Delta opioid receptor selective ligands; DPLPE-deltorphin chimeric peptide analogues†

Further efforts to correlate the topography of the bioactive structures of DPDPE and the deltorphins, two δ-opioid receptor active peptide families, are reported. A number of DPLPE-deltorphin chimeric peptides have been synthesized in which the C-terminal dipeptide δ-address of the deltorphins (-Val-GlyNH₂, -Nle-GlyNH₂) have been linked to the highly δ-opioid selective cyclic peptides DPDPE or DPLPE. These studies demonstrate that a major structural feature determining high potency of hybrid analogues is the chirality of the amino acid residue in position 5. The radioligand binding assays have revealed a decrease in potency (compared to DPDPE) at §-receptors when the C-terminal dipeptides were added to DPDPE. On the other hand, chimeric peptides of DPLPE with these same C-terminal dipeptides retained high δ-selectivity and affinity. Similar results were obtained using the mouse vas deferens (MVD) and guinea pig ileum (GPI) bioassays. The importance of the hydrophilicity of amino acids in positions 2 and 5 for δ-selectivity is consistent with the previous finding for DPLPE and DPDPE. On the other hand, the replacement of phenylalanine-4 with p-chlorophenylalanine-4 did not increase δ-selectivity as in DPDPE. These findings suggest that the δ-receptor interacts with hybridized enkephalins and deltorphins somewhat differently than with DPDPE.     

Accuracy of Equations to Predict Basal Metabolic Rate in Older Women

Objective To assess the accuracy of several published equations for predicting basal metabolic rate (BMR) in older women.

Design BMR was assessed in 116 healthy, older white women, aged 60 to 82 years, on three successive mornings by indirect calorimetry. Body composition was determined by dual energy X-ray absorptiometry or hydrostatic weighing. The measured BMRs were compared with values obtained from eight published prediction equations that used solely, or in various combinations, measures of height, weight, fat-free mass, age, and menopausal status.

Statistical analyses performed The root mean squared prediction error (RMSPE) was used to determine how accurately predicted BMR matched actual BMR for each subject. In addition, regression analysis was used to evaluate accuracy of predicted BMR vs directly measured BMR.

Results Predicted mean BMR determined using all eight equations was significantly correlated to measured BMR (P=.0001), accounting for 30% to 52% of the variance of measured BMR. When analyzed by RMSPE, however, the equations of Owen et al (1986), Fredrix et al (1990), and Harris-Benedict (1919) predicted actual BMR for each subject within an average of 116 kcal/day, and the equation of Cunningham (1980) resulted in the largest prediction error at 208 kcal/day.

Applications/conclusions The regression equations of Owen et al (1986), which used body weight, Fredrix et al (1990), which used body weight and age, and Harris-Benedict (1919), which used age, weight, and height as variables, were most accurate in predicting BMR in our sample of healthy older women. J Am Diet Assoc. 1995; 95:1387-1392.     

Interaction of glucagon with artificial lipid bilayer membranes

The enhancement of fluorescence emission from the tryptophan residue of glucagon, the quenching of that emission with acrylamide and with 5-doxyl and 16-doxyl stearic acid, circular dichroism spectra, the release of 6-carboxytluorescein, and polarized infrared attenuated total reflection (IR-ATR) spectra were used to study the interaction of glucagon with intact lipid vesicles and flat bilayers. Dimyristoylphosphatidylcholine bound the peptide only below the main transition temperature, thus confirming earlier results of Epand et al. (1977). However, the peptide is also bound by vesicles of unsaturated lipids above their transition temperature, suggesting an influence of lipid area on the binding process. Circular dichroism showed that binding to such vesicles also increases the helix content of glucagon. The IR-ATR study and a comparison with dynorphin-A-(I-13)-tridecapeptide revealed profound differences in orientation of the two peptides. The dichroic ratios and the derived order parameters indicated an isotropic orientation of the helical segments of glucagon, but did not exclude a principal orientation of the molecules lying flat on the nienibrane surface. In contrast, the axis of the dynorphin helix is clearly oriented normal to the interface. The two peptides also differ in their rates of 6-carboxyfluorescein release, suggesting a deeper penetration of the primary amphiphilic helix of dynorphin A-(I-13) than of the secondary amphiphilic helix of glucagon.     

Cholesterol screening: observed cholesterol reduction in a prospective study in Norway

The general public of the City of Bergen, Norway was Invitedto participate in a cholesterol screening programme in October1988. Participants received the results of the cholesterol screeningand nutritional information from trained health personnel. Ashort questionnaire was mailed to all 354 participants 1–2weeks after the initial cholesterol screening. In March 1990,all participants were invited to have their cholesterol levelsre-examined. Psychosocial factors believed to be predictiveof future serum cholesterol changes were assessed at baselinealong with demographic variables. The majority of participants(61%) reduced their cholesterol level from October 1988 to March1990, and the average reduction in cholesterol level for thetotal population was 4.0%. Baseline cholesterol levels, beingconfident of one's own ability to change one's diet (self-efficacy),seeing heart disease risk reduction as very important, and maritalstatus were factors that significantly predicted successfulcholesterol reduction 18 months later.     

