bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human skin permeation of Δ8-tetrahydrocannabinol, cannabidiol and cannabinol
Authors: Stinchcomb Audra L , Valiveti Satyanarayana , Hammell Dana C , Ramsey Diana R 
Published: March 2004

Abstract
The purpose of this study was to quantify the in-vitro human skin transdermal flux of Δ8-tetrahydrocannabinol (Δ8-THC), cannabidiol (CBD) and cannabinol (CBN). These cannabinoids are of interest because they are likely candidates for transdermal combination therapy. Differential thermal analysis and in-vitro diffusion studies with human tissue were completed for the compounds. Heats of fusion, melting points and relative thermodynamic activities were determined for the crystalline compounds, CBD and CBN. Flux, permeability, tissue concentration and lag times were measured in the diffusion experiments. CBN had a lower heat of fusion and corresponding higher calculated relative thermodynamic activity than CBD. Ethanol concentrations of 30 to 33% significantly increased the transdermal flux of Δ8-THC and CBD. Tissue concentrations of Δ8-THC were significantly higher than for CBN. Lag times for CBD were significantly smaller than for CBN. The permeabilities of CBD and CBN were 10-fold higher than for Δ8-THC. Combinations of these cannabinoids with ethanol will be further studied in transdermal patch formulations in vitro and in vivo, as significant flux levels of all the drugs were obtained. CBD, the most polar of the three drugs, and other more polar cannabinoids will also be the focus of future drug design studies for improved transdermal delivery rates.
Pharmacokinetic interaction of ibuprofen enantiomers in rabbits
Authors: Lin Wenhui , Hayakawa Toru , Yanaguimoto Hitomi , Kuzuba Mamoru , Obara Takako , Inotsume Nobuo , Lin Wenhui , Cui Fude , Ding Guohua 
Published: March 2004

Abstract
The potential interaction between two ibuprofen enantiomers was studied after intravenous administration of R-(–)-, S-(+)- and racemic ibuprofen to rabbits. The total body clearance values calculated by compartmental model analysis (0.65+0.21 for R-(–)-ibuprofen and 0.63+0.34 for S-(+)-ibuprofen) after intravenous administration of the racemate of ibuprofen were significantly smaller than those of individual enantiomers (0.95+0.23 for R-(–)-ibuprofen and 1.03+0.23 for S-(+)-ibuprofen), indicating that the enantiomer–enantiomer interaction results in a mutual inhibition. The enantiomeric interaction in the pharmacokinetic behaviour of ibuprofen after racemic administration is considered to be a result of an alteration in the metabolic or excretion phase (or both) rather than stereoselective protein binding in the systemic distribution.
Pharmacokinetics and distribution of sodium 3,4-diaminonaphthalene-1-sulfonate, a Congo Red derivative active in inhibiting PrPres replication
Authors: Gervasoni M , Pirola R , Mantegazza P , Bareggi S R , Pollera C , Poli G , Villa S , Cignarella G , Gervasoni M , Pirola R , Pollera C , Villa S , Cignarella C , Mantegazza P , Poli G , Bareggi S R 
Published: March 2004

Abstract
Sodium 3,4-diaminonaphthalene-1-sulfonate (CRA) is a compound, synthesised by our group from Congo Red (CR), that is active in preventing the pathological conversion of normal prion protein (PrP). As the precise mechanisms controlling the ways in which prions are distributed and infect the brain and other organs are not fully understood, studying the pharmacokinetics of drugs that are active against prions may clarify their targets and their means of inhibiting prion infection. This paper describes the pharmacokinetics of CRA in plasma, spleen and brain after single or repeated intraperitoneal or subcutaneous administration, as determined by means of specific and sensitive fluorimetric HPLC. A single intraperitoneal administration led to peak plasma CRA concentrations after 15 min, followed by biphasic decay with an apparent half-life of 4.3 h. After subcutaneous administration, Tmax was reached after 30 min, and was followed by a similar process of decay: Cmax and the AUC0-last were 25% those recorded after intraperitoneal administration. The mean peak concentrations and AUCs of CRA after a single intraperitoneal or subcutaneous administration in peripheral tissue (spleen) were similar to those observed in blood, whereas brain concentrations were about 2% those in plasma. After repeated intraperitoneal or subcutaneous doses, the Cmax values in plasma, brain and spleen were similar to those observed at the same times after a single dose. After repeated intraperitoneal doses, CRA was also found in the ventricular cerebrospinal fluid at concentrations of 1.8 + 0.2 μg mL−1, which is similar to, or slightly higher than, those found in brain. Brain concentrations may be sufficient to explain the activity of CRA on PrP reproduction in the CNS. However, peripheral involvement cannot be excluded because the effects of CRA are more pronounced after intraperitoneal than after intracerebral infection.
Small intestinal glucose absorption in cystic fibrosis: a study in human and transgenic ΔF508 cystic fibrosis mouse tissues
Authors: Hardcastle J , Harwood M D , Taylor C J 
Published: March 2004

