bluuebunny/crossref_metadata_2025 huggingface dataset:
Anesthetic Induction With Ketamine Inhibits Platelet Activation Before, During, and After Cardiopulmonary Bypass in Baboons
Authors: Ündar Akif , Eichstaedt Harald C. , Clubb Jr. Fred J. , Lu Mason , Bigley Joyce E. , Deady Blake A. , Porter Aimee , Vaughn William K. , Fung Michael
Published: September 2004

Abstract: The objective of this study was to investigate the effects of antifactor D monoclonal antibody (Mab) 166‐32 on platelet activation during and after hypothermic cardiopulmonary bypass (CPB) in baboons. Fourteen baboons (mean weight, 15 kg) underwent hypothermic CPB. Seven of them were treated with a single injection of antifactor D Mab 166‐32 (5 mg/kg) and the other seven animals were given saline as control. Each baboon was sedated with an intramuscular injection of 10 mg/kg of ketamine hydrochloride. A 20‐gauge angiocatheter was placed in the cephalic vein, and 5 mg of diazepam was administered intravenously. Anesthesia was maintained with 0.80% to 2.25% isoflurane, 100% O2, and an inspiratory tidal volume of 13 mL/kg at a rate of 13 breaths per minute throughout the surgical procedure except during CPB. Pancuronium bromide, 0.1 mg/kg, was administered to achieve adequate muscle paralysis. Blood samples were collected before CPB, during CPB, and 1, 2, 3, and 6 h after CPB. Assays were performed to measure platelet activation [CD62P (P‐selectin)] using immunofluorocytometric methods. There were no significant differences on CD62P expression of platelets between control and antibody groups before CPB (105 ± 12% vs. 99 ± 8%, P = NS), during normothermic CPB (62 ± 6% vs. 63 ± 19%, P = NS), during hypothermic CPB (55 ± 8% vs. 54 ± 13%, P = NS), and 1, 3, or 6 h after CPB (74 ± 20% vs. 81 ± 11%, P = NS). Anesthetic induction with ketamine caused significant reduction in the platelet activation in both groups. Ketamine did not affect complement, neutrophil, and monocyte activation or cytokine production. Further studies on the mechanisms of platelet inhibition by ketamine are warranted.
Comparison of Hydraulic and Hemolytic Properties of Different Impeller Designs of an Implantable Rotary Blood Pump by Computational Fluid Dynamics
Authors: Arvand Arash , Hahn Nicole , Hormes Marcus , Akdis Mustafa , Martin Michael , Reul Helmut
Published: September 2004

Abstract: A mixed‐flow blood pump for long‐term applications has been developed at the Helmholtz‐Institute in Aachen, Germany. Central features of this implantable pump are a centrally integrated motor, a blood‐immersed mechanical bearing, magnetic coupling of the impeller, and a shrouded impeller, which allows a relatively wide clearance. The aim of the study was a numerical analysis of hydraulic and hemolytic properties of different impeller design configurations. In vitro testing and numerical simulation techniques (computational fluid dynamics [CFD]) were applied to achieve a comprehensive overview. Pressure–flow charts were experimentally measured in a mock loop in order to validate the CFD data. In vitro hemolysis tests were performed at the main operating point of each impeller design. General flow patterns, pressure–flow charts, secondary flow rates, torque, and axial forces on the impeller were calculated by means of CFD. Furthermore, based on streak line techniques, shear stress (stress loading), exposure times, and volume percentage with critical stress loading have been determined. Comparison of CFD data with pressure head measurements showed excel‐lent agreement. Also, impressive trend conformity was observed between in‐vitro hemolysis results and numerical data. Comparison of design variations yielded clear trends and results. Design C revealed the best hydraulic and hemolytic properties and was chosen as the final design for the  mixed‐flow  rotary blood pump.
Physiologic‐insensitive Left Ventricular Assist Predisposes Right‐sided Circulatory Failure: A Pilot Simulation and Validation Study
Authors: Reesink Koen , Dekker André , Van Der Nagel Theo , Blom Hans , Soemers Cecile , Geskes Gijs , Maessen Jos , Van Der Veen Erik
Published: September 2004

Abstract: Right‐sided circulatory failure (RSCF) is a serious complication in 15–30% of patients receiving a left ventricular assist device (LVAD). It is hypothesized that left ventricular support which lacks physiologic properties predisposes to RSCF.  An integral computer simulation and experimental validation protocol was performed. The results suggest that with conventional insensitive left ventricular support right‐sided circulatory function is compromised, which may form a substrate for the onset or progress of RSCF. Feedback control of the LVAD could provide a means to counter this problem. A control concept for the LVAD which aims to preserve right‐sided circulatory  function,  while  supporting  peripheral  perfusion, is  proposed
Magnevad—The World's Smallest Magnetic‐bearing Turbo Pump
Authors: Goldowsky Michael
Published: September 2004

