bluuebunny/crossref_metadata_2025 huggingface dataset:
Tetrahydrobiopterin increases insulin sensitivity in patients with type 2 diabetes and coronary heart disease
Authors: Nyström Thomas , Nygren Arne , Sjöholm Åke
Published: July 2004

Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase that improves endothelial function in diabetics, smokers, and patients with hypercholesterolemia. Insulin resistance has been suggested as a contributing factor in the development of endothelial dysfunction via an abnormal pteridine metabolism. We hypothesized that BH4would restore flow-mediated vasodilation (FMD, endothelial-dependent vasodilation), which may affect insulin resistance in type 2 diabetic patients. Thirty-two subjects (12 type 2 diabetic subjects, 10 matched nondiabetic subjects, and 10 healthy unmatched subjects) underwent infusion of BH4or saline in a random crossover study. Insulin sensitivity index (SI) was measured by hyperinsulinemic isoglycemic clamp. FMD was measured using ultrasonography. BH4significantly increased SIin the type 2 diabetics [3.6 ± 0.6 vs. 4.9 ± 0.7 × 10−4dl·kg−1·min−1/(μU/ml), P < 0.05], while having no effects in nondiabetics [8.9 ± 1.1 vs. 9.0 ± 0.9 × 10−4dl·kg−1·min−1/(μU/ml), P = 0.92] or in healthy subjects [17.5 ± 1.6 vs. 18 ± 1.8 × 10−4dl·kg−1·min−1/(μU/ml), P = 0.87]. BH4did not affect the relative changes in brachial artery diameter from baseline FMD (%) in type 2 diabetic subjects (2.3 ± 0.8 vs. 1.8 ± 1.0%, P = 0.42), nondiabetic subjects (5.3 ± 1.1 vs. 6.6 ± 0.9%, P = 0.32), or healthy subjects (11.9 ± 0.6 vs. 11.0 ± 1.0%, P = 0.48). In conclusion, BH4significantly increases insulin sensitivity in type 2 diabetic patients without any discernible improvement in endothelial function.
Glutamine kinetics and protein turnover in end-stage renal disease
Authors: Raj Dominic S. C. , Welbourne Tomas , Dominic Elizabeth A. , Waters Debra , Wolfe Robert , Ferrando Arny
Published: July 2004

Alanine and glutamine constitute the two most important nitrogen carriers released from the muscle. We studied the intracellular amino acid transport kinetics and protein turnover in nine end-stage renal disease (ESRD) patients and eight controls by use of stable isotopes of phenylalanine, alanine, and glutamine. The amino acid transport kinetics and protein turnover were calculated with a three-pool model from the amino acid concentrations and enrichment in the artery, vein, and muscle compartments. Muscle protein breakdown was more than synthesis (nmol·min−1·100 ml leg−1) during hemodialysis (HD) (169.8 ± 20.0 vs. 125.9 ± 21.8, P < 0.05) and in controls (126.9 ± 6.9 vs. 98.4 ± 7.5, P < 0.05), but synthesis and catabolism were comparable pre-HD (100.7 ± 15.7 vs. 103.4 ± 14.8). Whole body protein catabolism decreased by 15% during HD. The intracellular appearance of alanine (399.0 ± 47.1 vs. 243.0 ± 34.689) and glutamine (369.7 ± 40.6 vs. 235.6 ± 27.5) from muscle protein breakdown increased during dialysis (nmol·min−1·100 ml leg−1, P < 0.01). However, the de novo synthesis of alanine (3,468.9 ± 572.2 vs. 3,140.5 ± 467.7) and glutamine (1,751.4 ± 82.6 vs. 1,782.2 ± 86.4) did not change significantly intradialysis (nmol·min−1·100 ml leg−1). Branched-chain amino acid catabolism (191.8 ± 63.4 vs. −59.1 ± 42.9) and nonprotein glutamate disposal (347.0 ± 46.3 vs. 222.3 ± 43.6) increased intradialysis compared with pre-HD (nmol·min−1·100 ml leg−1, P < 0.01). The mRNA levels of glutamine synthase (1.45 ± 0.14 vs. 0.33 ± 0.08, P < 0.001) and branched-chain keto acid dehydrogenase-E2 (3.86 ± 0.48 vs. 2.14 ± 0.27, P < 0.05) in the muscle increased during HD. Thus intracellular concentrations of alanine and glutamine are maintained during HD by augmented release of the amino acids from muscle protein catabolism. Although muscle protein breakdown increased intradialysis, the whole body protein catabolism decreased, suggesting central utilization of amino acids released from skeletal muscle.
Quantitative trait locus dissection in congenic strains of the Goto-Kakizaki rat identifies a region conserved with diabetes loci in human chromosome 1q
Authors: Wallace Karin J. , Wallis Robert H. , Collins Stephan C. , Argoud Karène , Kaisaki Pamela J. , Ktorza Alain , Woon Peng Y. , Bihoreau Marie-Thérèse , Gauguier Dominique
Published: July 2004