Abstract
Intestinal transport is disturbed in cystic fibrosis (CF), with both defective Cl− secretion and changes in absorption being reported. We have examined the effects of the disease on Na+-dependent glucose absorption by the small intestine. Active glucose absorption was monitored as changes in short-circuit current (SCC) in intact and stripped intestinal sheets from normal (Swiss) and transgenic CF (Cftrtm 1 Eur and Cftrtm 2 Cam) mice with the ΔF508 mutation, and in jejunal biopsies from children with CF and normal controls. Na+-dependent glucose uptake at the luminal membrane was measured in brush-border membrane vesicles (BBMVs). Intact and stripped sheets of jejunum and midintestine from Swiss mice exhibited a concentration-dependent increase in SCC with glucose. Apparent Km values were similar in the two preparations, but the apparent Vmax was greater in stripped sheets. This difference was not due to a loss of neural activity in stripped sheets as tetrodotoxin did not influence the glucose-induced SCC in intact sheets. Similar results were observed in stripped sheets of jejunum and mid-intestine from wild-type Cftrtm 1 Eur mice, but in tissues from CF mice the apparent Vmax value was reduced significantly. A lower Vmax was also obtained in intact sheets of mid-intestine from CF (Cftrtm 2 Cam) mice. Jejunal biopsies from CF patients however, exhibited an enhanced glucose-dependent rise in SCC. Na+-dependent uptake by BBMVs from CF (Cftrtm 1 Eur) mice was not reduced compared with wild-type and Swiss BBMVs. It was concluded that, in contrast to human intestine, intestinal glucose absorption was reduced in transgenic mouse models of CF with the ΔF508 mutation, but that this could not be detected in an isolated preparation of brush-border membranes. Transgenic mouse models of CF may not accurately reflect all aspects of intestinal dysfunction in the human disease.
The emulsification and solubilisation properties of polyglycolysed oils in self-emulsifying formulations
Authors: Devani Manisha , Ashford Marianne , Craig Duncan Q M 
Published: March 2004

Abstract
Self-emulsifying drug delivery systems (SEDDS), whereby drugs are dispersed in an oil–surfactant mix that emulsifies on contact with water, represent a highly promising approach for enhancing oral bioavailability. However, the choice of formulation is, at present, largely empirical both in terms of the composition dependence of the emulsification process and the solubilisation of the drug in the initial oil–surfactant mixture. In this investigation, a range of chemically related self-emulsifying systems have been studied, based on the Labrafil family of polyglycolysed oils, using Tween 80 and Tween 20 as surfactants. The ease of emulsification, the particle size distribution and the appearance of the emulsion droplets were studied as a function of composition, while the solubility of danazol and mefenamic acid in the various oil–surfactant mixes was measured. It was noted that dilution of the emulsions led to apparent change in particle size distribution. The more hydrophilic oil–surfactant mixes showed a greater ease of emulsification and a lower particle size. It was also noted that multiple emulsions could be formed using systems of lower polarity. A linear relationship was observed between the hydrophile–lipophile balance (HLB) of the mix and the solubility of both danazol and mefenamic acid, with more hydrophilic mixes showing greater drug solubility values. The study has indicated that, within the range studied, more hydrophilic mixes tend to result in superior emulsification properties and greater drug solubility.
Histatins: antimicrobial peptides with therapeutic potential
Authors: Kavanagh Kevin , Dowd Susan 
Published: March 2004

