Threefold helical assembly via hy-droxy hydrogen bonds: the 2:1 co-crystal of bi-cyclo-[3.3.0]octane-endo-3,endo-7-diol and bi-cyclo-[3.3.0]octane-endo-3,exo-7-diol.

Reduction of bi-cyclo-[3.3.0]octane-3,7-dione yields a mixture of the endo-3,endo-7-diol and endo-3, exo-7-diol (C8H14O2) isomers (5 and 6). These form (5)2·(6) co-crystals in the monoclinic P21/n space group (with Z = 6, Z' = 1.5) rather than undergoing separation by means of fractional recrystallization or column chromatography. The mol-ecule of 5 occupies a general position, whereas the mol-ecule of 6 is disordered over two orientations across a centre of symmetry with occupancies of 0.463 (2) and 0.037 (2). Individual diol hy-droxy groups associate around a pseudo-threefold screw axis by means of hydrogen bonding. The second hy-droxy group of each diol behaves in a similar manner, generating a three-dimensional hydrogen-bonded network structure. This hydrogen-bond connectivity is identical to that present in three known helical tubuland diol-hydro-quinone co-crystals, and the new crystal structure is even more similar to two homologous aliphatic diol co-crystals.

7α,15α-Dibromo-8,16-diphenyl-6,7,14,15-tetra-hydro-6α,14α-epithio-cyclo-octa-[1,2-b:5,6-b']diquinoline deuterochloro-form solvate.

In the racemic title compound, C(34)H(22)Br(2)N(2)S·CDCl(3), pairs of diquinoline host mol-ecules form centrosymmetric brick-like dimers utilizing three different aryl edge-to-face inter-actions (EF(1-3)). The dimeric (EF)(6) (i.e. 2 × EF(1-3)) building blocks pack with the deuterochloro-form guest mol-ecules positioned near each of their corners. The Cl atoms of the latter are disordered over two sets of sites in a 0.53 (2):0.47 (2) ratio.

8-Methyl-5-methyl-ene-2-oxotricyclo[5.3.1.1]dodecan-endo-8-ol.

The title compound, C(14)H(20)O(2), crystallizes with homochiral chains of mol-ecules hydrogen bonded together along the b axis. Adjacent chains in the ab plane contain mol-ecules of the same chirality, leading to a chiral segregation of the mol-ecules into layers.

Studies on two closely related species of octocorallians: biochemical and molecular characteristics of the organic matrices of endoskeletal sclerites.

Two species of alcyonarian corals, Lobophytum crassum and Sinularia polydactyla, are closely related to each other. It is reported that the calcified organic substances in the skeletons of both contain a protein-polysaccharide complex playing a key role in the regulation of biocalcification. However, information on the matrix proteins of endoskeletal sclerite has been lacking. Hence we studied the proteinaceous organic matrices of sclerites for both species, to analyze the sequences and the functional properties of the proteins present. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the preparations showed four bands of proteins with apparent molecular masses of 102, 67, 48, and 37 kDa for L. crassum and seven bands of 109, 83, 70, 63, 41, 30, and 22 kDa for S. polydactyla. A major protein band of about 67 kDa in L. crassum and two bands of proteins of about 70 and 63 kDa in S. polydactyla yielded N-terminal amino acid sequences. Periodic acid-Schiff staining indicated that the 67-kDa protein in L. crassum, and 83- and 63-kDa proteins in S. polydactyla were glycosylated. For detection of calcium binding proteins, a Ca(2+) overlay analysis was conducted in the extract via (45)Ca autoradiography. The 102- and 67-kDa calcium binding proteins in L. crassum, and the 109- and 63-kDa Ca(2+) binding proteins in S. polydactyla were found to be radioactive. An assay for carbonic anhydrase (CA), which is thought to play an important role in the process of calcification, revealed specific activities. Newly derived protein sequences were subjected to standard sequence analysis involving identification of similarities to other proteins in databases. The significantly different protein expressions and compositional analysis of sequences between two species were demonstrated.

Analysis of proteinaceous components of the organic matrix of endoskeletal sclerites from the alcyonarian Lobophytum crassum.