Genetic studies in human populations and rodent models have identified regions of human chromosome 1q21–25 and rat chromosome 2 showing evidence of significant and replicated linkage to diabetes-related phenotypes. To investigate the relationship between the human and rat diabetes loci, we fine mapped the rat locus Nidd/ gk2 linked to hyperinsulinemia in an F2 cross derived from the diabetic (type 2) Goto-Kakizaki (GK) rat and the Brown Norway (BN) control rat, and carried out its genetic and pathophysiological characterization in BN.GK congenic strains. Evidence of glucose intolerance and enhanced insulin secretion in a congenic strain allowed us to localize the underlying diabetes gene(s) in a rat chromosomal interval of ∼3–6 cM conserved with an 11-Mb region of human 1q21–23. Positional diabetes candidate genes were tested for transcriptional changes between congenics and controls and sequence variations in a panel of inbred rat strains. Congenic strains of the GK rats represent powerful novel models for accurately defining the pathophysiological impact of diabetes gene(s) at the locus Nidd/ gk2 and improving functional annotations of diabetes candidates in human 1q21–23.
Endothelial Cell-to-Cell Junctions: Molecular Organization and Role in Vascular Homeostasis
Authors: Bazzoni Gianfranco , Dejana Elisabetta
Published: July 2004

Intercellular junctions mediate adhesion and communication between adjoining endothelial and epithelial cells. In the endothelium, junctional complexes comprise tight junctions, adherens junctions, and gap junctions. The expression and organization of these complexes depend on the type of vessels and the permeability requirements of perfused organs. Gap junctions are communication structures, which allow the passage of small molecular weight solutes between neighboring cells. Tight junctions serve the major functional purpose of providing a “barrier” and a “fence” within the membrane, by regulating paracellular permeability and maintaining cell polarity. Adherens junctions play an important role in contact inhibition of endothelial cell growth, paracellular permeability to circulating leukocytes and solutes. In addition, they are required for a correct organization of new vessels in angiogenesis. Extensive research in the past decade has identified several molecular components of the tight and adherens junctions, including integral membrane and intracellular proteins. These proteins interact both among themselves and with other molecules. Here, we review the individual molecules of junctions and their complex network of interactions. We also emphasize how the molecular architectures and interactions may represent a mechanistic basis for the function and regulation of junctions, focusing on junction assembly and permeability regulation. Finally, we analyze in vivo studies and highlight information that specifically relates to the role of junctions in vascular endothelial cells.
Structure and Function of Kv4-Family Transient Potassium Channels
Authors: Birnbaum Shari G. , Varga Andrew W. , Yuan Li-Lian , Anderson Anne E. , Sweatt J. David , Schrader Laura A.
Published: July 2004

Shal-type (Kv4.x) K+ channels are expressed in a variety of tissue, with particularly high levels in the brain and heart. These channels are the primary subunits that contribute to transient, voltage-dependent K+ currents in the nervous system (A currents) and the heart (transient outward current). Recent studies have revealed an enormous degree of complexity in the regulation of these channels. In this review, we describe the surprisingly large number of ancillary subunits and scaffolding proteins that can interact with the primary subunits, resulting in alterations in channel trafficking and kinetic properties. Furthermore, we discuss posttranslational modification of Kv4.x channel function with an emphasis on the role of kinase modulation of these channels in regulating membrane properties. This concept is especially intriguing as Kv4.2 channels may integrate a variety of intracellular signaling cascades into a coordinated output that dynamically modulates membrane excitability. Finally, the pathophysiology that may arise from dysregulation of these channels is also reviewed.
On the expansion theorem described by H(A, B) spaces
Authors: El-Sabbagh A. A.
Published: July 2004

The aim of this paper is to construct a generalized Fourier analysis for certain Hermitian operators. When A, B are entire functions, then H(A, B) will be the associated reproducing kernel Hilbert spaces of ℂn×n‐valued functions. In that case, we will construct the expansion theorem for H(A, B) in a comprehensive manner. The spectral functions for the reproducing kernel Hilbert spaces will also be constructed.
On birational monomial transformations of plane
Authors: Korchagin Anatoly B.
Published: July 2004

We study birational monomial transformations of the form , where ϵ1, ϵ2 ∈ {−1, 1}. These transformations form a group. We describe this group in terms of generators and relations and, for every such transformation φ, we prove a formula, which represents the transformation φ as a product of generators of the group. To prove this formula, we use birationally equivalent polynomials Ax + By + C and Axp + Byq + Cxrys. If φ is the transformation which carries one polynomial onto another, then the integral powers of generators in the product, which represents the transformation φ, can be calculated by the expansion of p/q in the continued fraction.
Osteochondral Defects in the Human Knee
Authors: Guettler Joseph H. , Demetropoulos Constantine K. , Yang King H. , Jurist Kenneth A.
Published: July 2004

Purpose

To determine the influence of osteochondral defect size on defect rim stress concentration, peak rim stress, and load redistribution to adjacent cartilage over the weightbearing area of the medial and lateral femoral condyles in the human knee.

Methods

Eight fresh-frozen cadaveric knees were mounted at 30° of flexion in a materials testing machine. Digital electronic pressure sensors were placed in the medial and lateral compartments of the knee. Each intact knee was first loaded to 700 N and held for 5 seconds. Dynamic pressure readings were recorded throughout the loading and holding phases. Loading was repeated over circular osteochondral defects (5, 8, 10, 12, 14, 16, 18, and 20 mm) in the 30° weightbearing area of the medial and lateral femoral condyles.

Results

Stress concentration around the rims of defects 8 mm and smaller was not demonstrated, and pressure distribution in this size range was dominated by the menisci. For defects 10 mm and greater, distribution of peak pressures followed the rim of the defect with a mean distance from the rim of 2.2 mm on the medial condyle and 3.2 mm on the lateral condyle. An analysis of variance with Bonferroni correction revealed a statistically significant trend of increasing radius of peak pressure as defect size increased for defects from 10 to 20 mm (P = .0011). Peak rim pressure values did not increase significantly as defects were enlarged from 10 to 20 mm. Load redistribution during the holding phase was also observed.

