用于白内障超声乳化训练的活体白内障动物模型

目的：制备用于白内障超声乳化训练的活体白内障动物模型。 方法：狗在全身麻醉下用26号带有斜面的针刺破左眼的晶状体前囊，制备白内障模型，形成白内障后，行超声乳化手术。 结果：眼部检查显示晶状体后部皮质混浊开始于穿刺术后5～7d，并于术后75d白内障全部形成，在所有的白内障形成的眼上行超声乳化手术，并植入人工晶状体，所有的狗均恢复了视力。 结论：考虑到无经验的眼科医生在行白内障超声乳化手术的初始阶段引起的巨大损失，我们认为这个活的动物模型明显优于目前用于训练超声乳化手术的尸体眼。     

Purified human early pregnancy factor from preimplantation embryo possesses immunosuppresive properties

This study was undertaken to determine whether early pregnancy factor secreted by preimplantation embryos has immunosuppressive properties. Human early pregnancy factor was purified from embryo growth media of in vitro fertilized ova with ion-exchange and gel filtration chromatography. During each step of purification the fractions were tested for (1) early pregnancy factor activity with the rosette inhibition assay, (2) immunosuppressive properties with a concanavalin A-stimulated lymphocyte proliferation assay, and (3) purity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Results indicate that (1) human early pregnancy factor has a basic molecular weight of 14 kd, (2) early pregnancy factor has immunosuppressive activity, (3) polymers of early pregnancy factor also appear to be present in the embryo growth media, and (4) immunosuppressive factors other than early pregnancy factor are also secreted by preimplantation human embryos. Early pregnancy factor and other factor(s) produced by the preimplantation embryo may play a role in suppressing maternal cellular immune responses, thereby preventing maternal rejection of the embryo.     

Improved outcome at 28 days of age for very low birth weight infants treated with a single dose of a synthetic surfactant

Two identical double-blind, controlled, randomized trials were initiated to determine whether the administration of a single 5 ml/kg dose of a synthetic surfactant (Exosurf Neonatal), soon after the delivery of infants with birth weights 700 to 1350 gm, would improve rates of survival without bronchopulmonary dysplasia. Both trials were terminated before enrolling their planned sample sizes because of the availability of Exosurf under the provisions of a Treatment Investigational New Drug program. We report the combined results of these trials. Study infants were stratified according to birth weight and gender before random assignment to a treatment regimen. One hundred ninety-two infants received Exosurf and 193 received an air placebo. The study groups were similar when a variety of demographic features describing the mothers, their pregnancies, the circumstances of the births, and the infants were compared. Exosurf-treated infants required significantly less oxygen and respiratory support during the first 3 days of life in comparison with the air-treated infants. Fewer infants in the Exosurf group had pulmonary interstitial emphysema (26 vs 13; p = 0.028). In the Exosurf group, there was a significant reduction in the combined outcome, neonatal death or survival with bronchopulmonary dysplasia (57 vs 39; p = 0.042), and there was a significant increase in rates of survival without this disease (128 vs 137; p = 0.042). There were no differences between treatment groups in the incidences of a variety of complications of prematurity, including apnea, patent ductus arteriosus, intraventricular hemorrhage, and necrotizing enterocolitis. We conclude that improvements in respiratory physiology after a single prophylactic dose of Exosurf result in an increased likelihood of neonatal survival without bronchopulmonary dysplasia.     

