Characteristic molecular packing in the crystal structure of tert-butoxycarbonyl-L-phenylalanyl-L-methionine methyl ester

The molecular conformation and association of the peptide Boc-L-Phe-L-Met-OMe have been studied in the solid state by X-ray diffraction. The peptide crystallizes in the orthorhombic system, space group P2₁2₁2₁, with cell parameters of a= 9.821(2), b= 25.394(6), c= 28.714(8) ų, V= 7161(3) ų. The structure has been solved by direct methods and refined to a final R of 0.079 for 5464 independent reflections with F_o≥σ(F_o). The crystal consists of three independent molecular conformations per asymmetric unit. Respective peptide backbones adopt an extended conformation with the side-chains of Phe and Met residues being arranged below and above the backbone chains. Contrary to the sheet structure most frequently observed in the crystal packing of the extended peptide conformations, three independent molecules lie spirally along the c-axis and form a pin-wheel-like crystal packing. The sheet structures formed by two of three independent molecules are almost at right angles to the backbone of the remaining molecule. This molecular packing mode would provide a possible interaction model between the intersecting β-sheet structure and single-strand structure of polypeptide. © Munksgaard 1994.     

Pregnancy enhances the antinociceptive effects of extradural lignocaine in the rat

We have compared the antinociceptive effect of extradural lignocaineon somatic and visceral noci-ception in pregnant (n=11) andnon-pregnant rats (n=9). Colorectal distension (CD) thresholdand tail flick (TF) latency were measured as visceral and somaticnociception. respectively, for 60 min after extradural injection.On days 19, 20 and 21 of pregnancy, rats received lignocaine200, 400 or 800 µg or normal saline via a chronicallyimplanted lumbar extradural catheter. Extradural lignocaineproduced dose-dependent antinociceptive effects on TF latencyand CD threshold. Lignocaine 200 or 400 µg produced significantlygreater peak effects in pregnant than in non-pregnant rats.Although the peak effects with lignocaine 800 µg werenot different between groups, the duration of the effects werelonger in pregnant compared with non-pregnant rats. We concludethat both somatic and visceral antinociceptive effects of extradurallignocaine were potentiated in pregnant rats near term comparedwith those in non-pregnant rats.     

Morphological study by an 'in vivo cryotechnique' of the shape of erythrocytes circulating in large blood vessels

Changes in the shape of erythrocytes circulating in large blood vessels of mice were examined by our 'in vivo cryotechnique'. The abdominal aorta and inferior vena cava (IVC) were cut vertically with a precooled knife and simultaneously an isopentane–propane mixture (−193°C) was poured over them for freezing. They were freeze-substituted in acetone containing 2% osmium tetroxide. Some specimens were embedded in Quetol-812, and thick or ultrathin sections were examined by light or transmission electron microscopy. Serial ultrathin sections were used to reconstruct 3-dimensional images of native erythrocytes. Others were transferred into t-butyl alcohol and freeze-dried for scanning electron microscopy. The tissue surfaces were sufficiently frozen to prevent large ice crystal formation, and erythrocyte shapes were also preserved. The shapes of circulating erythrocytes appeared to be varied in the abdominal aorta but typical biconcave discoid shapes were rarely observed. Conversely, erythrocytes were approximately biconcave discoid in shape in the IVC. Our in vivo cryotechnique was useful for clarifying the in vivo morphology of erythrocytes circulating in large blood vessels.     

Behavioral and psychological symptoms of dementia (BPSD) in dementia with Lewy bodies

Behavioral and psychological symptoms of dementia (BPSD) bother patients with dementia with Lewy bodies (DLB) and their families so frequently that early diagnosis of DLB before the appearance of prominent cognitive impairment is important. Because BPSD in DLB can be reduced or improved by early intervention, medical intervention is important. Of BPSD in DLB, vivid visual hallucinations and delusions are most important. Other visual cognitive impairments and sleep disturbances, including disorders in rapid eye movement (REM) sleep, are also frequently seen. Cholinesterase inhibitors, including donepezil chloride, are the first choice for the therapy of BPSD; Yokukansan (a type of Kanpo (traditional Chinese herbal) medicine) is the second choice. When neither treatment is effective, atypical antipsychotics, such as quetiapine, risperidone, and aripiprazol, may be used.     