Conclusions

Rim stress concentration was demonstrated for osteochondral defects 10 mm and greater in size. This altered load distribution has important implications relating to the long-term integrity of cartilage adjacent to osteochondral defects in the human knee. Although the decision to treat osteochondral lesions is certainly multifactorial, a size threshold of 10 mm, based on biomechanical data, may be a useful adjunct to guide clinical decision making.
Injury Patterns in Big Ten Conference Football
Authors: Albright John P. , Powell John W. , Martindale Al , Black Robert , Crowley Edward , Schmidt Paul , Monroe Jeff , Locy Doug , Aggler Tory , Davis W. R. , Salvaterra George , Miller Dennis , Helwig Dennis , Soboroff Stephen , Nivens Jim , Carpenter James , Kovan Jeff , Arndt Elizabeth , Sweeney Howard , Lombardo John , Sebastianelli Wayne J. , Krauss Michael , Landry Greg
Published: July 2004

Background

In 1998, the National Collegiate Athletic Association legislated a decrease in the number of scrimmages and full-contact practices allowed during the spring season.

Hypothesis

A significantly increased risk of injury faced by the same player during the spring versus fall practice sessions does exist, but the National Collegiate Athletic Association regulations will not have the intended effect of reducing injury rates to equal or below those of the fall practice sessions.

Study Design

Retrospectively analyzed, descriptive study of prospectively collected injury surveillance data followed by a prospective, controlled, repeated-measures study after the rule change.

Methods

Phase 1: the Big Ten Conference Sports Injury Surveillance System database was reviewed from spring 1992 through fall 1997 for all reportable injuries. Phase 2: a prospective investigation was instituted from spring 1998 through fall 2000. This protocol was modified to also document updated individual player position descriptions and string as well as exposures for the old fall and spring practice categories (scrimmages, full contact, and limited contact) and the new spring practice designations (full pads with and without tackling, helmets only, spring game, and other scrimmages).

Results

Phase 1: There were 3950 fall injuries and 1007 spring injuries, with 469 of the 1007 attributable to the “spring risk factor.” There was a statistically significant increase in injury rate in the spring (19.8) versus fall (10.6). Scrimmages (incidence density ratio = 2.4) and limited-contact practices (incidence density ratio = 2.5) showed more than twice the fall injury rate. Phase 2: There were 1502 fall injuries and 648 spring injuries, with 192 attributable to the spring risk factor. There was a 3-fold increase in injury rate in the spring (incidence density ratio = 3.2). Although the noncontact, helmets-only practices produced the lowest injury rates, the nonspring game scrimmages and the limited-contact practices defined as “practice with pads but without tackling” displayed the highest injury rates. In both spring and fall, nonplayers exhibited the highest injury rates for all string groups.

Conclusions

There was and still is a statistically significant increase in spring practice injury risk. The 1998 rule change resulted in an even greater increase in spring practice injury risk. If the goal is to minimize the number of spring practice injuries, it will be best accomplished by limiting the number of scrimmages and limited-contact sessions.
Differential regulation of actin stress fiber assembly and proplatelet formation by α2β1 integrin and GPVI in human megakaryocytes
Authors: Sabri Siham , Jandrot-Perrus Martine , Bertoglio Jacques , Farndale Richard W. , Mas Véronique Mansat-De , Debili Najet , Vainchenker William
Published: July 2004

The actin cytoskeleton plays a major role in platelet function. In contrast, its precise role in the function of megakaryocytes (MKs) is less understood but may be important for a chemoattractive response and an efficient proplatelet formation. In the marrow microenvironment, mature MKs are in contact with the extracellular matrix, including fibrillar collagen type I. MKs express α2β1 integrin and the immunoglobulin superfamily member glycoprotein VI (GPVI), the main receptors for collagen. Using function-blocking antibodies or specific ligands, we investigated in primary human MKs how α2β1 integrin and GPVI regulate stress fiber formation, the primary actin structures needed for cell contraction. Stress fiber assembly requires synergistic activation of the MAPK/Erk1/2 pathway and the small guanosine triphosphatase Rho via its effector, Rho-associated coiled-coil kinase (ROCK). α2β1 integrin is crucial for stress fiber formation, whereas GPVI triggers rapid and sustained activation of the Erk1/2 pathway. Strikingly, after a longer adhesion time, proplatelet formation was significantly inhibited by the engagement of α2β1 integrin, not by GPVI, likely through the Rho/ROCK pathway. Thus, proplatelet formation in human MKs could be tightly regulated by differential interactions with their collagen receptors. We propose that this interaction with collagen prevents proplatelet formation within the marrow.
Oral anticoagulant treatment: friend or foe in cardiovascular disease?
Authors: Schurgers Leon J. , Aebert Hermann , Vermeer Cees , Bültmann Burkhard , Janzen Jan
Published: July 2004

Calcification is a common complication in cardiovascular disease and may affect both arteries and heart valves. Matrix γ-carboxyglutamic acid (Gla) protein (MGP) is a potent inhibitor of vascular calcification, the activity of which is regulated by vitamin K. In animal models, vitamin K antagonists (oral anticoagulants [OACs]) were shown to induce arterial calcification. To investigate whether long-term OAC treatment may induce calcification in humans also, we have measured the grade of aortic valve calcification in patients with and without preoperative OAC treatment. OAC-treated subjects were matched with nontreated ones for age, sex, and disease. Calcifications in patients receiving preoperative OAC treatment were significantly (2-fold) larger than in nontreated patients. These observations suggest that OACs, which are widely used for antithrombotic therapy, may induce cardiovascular calcifications as an adverse side effect.
CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin
Authors: Karamatic Crew Vanja , Burton Nicholas , Kagan Alexander , Green Carole A. , Levene Cyril , Flinter Frances , Brady R. Leo , Daniels Geoff , Anstee David J.
Published: July 2004

