Protective Effects of Hyperpolarizing Cardioplegia with Pinacidil on Myocardium in Rats

Whether the ATP-sensitive potassium channel opener pinacidil can provide myocardial protective effects in prolonged isolated global ischemic rat heart was investigated. On modified isolated rat working heart model, 40 hearts were divided into four groups randomly: Hyperpolarized arrest H-K solution containing pinacidil (50 tmol/L) (P1 and P2) and depolarized arrest St. Thomas‘ solution (S1 and S2) subjected to 15 C hypothermia, 60 min (P1 and S1) or 120 min (P1 and S2) of ischemia and 30 min reperfusion. The experimental indices included cardioplegic efficiency, cardiac function, coronary blood flow, myocardial enzyme release, myocardial water and ATP content. Hyperpolarized arrest provided significantly better recovery of cardiac function than depolarized arrest.Postischemic coronary flow and myocardial ATP content were higher. The arrest time of electro-mechanical activities were longer than depolarized arrest. There were no differences among the groups in myocardial water contents. The hyperpolarized arrest solution containing pinacidil can provide a marked myocardial protective effect during prolonged hypothermic myocardial ischemia.     

Preparation of protected peptidyl thioester intermediates for native chemical ligation by Nα‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry: considerations of side‐chain and backbone anchoring strategies,and compatible protection for N‐terminal cysteine*,†

Abstract: Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C‐terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of N^α‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use N^α‐t‐butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side‐chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N‐terminal cysteine residue have been developed: (i) incorporation of N^α‐9‐fluorenylmethoxycarbonyl‐S‐(N‐methyl‐N‐phenylcarbamoyl)sulfenylcysteine [Fmoc‐Cys(Snm)‐OH], allowing creation of an otherwise fully protected resin‐bound intermediate with N‐terminal free Cys; (ii) incorporation of N^α‐9‐fluorenylmethoxycarbonyl‐S‐triphenylmethylcysteine [Fmoc‐Cys(Trt)‐OH], generating a stable Fmoc‐Cys(H)‐peptide upon acidolytic cleavage; and (iii) incorporation of N^α‐t‐butyloxycarbonyl‐S‐fluorenylmethylcysteine [Boc‐Cys(Fm)‐OH], generating a stable H‐Cys(Fm)‐peptide upon cleavage. In separate stages of these strategies, thioesters are established at the C‐termini by selective deprotection and coupling steps carried out while peptides remain bound to the supports. Pilot native chemical ligations were pursued directly on‐resin, as well as in solution after cleavage/purification.     

Analysis of the circumstances at the end of life in children with cancer: Symptoms, suffering and acceptance

BACKGROUND: In an effort to improve the quality of life of children with cancer, this study analyzes the signs and symptoms at the end of life in such children. It is hoped that these data will contribute to the development of appropriate programs to address the challenges faced by these children. PROCEDURE: Between 1994 and 2000, 28 children died after treatment for cancer at Hamamatsu University Hospital, Japan. The circumstances, signs and symptoms at the end of life of these children were analyzed through their medical records. RESULTS: Of the 28 children, the underlying diseases were leukemia/lymphoma (LL group; n=11), brain tumors (BT group; n=7), and other solid tumors (OST group; n=10). Records showed poor appetite (100%), dyspnea (82.1%), pain (75.0%), fatigue (71.4%), nausea/vomiting (57.1%), constipation (46.4%) and diarrhea (21.4%) among these children. Anxiety was reported in 53.6% of the entire group of 28 children; however, no child in the BT group manifested anxiety. However, disturbance of consciousness was reported in all children in the BT group, which was significantly greater than in the other groups. Awareness, fear or acceptance of the imminence of his/her own death as indicated by verbal expression was reported in nine children (32.1%). CONCLUSIONS: Using the data obtained in the present study, we describe situations faced in the terminal care of children. It is important to address the problems revealed by this analysis in order to achieve improvements in both the physical and psychological care of children with terminal cancer.     

Terminal home care in the Netherlands: An overview

Beginning in the late 1980s, after a long period of declining interest in home care for the terminally ill, several projects and experiments were initiated in the Netherlands. This article describes this trend and provides background information on the Dutch health services, a definition of terminal home care, and statistical information about the different types of home care in the Netherlands. Findings from 3 recent studies of these projects and experiments are presented along with the guidelines for providing good terminal home care formulated by the Dutch Health Council in 1991.     

Expression of Lewis Y (Ley) Antigen in Human Anagen Hair Follicles

Lewis Y (Le^y) antigen, a difucosylated tetrasaccharide found on type 2 blood group oligosaccharides of glycolipids and glycoproteins, is thought to be a phenotypic marker predictive of cell differentiation. The distribution of this antigen in human anagen hair follicles was examined by immunohistochemical staining using a monoclonal antibody (AH-6) to Le^y. In the bulbar and suprabulbar portion of anagen hair follicles, Le^y antigen was detected in the three layers of the inner root sheath. Subsequently, the positive staining became translocated to the innermost layer of the outer root sheath in the middle part of the hair follicles. In the upper portion of the hair follicles, Le^y antigen was found in the outer cells of the outer root sheath. These findings suggested that the expression of Le^y antigen in the anagen hair follicles was correlated with the processes of keratinization or terminal differentiation.     

Closed-Chest Cardiopulmonary Bypass and Cardioplegia: Basis for Less Invasive Cardiac Surgery

Background. We developed a method of closed-chest cardiopulmonary bypass to arrest and protect the heart with cardioplegic solution. This method was used in 54 dogs and the results were retrospectively analyzed.