Abstract: The first animal implant of our Magnevad LVAD is scheduled for the fourth quarter of 2003. This is being performed by the George E. Reed Heart Center of Westchester Medical Center and by New York Medical College; both are in Valhalla, NY. This article summarizes 3 years of development of the miniature axial flow LVAD. Our LVAD has new innovations not found in any other turbo pump to minimize thrombus, blood turbulence, flow separation, and the generation of microemboli. The Magnevad is only 25 mL in volume, similar in size to the Micromed & Jarvik 2000 axial flow turbo pumps that have contacting bearings. US Patent 6 527 699 was issued to Gold Medical on March 4, 2003 and World Wide PCT patents are pending. The discussed improvements (patents pending) are designed to minimize flow separation and turbulence, the precursors of microemboli that lodge in end organs. This problem has been largely ignored in the published literature. A new long‐term stable miniature ultrasonic position sensor is used for bearing control. It measures the axial position of the rotor to obtain LVAD differential pressure. Differential pressure is used to obtain pulsating flow and automatic physiologic control. The term “fourth generation pump” is being coined for the Magnevad because in addition to being noncontacting, it inherently measures pump differential pressure on which physiologic control can be based.
Detection and Management of Cognitive Impairment in Primary Care: The Steel Valley Seniors Survey
Authors: Ganguli Mary , Rodriguez Eric , Mulsant Benoit , Richards Stephanie , Pandav Rajesh , Bilt Joni Vander , Dodge Hiroko H. , Stoehr Gary P. , Saxton Judith , Morycz Richard K. , Rubin Robert T. , Farkas Barry , DeKosky Steven T.
Published: September 2004

Objectives: To identify characteristics of older primary care patients who were cognitively impaired and who underwent mental status testing by their physicians.

Design: Cross‐sectional and retrospective analysis.

Setting: Seven small‐town primary care practices.

Participants: A total of 1,107 patients with a mean±standard deviation age of 76.3±6.6, screened using the Mini‐Mental State Examination (MMSE); medical records reviewed.

Measurements: Demographics, MMSE, medical record information. Odds ratios (OR) with 95% confidence intervals (CI), adjusted for age, sex, and education.

Results: Thirty‐one percent of the sample had MMSE scores of less than 25. Among these patients, physicians documented memory loss in only 23% which was significantly more often than in the higher scoring group (OR=1.9, 95% CI=1.3–2.8), basic activity of daily living (ADL) impairment in 7.9% (OR=2.4, 95% CI=1.3–4.4), instrumental ADL (IADL) impairment in 6.7% (OR=2.2, 95% CI=1.1=4.2), dementia in 12.2% (OR=3.7, 95% CI=2.0–6.8), and prescription of cholinesterase inhibitors in 7.6% (OR=4.4, 95% CI=1.9–10.2). Physicians recorded mental status testing largely in patients with research MMSE scores of 24 to 28, significantly more often when they also documented memory loss (OR=3.8, 95% CI=2.5–5.6) or impaired IADLs (OR=2.7, 95% CI=1.4–5.2), diagnosed dementia (OR=4.9, 95% CI=2.8–8.6), referred to specialists (OR=6.3, 95% CI=2.5–16.2) or social services (OR=3.6, 95% CI=1.8–7.3), or prescribed cholinesterase inhibitors (OR=8.5, 95% CI=4.2–17.5).

Conclusion: Physicians noted impairment in a minority of impaired patients. They tested mental status in those with documented cognitive and functional difficulties, in very mildly impaired patients, and in those for whom they intervened.
Improvement of Weight and Fat‐Free Mass with Oral Nutritional Supplementation in Patients with Alzheimer's Disease at Risk of Malnutrition: A Prospective Randomized Study
Authors: Lauque Sylvie , Arnaud‐Battandier Franck , Gillette Sophie , Plaze Jean‐Marie , Andrieu Sandrine , Cantet Christelle , Vellas Bruno
Published: September 2004

Objectives: To study the effects of oral nutritional supplements (OS) on body weight, body composition, nutritional status, and cognition in elderly patients with Alzheimer's disease (AD).

Design: Prospective, randomized, controlled study.

Setting: Geriatric wards and day care centers in the Toulouse area, France.

Participants: Ninety‐one subjects with AD aged 65 and older at risk of undernutrition as evaluated using the Mini Nutritional Assessment.

Intervention: After randomization, 46 patients (intervention group) received 3‐month OS. The other 45 patients (control group) received usual care.

Measurements: Weight, body composition (evaluated using dual‐energy x‐ray absorptiometry), cognitive function, activities of daily living, eating behavior, and dietary intakes were evaluated at the beginning of the study and at 3 months and 6 months. Supplement compliance was recorded each day.

Results: Between baseline and 3 months, energy and protein intakes significantly improved in the intervention group, resulting in a significant increase in weight and fat‐free mass, but no significant changes were found for dependence, cognitive function, or biological markers. The nutritional benefit was maintained in the intervention group after discontinuation of OS at 3 months.

Conclusion: Three‐month daily OS significantly improves body weight. It is practicable and effective, and the patients accepted it well. The improvement that was observed even in the control group showed that caregiver education is an important factor in maintaining the nutritional status of patients with AD. Moreover, regular courses of OS may help to maintain the increase in fat‐free mass and improve the nutritional status of these patients.
Nursing Home Characteristics and Potentially Preventable Hospitalizations of Long‐Stay Residents
Authors: Intrator Orna , Zinn Jacqueline , Mor Vincent
Published: September 2004

Objectives: To examine the association between having a nurse practitioner/physician assistant (NP/PA) on staff, other nursing home (NH) characteristics, and the rate of potentially preventable/avoidable hospitalizations of long‐stay residents, as defined using a list of ambulatory care–sensitive (ACS) diagnoses.

Design: Cross‐sectional prospective study using Minimum Data Set (MDS) assessments, Centers for Medicare and Medicaid Services inpatient claims and eligibility records, On‐line Survey Certification Automated Records, (OSCAR) and Area Resource File (ARP).

Setting: Freestanding urban NHs in Maine, Kansas, New York, and South Dakota.

Participants: Residents of 663 facilities with a quarterly or annual MDS assessment in the 2nd quarter of 1997, who had a prior MDS assessment at least 160 days before, and who were not health maintenance organization members throughout 1997 (N=54,631).