Tetraspanins are thought to facilitate the formation of multiprotein complexes at cell surfaces, but evidence illuminating the biologic importance of this role is sparse. Tetraspanin CD151 forms very stable laminin-binding complexes with integrins α3β1 and α6β1 in kidney and α3β1 and α6β4 in skin. It is encoded by a gene at the same position on chromosome 11p15.5 as the MER2 blood group gene. We show that CD151 expresses the MER2 blood group antigen and is located on erythrocytes. We examined CD151 in 3 MER2-negative patients (2 are sibs) of Indian Jewish origin with end-stage kidney disease. In addition to hereditary nephritis the sibs have sensorineural deafness, pretibial epidermolysis bullosa, and β-thalassemia minor. The 3 patients are homozygous for a single nucleotide insertion (G383) in exon 5 of CD151, causing a frameshift and premature stop signal at codon 140. The resultant truncated protein would lack its integrin-binding domain. We conclude that CD151 is essential for the proper assembly of the glomerular and tubular basement membrane in kidney, has functional significance in the skin, is probably a component of the inner ear, and could play a role in erythropoiesis.
Activation of the pheromone-responsive MAP kinase drives haploid cells to undergo ectopic meiosis with normal telomere clustering and sister chromatid segregation in fission yeast
Authors: Yamamoto Takaharu G. , Chikashige Yuji , Ozoe Fumiyo , Kawamukai Makoto , Hiraoka Yasushi
Published: July 2004

Meiosis is a process of importance for sexually reproducing eukaryotic organisms. In the fission yeast Schizosaccharomyces pombe, meiosis normally proceeds in a diploid zygote which is produced by conjugation of haploid cells of opposite mating types. We demonstrate that activation of the pheromone-responsive MAPK, Spk1, by the ectopic expression of a constitutively active form of Byr1 (MAPKK for Spk1) induced the cells to undergo meiosis while in the haploid state. Moreover, the induction of meiosis required Mei2 (a key positive regulator of meiosis), but did not require Mei3; Mei3 is normally required to inactivate the Pat1 kinase (a negative regulator of Mei2) thereby allowing Mei2 to drive meiosis. Therefore, expression of a constitutively active form of Byr1 activates Mei2 without the need of Mei3. In cells induced to undergo meiosis by activating the Spk1 MAPK signaling pathway, telomeres clustered at the spindle pole body (SPB) and centromeres detached normally from the SPB during meiotic prophase, and the cells showed the correct segregation of sister chromatids during meiotic divisions. In contrast, in meiosis induced by inactivation of Pat1, sister chromatids segregate precociously during the first meiotic division. Thus, these results suggest that activation of Spk1 drives meiosis in S. pombe.
Zeolite SUZ-4 as Selective Dehydration Catalyst for Methanol Conversion to Dimethyl Ether
Authors: Jiang Shan , Hwang Young Kyu , Jhung Sung Hwa , Chang Jong-San , Hwang Jin-Soo , Cai Tianxi , Park Sang-Eon
Published: July 2004

Zeolite SUZ-4 is found to be a very selective and stable catalyst for producing dimethyl ether in methanol dehydration because the formed dimethyl ether is hardly converted to hydrocarbons, different from ZSM-5 zeolite.
Development and Validation of the Medication Regimen Complexity Index
Authors: George Johnson , Phun Yee-Teng , Bailey Michael J , Kong David CM , Stewart Kay
Published: July 2004

BACKGROUND:

Medication regimen attributes, such as the number of drugs, dosage frequency, administration instructions, and the prescribed dosage forms, have been shown to influence patient outcomes. No single tool for quantifying the complexity of general medication regimens has been published in the medical literature.

OBJECTIVE:

To develop and validate a tool to quantify the complexity of prescribed medication regimens.

METHODS:

Literature findings and the expertise of the authors were used for developing the tool. Eight pharmacy researchers helped in establishing the tool's face and content validity. The new tool was tested on 134 medication regimens from patients with moderate to severe chronic obstructive pulmonary disease. Six regimens with a spread of scores on the tool were presented to a 5–member expert panel that subjectively ranked these regimens to confirm the tool's criterion-related validity. The relationships between scores on the tool and various independent variables were tested to judge the tool's construct validity. Two raters scored 25 regimens using the tool to test its inter-rater and test—retest reliabilities.

RESULTS:

A 65–item Medication Regimen Complexity Index (MRCI) was developed. The expert panel had strong agreement (Kendall's W = 0.8; p = 0.001) on their individual rankings of the 6 regimens. The panel's consensus ranking had perfect correlation with the MRCI ranking. The total MRCI score had significant correlation with the number of drugs in the regimen (Spearman's Rho = 0.9; p < 0.0001), but not with the age and gender of the patients. Inter-rater and test—retest reliabilities for the total score and scores for individual sections on the MRCI were ≥0.9.

CONCLUSIONS:

The MRCI is a reliable and valid tool for quantifying drug regimen complexity with potential applications in both practice and research.
Lack of Pharmacokinetic or Pharmacodynamic Interaction Between Memantine and Donepezil
Authors: Periclou Antonia P , Ventura Daniel , Sherman Tyler , Rao Niranjan , Abramowitz Wattanaporn T
Published: July 2004

BACKGROUND:

Memantine, a low- to moderate-affinity, uncompetitive N-methyl-d-aspartate receptor antagonist, was approved in the US for treatment of moderate to severe Alzheimer's disease in October 2003.

