Crystallography Open Database - an open-access collection of crystal structures.

The Crystallography Open Database (COD), which is a project that aims to gather all available inorganic, metal-organic and small organic molecule structural data in one database, is described. The database adopts an open-access model. The COD currently contains ∼80 000 entries in crystallographic information file format, with nearly full coverage of the International Union of Crystallography publications, and is growing in size and quality.

Correlation of inhaled nitric-oxide induced reduction of pulmonary artery pressure and vascular changes.

The purpose of the present study was to determine the relationship between hypertensive pulmonary vascular remodelling and the changes in mean pulmonary artery pressure (mPAP) during low-dose nitric oxide (NO) inhalation. Rats were exposed to chronic hypobaric hypoxia (air at 50.5 kPa (380 mmHg), 10% oxygen, for 5-29 days) to induce chronic pulmonary hypertension (PH) with pulmonary vascular structural changes. After the chronic hypoxic exposure, the rats had an indwelling pulmonary artery catheter inserted and changes in mPAP with NO were correlated to morphometrical analysis of pulmonary vascular changes. All concentrations of inhaled NO (0.1-2.0 parts per million) reduced mPAP with a similar per cent reduction from baseline mPAP in PH rats, while no changes were observed in control rats. During NO inhalation in PH rats, the absolute value of the decrease in mPAP, but not per cent reduction in mPAP, significantly correlated with baseline mPAP, the percentage of muscularised arteries at the alveolar wall level and at the alveolar duct level, and the per cent medial wall thickness of muscularised arteries. In the chronic hypoxic pulmonary hypertension model, the severity of pulmonary vascular remodelling did not alter the reactivity of the pulmonary arteries to nitric oxide and might, in part, determine the magnitude of nitric-oxide induced absolute reduction in mean pulmonary artery pressure.

Transannular nitrone cycloaddition. A stereocontrolled entry to the spirocyclic core of pinnaic acid.

[figure: see text] Thermolysis of lactone 18 initiated a stereospecific transannular nitrone-olefin [3 + 2] cycloaddition to yield tetracycle 19. Methanolysis followed by reductive cleavage of the isoxazolidine yielded 20, representing the azaspirocyclic core of pinnaic acid (1).

Modulated vasodilator responses to natriuretic peptides in rats exposed to chronic hypoxia.

Natriuretic peptides (NPs), such as atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP), and adrenomedullin (ADM), are endogenous vasodilators acting via specific receptors. This study addressed the question of how pulmonary artery (PA) responses to these peptides and the gene expression of their receptors are modulated in pulmonary hypertension rat models exposed to chronic hypoxia. In this study, isometric tension was measured in PA rings exposed to these NPs and 8-bromoguanosine 3', 5'-cyclic monophosphate (8-bromo-cGMP). It was compared with messenger ribonucleic acid (mRNA) levels of NP-A and -B receptors, which bind to ANP and CNP, respectively, as determined by ribonuclease (RNase) protection assay. Chronic hypoxia increased the maximal relaxation elicited by ANP, but the responses to CNP and 8-bromo-cGMP were unchanged. Chronic hypoxia did not change NP-A and -B receptor mRNA levels. The results showed that pulmonary artery response to atrial natriuretic peptide is selectively enhanced, possibly via a post-transcriptional modulation of its receptor in chronically hypoxia rats. These pharmacological characteristics of atrial natriuretic peptide are consistent with the hypothesis that the atrial natriuretic peptide system is protective against the progression of pulmonary hypertension.

Effects of the endothelin ET(A) receptor antagonist, TA-0201, on pulmonary arteries isolated from hypoxic rats.