Abstract
Histatins are a group of antimicrobial peptides, found in the saliva of man and some higher primates, which possess antifungal properties. Histatins bind to a receptor on the fungal cell membrane and enter the cytoplasm where they target the mitochondrion. They induce the non-lytic loss of ATP from actively respiring cells, which can induce cell death. In addition, they have been shown to disrupt the cell cycle and lead to the generation of reactive oxygen species. Their mode of action is distinct from those exhibited by the conventional azole and polyene drugs, hence histatins may have applications in controlling drug-resistant fungal infections. The possibility of utilising histatins for the control of fungal infections of the oral cavity is being actively pursued with the antifungal properties of topical histatin preparations and histatin-impregnated denture acrylic being evaluated. Initial clinical studies are encouraging, having demonstrated the safety and efficacy of histatin preparations in blocking the adherence of the yeast Candida albicans to denture acrylic, retarding plaque formation and reducing the severity of gingivitis. Histatins may represent a new generation of antimicrobial compounds for the treatment of oral fungal infections and have the advantage, compared with conventional antifungal agents, of being a normal component of human saliva with no apparent adverse effects on host tissues and having a mode of action distinct to azole and polyene antifungals.
Increased phosphorylation of AKAP by inhibition of phosphatidylinositol 3-kinase enhances human sperm motility through tail recruitment of protein kinase A
Authors: Luconi Michaela , Carloni Vinicio , Marra Fabio , Ferruzzi Pietro , Forti Gianni , Baldi Elisabetta 
Published: March 2004

Sperm motility is regulated by a complex balance between kinases and phosphatases. Among them, phosphatidylinositol 3-kinase (PI 3-kinase) has been recently suggested to negatively regulate sperm motility (Luconi, M., Marra, F., Gandini, L., Lenzi, A., Filimberti, E., Forti, G. and Baldi, E. (2001). Hum. Reprod. 16, 1931-1937). We demonstrate the presence and activity of PI 3-kinase in human spermatozoa and have investigated the molecular mechanism(s) by which the PI 3-kinase inhibitor, LY294002, triggers an increase in sperm motility. PI 3-kinase inhibition results in an increase in intracellular cAMP levels and in tyrosine phosphorylation of the protein kinase A-anchoring protein AKAP3. These effects finally result in a stimulation of protein kinase A (PKA) binding to AKAP3 in sperm tails through the regulatory subunit RIIβ. The increased binding of RIIβ to AKAP3 induced by LY294002 is mainly due to tyrosine phosphorylation of AKAP3, since it is completely blocked by the tyrosine kinase inhibitor erbstatin, which also reverses the effects of LY294002 on motility and suppresses PKA-AKAP3 interaction. The requirement of PKA binding to AKAP3 for sperm motility is confirmed by the reduction of motility induced by an inhibitor of RIIβ-AKAP3 binding, Ht31, whose effects on sperm motility and PKA binding to AKAP3 are reversed by LY294002.These results demonstrate that PI 3-kinase negatively regulates sperm motility by interfering with AKAP3-PKA binding, providing the first evidence of a molecular mechanism by which PKA can be targeted to sperm tails by interaction with tyrosine phosphorylated form of AKAP3.
Dehydration Polymerization in Aqueous Medium Catalyzed by Lipase
Authors: Kobayashi Shiro , Uyama Hiroshi , Suda Sakae , Namekawa Shuhei 
Published: March 2004

Abstract
Dehydration polymerization of a dicarboxylic acid and glycol proceeded in an aqueous medium by using lipase catalyst to produce an aliphatic polyester. Enzyme origin and the monomer structure affected the yield and molecular weight of the product polyester.
An Efficient Algorithm for Real-Time Estimation and Prediction of Dynamic OD Tables
Authors: Bierlaire M. , Crittin F. 
Published: March 2004

The problem of estimating and predicting Origin-Destination (OD) tables is known to be important and difficult. In the specific context of Intelligent Transportation Systems (ITS), the dynamic nature of the problem and the real-time requirements make it even more intricate. We consider here a least-square modeling approach for solving the OD estimation and prediction problem, which seems to offer convenient and flexible algorithms. The dynamic nature of the problem is represented by an autoregressive process, capturing the serial correlations of the state variables. Our formulation is inspired from Cascetta et al. (1993) and Ashok and Ben-Akiva (1993). We compare the Kalman filter algorithm to LSQR, an iterative algorithm proposed by Paige and Saunders (1982) for the solution of large-scale least-squares problems. LSQR explicitly exploits matrix sparsity, allowing to consider larger problems likely to occur in real applications. We show that the LSQR algorithm significantly decreases the computation effort needed by the Kalman filter approach for large-scale problems. We also provide a theoretical number of flops for both algorithms to predict which algorithm will perform better on a specific instance of the problem.
Allocation of Railway Rolling Stock for Passenger Trains
Authors: Abbink Erwin , van den Berg Bianca , Kroon Leo , Salomon Marc 
Published: March 2004