Measurements: A 180‐day multinomial outcome was defined as having any hospitalization with primary ACS diagnosis, otherwise having been hospitalized, otherwise died, and otherwise remained in the facility.

Results: Multilevel models show that facilities with NP/PAs were associated with lower hospitalization rates for ACS conditions (adjusted odds ratio (AOR)=0.83), but not with other hospitalizations. Facilities with more physicians were associated with higher ACS hospitalizations (ACS, AOR=1.14, and non‐ACS, AOR=1.10). Facilities providing intravenous therapy, and those that operate a nurses' aide training program were associated with fewer hospitalizations of both types.

Conclusion: Employment of NP/PAs in NHs, the provision of intravenous therapy, and the operation of certified nurse assistant training programs appear to reduce ACS hospitalizations, and may be feasible cost‐saving policy interventions.
Effect of Antipsychotic Withdrawal on Behavior and Sleep/Wake Activity in Nursing Home Residents with Dementia: A Randomized, Placebo‐Controlled, Double‐Blinded Study The Bergen District Nursing Home Study
Authors: Ruths Sabine , Straand Jørund , Nygaard Harald A. , Bjorvatn Bjørn , Pallesen Ståle
Published: September 2004

Objectives: To explore the effect on sleep/wake activity and on behavioral and psychological symptoms of the withdrawal of antipsychotic medications from nursing home (NH) patients with dementia.

Design: Randomized, placebo‐controlled, double‐blind trial.

Setting: NHs in Bergen, Norway.

Participants: Thirty patients (mean age 83.5) taking haloperidol, risperidone, or olanzapine for nonpsychotic symptoms.

Intervention: Study participants were randomly assigned to withdrawal (intervention group) or continued treatment with antipsychotic medications (reference group) for 4 consecutive weeks.

Measurements: Behavioral rating using the Neuropsychiatric Inventory Questionnaire (NPI‐Q) and actigraphy.

Results: After antipsychotic withdrawal, behavioral scores remained stable or improved in 11 of 15 patients, whereas four had worsening scores. Actigraphy revealed decreased sleep efficiency after drug discontinuation and increased 24‐hour and night activity in both groups. Actigraphy records of nighttime and daytime activity indicated sleep problems and restlessness, in terms of the NPI‐Q. One patient was restarted on antipsychotics.

Conclusion: Antipsychotic drug withdrawal affected activity and sleep efficiency over the short term. Increases in total activity and impaired sleep quality after drug discontinuation should be monitored, because the long‐term effect of these changes is not known. The NPI‐Q and actigraphy are feasible tools that disclose relevant changes occurring during antipsychotic withdrawal in NH patients with dementia. Their use in clinical practice should be substantiated by larger studies.
Health Care for Older Persons in Argentina: A Country Profile
Authors: Montero‐Odasso Manuel , Przygoda Pablo , Redondo Nélida , Adamson Juan , Kaplan Roberto
Published: September 2004

Argentina is a large country situated at the southern end of the Americas. It is highly urbanized, and almost one‐third of the population lives in the capital city and its surrounding area (Buenos Aires). The population is composed of heterogeneous groups, formed primarily by descendants of European immigration who constitute 85% of the inhabitants. In the last 30 years, Argentina has witnessed a growth in the elderly population from less than 7% to nearly 10% of the total population. Additionally, in Buenos Aires City, more than 17% are aged 65 or older.

The healthcare systems for the elderly lack nationwide coverage. The Programa de Atención Médica Integral (PAMI) is the largest program for elderly care. It is a state‐run program for disabled and senior citizens. PAMI serves 65% of the approximately 3.6 million older people in Argentina. The quality of PAMI healthcare delivery has decreased in the last 2 decades and has largely declined since the Argentinean economic crisis of late 2001. The rehabilitation and long‐term care services are relatively underdeveloped, and fewer than 2% of senior citizens live in residential or nursing homes. Recently, the government has proposed a system of care built up from the primary care resources of the community.
The Role of Dissatisfaction and per Capita Income in Explaining Self–Employment across 15 European Countries
Authors: Noorderhaven Niels , Thurik Roy , Wennekers Sander , van Stel André
Published: September 2004

This article deals with explaining the sizable differences in the rate of self–employment (business ownership) across 15 European countries in the period 1978–2000, within a framework of occupational choice, focusing on the influence of dissatisfaction and of per capita income. Using two different measures of dissatisfaction, in addition to the level of economic development and controlling for several other variables, we find that, in addition to a negative and significant impact of per capita income, dissatisfaction at the level of societies has a positive and significant influence on self–employment levels. Both dissatisfaction with life and dissatisfaction with the way democracy works are found to influence self–employment. It is concluded that these are proxies for job dissatisfaction and at the same time represent other negative “displacements” known to promote self–employment. The findings indirectly point at the potential importance of push factors within the incentive structures of modern economies.
Prevalence and Characteristics of Idiopathic Outflow Tract Tachycardia with QRS Alteration Following Catheter Ablation Requiring Additional Radiofrequency Ablation at a Different Point in the Outflow Tract
Authors: TADA HIROSHI , HIRATSUJI TOMOYA , NAITO SHIGETO , KUROSAKI KENJI , UEDA MAREHIKO , ITO SACHIKO , SHINBO GORO , HOSHIZAKI HIROSHI , OSHIMA SHIGERU , NOGAMI AKIHIKO , TANIGUCHI KOICHI
Published: September 2004