The mesoglea of alcyonarians is occupied by an abundance of minute calcitic sclerites. The sclerites of the alcyonarian Lobophytum crassum contain a water-soluble organic matrix comprising 0.48% of the sclerite weight and a water-insoluble fraction comprising 1.15% of the sclerite weight. Analysis of proteinaceous components in the soluble fraction shows a particularly high content of aspartic acid, followed by alanine, glycine, and glutamate. Aspartic acid, glycine, alanine, and glutamate are the most abundant residues in the insoluble fraction. In both cases, the fractions show the highest concentration of aspartic acid from the total proteins. In an in vitro assay, we show that the matrix proteins extracted from the calcitic sclerites induce the formation of amorphous calcium carbonate prior to its transformation into the calcitic crystalline form. We also show scanning electron micrographs of the rhombohedral calcite crystals used as template, the protein imprinted with these crystals. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of both matrices shows the protein fractions at 67 and 48 kDa. The soluble matrix shows two additional faint bands. Both fractions stain for a carbohydrate at 67 kDa, indicating a glycoprotein at this molecular weight. A newly derived protein sequence was subjected to bioinformatics analysis involving identification of similarities to other acidic proteins. The identification of these proteins in alcyonarian endoskeletal sclerites emphasizes the fundamental importance of such acidic proteins and sheds more light on the functions of these proteins in the processes of biocalcification.

Accuracy and repeatability of blood volume measurement by pulse dye densitometry compared to the conventional method using 51Cr-labeled red blood cells.

OBJECTIVE: To determine the accuracy and repeatability of pulse dye densitometry (PDD) in measuring blood volume (BV) by comparing it with the conventional method using 51Cr-labeled red blood cells (RI method) and by assessing sequential measurements. DESIGN: Prospective clinical study. SETTING: University hospital. PATIENTS AND PARTICIPANTS: Eleven adult ICU patients who received cardiac surgery (1st ICU day). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: After injecting indocyanine green (10 or 20 mg) into the right atrium, its arterial concentration was continuously monitored at the nose and finger by PDD, and BV was calculated by back extrapolating the logarithmic dye concentration on the dye elimination curve between 2.5 and 5.5 min after mean transit time to each mean transit time with the least squares method. These measurements were repeated in eight patients and performed only once in the other three, and the BV was measured concurrently by the RI method one time. The Bland-Altman method was used for evaluating differences between methods and within methods. The (percentage) biases and standard deviations between the PDD and RI methods and between the successive measurements by PDD at the finger and nose were 0.26 +/- 0.491 (8.8 +/- 15.3%) and 0.004 +/- 0.251 (0.06 +/- 5.9%) with the probe on a nostril, and 0.16 +/- 0.561 (2.5 +/- 14.4%) and 0.19 +/- 0.311 (4.7 +/- 7.3%) using the finger probe. The bias between methods was less than 10%, and the repeatability of PDD was better. CONCLUSIONS: As PDD can measure BV with good repeatability and with a small bias compared to the RI method, serial changes in BV can be evaluated at the bedside of critically ill patients noninvasively and repeatedly.

Second gas effect of N2O on oxygen uptake.

PURPOSE: The concept of the second gas effect is well known, however, there have been no studies that showed the relationship between alveolar oxygen concentration and arterial oxygen tension (PaO2) after the inhalation of nitrous oxide (N2O) in humans. The purpose of this study was to examine the changes in both end-tidal oxygen fraction (F(ET)O2) and PaO2 after N2O inhalation in patients under general anesthesia. METHODS: Fifteen patients scheduled for elective orthopedic surgery were enrolled in this study. Anesthesia was maintained with the continuous infusion of propofol and with nitrogen (N2) and oxygen (O2) (6 L x min(-1), F1O2, 0.33). In all patients, the lungs were ventilated with a Servo 900C ventilator equipped with a gas mixer for O2, N2O, and N2. After obtaining baseline data, N2 was replaced with N2O maintaining FIO2 constant at 0.33. The changes in fractional concentration of O2, N2O, and N2 were continuously measured using mass spectrometer in a breath-by-breath basis. PaO2 and hemodynamic data were obtained at 1, 5, 10, 30 and 60 min after the start of N2O inhalation. RESULTS: Five minutes after N2O inhalation, F(ET)O2 increased from 0.27+/-0.01 to 0.31+/-0.02 (P<0.01) and PaO2 increased from 172.0+/-22.5 mm Hg to 201.0+/-10.3 mm Hg (P<0.01). These effects produced by N2O were observed for 30 min. CONCLUSIONS: These results confirm the concept of second gas effect of N2O on oxygen uptake in humans and provide evidence that the PaO2 increase correlated with the increase in F(ET)O2 after N2O inhalation.