To investigate the roles of endothelin-1 in the pathogenesis of hypoxic pulmonary hypertension, we studied the effects of a selective endothelin ET(A) receptor antagonist, TA-0201 (N-(6-(2-(5-Bromopyrimidin-2-yloxy) ethoxy)-5-(4-methylphenyl) pyrimidin-4-yl)-4-(2-hydroxy-1,1-dimethylethyl) benzensulfonamide sodium salt sesquihydrate), on helical strips of pulmonary arteries isolated from hypoxia-induced pulmonary hypertensive rats as compared with those of normoxic rats. Endothelin-1-induced maximum contractions were significantly inhibited by exposure to hypoxia in the pulmonary arterial strips, but not in the mesenteric arterial strips. The hypoxia also induced right ventricular hypertrophy in rats. Addition of TA-0201 to the bath inhibited the endothelin-1-induced contraction of pulmonary arterial strips isolated from hypoxic rats more effectively than in those of normoxic rats. Oral administration of TA-0201 to hypoxic rats inhibited the hypoxia-induced right ventricular hypertrophy, and decreased the maximum contractile response to endothelin-1 in pulmonary arterial strips isolated from these rats. Those inhibitory effects induced by the oral administration of TA-0201 were not observed in the pulmonary arteries from normoxic rats or in the mesenteric arteries from both hypoxic and normoxic rats. These results suggest that endothelin-1 has important pathophysiological roles in hypoxia-induced pulmonary hypertension, and that TA-0201 may inhibit the endothelin-l-induced contraction through a change in the function of endothelin ET(A) receptor as well as competitive inhibition for endothelin ET(A) receptor.

Acetylcholine-induced endothelium-derived contracting factor in hypoxic pulmonary hypertensive rats.

We determined the role of an endothelium-derived contracting factor in the impaired relaxation response to ACh of conduit pulmonary arteries (PAs) isolated from rats with hypoxic pulmonary hypertension (PH). A PGH2/thromboxane A2 (TxA2)-receptor antagonist (ONO-3708) partially restored the impairment of ACh-induced relaxation, whereas TxA2 synthase inhibitors (OKY-046 and CV-4151) did not affect the impaired relaxation in phenylephrine-precontracted hypertensive PAs. Endothelium-denuded hypertensive PA rings showed no difference in the response to ACh between preparations with and without ONO-3708. In both endothelium-denuded control and hypertensive PAs, exogenous PGH2 induced contractions, and the magnitude of the contractions was greater in the control than in hypoxic PH preparations. An endothelin A-receptor antagonist (BQ-485), an endothelin B-receptor antagonist (BQ-788), and a superoxide anion scavenger (superoxide dismutase) did not restore the impaired response to ACh in hypertensive PAs. These findings suggest that PGH2 produced from the conduit PAs of rats with chronic hypoxic PH may be the endothelium-derived contracting factor responsible for the impairment of ACh-mediated vasorelaxation.

Synthesis and Characterization of the Series of Compounds Ru(2)(O(2)CMe)(x)()(admp)(4)(-)(x)()Cl (Hadmp = 2-Amino-4,6-dimethylpyridine, x = 3, 2, 1, 0).

The reaction between Ru(2)(O(2)CMe)(4)Cl and Hadmp (Hadmp = 2-amino-4,6-dimethylpyridine) under different conditions has been investigated. By conducting the reaction in a methanol solution at room temperature the product obtained was Ru(2)(admp)(O(2)CMe)(3)Cl (1). In a melt reaction at 65 degrees C the product isolated is Ru(2)(admp)(2)(O(2)CMe)(2)Cl (2); at 100 degrees C it is Ru(2)(admp)(3)(O(2)CMe)Cl (3); and at 140 degrees C it is Ru(2)(admp)(4)Cl (4). The generality of these reactions was confirmed by the deliberate preparation of Ru(2)(chp)(3)(O(2)CMe)Cl (5) and [Ru(2)(DPhTA)(3)(O(2)CMe)(NCMe)(2)][BF(4)] (6). The structures of 1, 2, and 3 were determined by X-ray crystallography. The structure of 1 was determined from crystals of 1.3CH(2)Cl(2) (C(16)H(24)Cl(7)N(2)O(6)Ru(2)), triclinic, P&onemacr; (No. 2), with a = 11.578(3) Å, b = 12.5607(13) Å, c = 20.903(3) Å, alpha = 99.927(14) degrees, beta = 100.222(9) degrees, gamma = 102.07(2) degrees, Z = 4; that of 2, from crystals of 2.2.5CH(2)Cl(2) (C(21)H(30)Cl(7)N(4)O(4)Ru(2)), monoclinic, P2(1)/n (No. 14), with a = 13.091(3) Å, b = 19.098(4) Å, c = 13.720(3) Å, beta = 105.51(3) degrees; that of 3, from crystals of 3.Hadmp.C(6)H(6) (C(36)H(46)ClN(8)O(2)Ru(2)), monoclinic, P2(1)/n (No. 14), with a = 15.979(2) Å, b = 14.9294(14) Å, c = 17.131(4) Å, beta = 109.21(2) degrees. The magnetic susceptibilities and electrochemistry of the four title compounds were also studied. It was observed that while compounds 1, 2, and 3 display magnetic moments compatible with the presence of three unpaired electrons and all yield stable one-electron oxidation products, 4 shows only one unpaired electron and the product of its one-electron oxidation decays sufficiently rapidly that no return wave is observed.

