Microencapsulated dopamine (DA)-induced restitution of function in 6-OHDA-denervated rat striatum in vivo: comparison between two microsphere excipients.

Biodegradable controlled-release microsphere systems made with the biocompatible biodegradable polyester excipient poly [DL lactide-co-glycolide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microspheres encapsulated within two different polymer excipients into denervated-striatal tissue assures a prolonged release of the transmitter in vivo. Moreover, in this regard, the results show that there were clear cut temporal differences in the effect of the two DA microsphere formulations compared in this study, probably reflecting variations in the actual composition (i.e., lactide to glycolide ratio) of the two copolymer excipients examined. This technology has considerable potential for basic research with possible clinical application.     

Cell transplantation to improve ventricular function in the failing heart

Current therapies for congestive heart failure are limited in efficacy or in applicability. Cardiac cell transplantation offers a novel therapeutic approach to improve heart function. Although significant progress has been made over the past decade in the development of cell transplantation, only recently have investigators studied the changes in ventricular function following cell transplantation. This review article describes the latest research developments, evaluates recent studies of ventricular function after cell transplantation, and discusses the future directions of cell transplantation as a new therapy to ‘repair broken hearts’.     

Venomous snakebite: past, present, and future treatment options.

BACKGROUND: Venomous snakebites continue to cause great morbidity, and treatment options are confusing the attending physician. In the United States approximately 45,000 snakebites occur each year, of which some 8000 are by 20 species of venomous snakes. METHODS: Information on venomous snakes and snakebite treatment was gathered from the libraries of the Wilderness Medical Society and the Rocky Mountain Center for Wilderness Medicine in Boise, Idaho (co-supported by the Boise State University and the Family Practice Residency of Idaho), as well as from current literature files of physicians practicing wilderness medicine. RESULTS AND CONCLUSIONS: Three genera of venomous snakes account for the majority of poisonous snake envenomations in this country. Most hospitalized victims are bitten either by rattlesnakes or copperheads or by unidentified snakes. Most of these bites occur during the summer months and are found on the extremities. Field treatment focuses on the application of a vacuum extractor and transportation to the nearest medical facility. Although constriction band use can be helpful, tourniquets, incision and suction, and ice therapy are contraindicated. Electric shock therapy is of no use and could cause serious injury. Hospital management focuses on rapid clinical evaluation and laboratory tests to establish the degree of envenomation, looking for clotting abnormalities. If envenomation has occurred and is reactive, polyvalent antivenin should be administered according to the degree of envenomation. Errors in diagnosis and treatment result in increased morbidity and put attending physicians at risk for litigation. Prevention remains the most successful approach to snakebite management.     

Application of an immunosensor for the detection of the β-lactam antibiotic, cephalexin

Public concern surrounding antibiotic contamination in food and food products has made it imperative to develop analytical methods for their detection. Polyclonal antibodies were used in the development of a surface plasmon resonance (SPR)-based inhibition immunoassay for cephalexin. A conjugate consisting of cephalexin-bovine serum albumin (BSA) was immobilized on the dextran gel surface of the sensor chip. Binding/regeneration studies of antibody to immobilized cephalexin were studied and dissociation of the antibody from the immobilized cephalexin was easily achieved with 10 mmol l^-1 NaOH. Forty surface regeneration cycles were carried out and found to be reproducible with only a 7.4% decrease in binding over this number of regenerations. Model inhibition immunoassays for cephalexin were developed in PBS and spiked milk samples with detection ranges of 4.88 to 2,500 ng ml^-1 and 244 to 3,906 pg ml^-1, respectively.     

Effect of Zonisamide (CI-912) on a Synaptic System Model

The effect of the experimental antiepileptic drug zonisamide (1,2-benzisoxazole-3-methanesulfonamide, ZNS) on the trigeminal complex of cats was compared with the effect of established antiepileptic drugs. Intravenous administration of 10-40 mg/kg ZNS significantly depresses descending excitatory mechanisms, as well as segmental and descending inhibitory mechanisms, but has only a minor effect on segmental excitatory mechanisms. This spectrum of activity is similar to that of valproate, and suggests that ZNS should also be a broad-spectrum antiepileptic drug. In agreement with our experimental observations, it has been found that ZNS is effective against complex partial, generalized tonic clonic, and myoclonic seizures. The antiepileptic profile of ZNS in conventional screening tests resembles that of carbamazepine (CBZ) and phenytoin. However, CBZ exacerbates rather than prevents myoclonic seizures. Our experimental model thus provides a more accurate prediction of ZNS's clinical spectrum of activity. The relationship of these findings to the mechanism of action of antiepileptic drugs is discussed.     

Platelet transfusions are not associated with increased morbidity or mortality in cardiac surgery

PURPOSE: To determine the independent relationship between leukoreduced platelet transfusions and adverse events in cardiac surgery. METHODS: In this observational study, detailed baseline and perioperative data were prospectively collected on consecutive patients who underwent cardiac surgery at a single institution from 1999 to 2004. The independent associations of platelet transfusion with clinical outcomes (low output syndrome, myocardial infarction, stroke, renal failure, sepsis, and death) were determined by multivariable logistic regression analysis and propensity score case-control analysis. RESULTS: Of the 11,459 patients analyzed, 2,174 (19%) received (leukoreduced) platelets - 1,408 received 5 U, 471 received 10 U, 140 received 15 U, and 155 received 20 or more units. Although all measured adverse event rates were higher in those who received platelets, in neither the logistic regression analyses nor the propensity score analyses was there any association between platelet transfusion and any of the adverse events. CONCLUSIONS: Transfusion of leukoreduced platelets in cardiac surgery is not associated with adverse clinical outcomes when adjustments are made for important confounders.