OBJECTIVE:

To determine whether an in vivo pharmacokinetic interaction exists between memantine and the acetylcholinesterase (AChE) inhibitor donepezil.

METHODS:

In this open-label, multiple-dose study, 24 healthy subjects (aged 18–35 y) received oral administration of memantine 10 mg on day 1. Following a 14-day washout period, subjects were orally administered donepezil 5 mg once daily for 7 days on an outpatient basis. Beginning on day 22, the donepezil dosage was doubled for 22 days to the target dose of 10 mg once daily, with the last donepezil dose concomitantly administered with memantine 10 mg on day 43. Assessments included pharmacokinetic as well as safety parameters. In addition, AChE inhibition was measured in red blood cells by radiolabeled-enzyme assay following administration of donepezil alone and after a single memantine dose.

RESULTS:

Data from 19 subjects who completed the study indicated no significant pharmacokinetic interactions between a single dose of memantine and multiple doses of donepezil. Percent maximum inhibition of AChE activity (mean ± SD) by donepezil was 77.8 ± 7.3% and not significantly different upon coadministration of a single dose of memantine (81.1 ± 5.7%). Two subjects withdrew due to adverse events while taking donepezil alone. Single memantine doses administered with multiple donepezil doses were well tolerated.

CONCLUSIONS:

The pharmacokinetic and pharmacodynamic data from this study indicated a lack of interaction between memantine and donepezil, suggesting that memantine and donepezil may be safely and effectively used in combination.
Clinical and Economic Analysis of Methicillin-Susceptible and -Resistant Staphylococcus aureus Infections
Authors: Kopp Brian J , Nix David E , Armstrong Edward P
Published: July 2004

BACKGROUND:

The rate of methicillin-resistant Staphylococcus aureus (MRSA) has increased significantly over the last decade. Previous cohort studies of patients with MRSA bacteremia have reported higher mortality rates, increased morbidity, longer hospital length of stay (LOS), and higher costs compared with patients with methicillin-susceptible S. aureus (MSSA) bacteremia. The clinical and economic impact of MRSA involving other sites of infection has not been well characterized.

OBJECTIVE:

To determine the clinical and economic implications of MRSA compared with MSSA infections across a variety of infection sites and severity of illnesses.

METHODS:

A retrospective, case—control analysis comparing differences in clinical and economic outcomes of patients with MRSA and MSSA infections was conducted at an academic medical center. Case patients with MRSA infection were matched (1:1 ratio) to control patients with MSSA infection according to age, site of infection, and type of care.

RESULTS:

Thirty-six matched pairs of patients with S. aureus infection were identified. Baseline characteristics of patients with MSSA and MRSA infection were similar. Patients with MRSA infections had a trend toward longer hospital LOS (15.5 vs 11 days; p = 0.05) and longer antibiotic-related LOS (10 vs 7 days; p = 0.003). Median hospital cost associated with treatment of patients with MRSA infections was higher compared with patients with MSSA infections ($16 575 vs $12 862; p = 0.11); however, this difference was not statistically significant. Treatment failure was common in patients with MRSA infection. Among patients with MSSA infections, treatment failure was associated with vancomycin use.

CONCLUSIONS:

Patients with MRSA infections had worse clinical and economic outcomes compared with patients with MSSA infections.
Endocrine Regulation of Energy Metabolism: Review of Pathobiochemical and Clinical Chemical Aspects of Leptin, Ghrelin, Adiponectin, and Resistin
Authors: Meier Ursula , Gressner Axel M
Published: July 2004

Background: Recent studies point to the adipose tissue as a highly active endocrine organ secreting a range of hormones. Leptin, ghrelin, adiponectin, and resistin are considered to take part in the regulation of energy metabolism.

Approach: This review summarizes recent knowledge on leptin and its receptor and on ghrelin, adiponectin, and resistin, and emphasizes their roles in pathobiochemistry and clinical chemistry.

Content: Leptin, adiponectin, and resistin are produced by the adipose tissue. The protein leptin, a satiety hormone, regulates appetite and energy balance of the body. Adiponectin could suppress the development of atherosclerosis and liver fibrosis and might play a role as an antiinflammatory hormone. Increased resistin concentrations might cause insulin resistance and thus could link obesity with type II diabetes. Ghrelin is produced in the stomach. In addition to its role in long-term regulation of energy metabolism, it is involved in the short-term regulation of feeding. These hormones have important roles in energy homeostasis, glucose and lipid metabolism, reproduction, cardiovascular function, and immunity. They directly influence other organ systems, including the brain, liver, and skeletal muscle, and are significantly regulated by nutritional status. This newly discovered secretory function has extended the biological relevance of adipose tissue, which is no longer considered as only an energy storage site.

Summary: The functional roles, structures, synthesis, analytical aspects, and clinical significance of leptin, ghrelin, adiponectin, and resistin are summarized.
Biochemistry of Pro-B-Type Natriuretic Peptide-Derived Peptides: The Endocrine Heart Revisited
Authors: Goetze Jens Peter
Published: July 2004

Background: Since the discovery of cardiac hormones almost 25 years ago, a vast amount of clinical research has identified the cardiac natriuretic peptides and their precursors as markers of heart failure. It even seems likely that the pro-B-type natriuretic peptide (proBNP)-derived peptides in plasma may become the most frequently measured peptides in the daily diagnosis and control of therapy. In contrast, the biochemistry of the peptides has received less attention.

Methods: Published data available on the National Library of Medicine (NLM) were used as the basis for the review.

