Autonomic Regulation of Voltage-Gated Cardiac Ion Channels

Altering voltage-gated ion channel currents, by changing channel number or voltage-dependent kinetics, regulates the propagation of action potentials along the plasma membrane of individual cells and from one cell to its neighbors. Functional increases in the number of cardiac sodium channels (Na_V1.5) at the myocardial sarcolemma are accomplished by the regulation of caveolae by β adrenergically stimulated G-proteins. We demonstrate that Na_V1.5, Ca_V1.2a, and K_V1.5 channels specifically localize to isolated caveolar membranes, and to punctate regions of the sarcolemma labeled with caveolin-3. In addition, we show that Na_V1.5, Ca_V1.2a, and K_V1.5 channel antibodies label the same subpopulation of isolated caveolae. Plasma membrane sheet assays demonstrate that Na_V1.5, Ca_V1.2a, and K_V1.5 cluster with caveolin-3. This may have interesting implications for the way in which adrenergic pathways alter the cardiac action potential morphology and the velocity of the excitatory wave.     

Interferon Alfa-2b or Not 2b? Significant Differences Exist in the Decision-Making Process between Melanoma Patients Who Accept or Decline High-Dose Adjuvant Interferon Alfa-2b Treatment

BACKGROUND: Patients with thick (Breslow>4 mm) primary melanoma and/or regional nodal metastasis have a high risk of tumor recurrence. High-dose adjuvant interferon (IFN) alfa-2b offers/=50% risk of recurrence/disease-related mortality and offered IFN. Telephone surveys delineated reasons behind patients' decisions to accept IFN. RESULTS: Acceptors, 60 of 135 (45%), decided to take IFN alfa-2b whereas 75 of 135 (55%) declined. Being female (OR, 2.4; 95% CI, 1.17-5.03; p=.017) and positive SLN status (OR, 2.2; 95% CI, 1.01-4.97; p=.048) were strongly associated with patients who chose IFN. Acceptors of IFN were younger, more influenced by physicians, and less affected by depression and side effect profile (p<.05 for all). Decliners were more concerned by strained relationships with family and social life (p<.05). CONCLUSIONS: Gender and positive SLN were predictive of high-risk melanoma patients' acceptance of IFN treatment. Physician insight into melanoma patients' therapeutic decision-making process can guide patients through this difficult disease.     

Comparison of Energy Estimation Equations with Measured Energy Expenditure in Obese Adolescent Patients with Cancer

Obesity is increasing in the US adolescent population. As the number of obese adolescents increases, obesity is becoming a more frequent problem in the hospital setting, sometimes causing patients to have complicated and prolonged hospital stays. Calculation of the energy requirements of obese adolescent patients with chronic diseases such as cancer is complicated by increased energy requirements as a result of disease state and growth. This study examined the accuracy of the commonly used equations for calculating energy requirements. Estimated energy expenditure was compared with measured energy expenditure determined by indirect calorimetry. All energy estimation equations were inaccurate, which indicates the need for a specific equation for determination of energy needs in this special patient population. Until further research is done, indirect calorimetry is recommended for all obese adolescent patients with cancer who require nutrition support.     

Synthesis and characterization of defensin NP-1

Defensins are a group of small, cationic, antimicrobial proteins found in the cytoplasmic granules of neutrophils and macrophages of a variety of mammalian species. One such defensin, NP-1, isolated from rabbit neutrophils, has been shown to consist of 33 amino acids rich in arginine and cysteine residues (6). We have synthesized NP-1 on an Applied Biosystems Model 431A peptide synthesizer using FastMoc? chemistry involving HBtu [2-1H-benzotriazol-1-y1)-1,1,3,3-tetramethyluronium hexafluorophosphate] activation for coupling amino acids. The linear peptide was folded by air oxidation to the biologically active form containing three disulfide bonds and purified by reverse phase chromatography. The amino acid sequence of the synthetic peptide was confirmed by Edman degradation. Molecular weight determination by plasma desorption mass spectroscopy (PDMS) gave a value of 3898.6, in agreement with the expected molecular weight of 3898. The biological activity of the synthetic peptide, as measured by its antifungal activity against several pathogenic fungi, was indistinguishable from that of the natural NP-1. Also, the CD spectrum was equivalent to that of natural NP-1, indicating conformational identity of the two species.     