Changes in gastric intramucosal pH and circulating blood volume following coronary artery bypass grafting.

PURPOSE: To determine the changes in gastric intramucosal pH (pHi) following coronary artery bypass grafting (CABG) in comparison with systemic hemodynamic variables and circulating blood volume (BVc). METHODS: Twenty patients who underwent CABG under mild hypothermic cardiopulmonary bypass (CPB) were included. Hemodynamic variables and the values of pHi were obtained at 3,6, 12 and 24 hr after admission to the intensive care unit (ICU). The pHi was measured by gastric tonometric catheter. The BVc was measured by carbon monoxide (CO)-labeled hemoglobin (CO-Hb) dilution method (CO method) at 6 and 24 hr after ICU admission. RESULTS: Systemic vascular resistance index (SVRI) and pulmonary vascular resistance index (PVRI) decreased with time. Systemic oxygen delivery index (DO2I) and systemic oxygen consumption index (VO2I) showed a gradual increase during the study period. By contrast, pHi decreased to the lowest value (7.26+/-0.05) at six hours and returned to normal levels (7.34+/-0.04) at 24 hr after ICU admission. Changes in BVc between six and 24 hr ranged from -242 ml to 978 ml (mean, 334+/-338 ml). The pHi increased in patients whose BVc increased by > 300 ml. Mean fluid balance was negative in this period (-386+/-667 ml; range, -1786 - + 423 ml). CONCLUSION: The pHi showed the lowest value at six hours and returned to normal at 24 hr after ICU admission. The pHi increased with the decrease in vascular resistance and with the increases in BVc in this period. The improvement of pHi, an indicator of splanchnic perfusion, appears to be related to systemic vasodilatation and an increase in BVc.

Accuracy of carboxyhemoglobin dilution method for the measurement of circulating blood volume.

PURPOSE: The management of circulating blood volume (BVc) is crucial in intensive care unit (ICU) patients. The purpose of this study was to verify the accuracy and precision of the carbon monoxide-labeled hemoglobin (CO-Hb) dilution method (CO method) by comparing it with the 51Cr-labeled erythrocyte dilution method (51Cr method) for the measurement of BVc. METHODS: A prospective study was performed in 18 patients who underwent coronary artery bypass grafting (CABG) under mild hypothermic cardiopulmonary bypass (CPB). The BVc was measured by both the CO method and the 51Cr method at 24 hr after ICU admission in order to verify the accuracy and precision of the CO method. Paired data were assessed in absolute terms, and percentage errors were calculated by the degree of agreement. RESULTS: Small mean differences and standard deviations between the CO method and the 51Cr method (-70.2 +/-184.8 mL) and small percentage errors (-0.49+/-1.29%) indicated the accuracy and precision of the CO method, and a close correlation was observed (r = 0.97). CONCLUSION: The CO method can measure BVc with a similar degree of accuracy as the 51Cr method. It is simple, repeatable and safe without the risk of exposure to radioactivity in the ICU.

[A case of water intoxication during transcervical resection of the uterine myoma].

A 28-year-old woman underwent trans-cervical resection (TCR) of the uterine myoma. She had no history of complications except for anemia. Anesthesia was maintained with inhalation anesthesia. After 120 min from introducing the resectoscope, her serum sodium dropped to 86.1 mEq.l-1. But her heart rate and the systolic arterial pressure were stable. She was treated with steroid, mannitol, isotonic saline, and 7% NaHCO3. Soon after the end of the operation, she recovered consciousness. At two hours postoperatively, her serum sodium was 119.6 mEq.l-1. On the 1st postoperative day, her serum sodium returned to the normal range (137 mEq.l-1). We should be aware of asymptomatic water intoxication during TCR.

[AIDS through blood contamination (early 1980s) and urethane shock (1975)].