Outcome: This review shows that the present understanding of the biochemistry of peptides is far from complete. In particular, cellular synthesis, including posttranslational precursor maturation, is poorly understood. Moreover, elimination of the precursor fragments is unknown. Elucidation of the molecular heterogeneity of proBNP products will therefore contribute to the understanding of the endocrine heart and may also have important diagnostic consequences. Above all, the different proBNP-derived peptides may not always be equal markers of the same pathophysiologic processes. A different metabolism and peripheral elimination may also impose new and peptide-specific limitations for diagnostic use.

Conclusions: It is necessary to focus more on the biology of the proBNP-derived peptides. In turn, new insight into the biochemistry could pave the way for more sensitive and disease-specific assays in the clinical setting.
Brain Steroidogenesis Mediates Ethanol Modulation of GABAAReceptor Activity in Rat Hippocampus
Authors: Sanna Enrico , Talani Giuseppe , Busonero Fabio , Pisu Maria Giuseppina , Purdy Robert H. , Serra Mariangela , Biggio Giovanni
Published: July 2004

An interaction with the GABA type A (GABAA) receptor has long been recognized as one of the main neurochemical mechanisms underlying many of the pharmacological actions of ethanol. However, more recent data have suggested that certain behavioral and electrophysiological actions of ethanol are mediated by an increase in brain concentration of neuroactive steroids that results from stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. Neuroactive steroids such as 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP) are, in fact, potent and efficacious endogenous positive modulators of GABAAreceptor function. Because neurosteroids can be synthesizedde novoin the brain, we have investigated whether ethanol might affect both neurosteroid synthesis and GABAAreceptor function in isolated rat hippocampal tissue. Here, we show that ethanol increases the concentration of 3α,5α-THP as well as the amplitude of GABAAreceptor-mediated IPSCs recorded from CA1 pyramidal neurons in isolated hippocampal slices. These effects are shared by the neurosteroid precursor progesterone, the peripheral benzodiazepine receptor-selective agonist CB34, and γ-hydroxybutyrate, all of which are known to increase the formation of neuroactive steroids in plasma and in the brain. The action of ethanol on GABAAreceptor-mediated IPSC amplitude is biphasic, consisting of a rapid, direct effect on GABAAreceptor activity and an indirect effect that appears to be mediated by neurosteroid synthesis. Furthermore, ethanol affects GABAAreceptor activity through a presynaptic action, an effect that is not dependent on neurosteroid formation. These observations suggest that ethanol may modulate GABAAreceptor function through an increase inde novoneurosteroid synthesis in the brain that is independent of the HPA axis. This novel mechanism may have a crucial role in mediating specific central effects of ethanol.
Modulation of Synaptic Plasticity by Antimanic Agents: The Role of AMPA Glutamate Receptor Subunit 1 Synaptic Expression
Authors: Du Jing , Gray Neil A. , Falke Cynthia A. , Chen Wenxin , Yuan Peixiong , Szabo Steven T. , Einat Haim , Manji Husseini K.
Published: July 2004

Increasing data suggest that impairments of cellular plasticity underlie the pathophysiology of bipolar disorder. In this context, it is noteworthy that AMPA glutamate receptor trafficking regulates synaptic plasticity, effects mediated by signaling cascades, which are targets for antimanic agents. The present studies were undertaken to determine whether two clinically effective, but structurally highly dissimilar, antimanic agents lithium and valproate regulate synaptic expression of AMPA receptor subunit glutamate receptor 1 (GluR1). Chronic (but not acute) treatment of rats with therapeutically relevant concentrations of lithium or valproate reduced hippocampal synaptosomal GluR1 levels. The reduction in synaptic GluR1 by lithium and valproate was attributable to a reduction of surface GluR1 distribution onto the neuronal membrane as demonstrated by three independent assays in cultured hippocampal neurons. Furthermore, these agents induced a decrease in GluR1 phosphorylation at a specific PKA site (GluR1p845), which is known to be critical for AMPA receptor insertion. Sp-cAMP treatment reversed the attenuation of phosphorylation by lithium and valproate and also brought GluR1 back to the surface, suggesting that phosphorylation of GluR1p845 is involved in the mechanism of GluR1 surface attenuation. In addition, GluR1p845 phosphorylation also was attenuated in hippocampus from lithium- or valproate-treated animalsin vivo. In contrast, imipramine, an antidepressant that can trigger manic episodes, increased synaptic expression of GluR1 in hippocampusin vivo. These studies suggest that regulation of glutamatergically mediated synaptic plasticity may play a role in the treatment of bipolar disorder and raise the possibility that agents more directly affecting synaptic GluR1 may represent novel therapies for this devastating illness.
Shaggy, the Homolog of Glycogen Synthase Kinase 3, Controls Neuromuscular Junction Growth inDrosophila
Authors: Franco Bénédicte , Bogdanik Laurent , Bobinnec Yves , Debec Alain , Bockaert Joël , Parmentier Marie-Laure , Grau Yves
Published: July 2004

A protein-trap screen using theDrosophilaneuromuscular junction (NMJ) as a model synapse was performed to identify genes that control synaptic structure or plasticity. We found that Shaggy (Sgg), theDrosophilahomolog of the mammalian glycogen synthase kinases 3 α and β, two serine-threonine kinases, was concentrated at this synapse. Using various combinations of mutant alleles ofshaggy, we found that Shaggy negatively controlled the NMJ growth. Moreover, tissue-specific expression of a dominant-negative Sgg indicated that this kinase is required in the motoneuron, but not in the muscle, to control NMJ growth. Finally, we show that Sgg controlled the microtubule cytoskeleton dynamics in the motoneuron and that Futsch, a microtubule-associated protein, was required for Shaggy function on synaptic growth.
Processing of Odor Mixtures in the Zebrafish Olfactory Bulb
Authors: Tabor Rico , Yaksi Emre , Weislogel Jan-Marek , Friedrich Rainer W.
Published: July 2004