For a commercially operating railway company, providing a high level of service for the passengers is of utmost importance. The latter requires high punctuality of the trains and an adequate rolling stock capacity. Unfortunately, the latter is currently (in 2002) one of the bottlenecks in the service provision by the main Dutch railway operator NS Reizigers. Especially during the morning rush hours, many passengers cannot be transported according to the usual service standards because of a shortage of the rolling stock capacity. On the other hand, a more effective allocation of the available rolling stock capacity seems to be feasible, because there are also several trains with some slack capacity. The effectiveness of the rolling stock capacity is determined mainly by the allocation of the train types and subtypes to the lines. Therefore, we describe in this paper a model that can be used to find an optimal allocation of train types and subtypes to the lines. This optimal allocation is more effective than the manually planned one, which is accomplished by minimizing the shortages of capacity during the rush hours. The model is implemented in the modeling language OPL Studio 3.1, solved by CPLEX 7.0, and tested on several scenarios based on the 2001–2002 timetable of NS Reizigers. The results of the model were received positively, both by the planners and by the management in practice, because these results showed that a significant service improvement over the manually planned allocation can be achieved within a shorter throughput time of the involved part of the planning process.
Serum Sickness–Like Reaction Associated with Griseofulvin
Authors: Colton Roberta L , Amir Jacob , Mimouni Marc , Zeharia Avraham 
Published: March 2004

OBJECTIVE To describe a serum sickness—like reaction associated with griseofulvin in a child being treated for tinea capitis. CASE SUMMARY A previously healthy 5-year-old boy presented with tactile fever, rash on his legs and back, swelling of his toes and fingers, and leg pain. He was being treated at the time with griseofulvin for tinea capitis. Laboratory evaluation including immunologic workup revealed no abnormalities. Replacement of griseofulvin with itraconazole, along with an antihistamine and a nonsteroidal antiinflammatory drug, led to complete resolution of the patient's symptoms. An objective causality assessment revealed that the adverse reaction was probable. DISCUSSION Serum sickness—like reactions may occur 7–21 days following exposure to an offending agent. Clinical manifestations are similar to those of serum sickness, with fever, malaise, and cutaneous eruption. However, on laboratory workup, complement levels are normal. Management of serum sickness—like reaction includes replacing the offending agent and providing symptomatic relief. CONCLUSIONS Clinicians should be aware of the possibility of serum sickness—like reaction associated with griseofulvin therapy and consider the possibility when choosing between griseofulvin and newer, more expensive drugs.
Nephrotoxic Potential of Selective Cyclooxygenase-2 Inhibitors
Authors: Sandhu Gurbir K , Heyneman Catherine A 
Published: March 2004

OBJECTIVE To determine the relative nephrotoxic potential of cyclooxygenase (COX)-2 inhibitors. DATA SOURCES A MEDLINE search (1996—February 2004) identified clinical trials evaluating the nephrotoxicity of COX-2 inhibitors versus traditional nonsteroidal antiinflammatory drugs (NSAIDs). Key search terms included cyclooxygenase inhibitors, nonsteroidal antiinflammatory agents, nephrotoxicity, and chemically induced. DATA SYNTHESIS Three clinical trials determined that COX-2 inhibitors have similar adverse effects on the kidney when compared with nonselective NSAIDs, while 2 studies concluded that COX-2 inhibitors are less nephrotoxic than nonselective NSAIDs. All 5 trials utilized low numbers of subjects, short-term therapy, and surrogate markers of kidney damage. CONCLUSIONS COX-2 inhibitors may not offer distinct advantages over nonselective NSAIDs with respect to kidney function. Longer trials in patients with comorbidities are warranted. These agents should be used cautiously or not at all in patients with predisposing conditions.
HIV Infection: Point-of-Care Testing
Authors: Donovan Brian J , Rublein John C , Leone Peter A , Pilcher Christopher D 
Published: March 2004

