Cephalosporin-probenecid drug interactions

The effect of concurrent probenecid administration on the pharmacokinetics of cephalosporin antibiotics varies with the available cephalosporins. Most cephalosporins are affected to some degree by concurrent probenecid administration, although ceforanide, ceftazidime, ceftriaxone and latamoxef (moxalactam) have no significant changes in pharmacokinetics. For those cephalosporins affected by probenecid, the predominant findings are impairment in renal clearance resulting in increased peak serum concentrations, an increased area under the concentration-time curve (AUC), and both delayed and prolonged recovery of the cephalosporin in the urine. The distribution of the cephalosporins is affected to varying degrees, with reports of increased penetration into ocular, central nervous system and blister fluids noted with some agents. The clinical relevance of the changes in cephalosporin distribution associated with probenecid administration has not been investigated. The dose and timing of probenecid administration appear to be major determinants in any possible interaction. Studies with ceftizoxime and cefoxitin suggest that larger probenecid doses result in greater changes in the pharmacokinetics of cephalosporins. Prolonged probenecid therapy before administration of a cephalosporin did not seem to be as relevant as the probenecid dosage in determining the magnitude of the interaction. Probenecid administration with or immediately before cephalosporin administration appears able to produce these documented changes in cephalosporin pharmacokinetics. The route of administration (oral versus parenteral) of either prolosporin pharmacokinetics. The route of administration (oral versus parenteral) of either probenecid or the cephalosporin does not appear to influence the characteristics of the interactions. The therapeutic efficacy of a combination of a cephalosporin with probenecid has been most thoroughly studied for single-dose treatment of gonorrhoea. The addition of probenecid to cephalosporin therapy results in sustained systemic concentrations adequate for eradication of Neisseria gonorrhoeae. Regimens involving either second or third generation cephalosporins demonstrate good success rates with single-dose therapy. However, the success of ceftriaxone administered alone for treatment of both penicillase-producing and non-penicillase-producing strains of N. gonorrhoeae suggests that the addition of probenecid is unnecessary. The use of probenecid, in combination with cephalosporins, to enhance the treatment of other venereal and systemic infections has preliminary, inconclusive support.     

Adhesive intercellular interactions

The process of intercellular interactions during morphogenesis, inflammation and malignant growth are considered from the point of view of possible intercellular contacts provided by cell adhesion molecules. The system analysis of different cell adhesion molecules classes? their structure and influence on functional cell activity is performed. Clinical importance of expression disturbances of cell adhesion molecules at various pathological processes is considered.     

Leukocyte-endothelial cell interactions

The movement of leukocytes from the blood circulation into organized lymphoid tissues or sites of inflammation requires cooperative interactions between signaling and adhesion molecules. Selectins mediate the initial rolling contacts of leukocytes with the endothelium. Following leukocyte activation, integrins strengthen adhesion and then direct migration beneath the endothelium. Unique combinations of signaling and adhesion molecules may regulate the subsets of leukocytes that are recruited into specific tissues.     

Campylobacter-host cell interactions

BACKGROUND: Leptin is likely to be involved in the homeostasis of body weight. Insulin is suggested to regulate both short-term and long-term circulating leptin levels. The present study aims to assess the relation between insulin and leptin levels in obese humans. METHODS: Some 53 obese subjects (body mass index 35.1 +/- 3.9 kg m-2 (mean +/- SD)) were prescribed a hypocaloric diet and randomized to either a placebo or the intestinal lipase inhibitor orlistat for 2 years. Serum leptin and insulin levels were determined repeatedly during these 2 years (5 times in the fasting condition and twice after an oral glucose load). RESULTS: Leptin concentrations appeared to be regulated at a specific level for each individual throughout the weight-loss period. The BMI explained 39.7% of the total variance in leptin levels, the body-fat distribution 17.2%, individual characteristics 30.3%; and the fasting serum insulin concentration 1.0%. After a mean weight loss of 7.7 +/- 4.9 kg, the time-integrated insulin response to an oral glucose load was significantly lower but the leptin response remained unchanged. CONCLUSIONS: The BMI is the main determinant of the circulating leptin concentration in obese humans. Individual characteristics seem to determine the leptin level, given the BMI. In a short-term observational study in obese humans, changes of insulin levels do not appear to be correlated to changes in leptin levels.     