Components of odor mixtures often are not perceived individually, suggesting that neural representations of mixtures are not simple combinations of the representations of the components. We studied odor responses to binary mixtures of amino acids and food extracts at different processing stages in the olfactory bulb (OB) of zebrafish. Odor-evoked input to the OB was measured by imaging Ca2+signals in afferents to olfactory glomeruli. Activity patterns evoked by mixtures were predictable within narrow limits from the component patterns, indicating that mixture interactions in the peripheral olfactory system are weak. OB output neurons, the mitral cells (MCs), were recorded extra- and intracellularly and responded to odors with stimulus-dependent temporal firing rate modulations. Responses to mixtures of amino acids often were dominated by one of the component responses. Responses to mixtures of food extracts, in contrast, were more distinct from both component responses. These results show that mixture interactions can result from processing in the OB. Moreover, our data indicate that mixture interactions in the OB become more pronounced with increasing overlap of input activity patterns evoked by the components. Emerging from these results are rules of mixture interactions that may explain behavioral data and provide a basis for understanding the processing of natural odor stimuli in the OB.
Cell Type-Specific Interleukin-1β Signaling in the CNS
Authors: Srinivasan Deepak , Yen Jui-Hung , Joseph Donald J. , Friedman Wilma
Published: July 2004

Interleukin-1β (IL-1β) is a potent and pleiotropic inflammatory cytokine that is highly produced in the CNS under conditions of damage, disease, or stress. This cytokine acts on CNS glia to effect inflammatory responses, mediated in part via activation of the nuclear factor-κB (NF-κB) transcription factor, and consequent induction of numerous cytokines. Neurons as well as astrocytes in the hippocampus also express the type 1 IL-1 receptor, indicating that this cytokine can influence neuronal function directly, yet IL-1β does not induce production of cytokines in neurons as it does in glia. In contrast, IL-1β regulates synaptic function of hippocampal neurons. Here we demonstrate that different signaling pathways mediate IL-1β actions in neurons as compared with astrocytes. IL-1β activates the p38 mitogen-activated protein kinase (MAPK) signaling pathway and induces the activation of CREB in hippocampal neurons, in contrast to the activation of NF-κB in hippocampal astrocytes, demonstrating cell type-specific signaling responses to IL-1 in the brain and yielding distinct functional responses.
Organisationsübergreifendes Geschäftsprozessmanagement (Business Process Management across Organisational Boundaries)
Authors: Lindert Frank , Wiedeler Markus
Published: July 2004

Die zunehmende Vernetzung und Zusammenarbeit von verschiedenen Unternehmen und Organisationen stellt besondere Anforderungen an die Gestaltung der Geschäftsprozesse. Die Geschäftsprozesse der in der Regel autonomen Beteiligten müssen so aufeinander abgestimmt werden, dass eine Kooperation ohne großen Transaktionsaufwand realisiert werden kann. Eine Lösung für die Unterstützung von organisationsübergreifenden Geschäftsprozessen ist die Einführung eines Diensteansatzes, bei dem die beteiligten Organisationen ihren Beitrag an der Kooperation jeweils als Dienst bereitstellen. In diesem Artikel werden die Anforderungen dargestellt, die im Rahmen von Kooperationen zu berücksichtigen sind. Ebenso wird ein Diensteansatz für die Koordination von Geschäftsprozessen beschrieben.
Enabling Technology: Ein J2EE-basiertes Business Process Management System zur Ausführung von BPEL- und Web Service-basierten Geschäftsprozessen (Enabling Technology: A J2EE based Business Process Management System for BPEL and Web services based business processes)
Authors: Kloppmann Matthias , König Dieter , Leymann Frank , Pfau Gerhard , Roller Dieter
Published: July 2004

Mithilfe von Web Services und BPEL (Business Process Execution Language for Web Services) können Geschäftsprozesse und deren Interaktion mit verschiedenen Partnern beschrieben werden. Zur Ausführung der Geschäftsprozesse finden Workflow Management Systeme Verwendung. Dieser Artikel beschäftigt sich, basierend auf den Grundlagen von Web Services und BPEL, mit der Implementierung eines Workflow Management Systems. Um den Anforderungen der Geschäftswelt zu genügen, muss ein Workflow Management System sowohl langlaufende, unterbrechbare als auch kurzlaufende Geschäftsprozesse mit ihren unterschiedlichen Quality-of-Service Eigenschaften unterstützen. Die Systeme müssen robust sein, sicher und hoch verfügbar. Der Artikel beschreibt die Implementierung eines J2EE-basierten Workflow Management System, das diesen Anforderungen entspricht. Dabei wird auf die Verwendung von Message Queuing Systemen und Datenbanken eingegangen, ebenso wie auf die Integration in einen Standard Application Server und die Verwendung dort zur Verfügung stehender Transaction Manager, EJB Container, People Directory und Deployment Infrastruktur.
P2P Evolution: From File-sharing to Decentralized Workflows (P2P Entwicklung: Vom Filesharing zu dezentralisierten Workflows)
Authors: Risse Thomas , Knežević Predrag , Wombacher Andreas
Published: July 2004