1) AIDS contracted through contaminated blood was first discovered in the early 1980s, and related law suits are now underway. The contamination of the blood is considered to ba a shared responsibility of the "government," "medical establishments" and "industry." The revision of the Pharmaceutical Affairs Law in 1979 gave the authority for commanding the recall of products to the Health and Welfare Ministry. This was a lesson learned from past cases of drug-induced suffering. However, the ministry did nothing regarding the blood contaminated with the AIDS virus. 2) "Urethane shock (drug-induced suffering)" occurred in 1975. Although it occurred before the revision of the Pharmaceutical Affairs Law, the Health and Welfare Ministry took the administrative measure of "an immediate recall," because the antipyretic analgesic injections used all over the country at that time contained 0.15 to 0.3g of urethane which is a carcinogenic substance, per ampoule. 3) Even the revision of the Pharmaceutical Affairs Law could not prevent cases of drug-induced suffering. I think that all concerned should have a full understanding, receive fair judgement and be encouraged to prevent such mistakes in the future.

Comparison of the hemodynamic effects of amrinone in patients who required low-to-moderate-dose and high-dose catecholamines after cardiac valve replacement.

OBJECTIVES: To determine hemodynamic response to amrinone in patients after cardiac surgery, in relation to the postoperative cardiac function, which was indicated by the required doses of catecholamines. DESIGN: Prospective clinical study. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: Fourteen patients who required a low-to-moderate dose of dopamine and dobutamine (group L) and 14 patients who required a high dose of dopamine and dobutamine (group H) after cardiac valve replacement. INTERVENTIONS: A loading dose of amrinone (0.75 mg/kg) was administered during a 15-min period and the continuous infusion was followed incrementally by doses of 5, 10, and 20 microg/kg/min every 60 mins on the first postoperative day. MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables were determined by the radial and pulmonary artery catheters at a dose of 0, 5, 10, and 20 microg/kg/min. Two-way repeated-measures analysis of variance showed significant interaction in the two groups in cardiac index and mean systemic arterial pressure. Cardiac index increased in a dose-dependent manner in group L but was unchanged in group H. Systemic vascular resistance index decreased in a dose-dependent manner in both groups. The mean systemic arterial pressure decreased in group L at a dose of 5 microg/kg/min and returned to the baseline level at doses of 10 and 20 microg/kg/min. On the other hand, the mean systemic arterial pressure significantly decreased in group H at a dose of 20 microg/kg/min. CONCLUSIONS: The inotropic effects of amrinone after cardiac valve replacement may be associated with the postoperative myocardial reserve, which was indicated by the required doses of catecholamines, although a similar vasodilative effect was observed in both groups.

Hemodynamic effects of alpha-human atrial natriuretic polypeptide on patients undergoing open-heart surgery.

BACKGROUND: A cardiac hormone, alpha-human atrial natriuretic polypeptide (alpha-hANP), acts as a vasodilator and a diuretic by activating cyclic GMP formation. We studied the hemodynamic effects of continuous intravenous infusion of alpha-hANP on patients undergoing open-heart surgery. METHODS: A total of 15 patients, including 7 with CABG, 4 with AVR, 2 with CABG plus AVR, and 2 with AVR plus MVR were involved in the study. They underwent open-heart surgery in our institute between July 1996 and April 1997. The mean age of patients was 68 years, ranging from 63 to 77. A dosage of 0.05 microg/kg/min of alpha-hANP was administered to all patients on postoperative day 1. Hemodynamics and blood and urine samples were measured at the following times: 2 hours before continuous intravenous infusion of alpha-hANP, 0, 1, 2, 3, 6, 12 and 24 hours after continuous intravenous infusion. We concomitantly measured urine volume and the plasma concentration of alpha-hANP. RESULTS: The plasma concentration of alpha-hANP increased sufficiently after the beginning of continuous intravenous infusion without any side effects, and the urine volume increased too. The administration of alpha-hANP induced a decrease in central venous pressure, pulmonary capillary wedged pressure and the pulmonary vascular resistance index. Systemic vascular resistance index and cardiac output remained unchanged. CONCLUSIONS: It is useful for the management of patients with associated volume overload following open-heart surgery because the administration of alpha-hANP decreases preload and facilitates satisfactory urination.