Imagined interactions.

Social scientists have been studying imagined interactions since the mid-1980s and have measured numerous physiological correlates (Honeycutt, 2010). In this commentary I assess the research reported in Crisp and Turner (May–June 2009) and highlight the underlying mechanisms of imagined interactions that have empirically been laid out across Thailand, Japan, and the United States through confirmatory factor analyses (e.g., McCann & Honeycutt, 2006). The research in imagined interactions has been so extensive that “II” is a common acronym for the construct. Crisp and Turner’s (2009) article is excellent in its premise that prejudice may be ameliorated through IIs. I agree with their contention that “imagined contact is . . . an exciting prospect because it provides a simple, flexible, and effective means of promoting more positive perceptions”. Continued research on IIs is needed to further our understanding of conflict persistence, whether individuals can be taught to utilize IIs in a constructive manner for the purpose of creating quality relationships, and how IIs are used to adjust to life events. Interpersonal communication is informed by a better understanding of intrapersonal processes affecting daily experiences (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Anesthetic drug interactions

A patient with bipolar disorder and previously undiagnosed Klinefelter's syndrome presented with acute mania refractory to pharmacotherapy and was successfully treated with electroconvulsive therapy. This case constitutes the 31st case report documenting the coexistence of bipolar disorder with chromosomal anomalies and the 14th such patient with Klinefelter's syndrome. The relevance of this case to understanding the genetics of bipolar disorder is explored through a review of previously published reports of bipolar patients with chromosomal abnormalities. The relatively high incidence of Klinefelter's syndrome among this group of patients is discussed in the context of evidence for linkage of bipolar illness to the X chromosome.     

Carbohydrate-carbohydrate interactions in adhesion

Cell-cell interactions play an important role in the development, maintenance, and pathogenesis of tissues. They are highly dynamic processes which include migration, recognition, signaling, adhesion, and finally attachment. Cells on their pathway to a final location have to pass and interact with their substratum formed of matrix and cell layers. Testing and recognition are important keys for the proper result of tissue formation. They can, however, also lead to diseases when they are misused in pathological situations, by microorganisms or malignant cells, for instance. Carbohydrates, which are the most prominent surface-exposed structures, must play an important role as recognition molecules in such processes. The rich variability of carbohydrate sequences which cell surfaces can present to lectins, adhesion molecules, and other ligands creates a refined pattern of potential attachment sites. The subtle control of the surface presentation density can provide variations in attachment strength. Not only the carbohydrate sequences but also the fact that carbohydrates can be branched while proteins cannot and that the oligosaccharide chains can be attached to the protein backbone in different densities and patterns will create yet more interaction possibilities. Maximal use of the combinatorial richness of carbohydrate molecules would be made when carbohydrate sequences could interact with other carbohydrate sequences. Such interactions have only very rarely been considered for biochemically and biologically relevant situations since they are difficult to measure. A few are known and will be summarized here with the hope that this wealth of possible chemical interactions may be considered more and more by surface cell biochemists when analyzing fine tuning in cellular interactions.     

Theory of hydrophobic interactions

An earlier theoretical approach to the hydrophobic interaction, based on statistical mechanical treatments of models for liquid water and for aqueous solutions of hydrocarbons, is summarized here. Experimental verification of the theoretical thermodynamic parameters for hydrophobic interactions, and applications of the theory to some aspects of protein structure, are presented.     