Subtle variations in QRS morphology occurs during idiopathic outflow tract ventricular tachycardia (OTVT), but no studies have clarified the prevalence and characteristics of the OTVT with altered QRS morphology following radiofrequency catheter ablation (RFA), which then require an additional RF application at a different portion of the outflow tract to abolish OTVT. Of 202 patients with a monomorphic VT or premature ventricular contraction (PVC) originating from the outflow tract, 6 (3%) showed changes in QRS morphology in the OTVT following RFA, requiring an additional RF application to the outflow tract at a different portion. In all six patients, RFA was applied for the first or second OTVT to a right or left ventricular endocardial site, with the other site being the left sinus of Valsalva. In each patient, OTVT before or after the changes in QRS morphology had characteristic ECG findings originating from a particular portion of the outflow tract. Changes in QRS morphology consistently included an increase or decrease in R wave amplitude in all inferior leads. Detailed continuous observation of QRS morphology in OTVT, especially R wave amplitude in inferior leads, is important for identifying changes of QRS morphology during catheter ablation. Mapping and ablation at a different portion of the outflow tract is then needed for cure.
Resumption of Atrioventricular Conduction by Levosimendan After Radiofrequency Ablation of the AV Node:
Authors: MAURY PHILIPPE , BAIXAS CECILE , RONCALLI JEROME , COUDERC PHILIPPE , DELAY MARC , PATHAK ATHUL , GALINIER MICHEL
Published: September 2004

We report the case of a patient in whom radiofrequency catheter ablation of the AV node was initially successfully performed for persistant atrial fibrillation with fast ventricular rate, but in whom atrioventricular conduction transiently resumes following therapy with levosimendan. Plausible hypothesis are discussed as well as potential implications.
Total Failure to Sense Ventricular Fibrillation with Inappropriate Defibrillator Sensitivity Adjustment
Authors: LIN DAVID , DIXIT SANJAY , RUSSO ANDREA M. , HSIA HENRY H.
Published: September 2004

Automatic Sensitivity Control, unique to St. Jude defibrillators, allows for programmable sensitivity threshold and refractory periods. However, inappropriate programming can lead to marked undersensing and potentially lethal complications. We report a case of complete failure to sense ventricular fibrillation with inappropriate sensitivity adjustments. Detailed review of the parameters with induction of ventricular fibrillation must be performed to assure adequate safety.
Recurrent Syncope Triggered by Inappropriate Sinus Tachycardia
Authors: MÖNNIG GEROLD , RIBBING MICHAEL , WASMER KRISTINA , BREITHARDT GÜNTER , ECKARDT LARS
Published: September 2004

A 25‐year‐old woman with daily episodes of syncope and several related traumatic injuries was referred for electrophysiological study. Structural heart disease was excluded. Electrophysiological study revealed inappropriate sinus tachycardia with heart rates up to 190 beats/min. A sinus node modulation was performed. However, 5 days later the patient again developed syncope during sinus tachycardia at rates of 140 beats/min with systolic blood pressure of 60 mmHg. The patient subsequently underwent AVN ablation and implantation of a dual chamber pacemaker. The patient has remained asymptomatic during a 12‐month follow‐up. This article reports on the first case of a moderate sinus tachycardia in a structurally normal heart as an underlying mechanism of recurrent episodes of syncope. While moderate supraventricular tachycardia in a structurally normal heart alone is unlikely to explain the severe symptoms, additional sympathovagal or humoral mechanisms induced by sinus tachycardia may contribute to syncopal events in this patient.
Effect of Itraconazole on the Pharmacokinetics of Inhaled Lidocaine
Authors: Isohanni Mika H. , Neuvonen Pertti J. , Olkkola Klaus T.
Published: September 2004

Abstract: Lidocaine is metabolized by cytochrome P450 3A4 and 1A2 enzymes (CYP3A4 and CYP1A2) in vitro. However, their relative contribution to the elimination of lidocaine depends on lidocaine concentration. We have studied the effect of a potent CYP3A4 inhibitor, itraconazole, on the pharmacokinetics of inhaled lidocaine in ten healthy volunteers using a randomized, two‐phase cross‐over study design. The interval between the phases was four weeks. The subjects were given orally itraconazole (200 mg once a day) or placebo for four days. On day 4, each subject inhaled a single dose of 1.5 mg/kg of lidocaine by nebulizer. Plasma samples were collected until 10 hr and the concentrations of lidocaine and its major metabolite monoethylglycinexylidide were measured by gas chromatography. The areas under the lidocaine and monoethylglycinexylidide concentration time curves were similar during both phases. No statistically significant differences were observed in any of the pharmacokinetic parameters; peak concentrations, concentration peak times or elimination half‐lives of lidocaine or monoethylglycinexylidide. The clinical implication of this study is that no lidocaine dosage adjustments are necessary if it is used to prepare the airway prior to endoscopic procedures or intubation in patients using itraconazole or other inhibitors of CYP3A4.
Protective Effects of Vitamin A and Vitamin E Succinate against 2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD)‐Induced Body Wasting, Hepatomegaly, Thymic Atrophy, Production of Reactive Oxygen Species and DNA Damage in C57BL/6J Mice
Authors: Alsharif Naser Z. , Hassoun Ezdihar A.
Published: September 2004