Primary osteogenic sarcoma of the skull

BACKGROUND: An osteogenic sarcoma of the skull is rare, particularly as a primary tumor. The incidence of primary osteogenic sarcomas of the skull is about 1 to 2% of all skull tumors. CASE DESCRIPTION: A 21-year-old male was initially evaluated because of a large mass that had been growing for 7 months. The patient had been experiencing frequent headaches and tenderness at the site of the lump for about a month before being seen by the neurosurgeon. A computed tomography scan revealed a large mass, 12 cm x 7 cm, involving the scalp extending from the right temporal region to the vertex. A magnetic resonance imaging (MRI) scan showed a large mass arising from the posterolateral aspect that was 90% extracranial and 10% intracranial on the right side of the skull. The MRI showed marked vascularity and neovascularity of the tumor. An angiogram was performed, which demonstrated that the mass was fed by the branches from the right external carotid artery. The patient subsequently underwent surgery for embolization of the right occipital and superficial temporal arteries and removal of the mass. Pathology evaluation of a specimen revealed a high-grade osteoblastic osteosarcoma. CONCLUSION: We review the literature of reported cases of primary osteogenic sarcomas of the skull to discuss the common clinical presentation, evaluation methods, and recommended treatment plans.     

Biomolecular targets for platinum antitumor drugs

Cis-diamminedichloroplatinum(II) (cisplatin) is widely used for the treatment of testicular, ovarian, and other forms of cancer. Several second generation platinum centered antitumor drugs have been approved or undergoing phase-3 clinical trial. Cisplatin arrests the cell cycle at the G2 phase by a mechanism commonly known as apoptosis. At the molecular level, it is generally believed that the anticancer properties of these compounds are due to the covalent binding to DNA. In addition to DNA binding, the platinum drugs bind and interact with proteins and enzymes. The toxic effects of the drugs have been usually attributed to protein binding. However, a growing body of work points to much more complex anticancer mechanisms involving direct and indirect interactions of platinum compounds with proteins and enzymes. In this review, a discussion on the strength and weaknesses of DNA binding mechanism followed by enzymes and protein interactions with the drugs are presented for the comprehensive understanding of apoptosis. The purpose of this review is to encourage researchers to explore metallobiochemistry of platinum drugs focusing attention to cellular and molecular events beyond DNA binding.     

Updating of hereditary haemoglobin disorders

Hereditary haemoglobin disorders (E-beta Thalassaemia & Thalassaemia) are inherited as recessive disorders so that the heterozygote subjects are generally healthy. They commonly present with progressive pallor, thalassaemic facies, splenohepatomegaly & growth retardation. Diagnosis of carriers & patients are usually confirmed by haemoglobin electrophoresis. Transfusion-chelation therapy is usually employed for their treatment. Allogenic bone marrow transplantation is the only definite cure. Gene therapy remains to be the major challenging goal of future curative therapy. During the last 10 years wit medical advances, the number of pregnancies in thalassaemia is increasing. Normal pregnancy can be maintained with regular packed blood cells transfusion given carefully. In Bangladesh, HHD can be prevented by I. carrier identification and marriage counseling, II. passing and enforcing laws against marriage between two carriers, III. introducing thalassaemia in school curriculum and IV. creating public awareness.     

Critical role of allyl groups and disulfide chain in induction of Pi class glutathione transferase in mouse tissues in vivo by diallyl disulfide,a naturally occurring chemopreventive agent in garlic

We have shown previously that the chemoprotective activity of diallyl disulfide (DADS), a naturally occurring anticancer agent in garlic, against benzo[a]pyrene (BP)-induced forestomach carcinogenesis in mice correlates strongly with its inductive effects on the expression of Pi class glutathione (GSH) transferase mGSTP1-1. The present structure-activity relationship studies were designed to define the role of allyl groups and the disulfide chain in mGSTP1-inducing activity of DADS. Hepatic mGSTP1 mRNA levels rose rapidly upon treatment of mice with DADS, reached a maximum between 12 and 24 h (< or =5.7-fold induction) and fell to control levels by 48 h after DADS treatment. Induction of mGSTP1 mRNA in the forestomach was maximal between 6 and 12 h after DADS treatment (< or =4.7-fold induction). The mGSTP1 mRNA expression was either unaltered (liver) or moderately increased (forestomach) upon treatment of mice with dipropyl disulfide (DPDS), which is a naturally occurring saturated analog of DADS. These results indicated that the allyl groups are critical for the mGSTP1-inducing activity of DADS. A statistically significant increase in the expression of mGSTP1 mRNA was also observed in the liver and forestomach of mice treated with diallyl monosulfide (DAMS), albeit to a much lesser extent compared with DADS. These results indicated that the oligosulfide chain length in garlic organosulfides (OSCs) is equally important for their mGSTP1-inducing activity. The role of the disulfide chain in DADS-mediated induction of mGSTP1 was further investigated by testing a pair of alkadienes (1,7-octadiene and 1,8-nonadiene) having structural similarity to DADS. Both DADS and the alkadienes carry allyl groups at both ends of a linear molecule and the distance between the allylic carbon atoms is similar in both compounds, but the central disulfide chain of DADS is replaced with an alkyl chain in the alkadienes. The alkadienes were either ineffective or moderately active in increasing mGSTP1 expression. In conclusion, the results of the present study clearly indicate that the presence of terminal allyl groups as well as the central disulfide chain is required for maximum induction of mGSTP1 in vivo by garlic-derived OSCs.     