Platelet-streptococcal interactions in endocarditis

Infective endocarditis is characterized by the formation of septic masses of platelets on the surfaces of heart valves and is most commonly caused by viridans streptococci. Streptococcal virulence in endocarditis involves factors that promote infectivity and pathogenicity. Adhesins and exopolysaccharide (glycocalyx) contribute to infectivity. Although many factors may contribute to pathogenicity, the platelet aggregation-associated protein (PAAP) of Streptococcus sanguis contributes directly to the development of experimental endocarditis. PAAP is synthesized as a rhamnose-rich glycoprotein of 115 kDa and contains a collagen-like platelet-interactive domain, pro-gly-glu-gln-gly-pro-lys. Expressed on the cell wall of platelet aggregation-inducing strains (Agg+) of S. sanguis, PAAP apparently interacts with a signal-transducing receptor complex on platelets, which includes a novel 175-kDa alpha 2-integrin-associated protein and a 65-kDa collagen-binding component. From available data, the role of PAAP in the pathogenesis of experimental endocarditis may be explained by a proposed mechanistic model. On injured heart valves, PAAP first enhances platelet accumulation into a fibrin-enmeshed thrombus (vegetation), within which S. sanguis colonizes. Colonizing bacteria must resist platelet microbicidal protein (PMPR). The aggregation of platelets on the heart valve may be potentiated by an ectoATPase expressed on the surface of the S. sanguis and platelet alpha-adrenoreceptors that respond to endogenous catecholamines. The expression of PAAP may be modified during infection. Collagen is exposed on damaged heart valves; fever (heat shock) occurs during endocarditis. In response to heat shock or collagen in vitro, PAAP expression is altered. After colonization, streptococcal exotoxin(s) may cause fever. Proteases and other enzymes from streptococci and host sources may directly destroy the heart valves. When PAAP is unexpressed or neutralized with specific antibodies, experimental endocarditis runs a milder course and vegetations are smaller. The data suggest strongly, therefore, that the role of PAAP may overlap the colonization function of putative adhesins such as FimA or SsaB. Finally, PAAP also contributes to the development of the characteristic septic mural thrombus (vegetation) of infective endocarditis and the signs of valvular pathology.     

Dyadic social interactions.

Kraemer and Jacklin (1979) proposed a method of analysis of univariate dyadic social interactions or relational data, and Mendoza and Graziano (1982) extended this method to multivariate relations. Their approach is based on an analysis-of-variance-type model that contains parameters characterizing the behavior of actors and partners and their interactions on each relation. The techniques presented in this article offer an alternative approach to the multivariate analysis of social interactions by realizing that many relations yield discrete-valued data and thus are better modeled by using methods designed for categorical data. This alternative approach is also more general because it allows more types of models to be fit. We illustrate, using the same data analyzed by the earlier methods. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Drug interactions and antibiotics

Situations that require the use of systemic antibiotic therapy are common and drug interactions are potentially frequent. These interactions may be deleterious and lead to reduction of therapeutic index, enhancement of toxic risk or may be favourable, with optimization of pharmacokinetics or pharmacodynamics. The mechanisms of these interactions are discussed.     

Understanding drug interactions.

Discusses the importance of understanding the manner in which drugs taken concomitantly may interact. The clinical significance of drug interactions can vary from relatively benign to quite serious, or even fatal. In the literature, the potential for a specific drug to demonstrate adverse interactions is discussed on the basis of the evidence available for making such a determination. It is pointed out that while the term "drug interaction" may connote the pharmacological activity of a synthetic or pharmaceutical product, interactions can occur with nonpharmaceutical products, such as alcohol, foods, and herbal preparations. Drug interactions are discussed from the perspective of pharmacodynamic interactions (i.e., what the drug does to the body), pharmacokinetic interactions (i.e., what the body does to the drug), and the cytochrome P450 enzyme system (i.e., enzymes involved in drug metabolism). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Protein-carbohydrate interactions during fertilization

Interaction between gametes during fertilization is at least in part regulated by carbohydrate moieties of the zona pellucida (ZP) and carbohydrate binding proteins of the sperm surface. This review focuses on the protein-carbohydrate interactions during the primary binding of the sperm to the ZP in different species. Synthesis, structure and composition of the ZP are summarized. The functional significance of carbohydrate residues of the ZP as sperm receptor is discussed. Sperm surface proteins known to have specific ZP and carbohydrate-binding sites including the mouse beta1, 4-galactosyltransferase and sp56, the rabbit protein Sp17, a human mannose-binding protein and several members of the spermadhesin family are presented.