OBJECTIVE To review the data regarding point-of-care testing for the diagnosis of HIV infection in the US. DATA SOURCES English-language literature was identified via MEDLINE (1980—August 2003) using key words such as rapid HIV tests and HIV antibody testing. Textbooks and other pertinent resources were also reviewed. STUDY SELECTION AND DATA EXTRACTION All articles identified through the data sources above were evaluated and reviewed if pertinent to the objective. DATA SYNTHESIS The Centers for Disease Control and Prevention (CDC) has announced an effort to expand currently recommended strategies to prevent new infections with HIV. The cornerstone of this initiative is the availability of the new rapid test for antibodies to HIV (OraQuick Rapid HIV-1 Antibody Test, OraSure Technologies, Bethlehem, PA). The effectiveness, sensitivity, and specificity of this test have been evaluated in a number of cross-sectional studies using previously or simultaneously performed HIV enzyme immunoassays with Western blot confirmation as a reference standard. Although there are several limitations to consider, results of these studies suggest that this test has comparable ability to detect HIV antibodies to other commercially available tests. CONCLUSIONS The OraQuick test is simple enough to be performed in many settings including those that facilitate achievement of the goals outlined by the CDC. Availability of this test should have a dramatic impact on HIV detection and prevention strategies.
Possible Gatifloxacin-Induced Hyperglycemia
Authors: Donaldson Amy R , Vandiver Jeremy R , Finch Christopher K 
Published: March 2004

OBJECTIVE To report a case of possible gatifloxacin-induced hyperglycemia in a nondiabetic middle-aged woman. CASE SUMMARY A 64-year-old Indian woman with an extensive cardiovascular history was admitted for urosepsis. On admission, her blood glucose was 117 mg/dL. She was empirically started on gatifloxacin 400 mg/day; after 3 days of gatifloxacin therapy, her blood glucose was 607 mg/dL. On day 4, therapy was changed to cefazolin for sensitive Escherichia coli and her blood glucose levels began to return to normal. DISCUSSION Although gatifloxacin has been previously reported as a potential cause of both hyper- and hypoglycemia, the exact mechanism is unknown. Several factors that may have been involved in our patient's hyperglycemia are discussed. She experienced hyperglycemic changes more rapidly than did the typical patients of previous reports. The Naranjo probability scale suggests a possible drug-related event. CONCLUSIONS The temporal relationship between gatifloxacin administration and the patient's hyperglycemia suggests an iatrogenic cause. Based on our experience and the product labeling, clinicians should be more aware of the blood glucose—altering effects of gatifloxacin.
Adefovir Dipivoxil in the Treatment of Chronic Hepatitis B
Authors: Rivkin Anastasia M 
Published: March 2004

OBJECTIVE To evaluate properties of the new acyclic nucleotide analog adefovir dipivoxil in the treatment of chronic hepatitis B (CHB). DATA SOURCES MEDLINE and PubMed searches from 1966 to December 2003 were performed with the headings chronic hepatitis B, interferon alfa-2b, lamivudine, liver transplant, and adefovir dipivoxil. STUDY SELECTION AND DATA EXTRACTION Randomized controlled studies and meta-analyses were evaluated in detail. A manual search was performed using references from retrieved primary literature, review articles, editorials, postgraduate course syllabi from national meetings, and textbooks. Emphasis was placed on controlled, prospective, randomized trials. National meeting abstract presentations were included if the information offered was original. DATA SYNTHESIS CHB is a major viral infection with an estimated 400 million carriers worldwide. Medications available to treat CHB include interferon alfa-2b and lamivudine, both agents having significant limitations. Adefovir dipivoxil is a novel nucleotide analog which, when given at 10 mg/day for 48 weeks, improved liver histology in 28% more patients with hepatitis B e antigen (HBeAg)-positive CHB, and in 31% more patients with HBeAg-negative CHB compared with placebo (p < 0.001). Additionally, adefovir dipivoxil therapy significantly improved virologic and biochemical parameters in both HBeAg-positive and -negative CHB patients. Adefovir dipivoxil offers important advantages over other CHB treatment options: it maintains activity against lamivudine-resistant CHB, has good efficacy against HBeAg-negative CHB, and has minimal adverse effects at the 10-mg/day Food and Drug Administration–approved dose. CONCLUSIONS Approved medications for the treatment of CHB have many limitations, and adefovir dipivoxil provides a new important option as an initial treatment, as well as treatment in lamivudine-resistant patients. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-04-013-H01