Characteristics and practices of birth centres in Australia

Background: Around 2% of women who give birth in Australia each year give birth in a birth centre. There is currently no standard definition of a birth centre in Australia.
Aims: This study aimed to locate all birth centres nationally, describe their characteristics and procedures, and develop a definition.
Methods: Surveys were sent to 23 birth centres. Questions included: types of procedures, equipment and pain relief available, staffing, funding, philosophies, physical characteristics and transfer procedures. Of the birth centres, 19 satisfied the inclusion criteria and 16 completed surveys.
Results: Three constructs of a birth centre were identified. A 'commitment to normality of pregnancy and birth' was most commonly reported as the most important philosophy (44%). The predominant model of care was group practice/caseload midwifery (63%).
Thirteen birth centres were located within/attached to a hospital, two were on a hospital campus and one was freestanding. The distance to the nearest labour ward ranged from 2 m to 15 km. Reported intrapartum transfer rates ranged from 7% to 29%. Thirteen centres had a special care nursery or neonatal intensive care unit onsite, or both.
Eight centres undertook artificial rupture of membranes for induction of labour, while two administered oxytocin or prostaglandins. All centres offered nitrous oxide and local anaesthetic. Twelve centres had systemic opioids available and one offered pudendal analgesia. Fetal monitoring was used in all birth centres. Only three centres conducted instrumental deliveries, while 15 performed episiotomies.
Conclusion: Birth centres vary in their philosophies, characteristics and service delivery.     

Subchronic Toxicity of Orally Administered (Gavage and Dosed-Feed) Theophylline in Fischer 344 Rats and B6C3F2 13 Mice

Subchronic Toxicity of Orally Administered (Gavage and Dosed-Feed)Theophylline in Fischer 344 Rats and B6C3F, Mice.COLLINS, J.J., ELWELL, M. R., LAMP, J. C, IV, MANUS, A. C, HEATH, J. E.,and MAKOVEC, G. T. (1988). Fundam Appl Toxicol. 11, 472—484.Theophylline, a methylated xanthine closely resembling caffeineand theobromine, is a widely used pharmaceutical agent for thetreatment of respiratory disorders and certain acute cardiovascularconditions. The National Toxicology Program has conducted 13-weeksubchronic toxicity studies in F344 rats and B6C3F₁ mice (10animals/group) following administration of theophylline viathe diet or by gavage. Administration of theophylline in thefeed (0, 1000, 2000, and 4000 ppm) resulted in no mortalityor body weight effects in F344 rats, but did induce periarteritisof the arteries adjacent to mesenteric lymph nodes and the pancreas,particularly arterioles in the latter. Also observed in ratsdosed with theophylline via the diet was an increased severityof chronic nephropathy in males, especially at the high dose.Administration of theophylline at the same concentrations inthe feed to B6C3Fi 2 mice resulted in no mortality, but terminalbody weights were significantly decreased in all dosed groups.An increased incidence of hepatocellular glycogen depletionwas observed in male and female mice, and this change is believedto represent a physiological alteration exacerbated by the administrationof theophylline. Administration of theophylline by gavage toF344 rats (0, 37.5, 75, and 150 mg/kg) resulted in the earlydeath of one high-dose male and female and significantly decreasedor increased terminal body weights of high-dose males and females,respectively. Similar to the results of the dosed-feed study,male and female rats receiving theophylline by gavage demonstrated a dose-related increase in the incidence and severityof perivascular inflammation of mesen teric arteries. Gavageadministration of theophylline to B6C3F, mice (0, 75, 150, and300 mg/kg) resulted in the early death of all high-dose femalesand 3/10 high-dose males and significant depres sion of terminalbody weights in high- and mid-dose males and low-dose females.As in the dosed feed study, the primary histopathologk changein the mouse subchronic gavage study was hepatocel lular glycogendepletion, although in this case it was seen only in females.In summary, the major target organs for orally administeredtheophylline in 13-week subchronic toxicity studies appear tobe the mesenteric arteries in F344 rats and the liver in B6C3F₁mice. On the basis of organ weight changes and/or minor histopathologiceffects, many other tissues were also affected, particularlythe kidneys in dosed-feed male rats and the uterus in gavage-dosedfemale rats.