A comparative study of the vasodilator effects of prostaglandin E1 in patients with pulmonary hypertension after mitral valve replacement and with adult respiratory distress syndrome.

UNLABELLED: To determine whether the vasodilator effects of prostaglandin E1 (PGE1) differ according to the etiology and pathophysiology of pulmonary hypertension, we studied 30 patients with pulmonary hypertension after mitral valve replacement (MVR) (n = 16) or with the adult respiratory distress syndrome (ARDS) (n = 14). PGE1 was administered to decrease the mean pulmonary artery pressure to below 30 mm Hg in both groups. Cardiac index and oxygen delivery tended to increase, whereas mean systemic artery pressure, mean pulmonary artery pressure, systemic vascular resistance index (SVRI), and pulmonary vascular resistance index (PVRI) significantly decreased in both groups. A vasodilatory index was defined in this study to allow evaluation of vasodilation relative to PGE1 dose: systemic vasodilatory index (VIs) = SVRI change/PGE1 dose; and pulmonary vasodilatory index (VIp) = PVRI change/PGE1 dose. The VIp was similar in both groups, but the VIs was significantly greater in the ARDS group compared with the MVR group (13.3 +/- 7.8 vs 4.8 +/- 5.1, P < 0.01). A good correlation was found between the pretreatment intrapulmonary shunt fraction (Qs/Qt [%]) value and PGE1 extraction rate in the lung (r = 0.60), and between the pretreatment Qs/Qt value and PGE1 concentration in the radial artery (r = 0.65) in an additional 15 patients. We conclude that the vasodilator effects of PGE1 on the pulmonary circulation are similar in the two groups, whereas the vasodilator effects on the systemic circulation are significantly greater in the ARDS group and that significant reduction in VIs in the ARDS group was associated with decreased PGE1 extraction in the lung. IMPLICATIONS: Pulmonary hypertension after mitral valve replacement, or with adult respiratory distress syndrome, is a major medical problem. The authors found that administration of prostaglandin E1 significantly dilated the pulmonary circulation with a concomitant decrease in pulmonary artery pressure. Because the systemic vasodilatory effect was greater in the adult respiratory distress syndrome group, the authors concluded that prostaglandin E1 concentrations in the systemic circulation depend on the severity of lung injury.

[Application of alpha-hANP for the management following open-heart surgery: report of two cases].

Alpha-human atrial natriuretic peptide (alpha-hANP) has a vasodilating and diuretic action. Intravenous continuous administration of alpha hANP (0.05 microgram/kg/min) was attempted for two patients with low urine output despite good hemodynamics following open-heart surgery. Following the administration of alpha-hANP, urine volume increased markedly, and central venous and pulmonary capillary wedge pressures immediately decreased. Intravenous continuous administration of alpha-hANP is useful for the management of patients associated with the volume overload following open-heart surgery.

Noninvasive nasal mask BiPAP management for prolonged respiratory failure following cardiovascular surgery.

The purpose of this study was to assess the efficacy of nasal mas bi-level positive airway pressure (BiPAP) support in managing respiratory failure following cardiovascular surgery. A total of 20 patients requiring postoperative prolonged respiratory support of 72 hours or longer were studied. BiPAP support was used for eight patients (BiPAP group); the other 12 patients were managed using ordinary oxygen mask treatment (control group). The mean age of the BiPAP group and control group was 65 and 58 years of age, respectively. The mean period of postoperative endotracheal intubation of the BiPAP group and control group was 12 +/- 5 days and 7 +/- 1 days, respectively. Reintubation was necessary in two patients of the control group. The BiPAP group patients required no reintubation. BiPAP support was discontinued within 48 hours in 6 out of 8 patients. The respiratory rates of control group increased (p < 0.1) 24 hours after extubation, however, the respiratory rates of the BiPAP group remained unchanged. The values of the respiratory index of the BiPAP group improved significantly (p < 0.01) after BiPAP management (from 1.5 +/- 0.2 to 0.9 +/- 0.2). The values of the control group, however, remained unchanged. A-aDO2 and Qs/Qt decreased (p < 0.1) in the BiPAP group. There were no significant differences in central venous pressure or circulatory status between the two groups. In conclusion, BiPAP support is a noninvasive management technique for postoperative respiratory failure and may also prevent prolonged endotracheal intubation.

