhibition of inflammatory pain
Authors: Machelska Halina , Brack Alexander , Mousa Shaaban A , Schopohl Julia K , Rittner Heike L , Schäfer Michael , Stein Christoph 
Published: June 2004

Control of inflammatory pain can result from activation of opioid receptors on peripheral sensory nerves by opioid peptides secreted from leukocytes in response to stress (e.g. experimental swim stress or surgery). The extravasation of immunocytes to injured tissues involves rolling, adhesion and transmigration through the vessel wall, orchestrated by various adhesion molecules.
Here we evaluate the relative contribution of selectins, integrins α4 and β2, and platelet–endothelial cell adhesion molecule‐1 (PECAM‐1) to the opioid‐mediated inhibition of inflammatory pain.
We use flow cytometry, double immunofluorescence and nociceptive (paw pressure) testing in rats with unilateral hind paw inflammation induced by complete Freund's adjuvant.
In inflamed tissue, 43–58% of hematopoietic cells (CD45+) expressed opioid peptides. L‐selectin and β2 were coexpressed by 7 and 98% of opioid‐containing leukocytes, respectively. Alpha4 integrin was expressed in low levels by the majority of leukocytes. Opioid‐containing cells, vascular P‐ and E‐selectin and PECAM‐1 were simultaneously upregulated.
Swim stress produced potent opioid‐mediated antinociception in inflamed tissue, unaffected by blockade of PECAM‐1. However, blockade of L‐ and P‐selectins by fucoidin, or of α4 and β2 by monoclonal antibodies completely abolished peripheral stress‐induced antinociception. This coincided with a 40% decrease in the migration of opioid‐containing leukocytes to inflamed tissue.
These findings establish selectins and integrins α4 and β2, but not PECAM‐1, as important molecules involved in stress‐induced opioid‐mediated antinociception in inflammation. They point to a cautious use of anti‐inflammatory treatments applying anti‐selectin, anti‐α4 and anti‐β2 strategies because they may impair intrinsic pain inhibition.

British Journal of Pharmacology (2004) 142, 772–780. doi:10.1038/sj.bjp.0705837
The contribution of adrenoceptor subtype(s) in the renal vasculature of diabetic spontaneously hypertensive rats
Authors: Armenia A , Munavvar A S , Abdullah N A , Helmi A , Johns E J 
Published: June 2004

Diabetes and hypertension are both associated with an increased risk of renal disease and are associated with neuropathies, which can cause defective autonomic control of major organs including the kidney. This study aimed to examine the α1‐adrenoceptor subtype(s) involved in mediating adrenergically induced renal vasoconstriction in a rat model of diabetes and hypertension.
Male spontaneously hypertensive rats (SHR), 220–280 g, were anaesthetized with sodium pentobarbitone 7‐day poststreptozotocin (55 mg kg−1 i.p.) treatment. The reductions in renal blood flow (RBF) induced by increasing frequencies of electrical renal nerve stimulation (RNS), close intrarenal bolus doses of noradrenaline (NA), phenylephrine (PE) or methoxamine were determined before and after administration of nitrendipine (Nit), 5‐methylurapidil (5‐MeU), chloroethylclonidine (CEC) and BMY 7378.
In the nondiabetic SHR group, mean arterial pressure (MAP) was 146±6 mmHg, RBF was 28.0±1.4 ml min−1 kg−1 and blood glucose was 112.3±4.7 mg dl−1, and in the diabetic SHR Group, MAP was 144±3 mmHg, RBF 26.9±1.3 ml−1 min kg−1 and blood glucose 316.2±10.5 mg dl−1. Nit, 5‐MeU and BMY 7378 blunted all the adrenergically induced renal vasoconstrictor responses in SHR and diabetic SHR by 25–35% (all P<0.05), but in diabetic rats the responses induced by RNS and NA treated with 5‐MeU were not changed. By contrast, during the administration of CEC, vasoconstrictor responses to all agonists were enhanced by 20–25% (all P<0.05) in both the SHR and diabetic SHR.
These findings suggest that α1A and α1D‐adrenoceptor subtypes contribute in mediating the adrenergically induced constriction of the renal vasculature in both the SHR and diabetic SHR. There was also an indication of a greater contribution of presynaptic adrenoceptors, that is, α1B‐, and/or α2‐subtypes.