Gender Differences in the Effect of Auditory Stimuli on Ventricular Repolarization in Healthy Subjects

Introduction: Gender differences in the incidence of ventricular arrhythmias have been reported and torsade de pointes associated with long-QT syndrome (LQTS) is more common in women than men. Although auditory stimulation has been recognized as an important trigger of torsade de pointes in LQT2 patients, the normal response and gender differences in ventricular repolarization induced by auditory stimuli remained to be evaluated systematically.
Methods: Holter ECGs were recorded in 30 healthy volunteers (14 men aged 25 ± 4 years and 16 women aged 23 ± 2 years). They were awakened by an alarm clock at 5:00 am. The RR and QT (QTc) intervals and the T-wave amplitude were measured before and after alarm ringing.
Results: The morphology of the T-wave changed dynamically and transiently during awakening. The RR interval significantly decreased just after sounding of the alarm in both sexes (P < 0.0001). The QT interval changed little after the alarm ringing and was significantly longer in women than men (P < 0.0001). The QTc intervals were significantly prolonged just after alarm ringing in both sexes (P < 0.0001); QTc prolongation was significantly longer and more sustained in women than men (P < 0.0001). The T-wave amplitude decreased after the alarm and was significantly lower in women than men (P = 0.0001).
Conclusion: Auditory stimulation abruptly and abnormally modulated the dynamics of ventricular repolarization in healthy subjects; the effect was more pronounced in women than men. This gender difference may partially account for the increased susceptibility of women with electrically unstable hearts to arrhythmogenesis.     

Comparison of continuous epidural infusion of morphine/bupivacaine with fentanyl/ bupivacaine for postoperative pain relief

The efficacy and safety of postoperative analgesia with continuous epidural infusion of either morphine or fentanyl in combination with bupivacaine were evaluated in 85 patients, ASA physical status I or II, undergoing thoracic and/or upper abdominal surgery. Patients were treated with one of the combinations for 48 h after surgery. The morphine/bupivacaine group (MB; n = 45) received morphine at the rate of 0.2 mg h^-1, and bupivacaine at the rate of 10 mg h^-1 for the first 24 h or 5 mg h^-1 for the second 24 h; the fentanyl/bupivacaine group (FB; n = 40) received fentanyl at the rate of 20 μg–h^-1, and bupivacaine at the rate of 10 mg h^-1 for the first 24 h or 5 mg h^-1 for the second 24 h. The degree of pain relief assessed by the visual pain scale and the modified Prince Henry pain scale was satisfactory in most patients in both groups. In group MB 74% and in group FB 76% of patients did not need any supplementary analgesics. No significant differences were observed between the groups in assessment of pain. The incidence of hypotension ( P < 0.05) and pruritus ( P < 0.05) was higher in group MB than in group FB. None of the patients developed respiratory depression in either group.     

Increased incidence of dementia with Lewy bodies in patients carrying the ɛ4-allele of apolipoprotein E

Background: The apolipoprotein ∈4 (APOE4) allele is a risk factor for Alzheimer's disease, but it remains undetermined whether this allele is related to the pathological development of neurofibrillary tangles (NFT) and the formation of Lewy bodies. Methods: In the present study, we examined the relationship between these changes and the APOE4 allele in 255 consecutive neuropathologically diagnosed cases. APOE genotyping was carried out by the polymerase chain reaction–restriction fragment length polymorphism method. Results: Nearly all our cases of dementia with Lewy bodies (DLB) showed the common form, having numerous senile plaques in the cerebral cortex and NFT in the parahippocampal and hippocampal regions and were also associated with the APOE4 allele. Limbic neurofibrillary tangle dementia (LNTD), characterized by the presence of NFT in limbic areas as well as the absence of senile plaques, did not appear to be associated with the APOE4 allele. Conclusions: The APOE4 allele is a risk factor for DLB as well as Alzheimer's disease and cerebral amyloid angiopathy, but not for LNTD.     

Effect of Selective PEEP on Pulmonary Blood Flow following Unilateral Hydrochloric Acid Aspiration in the Dog

We investigated the effect of unilateral or bilateral positive end-expiratory pressure (PEEP) on pulmonary perfusion in 12 dogs with a hydrochloric acid aspiration injury of the left lung. The lungs were ventilated separately and PEEP was applied to the left lung at 10 cmH2O (1.0 kPa) in six and at 15 cmH2O (1.5 kPa) in six others. Measurements of the right and left pulmonary arterial blood flows (QR and QL) and venous admixture were made before, during and after PEEP. After this study, 5 and 10 cmH2O (0.5 and 1.0 kPa) PEEP were applied to both lungs in six dogs and measurements were repeated. Following the application of PEEP to the left lung, a significant decrease in QL and increase in QR were observed. However, the application of PEEP to both lungs was followed by significant decreases in both QL and QR. The cardiac output decreased slightly during unilateral PEEP and markedly during bilateral PEEP. The venous admixture decreased significantly during PEEP in all the groups. These findings indicate that selective PEEP causes a transfer of pulmonary blood flow from the injured lung to the normal lung, improving ventilation-perfusion inequality, and improves gas exchange without impeding oxygen delivery.