Abstract: The protective effect of vitamin A and vitamin E succinate against 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD)‐induced acute toxicity and measures of oxidative stress was studied. Ten mice were treated with either vitamin A (50 mg/kg every other day for eight days) or vitamin E succiante (150 mg/kg/day followed by a dose of 40 mg/kg/day for five additional days). Half of each of the above groups of animals received TCDD on day 4. Five mice received corn oil or TCDD alone. After five days of TCDD treatment, antioxidant combination treatment with vitamin A and TCDD or vitamin E succinate and TCDD resulted in a significant reduction in indicators of acute toxicity including the decrease in total body and thymus weight as compared to TCDD alone (P<0.05). The combination treatment produced also a significant reduction in the increase in liver weight as compared to TCDD only (P<0.05). Following one day of treatment with 50 μg TCDD/kg, vitamin A and vitamin E succinate produced a significant decrease in the production of superoxide anion by peritoneal lavage cells (P<0.05) and in DNA‐single strand breaks in the same cells (P<0.05) as assessed by the reduction of cytochrome c and the alkaline elution technique, respectively. A significant decrease in DNA‐single strand breaks in peritoneal lavage cells was observed following 5 days treatment with 50 μg TCDD/kg (P<0.05). The results indicate a potential role for oxidative stress in the acute toxicity of TCDD and a protective effect for vitamin A and vitamin E succinate in the overall toxicity of TCDD including measures of oxidative stress.
Intra‐pulmonary shunt and pulmonary gas exchange during exercise in humans
Authors: Stickland Michael K. , Welsh Robert C. , Haykowsky Mark J. , Petersen Stewart R. , Anderson William D. , Taylor Dylan A. , Bouffard Marcel , Jones Richard L.
Published: September 2004

In young, healthy people the alveolar–arterial P difference (A‐aDO2) is small at rest, but frequently increases during exercise. Previously, investigators have focused on ventilation/perfusion mismatch and diffusion abnormalities to explain the impairment in gas exchange, as significant physiological intra‐pulmonary shunt has not been found. The aim of this study was to use a non‐gas exchange method to determine if anatomical intra‐pulmonary (I‐P) shunts develop during exercise, and, if so, whether there is a relationship between shunt and increased A‐aDO2. Healthy male participants performed graded upright cycling to 90% while pulmonary arterial (PAP) and pulmonary artery wedge pressures were measured. Blood samples were obtained from the radial artery, cardiac output was calculated by the direct Fick method and I‐P shunt was determined by administering agitated saline during continuous 2‐D echocardiography. A‐aDO2 progressively increased with exercise and was related to (r= 0.86) and PAP (r= 0.75). No evidence of I‐P shunt was found at rest in the upright position; however, 7 of 8 subjects developed I‐P shunts during exercise. In these subjects, point bi‐serial correlations indicated that I‐P shunts were related to the increased A‐aDO2 (r= 0.68), (r= 0.76) and PAP (r= 0.73). During exercise, intra‐pulmonary shunt always occurred when A‐aDO2 exceeded 12 mmHg and was greater than 24 l min−1. These results indicate that anatomical I‐P shunts develop during exercise and we suggest that shunt recruitment may contribute to the widened A‐aDO2 during exercise.
Bimodal role of conventional protein kinase C in insulin secretion from rat pancreatic β cells
Authors: Zhang Hui , Nagasawa Masahiro , Yamada Satoko , Mogami Hideo , Suzuki Yuko , Kojima Itaru
Published: September 2004

The present study was conducted to evaluate the role of conventional protein kinase C (PKC) in calcium‐evoked insulin secretion. In rat β cells transfected with green fluorescent protein‐tagged PKC‐α (PKC‐α–EGFP), a depolarizing concentration of potassium induced transient elevation of cytoplasmic free calcium ([Ca2+]c), which was accompanied by transient translocation of PKC‐α–EGFP from the cytosol to the plasma membrane. Potassium also induced transient translocation of PKC‐θ–EGFP, the C1 domain of PKC‐γ and PKC‐ɛ–GFP. A high concentration of glucose induced repetitive elevation of [Ca2+]c and repetitive translocation of PKC‐α–EGFP. Diazoxide completely blocked both elevation of [Ca2+]c and translocation of PKC‐α–EGFP. We then studied the role of conventional PKC in calcium‐evoked insulin secretion using rat islets. When islets were incubated for 10 min with high potassium, Gö‐6976, an inhibitor of conventional PKC, and PKC‐α pseudosubstrate fused to antennapedia peptide (Antp‐PKC19–31) increased potassium induced secretion. Similarly, insulin release induced by high glucose for 10 min was enhanced by Gö‐6976 and Antp‐PKC19–31. However, when islets were stimulated for 60 min with high glucose, both Gö‐6976 and Antp‐PKC19–31 reduced glucose‐induced insulin secretion. Similar results were obtained by transfection of dominant‐negative PKC‐α using adenovirus vector. Taken together, PKC‐α is activated when cells are depolarized by a high concentration of potassium or glucose. Conventional PKC is inhibitory on depolarization‐induced insulin secretion per se, but it also augments glucose‐induced secretion.
Carotid baroreflex control of leg vasculature in exercising and non‐exercising skeletal muscle in humans
Authors: Melvin Keller David , Fadel Paul J. , Ogoh Shigehiko , Matthew Brothers Robert , Hawkins Megan , Olivencia‐Yurvati Al , Raven Peter B.
Published: September 2004