British Journal of Pharmacology (2004) 142, 719–726. doi:10.1038/sj.bjp.0705842
Prostacyclin release and receptor activation: differential control of human pulmonary venous and arterial tone
Authors: Norel Xavier , Walch Laurence , Gascard Jean‐Pierre , Montpreville Vincent de , Brink Charles 
Published: June 2004

In human pulmonary vascular preparations, precontracted arteries were more sensitive to the relaxant effect of acetylcholine (ACh) than veins (pD2 values: 7.25±0.08 (n=23) and 5.92±0.09 (n=25), respectively). Therefore, the role of prostacyclin (PGI2) was explored to examine whether this mediator may be responsible for the difference in relaxation.
In the presence of the cyclooxygenase (COX) inhibitor, indomethacin (INDO), the ACh relaxations were reduced in arteries but not in veins. On the contrary, an inhibitor (L‐NOARG) of the nitric oxide synthase blocked preferentially the relaxation in veins.
A greater release of 6‐keto‐PGF1α, the stable metabolite of PGI2, was observed in arterial preparations than in venous preparations when stimulated with either ACh or arachidonic acid (AA).
Exogenous PGI2 produced a reduced relaxant effect in the precontracted vein when compared with the artery. In the presence of the EP1‐receptor antagonist AH6809, the PGI2 relaxation of veins was similar to arteries.
In veins, AA (0.1 mM) produced a biphasic response, namely, a contraction peak (0.4–0.5 g) followed by a relaxation. These contractions in venous preparations were abolished either in the absence of endothelium or in the presence of INDO or an EP1‐receptor antagonist (AH6809, SC19220). In the arterial preparations AA induced only relaxations.
In both vascular preparations, COX‐1 but not the COX‐2 protein was detected in microsomal preparations derived from homogenized tissues or freshly isolated endothelial cells.
The differential vasorelaxations induced by ACh may be explained, in part, by a more pronounced production and release of PGI2 in human pulmonary arteries than in the veins. In addition, while PGI2 induced relaxation by activation of IP‐receptors in both types of vessels, a PGI2 constrictor effect was responsible for masking the relaxation in the veins by activation of the EP1‐receptor.

British Journal of Pharmacology (2004) 142, 788–796. doi:10.1038/sj.bjp.0705843
Redox modulation of basal and β‐adrenergically stimulated cardiac L‐type Ca2+ channel activity by phenylarsine oxide
Authors: Sims Carl , Harvey Robert D 
Published: June 2004

Phenylarsine oxide (PAO) is commonly used to inhibit tyrosine phosphatase activity. However, PAO can affect a variety of different processes because of its ability to promote sulfhydryl oxidation. In the present study, we investigated the effects that PAO has on basal and β‐adrenergically stimulated L‐type Ca2+ channel activity in isolated cardiac myocytes.
Extracellular application of PAO transiently stimulated the basal L‐type Ca2+ channel activity, whereas it irreversibly inhibited protein kinase A (PKA)‐dependent regulation of channel activity by isoproterenol, forskolin and 8‐CPT‐cAMP (8‐p‐chlorophenylthioadenosine 3′,5′‐cyclic monophosphate). PAO also inhibited channel activity irreversibly stimulated in the presence of adenosine 5′‐(3‐thiotriphosphate) tetralithium salt.
Neither the stimulatory nor the inhibitory effects of PAO were affected by the tyrosine kinase inhibitor lavendustin A, suggesting that tyrosine phosphorylation is not involved.
Extracellular application of the sulfhydryl‐reducing agent dithiothreitol (DTT) antagonized both the stimulatory and inhibitory effects of PAO. Yet, following intracellular dialysis with DTT, only the inhibitory effect of PAO was antagonized.
The inhibitory effect of PAO was mimicked by intracellular, but not extracellular application of the membrane impermeant thiol oxidant 5,5′‐dithio‐bis(2‐nitrobenzoic acid).
These results suggest that the stimulatory effect of PAO results from oxidation of sulfhydryl residues at an extracelluar site and the inhibitory effect is due to redox regulation of an intracellular site that affects the response of the channel to PKA‐dependent phosphorylation. It is concluded that the redox state of the cell may play a critical role in modulating β‐adrenergic responsiveness of the L‐type Ca2+ channel in cardiac myocytes.