Vasodilatory effects of ketamine on pulmonary arteries in rats with chronic hypoxic pulmonary hypertension.

To study the effects of ketamine on structurally remodeled pulmonary arteries from rats with hypoxic pulmonary hypertension (PH) and the effects of ketamine on endothelium-dependent and -independent relaxation, rats were exposed to hypobaric hypoxia (air at 380 mm Hg for 10 days). We measured the responses to ketamine, acetylcholine, and sodium nitroprusside (SNP) in prostaglandin F2 alpha-precontracted ring segments from a left extrapulmonary artery (EPA, 1.4-1.6 mm in outside diameter [OD] and an intrapulmonary artery (IPA, 0.7-1.1 mm OD) obtained from control and PH rats. The effects of acetylcholine and SNP were decreased in EPA and IPA rings from PH rats compared with control rings. In contrast, ketamine produced a greater relaxation response in rings from PH rats at 3 x 10(-5) -3 x 10(-4) in the EPA and at 10(-4) -10(-3) M in the IPA compared to control rings. A nitric oxide synthase inhibitor, nitro-L-arginine (10(-4) M), inhibited the relaxation in response to acetylcholine in both control and PH rats. Pretreatment with ketamine (10(-4) M) had no effect on the relaxation response to any concentration of acetylcholine or SNP in either control or PH rats. We conclude that nitric-oxide-mediated relaxation, but not ketamine-induced relaxation, was impaired in structurally remodeled hypertensive pulmonary arteries. Ketamine had no effects on nitric oxide-mediated relaxation in either normal or PH rats.

[An anatomo-clinical case of sequelae of acute encephalopathy. Infantile spasm with hypsarrhythmia]. / Observation anatomo-clinique d'une séquelle d'encéphalopathie aiguë. Spasme infantile avec hypsarythmie.

Clinico-pathological studies of West syndrome are rather rare. A case of sequelae of acute encephalopathy which involved a nine-month-old boy with post-mortem data is reported. Birth and postnatal development had been normal until the onset of illness. Laboratory examinations ruled out bacterial or viral meningo-encephalitis and metabolic disorders. After the recovery from a coma lasting several days, spastic quadriplegia, severe mental retardation and intractable epileptic attacks were present. The latter were made of tonic spasms and myoclonic seizures. EEG records showed hypsarrhythmia. Neuropathological examination revealed almost symmetrical bilateral cystic cavities in the pontine tegmentum and lateral nuclei of both thalami. The corpus callosum was very thin. No finding suggested a congenital anomaly. In a search of the pathological basis for infantile spasms, this case was compared with the published data. It would appear that the lesions of the pontine tegmentum play a significant role in the pathogenesis of hypsarrhythmia or infantile spasms.

Phenytoin--allopurinol interaction: Michaelis--Menten kinetic parameters of phenytoin with and without allopurinol in a child with Lesch--Nyhan syndrome.

We analyzed Michaelis--Menten pharmacokinetic parameters of phenytoin with and without the coadministration of allopurinol (150 and 200 mg/day) in a child with Lesch--Nyhan syndrome. The Vmax and Km were estimated from at least two different sets of serum concentration--dosage data of phenytoin. The Vmax values (mg/kg/day) were 16.1 without allopurinol, and 12.4 and 10.9 with allopurinol (150 and 200 mg/day), respectively, whereas those for Km remained relatively constant (3.9 to 4.9 microgram/ml). Our results suggest that allopurinol is a drug that inhibits the hepatic metabolism of phenytoin.