Carotid baroreflex (CBR) function was examined in five men and three women (25 ± 1 years) using the variable‐pressure neck collar technique at rest and during dynamic, one‐legged knee extension exercise at 7 W and 25 W. The CBR exhibited control of leg vascular conductance (LVC) at rest and during exercise in both an exercising leg (EL) and a non‐exercising leg (NEL) across a wide range of pressures from +40 Torr neck pressure (NP) to −80 Torr neck suction (NS). Specifically, increases in LVC (% change) in response to NS were no different across −20 to −80 Torr in either EL or NEL compared to rest, P > 0.05. However, CBR‐mediated decreases in percentage LVC in response to NP were attenuated in EL at both 7 W (16 ± 1%) and 25 W (12 ± 1%) compared to rest (40 ± 3%; P < 0.05) as well as compared to responses in the NEL (36 ± 6% at 7 W and 36 ± 7% at 25 W; P < 0.05). This decrease in vascular responsiveness in EL was associated with a reduction in the gain of the percentage muscle sympathetic nerve activity (%MSNA)–%LVC relationship compared to rest (P < 0.05). Collectively, these data indicate that, despite a clear attenuation of the vascular response to MSNA in the exercising leg, CBR‐mediated changes in mean arterial pressure were no different between rest and exercise.
Exercise rapidly increases expression of the monocarboxylate transporters MCT1 and MCT4 in rat muscle
Authors: Coles Lisa , Litt Jennifer , Hatta Hideo , Bonen Arend
Published: September 2004

We examined the effect of a single exercise session on the protein and mRNA expression of the monocarboxylate transporters MCT1 and MCT4 in rat soleus (SOL), and red (RG) and white gastrocnemius (WG) muscles. Muscle samples were obtained at rest before 2 h of treadmill exercise (21 m min−1, 15% grade) and immediately after exercise, as well as 5, 10 and 24 h after exercise. During the 2 h exercise bout, MCT1 proteins in RG (+60%) and WG (+56%) were increased (P < 0.05). MCT1 protein was further increased thereafter, with peak increments occurring 10 h after exercise in RG (+157%), WG (+193%) and SOL (+179%) (P < 0.05). Twenty‐four hours after exercise, MCT1 protein was still up‐regulated in WG (+100%) and SOL (+55%) (P < 0.05), but not in RG. MCT1 mRNA was up‐regulated during exercise in RG (+53%) and WG (+98%) and remained elevated until 24 h post‐exercise in RG (P < 0.05), but in WG, MCT1 mRNA decreased transiently to pre‐exercise levels at 5 and 10 h after exercise, before increasing again at 24 h (+150%) (P < 0.05). MCT4 protein and mRNA were not increased in WG muscle during and after exercise (P > 0.05). In contrast, during exercise, in RG (+41%) and SOL (+98%) MCT4 protein was increased (P < 0.05). Peak increases in MCT4 protein were observed 10 h after exercise in RG (+131%) and SOL (+323%) (P < 0.05). MCT4 protein was still up‐regulated 24 h after exercise (RG: +106%; SOL +225%) (P < 0.05). MCT4 mRNA in RG was not increased until 10 (+132%) and 24 h after exercise (+55%) (P < 0.05). These studies have shown that MCT1 and 4 proteins are transiently up‐regulated by a single bout of exercise, involving post‐transcriptional and transcriptional mechanisms. Thus, MCT1 and MCT4 belong to a class of selected metabolic genes that are very rapidly up‐regulated with an exercise stimulus.
Circulating leptin mediates lipopolysaccharide‐induced anorexia and fever in rats
Authors: Sachot Christelle , Poole Stephen , Luheshi Giamal N.
Published: September 2004

Anorexia and fever are important features of the host's response to inflammation that can be triggered by the bacterial endotoxin lipopolysaccharide (LPS) and the appetite suppressant leptin. Previous studies have demonstrated that LPS induces leptin synthesis and secretion in the periphery, and that the action of leptin on appetite suppression and fever are dependent on brain interleukin (IL)‐1β. However, the role of leptin as a neuroimmune mediator of LPS‐induced inflammation has not been fully elucidated. To address this issue, we neutralized circulating leptin using a leptin antiserum (LAS) and determined how this neutralization affected LPS‐induced anorexia, fever and hypothalamic IL‐1β. Adult male rats were separated into four treatment groups, namely LPS + normal sheep serum (NSS), LPS + LAS, saline + LAS and saline + NSS. Intraperitoneal injection of LPS (100 μg kg−1) induced a significant reduction in food intake and body weight, which were significantly reversed in the presence of LAS (1 ml kg−1), 8 and 24 h after treatment. In addition, LPS‐induced fever was significantly attenuated by LAS over the duration of the fever response (8 h). Lipopolysaccharide induced an increase of circulating IL‐6, another potential circulating pyrogen, which was not affected by neutralization of leptin at 2 h. Interleukin‐1β mRNA at 1 and 8 h, and IL‐1 receptor antagonist (ra) at 2 h were significantly upregulated in the hypothalamus of LPS‐treated animals. The induction of these cytokines was attenuated in the presence of LAS. These results are the first to demonstrate that leptin is a circulating mediator of LPS‐induced anorexia and fever, probably through a hypothalamic IL‐1β‐dependent mechanism.
Taking the Long View
Authors: Aschwanden Christie
Published: September 2004

In the past half-century, longitudinal studies have proven themselves to be powerful tools for research on aging and its attendant diseases. These projects track the health of a group of subjects for years, observing factors that might predict the incidence of age-related diseases or influence processes commonly associated with normal aging, such as fading eyesight and hearing loss. Huge investments in these expensive, big-team, delayed-gratification enterprises have paid off handsomely. They have revealed risk factors for heart disease, cancer, and Alzheimer's disease, among others, and in some cases they've forced experts to rethink dogma on how to avoid illness. This tour highlights the strengths, weaknesses, quirks, and likely futures of some of the most important longitudinal studies.
Spiraling Toward Death
Authors: Beckman Mary
Published: September 2004

Cinnamon rolls are bad for dieters, and mitochondria that resemble cinnamon rolls don't do fruit flies any favors, either. Insects that accumulate these abnormal structures die early, new research shows. The swirls arise in response to oxidative stress and as flies age, offering researchers a visible marker for both processes.
All Pain, No Gain
Authors: Leslie Mitch
Published: September 2004