Methods. Bypass cannulas were placed in the right femoral vessels. A balloon occlusion catheter was passed via the left femoral artery and positioned in the ascending aorta. A pulmonary artery vent was placed via the jugular vein. In 17 of the dogs retrograde cardioplegia was provided with a percutaneous coronary sinus catheter.

Results. Cardiopulmonary bypass time was 111 ± 27 minutes (mean ± standard deviation) and cardiac arrest time was 66 ± 21 minutes. Preoperative cardiac outputs were 2.9 ± 0.70 L/min and postoperative outputs were 2.9 ± 0.65 L/min (p = not significant). Twenty-one-French and 23F femoral arterial cannulas that allowed coaxial placement of the ascending aortic balloon catheter were tested in 3 male calves. Line pressures were higher, but not clinically limiting, with the balloon catheter placed coaxially.

Conclusions. Adequate cardiopulmonary bypass and cardioplegia can be achieved in the dog without opening the chest, facilitating less invasive cardiac operations. A human clinical trial is in progress.     

结肠回肠反流与回肠黏膜结肠化相关性的实验研究

目的探讨结肠回肠反流后回肠末端黏膜结肠化的机制.方法取SD大鼠60只,均为雄性,体重25¨3∞g,随机分为实验组和对照组,分别进行末端回肠-盲肠侧侧吻合术或回肠末端手术缝线,2个月后处死动物并取组织进行观察.结果实验组术后一般状况良好.大体形态学观察:实验组回肠末端黏膜表现为绒毛萎缩、间距增宽、沟变浅、光滑性增强.病理组织学:实验组表现为黏膜绒毛萎缩、间距增宽、沟变浅、上皮细胞变短、杯状细胞增多.电镜观察:实验组可见绒毛变小、变短或脱落;微绒毛变短、分布不均匀;杯状细胞数目在非坏死区增多.结论结肠-回肠反流后可导致回肠末端黏膜结肠化的变化,它可能是慢性末端回肠炎的发病基础或前期表现.     

Responses of periodontal nerve terminals to experimentally induced occlusal trauma in rat molars: an immunohistochenmical study using PGP 9.5 antibody

The response of periodontal nerves to experimentally induced occlusal trauma in rat molars was assessed by immunohistochemistry for protein gene product 9.5 (PGP 9.5) at light and electron microscopic levels, and by computerized image analysis. The occlusal surface on the left upper first molar of 8-wk-old male Wistar rats was raised approximately 1 min under ether anaesthesia. The rats were perfusion-fixed on d 1, 2, 3, 4, and 7 after bite-raising and then decalcified for 2–3 wk. Frozen sagittal cryostat sections were stained by the avidin-biotin complex method. By the second day after bite-raising many Ruffini endings were swollen and their outline unclear at the light microscopic level. Transmission electron microscopy disclosed PGP 9.5 reaction products within Ruffini endings that had unusually long cytoplasmic projections extending through enlarged slits of the Schwann sheaths and also diffuse extracellular PGP 9.5-immunoreactivity near the Ruffini endings. From d 2 to 4, thin nerve fibres on the pressure side of the periodontal ligament were orientated irregularly and had a prominent beaded appearance. An increase in beaded nerve terminals occurred at d 2–4 post elevation, and decreased later. These results suggest that occlusal trauma induces specific changes in the distribution and shape of nerve terminals in the periodontal ligament.     

Development of specificity in corticospinal connections by axon collaterals branching selectively into appropriate spinal targets

Corticospinal projections in adult rodents arise exlusively from layer V neurons in the sensorimotor cortex. These neurons are topographically organized in their connections to spinal cord targets. Previous studies in rodents have shown that the mature distribution pattern of corticospinal neurons develops during the first 2 weeks postnatal from an initial widespread pattern that includes the visual cortex to a distribution restricted to the sensorimotor cortex. To determine whether specificity in corticospinal connections also emerges from an intially diffuse set of projections, we have studied the outgrowth of corticospinal axons and the formation of terminal arbors in developing hamsters. The sensitive fluorescent tracer 1, 1′, dioctadecyl-3, 3, 3′, 3′-tetramethylindocarbocyanine perchlorat (DiI) was used to label corticospinal axons from the visual cortex or from small regions of the forelimb or hindlimb sensorimotor cortex in living animals at 4–17 days postnatal. Initially axon outgrowth was imprecise. Some visual cortical axons extended transiently beyond their permanent targets in the pontine nuclei, by growing through the pyramidal decussation and in some cases extending as far caudally as the lumbar enlargement. Forelimb sensorimotor axons also extended past their targets in the cervical enlargement, in many cases growing in the corticospinal tract to lumbar levels of the cord. By about 17 days postnatal these misdirected axons or axon segments were withdrawn from the tract. Despite these errors in axon trajectories within the corticospinal tract, terminal arbors branching into targets in the spinal gray matter were topographically appropriate from the earliest stages of innervation. Thus visula cortical axons never formed connections in the spinal cord, forelimb sensorimotor axons arborized only in the cervical enlargement, and hindlimb cortical axons terminated only in the lumbar cord at all stages of development examined. Corticospinal arbors formed from collaterals that extended at right angles from the shafts of primary axons, most likely by the process of interstitial branching after the primary growth cone had extended past the target. Once collaterals extended into the spinal gray matter, highly branched terminal arbors formed within 2–4 days, beginning at about 4 and 8 days postnatal for the cervical and lumbar enlargements, respectively. These results show that specificity in connectivity is achieved by selectivty growth of axon collaterals in to appropriate spinal targets from the beginning and not by the later remodeling of intially diffuse connections. In contrast, errors occur in the initial outgrowth of axons in the corticospinal tract, which are subsequently corrected. Copyright © 1994 Wiley-Liss, Inc.