British Journal of Pharmacology (2004) 142, 797–807. doi:10.1038/sj.bjp.0705845
Antiapoptotic mechanisms of benidipine in the ischemic/reperfused heart
Authors: Liu Hui‐Rong , Gao Feng , Tao Ling , Yan Wen‐Li , Gao Erhe , Christopher Theodore A , Lopez Bernard L , Hu Aihua , Ma Xin L 
Published: June 2004

Considerable evidence indicates that calcium plays a critical role in apoptosis. We have previously shown that benidipine, a vasodilatory calcium channel blocker, attenuates postischemia myocardial apoptosis. The present study was designed to determine the mechanisms by which benidipine exerts its antiapoptotic effect.
Adult male rats were subjected to 30 min of ischemia followed by 3 h of reperfusion. Rats were randomized to receive either vehicle or benidipine (10 μg kg−1, i.v.) 10 min before reperfusion.
Compared with rats receiving vehicle, those rats treated with benidipine had reduced postischemic myocardial apoptosis as evidenced by decreased TUNEL‐positive staining (8.4±1.2 vs 15.3±1.3%, P<0.01) and caspase‐3 activity (1.94±0.25 vs 3.43±0.29, P<0.01).
Benidipine treatment significantly reduced mitochondrial cytochrome c release and caspase‐9 activation, but had no effect on caspase‐8 activation, suggesting that benidipine exerts its antiapoptotic effect by inhibiting the mitochondrial‐mediated, but not death receptor‐mediated, apoptotic pathway.
Benidipine treatment not only increased the maximal activity of ERK1/2 at 10 min after reperfusion, but also prolonged the duration of ERK1/2 activation. Benidipine treatment had no significant effect on other apoptotic regulating molecules, such as p38 MAPK.
Taken together, our present study demonstrated for the first time the differential regulation of a calcium channel blocker. Benidipine tilted the balance between ERK1/2 and p38 MAPK toward an antiapoptotic state, decreased mitochondrial cytochrome c release, reduced caspase‐9 activation, and attenuated subsequent caspase‐3 activation and postischemic myocardial apoptosis.

British Journal of Pharmacology (2004) 142, 627–634. doi:10.1038/sj.bjp.0705847
Central blockade of nitric oxide synthesis reduces moxonidine‐induced hypotension
Authors: Moreira Thiago Santos , Takakura Ana Carolina Thomaz , Menani José V , Sato Monica Akemi , Colombari Eduardo 
Published: June 2004