Along with their strength and teeth, the elderly typically lose their responsiveness to vaccines. Researchers are uncovering what goes wrong as we age, knowledge that might allow them to tailor vaccines for older folks or pep up the aging immune system. One failing is the disappearance of the thymus, the gland in which T cells mature. The blood also fills with inert T cells lacking a key surface molecule. These cells might accumulate because of infection with microbes that can lurk in the body for decades. Although researchers can't yet rejuvenate the immune system, they are exploring options from reformulating vaccines to removing troublesome T cells from the blood.
Opposites Detract
Authors: Leslie Mitch
Published: September 2004

Sherlock Holmes had Professor Moriarty. Magic Johnson had Larry Bird. Britney Spears has Christina Aguilera. A less famous rivalry occurs in the body, pitting the weight-regulating hormones leptin and ghrelin against each other. The molecules not only exert opposite effects on appetite, but new research suggests that they trigger contrasting reactions from the immune system. The discovery might help researchers develop treatments that soothe diseases that can stem from inflammation, including diabetes and atherosclerosis.
Long in the Tooth
Authors: Davenport R. John
Published: September 2004

Whether it's the latest band or the newest fashion fad, young people are usually the ones on the cutting edge. But a new study suggests that old people helped foster early human ingenuity. Populations from tens of thousands of years ago had a higher proportion of old individuals than did previous populations, researchers surmise based on tooth wear. Because these ancestors created more sophisticated tools and art than did their predecessors, the rise of modern culture might have required a mature population.
Resveratrol to the Rescue
Authors: Leslie Mitch
Published: September 2004

A yeast is a worm is a fly is a person? At least the first three creatures live longer when they sup an extract of red wine, according to new research. The chemical activates related enzymes in all three organisms and might duplicate the effects of extreme dieting. By showing for the first time that the compound works in animals, the results bring human studies a step closer.
Wising Up to Diabetes
Authors: Leslie Mitch
Published: September 2004

Slide over, fat. Move back, muscle. The brain and liver mastermind the regulation of blood sugar, according to new work. The study shows that stimulating the insulin receptor only in these organs spares mice from diabetes, a finding that could help researchers devise new drugs to rein in blood sugar.
Progressive Supranuclear Palsy
Authors: Pourfar Michael , Vonsattel Jean-Paul
Published: September 2004

In this case study, we describe the symptoms, neurological examination, clinical course, and neuropathology of a patient with progressive supranuclear palsy (PSP). PSP is a relatively uncommon neurodegenerative disorder with many features similar to those of
Parkinson's disease
. It is characterized by slow motor function, ocular movement abnormalities, dystonia, and cognitive disabilities. PSP is largely a sporadic disorder caused by accumulation of the protein
tau
in diverse regions of the central nervous system. It is thus classified as one of several tauopathies. The exact cause of the disease remains unknown, and treatment is often limited. The following case provides a framework to explore the manifestations of PSP, as well as the progress made in understanding the nature of this challenging disorder.
Murine Models of Life Span Extension
Authors: Quarrie Jason K. , Riabowol Karl T.
Published: September 2004

Mice are excellent experimental models for genetic research and are being used to investigate the genetic component of organismal aging. Several mutant mice are known to possess defects in the growth hormone/insulin-like growth factor 1 (GH/IGF-1) neurohormonal pathway and exhibit dwarfism together with extended life span. Their phenotypes resemble those of mice subjected to caloric restriction. Targeted mutations that affect components of this pathway, including the GH receptor, p66Shc, and the IGF-1 receptor (IGF-1R), also extend life span; mutations that affect IGF-1R or downstream components of the pathway decouple longevity effects from dwarfism. These effects on life span may result from an increased capacity to resist oxidative damage.
Fast Burn
Authors: Leslie Mitch
Published: September 2004

Fat cells pack away grease like squirrels hoarding nuts in September, and making the cells less thrifty might help fend off obesity, according to new work in mice. The genetically altered rodents snarfed more food but lived long and remained lean. The results suggest that igniting fat metabolism might extend life span without drastic dieting.
Membranes of Death
Authors: Leslie Mitch
Published: September 2004

When the going gets tough, many cells give up. But some endure if they've got a protein that prevents a particular organelle from sparking cell suicide, new work suggests. The results might eventually help researchers identify ways to curtail cell loss associated with Alzheimer's disease and stroke.
Going the Extra Mile
Authors: Davenport R. John
Published: September 2004

It sounds like the dream of every potato-chip-devouring armchair athlete who aspires to Olympic glory: exceptional endurance without the tiresome training. Two new studies reveal molecular alterations that allow rodents to outpace their normal kin. The findings might eventually lead to drugs that fight obesity and diabetes without requiring exercise.
Stuck in the Craw
Authors: Leslie Mitch
Published: September 2004

Nuclear waste and plastic bottles might last forever, but proteins don't. Cells chop them up and reuse the pieces. A new study suggests that warped proteins found in rare forms of Parkinson's disease (PD) jam cellular recycling machinery. The results might explain why protein clots amass in common types of PD.
Déjà Vu
Authors: Chen Ingfei
Published: September 2004

Embryonic stem cells have the potential to turn into any type of cell, perhaps someday providing a way to replace tissues harmed by age-related and other diseases. But the complex ethical questions that swirl around this area of research--which requires the destruction of early embryos--are not new. The moral and philosophical issues in the stem cell debate trace their roots to the controversy over in vitro fertilization in the years surrounding the birth of the first "test tube baby" in 1978.
Aging of the Human Adrenal Cortex
Authors: Hornsby Peter J.
Published: September 2004