[Comparison of the effects of halothane, isoflurane and sevoflurane in the treatment of severe asthmatic attack: a case report].

A 19-year-old woman suffered from a severe asthmatic attack. She did not respond to any of the conventional therapies and eventually lapsed into a state of unconsciousness. We administered isoflurane 1-2% via an endotracheal tube, but, she still required a ventilator. This study was carried out in order to compare the effects of halothane, isoflurane and sevoflurane in the treatment of a severe asthmatic patient. The inhalation of isoflurane, halothane and sevoflurane decreased the airway resistance and systemic vascular resistance in direct relationship to the dosage administered. Because the patient's metabolic rate is low and the occurrence of arrhythmias is rare with isoflurane, we concluded that isoflurane is the best alternative for the patient with asthma.

Skeletal matrices, muci, and the origin of invertebrate calcification.

The sudden appearance of calcified skeletons among many different invertebrate taxa at the Precambrian-Cambrian transition may have required minor reorganization of preexisting secretory functions. In particular, features of the skeletal organic matrix responsible for regulating crystal growth by inhibition may be derived from mucous epithelial excretions. The latter would have prevented spontaneous calcium carbonate overcrusting of soft tissues exposed to the highly supersaturated Late Proterozoic ocean [Knoll, A. H., Fairchild, I. J. & Swett, K. (1993) Palaios 8, 512-525], a putative function for which we propose the term "anticalcification." We tested this hypothesis by comparing the serological properties of skeletal water-soluble matrices and mucous excretions of three invertebrates--the scleractinian coral Galaxea fascicularis and the bivalve molluscs Mytilus edulis and Mercenaria mercenaria. Crossreactivities recorded between muci and skeletal water-soluble matrices suggest that these different secretory products have a high degree of homology. Furthermore, freshly extracted muci of Mytilus were found to inhibit calcium carbonate precipitation in solution.

[Changes in gastric intramucosal pH and hepato-splanchnic oxygen extraction ratio after heart surgery].

The Do2/VO2 balance of splanchnic organs after heart surgery was evaluated using two different methods; the measurement of hepato-splanchnic oxygen extraction ratio (OERspl) and gastric intramucosal pH (pHi) employing a hepatic venous catheter and a gastric tonometric catheter. Systemic oxygen extraction ratio was within normal ranges during the 24 hours of the experiment, but pHi decreased and OERspl increased significantly at 6 hours after admission to the ICU. Both pHi and OERspl returned gradually to normal levels after 24 hours. We conclude that a period of 24 hours is required to restore sufficient blood flow in the visceral organs to meet oxygen demand and that the pHi reflects the splanchnic DO2/VO2 balance as well as OERspl.

[Repeated MK-801 administration but not methamphetamine produces up-regulation of muscarinic acetylcholine receptors in mice].

The author examined the effects of chronic treatment with MK-801 or methamphetamine (MAP) on the muscarinic acetylcholine receptors. Chronic treatment with MK-801 (0, 0.1, 0.5 and 1 mg.kg-1, daily treatment for 7 days) but not MAP produced an increase in total [3H] Quinuclidinyl bensilate (QNB) binding sites (Bmax) in the forebrain in a dose-dependent way without any effect of apparent affinity (the reciprocal of the dissociation constant, Kd). This was associated with the reduction in the behavior sensitivity to scopolamine (1 mg.kg-1, sc) (P < 0.05, at 0.5 and 1 mg.kg-1 compared with the control group). Coadministration of haloperidol (0, 0.125, 0.5 and 2 mg.kg-1), a dopamine receptor antagonist, prevented the up-regulation of muscarinic acetylcholine receptors (mAchR) induced by MK-801 (1 mg.kg-1) in a dose-dependent way, indicating involvement of the dopaminergic mechanism in the induction of up-regulation of mAchRs. The author concludes that chronic treatment with NMDA antagonists but not with MAP produces an up-regulation of mAchRs in the forebrain by facilitating dopamine release and these changes are associated with an alteration in Ach transmission in the central nervous system.