Clipping of cerebral aneurysm under hypothermic cardiac arrest and simultaneous coronary artery bypass grafting: case report

This report describes a case where joint neurological and cardiac surgery teams cooperated to perform simultaneous procedures of clipping a complex internal carotid artery under hypothermic cardiac arrest and coronary artery bypass grafting. A 69 year old man was evaluated for complaints of double vision, pain behind his right eye, and progressively worsening headaches. Examination showed bilateral upgoing toes and difficulty performing a tandem gait. The patient had a history of myocardial infarction. Brain MRI showed a 1.6 cm diameter, partially thrombosed aneurysm of the right internal carotid artery and posterior communicating artery. Cardiac catheterisation showed critical coronary artery disease of the distal segment of the right coronary artery with 90% stenosis of the midcircumflex artery and an ejection fraction of 40%. After initial exposure of the aneurysm, the cardiac team instituted hypothermic cardiac arrest (21 degree C). The aneurysmal sac was collapsed and dissected from the surrounding perforators. An encircling fenestrated clip was applied and a small part of the neck of the aneurysm was further clipped with straight clips. The cardiac surgery team performed the coronary artery bypass grafting procedure. The patient recovered fully, returned to his normal activities, and is functioning independently.     

A novel heparin-binding, human chimeric, superoxide dismutase improves myocardial preservation and protects from ischemia–reperfusion injury

BACKGROUND: The plasma membranes of endothelial cells are sites of physiologic injury caused by superoxide attack, whether the radicals are generated within the cell (i.e., from enzymatic sources such as xanthine oxidase or from ischemically injured mitochondria) or are generated within the interstitial spaces by activated neutrophils or macrophages. An extracellular superoxide dismutase (ECSOD) electrostatically bound to endothelial surfaces partially protects against this oxidative attack. To provide a therapeutic equivalent of this ECSOD activity, we evaluated the product of a fusion gene encoding a chimeric manganese SOD (chimeric-SOD) and the carboxyl-terminal 26-amino acid basic "tail" from ECSOD with high affinity for heparin-like proteoglycans on cell surfaces. METHODS: We tested the chimeric-SOD in isolated rabbit hearts during warm and cold ischemia. RESULTS: When perfused through an isolated rabbit heart, chimeric-SOD bound to endothelial surfaces and was displaced by a bolus dose of heparin. In an established model of no-flow ischemia followed by reperfusion of the isolated rabbit heart, the chimeric-SOD was as protective as native Mn-SOD or Cu,Zn-SOD, but at doses nearly 2 orders of magnitude lower. In a rabbit-heart preservation model, the chimeric-SOD provided better recovery of function after 4 hours of cold ischemia than did University of Wisconsin cardioplegia solution. CONCLUSION: This chimeric-SOD can bind to cell surfaces and may aid in preventing superoxide-mediated endothelial damage and may function as a rational therapeutic agent for treating free-radical-mediated diseases.