The most striking age-related change in the human adrenal cortex is the decline in secretion of dehydroepiandrosterone and its sulfate, steroids synthesized by the inner zone of the cortex, the zona reticularis. Because these steroids are of essentially unknown function, the importance of this age-related change is the subject of considerable debate. It is likely that the age-related change in these steroids results from loss of zona reticularis cells or impairment of their function. During aging, cumulative damage to the zona reticularis could occur through ischemia-related infarcts and other causes of cell death. Cellular senescence could contribute to a loss of the ability of the tissue to replace lost cells. In contrast, feedback mechanisms that regulate adrenocortical growth cause compensatory local tissue hyperplasias called nodules. The effect of imperfect repair of damage combined with compensatory overgrowth in the form of nodules leads to an increasingly abnormal tissue architecture.
Will a Filet a Day Keep the Neurologist Away?
Authors: Leslie Mitch
Published: September 2004

People who eat lots of fish might protect their brain from Alzheimer's disease, and new work helps explain why. Depriving mice of a fatty acid in fish stresses cells and sunders the neural links that transmit information through the brain.
TOR Pathway: Linking Nutrient Sensing to Life Span
Authors: Kapahi Pankaj , Zid Brian
Published: September 2004

Recent studies point to an emerging role for the TOR (target of rapamycin) pathway in the regulation of life span. In this Perspective, we discuss the possibility that this pathway is an important modulator of nutrient-dependent changes in life span. Additionally, we discuss the interactions between the TOR and insulin-like signaling pathways as well as the key downstream processes that TOR regulates.
Fatal Distraction
Authors: Beckman Mary
Published: September 2004

If an entire police force rushes to quell a political protest, muggers can prey on citizens unchallenged. Similarly, new research shows that the system called in to fix badly shaped proteins can exhaust resources needed to protect the cell from reactive oxygen species, leaving the cell prone to damage and death.
Tarnished Vision
Authors: Davenport R. John
Published: September 2004

Too much iron wrinkles vision, according to new work. Mice that lack two iron-oxidizing enzymes show signs of age-related macular degeneration, the most common cause of vision loss in elderly people. The study suggests that drugs that reduce iron amounts might prevent or slow the disease.
A Century of Population Aging in Germany
Authors: Hoffmann Elke , Menning Sonja
Published: September 2004

The population of Germany is becoming progressively more elderly, and this article focuses on the causes and implications of that trend. We discuss the demographic processes that occurred in Germany in the second half of the 20th century and describe the developments that the population of Germany will undergo in the next 50 years, which promise to exert a profound influence on the economic and social future of the country.
Acid Trip
Authors: Davenport R. John
Published: September 2004

Acid burns brains that suffer strokes, and a new study suggests why. The work identifies a channel protein that unleashes a dangerous calcium torrent when pH drops. Drugs that cinch up the channel might help save the brains of stroke patients.
Avian Extinction and Mammalian Introductions on Oceanic Islands
Authors: Blackburn Tim M. , Cassey Phillip , Duncan Richard P. , Evans Karl L. , Gaston Kevin J.
Published: September 2004

The arrival of humans on oceanic islands has precipitated a wave of extinctions among the islands' native birds. Nevertheless, the magnitude of this extinction event varies markedly between avifaunas. We show that the probability that a bird species has been extirpated from each of 220 oceanic islands is positively correlated with the number of exotic predatory mammal species established on those islands after European colonization and that the effect of these predators is greater on island endemic species. In contrast, the proportions of currently threatened species are independent of the numbers of exotic mammalian predator species, suggesting that the principal threat to island birds has changed through time as species susceptible to exotic predators have been driven extinct.
Vibrational Energy Transfer Across a Reverse Micelle Surfactant Layer
Authors: Deàk John C. , Pang Yoonsoo , Sechler Timothy D. , Wang Zhaohui , Dlott Dana D.
Published: September 2004

In a suspension of reverse micelles, in which the surfactant sodium dioctyl sulfosuccinate (AOT) separates a water nanodroplet from a bulk nonpolar CCl
4
phase, ultrafast vibrational spectroscopy was used to study vibrational energy transfer from the nanodroplet through the AOT interfacial monolayer to the surrounding CCl
4
. Most of the vibrational energy from the nanodroplet was transferred to the polar AOT head group within 1.8 picoseconds and then out to the CCl
4
within 10 picoseconds. Vibrational energy pumped directly into the AOT tail resulted in a slower 20- to 40-picosecond transfer of energy to the CCl
4
.
Canonical Wnt/β-catenin Signaling
Authors: Moon Randall T.
Published: September 2004

This animation provides an interactive presentation of the Wnt signaling pathway as it may occur in multiple cell types. This animation would be useful in teaching developmental biology, immunology, and cell signaling courses. Activation of Wnt pathways can modulate cell proliferation, cell survival, cell behavior, and cell fate. In the basal, unstimulated state in the absence of ligand, there is a constitutively active kinase, which phosphorylates target proteins, resulting in their degradation. Thus, the presence of the ligand Wnt inactivates the kinase allowing accumulation of β-catenin, which then translocates to the nucleus and acts as a transcriptional regulator.
β-catenin Signaling and Axis Specification
Authors: Moon Randall T.
Published: September 2004

This animation provides a representation of the β-catenin signaling pathway in response to fertilization and the process of axis specification that occurs early in development. The process shown is based on analysis of embryos of the amphibian
Xenopus.
This animation would be useful in illustrating events that occur early in embryogenesis and how embryos become polarized as a consequence of localized signaling processes.