Nitric oxide (NO) and α2‐adrenoceptor and imidazoline agonists such as moxonidine may act centrally to inhibit sympathetic activity and decrease arterial pressure.
In the present study, we investigated the effects of pretreatment with L‐NAME (NO synthesis inhibitor), injected into the 4th ventricle (4th V) or intravenously (i.v.), on the hypotension, bradycardia and vasodilatation induced by moxonidine injected into the 4th V in normotensive rats.
Male Wistar rats with a stainless steel cannula implanted into the 4th V and anaesthetized with urethane were used. Blood flows were recorded by use of miniature pulsed Doppler flow probes implanted around the renal, superior mesenteric and low abdominal aorta.
Moxonidine (20 nmol), injected into the 4th V, reduced the mean arterial pressure (−42±3 mmHg), heart rate (−22±7 bpm) and renal (−62±15%), mesenteric (−41±8%) and hindquarter (−50±8%) vascular resistances.
Pretreatment with L‐NAME (10 nmol into the 4th V) almost abolished central moxonidine‐induced hypotension (−10±3 mmHg) and renal (−10±4%), mesenteric (−11±4%) and hindquarter (−13±6%) vascular resistance reduction, but did not affect the bradycardia (−18±8 bpm).
The results indicate that central NO mechanisms are involved in the vasodilatation and hypotension, but not in the bradycardia, induced by central moxonidine in normotensive rats.

British Journal of Pharmacology (2004) 142, 765–771. doi:10.1038/sj.bjp.0705853
Effectiveness of the defence mechanism of the turnip sawfly,Athalia rosae(Hymenoptera: Tenthredinidae), against predation by lizards
Authors: Vlieger L. , Brakefield P.M. , Müller C. 
Published: June 2004

AbstractThe turnip sawfly,Athalia rosaeLinnaeus, is a pest on cruciferous crops. Larvae sequester secondary plant compounds, namely glucosinolates, in their haemolymph. When attacked, their integument is easily disrupted and a droplet of haemolymph is exuded (‘easy bleeding’). This has been shown to be an effective, chemical-based, defence against invertebrate predators. The efficiency of this proposed defence was tested against a vertebrate predator, using groups of the iguanid lizardAnolis carolinensisVoigt as a model predator. Caterpillars ofPieris rapaeLinnaeus andPieris brassicaeLinnaeus served as control prey species that do not sequester glucosinolates. Lizards attacked far fewer sawfly larvae than pierid caterpillars. Several of the sawfly larvae were rejected after an initial attack, demonstrating unpalatability to the lizards, while thePierislarvae were not rejected. However,P. rapaelarvae topically treated with extracts of haemolymph ofA. rosaehad no deterrent effect on the lizards and no avoidance learning occurred over a period of two weeks. Adult sawflies do not easy bleed but have glucosinolates carried over from the larval stage. Lizards attacked them at a higher rate than larvae and they were never rejected. The results suggest that for the defensive effectiveness of the pest sawfly species against vertebrates the chemical cue is not necessarily sufficient. Movement and colour may be important additional factors triggering the behaviour of vertebrate predators.
ON THE PIGMENT OF THE NEGRO'S SKIN AND HAIR
Authors: Abel John J. , Davis Walter S. 
Published: June 2004

The pigmentary granules of the negro's skin and hair can be freed in several ways from the cells in which they are lodged and collected in any desired amount.
As thus obtained, these granules are found to be insoluble in dilute alkalies, dilute hydrochloric acid (hot or cold), alcohol, or other organic solvents when applied in the order named. If, after they have been subjected to the action of dilute hydrochloric acid, they are again treated with dilute alkalies, they are found to give up their pigment, and, on the continued application of heat, the granules dissolve entirely in the alkaline solution, leaving only an insignificant residue.
The pigmentary granules are composed of a colourless ground substance or substratum, a pigment, and much inorganic matter. Their inorganic constituents, as thus far determined, are calcium, magnesium, iron, and silicic, phosphoric, and sulphuric acids; and these constituents possibly play an important part in the deposition and fixation of the colouring matter in the granules.
The pigment isolated from the granules, and sufficiently freed from adherent inorganic matter, contains only the merest trace of iron—so little, in fact, that we must think of it when entirely pure as free of iron. Heating the isolated pigment with barium hydrate at a temperature of 260° C. entirely frees it from the closely adherent ground substance, and it is then found that the vapours of pyrrol are no longer emitted when it is subjected to dry distillation, and the odour of burnt feathers is no longer discerned, although nitrogen is still present.
We can not conclude as the result of our work that the pigment is a derivative of hæmoglobin; it seems to us more probable that it is ultimately derived from the proteids of the parenchymatous juices.
The total quantity of soluble pigment in the skin of a negro of average size is found to weigh about 1 gramme; the weight of the pigmentary granules is about 3.3 grammes, if we are right in our assumption that they contain sixty-five per cent of water and five per cent of mineral constituents in their natural state in the epidermis.
The pigments of the epidermis and hair of the negro are very likely identical. In the present state of our knowledge we can only say that it seems highly probable that the pigment of the negro's hair is not different from the dark pigment found in the hair of the white races, and we may infer that the pigment of the black skin differs only in amount and not in kind from that deposited in the skin of the white man.
ON HÆMORRHAGIC CYSTS OF THE THYROID GLAND
Authors: Bradley W. I. 
Published: June 2004