Peer-to-peer (P2P) computing is currently receiving a great deal of attention. Much of the current attention is focused on the use of P2P computing for exchanging media files. But P2P systems have actually been around for a long time and many application scenarios exist. In this paper we discuss on one hand the evolution of P2P middleware from simple file-sharing to decentralized data storage; on the other hand the impact on the future development of decentralized workflows. Building up a P2P based data storage, with similar properties as a standard data store, opens many research issues. While P2P databases enable distributed data storage, distributed control flows are considered in decentralized workflows. The paper will present several research issues addressing the collaboration and coordination problem in distributed environments without a centralized coordination instance by means of a B2B application scenario.
Dietary Niacin Intake and Mortality Among Individuals With Nonalcoholic Fatty Liver Disease
Authors: Pan Jie , Zhou Yujia , Pang Nengzhi , Yang Lili
Published: February 2024

Importance

Evidence regarding the effect of dietary niacin intake on the risk of mortality among patients with nonalcoholic fatty liver disease (NAFLD) is scarce.

Objective

To examine the association of dietary niacin intake with all-cause mortality and cardiovascular disease (CVD) mortality among individuals with NAFLD.

Design, Setting, and Participants

This cohort study used data from the National Health and Nutrition Examination Survey (2003-2018). In total, 4315 adults aged 20 years or older with NAFLD were included, with NAFLD defined using the United States Fatty Liver Index.

Exposure

Dietary niacin intake levels.

Main Outcomes and Measures

Weighted Cox proportional hazards models and restricted cubic splines were used to estimate hazard ratios and 95% CIs for all-cause and CVD mortality. Data were analyzed March 1 to September 1, 2023.

Results

This cohort study included data from 4315 participants in the analysis (mean [SD] age, 52.5 [16.2] years; 1670 participants ≥60 years [weighted, 30.9%]; 2351 men [weighted, 55.0%]). During a median (IQR) follow-up of 8.8 (4.6-11.8) years, 566 deaths were recorded, of which 197 were attributed to CVD. Compared with participants with a niacin intake of 18.4 mg or lower (the lowest tertile), the multivariable-adjusted hazard ratios for participants with a niacin intake of 26.7 mg or higher (the highest tertile) were 0.70 (95% CI, 0.50-0.96) for all-cause mortality (P = .03 for trend) and 0.65 (95% CI, 0.35-1.20) for CVD mortality (P = .16 for trend).

Conclusions and Relevance

Findings from this cohort study suggest that higher dietary niacin intake may be associated with lower risk of all-cause mortality among individuals with NAFLD. There was no evident inverse association between dietary niacin intake and the risk of CVD mortality.
An Atypical Optic Nerve Head Mass
Authors: Maywood Michael J. , Govindaraju Viren K. , Begaj Tedi
Published: February 2024

A 47-year-old man presented with a sudden decrease in vision in the right eye and a history of binocular diplopia, bilateral cranial nerve 6 palsies, and an undifferentiated pontine mass. Examination revealed a large optic nerve head mass with optic disc hyperemia, scattered dot hemorrhages, a placoid lesion in the posterior pole, and a mass protruding out of the optic nerve head. What would you do next?
Diabetic Retinopathy and Quality of Life
Authors: Zayed Mohammed G. , Karsan Waseem , Peto Tunde , Saravanan Ponnusamy , Virgili Gianni , Preiss David
Published: February 2024

Importance

The association between diabetic retinopathy (DR) and quality of life (QoL) has not been thoroughly investigated.

Objective

To investigate the association between DR and both vision-related QoL (VRQoL) and general health-related QoL (HRQoL).

Data Sources

MEDLINE, EBSCO, Embase, and Web of Science were searched from their inception to April 2022.

Study Selection

Studies included adults with DR and a measure of QoL.

Data Extraction and Synthesis

Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Two assumption-free meta-analyses were conducted. Analysis 1 included studies with participants without DR as the referent group to which QoL scores of participants with DR, grouped according to DR severity, were compared. Analysis 2 included all studies with participants with DR and a measure of QoL. QoL scores were pooled within categories of DR severity, and comparisons were made between these categories.

Main Outcome and Measures

QoL measured using HRQoL and VRQoL scales.

Results

A total of 93 articles were included: 79 in the meta-analyses and 14 in the narrative results. VRQoL was recorded in 54 studies, HRQoL in 26, and both in 13 studies. The most commonly used scales were the National Eye Institute 25-item Visual Function Questionnaire (VFQ-25) (n = 49) for VRQoL and the Short Form (SF) Health Survey (n = 18) for HRQoL. Thirty-five studies reported VFQ-25 composite scores. Analysis 1 consisted of 8 studies including 1138 participants with DR and 347 participants without DR. Compared with participants without DR, the composite VFQ-25 score was 3.8 (95% CI, 1.0-6.7) points lower in those with non–vision-threatening DR (NVTDR), 12.5 (95% CI, 8.5-16.5) lower in those with any DR, and 25.1 (95% CI, 22.8-27.2) lower in VTDR (P < .001 for trend). Analysis 2 consisted of 35 studies including 6351 participants with DR. The pooled mean VFQ-25 composite score was 91.8 (95% CI, 91.0-92.7) for participants with NVTDR, 77.6 (95% CI, 76.9-78.3) for any DR, and 73.2 (95% CI, 72.6-73.7) for VTDR (P < .001 for trend). HRQoL scores had weak or no associations with NVTDR and strong associations with VTDR.

Conclusions and Relevance

This study found that VRQoL declined with the presence and severity of DR. Interventions to reduce progression of DR at both early and more advanced stages could improve VRQoL.