Use of the Pericardial Fat Pad in Pulmonary Transplantation

Historically, the healing of tracheal or bronchial anastomoses has been the Achilles heel in pulmonary transplantation. In the past, steps taken to enhance healing of these structures and have allowed single-lung, double-lung, and heart-lung transplantation to be accomplished safely. This report presents a simplified technique for protection of the tracheal anastomosis in heart-lung and double-lung transplantation. This technique, wherein the pericardial fat pad from the right side is utilized to wrap the tracheal anastomosis, not only allows for excellent healing of the anastomosis but separates the aorta from the trachea. In 19 patients having heart-lung (N = 13) or double-lung (N = 6) transplantation there were no tracheal healing problems, dehiscence or stenosis found.     

An Intrapleural Lung Prosthesis: Rationale, Design, and Testing

Abstract: Extracorporeal life support (ECLS or ECMO) is standard treatment for severe respiratory failure but poses many contraindications to future lung transplantation. The solution to this dilemma is the implantable gas exchange device (IGED) or artificial lung. Preliminary efforts to create such an artificial lung have been made since 1970 and include designs involving single devices, intravascular devices (i. e., IVOX), and combination heart–lung devices, Stringent requirements govern the design of such a device, the most important of which are high gas exchange efficiency, low resistance to blood flow, and size. This paper describes such a device. It incorporates large diameter inflow and outflow ports in close proximity and a low resistance wound hollow fiber core encapsulated in a compliant outer shell which conserves the work of the right ventricle. In a large animal model (adult sheep) this device was connected in line with the main pulmonary artery in series with the native lungs. This configuration has the advantages of using the lungs as an embolic filter, perfusing the lungs with fully oxygenated blood, and maintaining the integrity of the anatomy necessary for transplant. Laboratory experiments have run >8 h. Preliminary data show that the animals have remained hemodynamically stable while the devices have supported the animals completely by supplying 100% O₂ saturation with PO₂ values ranging from 250–350 mm Hg. Additionally, this model makes possible the study of respiratory failure without introducing other variables such as extracorporeal circuits or pumps. The other metabolic, endocrine, and reticuloendothelial functions of normal and injured lungs can now be studied more precisely by excluding these variables. Further studies are needed to evaluate this device in chronic (long–term implantation) experiments before clinical application.     

Multicenter Evaluation of Fixed-Wire PTCA Catheters with Modified Distal Tips: Initial and 2-Month Follow-Up Results

Lesions in the distal portion of coronary arteries are technological challenges with currently available percutaneous transluminal coronary angioplasty (PTCA) equipment. A study was performed at multiple centers to determine if new "fixed-wire" devices with a modified distal tip (a 2-cm flexible tip and 1-cm standard tip) would be useful in these situations. Three hundred twenty-three patients were included in the study, 75% male, mean age 63 ± 11 years. Four hundred ninety-three lesions were attempted; the overall success rate was 85%. Forty-six (14.2%) clinical complications occurred including: 5 deaths (1.1%); 2 nonfatal myocardial infarctions (0.6%); and 6 emergency coronary artery bypass grafting procedures (2.6%). A device malfunction was noted in 32 patients (9.9%), and included: 8 balloon ruptures or perforations (2.0%); 6 bent or damaged tips (1.9%); and 4 shaft/manifold leaks (1.2%). Two-month follow-up assessment for restenosis was done in 352 of 371 (95%) patients and at that time 89% were asymptomatic, had a negative functional test, or patent PTCA site by angiography. The new fixed-wire PTCA catheters with 1- and 2-cm flexible tips hold promise for dilating lesions in distal locations with an acceptable rate of complications. Additional investigation is needed to determine their role in the treatment of coronary artery disease with PTCA.     

Surgical anatomy of the singular nerve*

The course of the posterior ampullary (singular) nerve has been studied in 30 preserved human temporal bones. In 17 dissections (57%), the nerve was readily accessible in the floor of the round window niche without undue risk to the round window membrane or the ampulla of the posterior semicircular canal. In 5 bones (16%), the nerve was closely related to the round window membrane and could not have been approached without significant risk of damage to the membrane. In 8 (27%), the nerve ran more or less directly medially to the internal auditory meatus without entering the round window niche. The ampulla of the posterior semicircular canal would therefore have been at risk if the nerve were approached surgically. Keywords anatomy singular neurectomy