1. All the features peculiar to the gross cysts of the thyroid gland which possess fluid contents appear to indicate that they are essentially of hæmorrhagic origin.
2. While these gross cysts would seem more especially to occur in glands which already present the features of parenchymatous goitre, the theory of Wölfler that they originate as a consequence of spontaneous rupture of the vesicles is unsatisfactory.
3. It would seem more probable that these large cysts are due to rupture, traumatic or otherwise, of some of the vessels of the organ. The frequent signs of small hæmorrhages in cases of parenchymatous goitre without evidence of associated gross change in the surrounding vesicles, the structure of the organ and its exposed position, all appear to favour this view.
THE REGENERATION OF THE BLOOD
Authors: Hall Winfield S. , Eubank Marion D. 
Published: June 2004

a. The blood of apparently normal animals undergoes considerable variations within physiological limits.
b. After a loss of blood the regeneration is more rapid if there has been a transfusion of an artificial serum.
c. Regeneration after transfusion is less rapid during the first half of the regeneration period than during the second half.
d. The regenerative processes once stimulated into activity carry the blood, qualitatively, considerably beyond the established normal. (See Plate XXXIII.) Otto (2) observed a similar phenomenon.
e. The quantity of hæmoglobin per volume of red blood-corpuscles is not constant.
f. The volume of red blood-corpuscles varies as the product of the average volume of individual corpuscles and the number of corpuscles per unit volume. (V ∝ v x n).
g. When the number of the corpuscles increases the size decreases, and conversely, (n ∝½).
h. The quantity of hæmoglobin varies in general with the number of red blood-corpuscles per unit volume. (Hb. ∝ n).
THE IMMUNIZING POWER OF NUCLEOHISTON AND OF HISTON
Authors: Novy F. O. 
Published: June 2004

The results obtained in the preceding experiments may be briefly summarized as follows:
1. Nucleohiston does not protect against a separate and subcutaneous injection of tetanus toxin, diphtheria toxin, hog-cholera bacillus, or anthrax bacillus.
2. Mixtures of nucleohiston and either tetanus toxin or diphtheria toxin lose their specific toxic action—the latter much more rapidly than the former. Animals that recover after inoculation of such mixtures are not rendered immune.
3. In a mixture of nucleohiston and anthrax bacillus the latter is unaffected, even after the lapse of eleven days.
4. The destruction of specific toxins in a solution of nucleohiston, though in part due to sodium carbonate, is probably chiefly due to the nucleohiston.
5. Histon does not protect against a separate and subcutaneous injection of tetanus toxin, diphtheria toxin, hog-cholera bacillus, or anthrax bacillus.
6. In a mixture of histon and diphtheria toxin the latter is destroyed in a few minutes. This action is in part, if not wholly, due to the acidity of the histon solution. Similar mixtures of closely related bodies, serum globulin or albumoses, in Witte's pepton, give analogous results. The animals that recover from such inoculations are not rendered immune. Histon does not destroy the tetanus toxin as readily as the diphtheria toxin.
7. Histon possesses decided and marked toxic properties which are not due to the hydrochloric acid present.