In vitro displacement of phenytoin from protein binding by nonsteroidal antiinflammatory drugs tolmetin, ibuprofen, and naproxen in normal and uremic sera

Displacement of phenytoin (90% bound to albumin) by other highly albumin-bound drugs like salicylate has been well documented. Other widely used nonsteroidal antiinflammatory drugs like tolmetin, ibuprofen, and naproxen are also strongly bound to albumin and can potentially displace phenytoin. However, phenytoin-ibuprofen interaction has been poorly studied in the past, and interaction of phenytoin with tolmetin or naproxen has not been studied before. For normal serum pool (albumin 3.7 g/dl), we observed significant increases in free phenytoin concentrations only with antiinflammatory drug concentrations at the upper end of therapeutic or above therapeutic concentrations. However, for the uremic pool (albumin 2.9 g/dl), displacement of phenytoin was significant even at the lower end of therapeutic concentrations of those antiinflammatory drugs. Of the three antiinflammatory drugs we studied, ibuprofen caused the highest displacement of phenytoin.     

Induction of ermAMR from a clinical strain of Enterococcus faecalis by 16-membered-ring macrolide antibiotics

We cloned the MLSB resistance determinant by PCR from a clinical isolate of Enterococcus faecalis 373, which is induced more strongly by a 16-membered-ring macrolide, tylosin, than by erythromycin. To elucidate the molecular basis of resistance of E. faecalis 373, we analyzed the cloned gene, designated ermAMR, by site-directed mutagenesis and reporter gene assay. Our results showed that an arginine-to-cysteine change in the seventh codon of the putative leader peptide endowed tylosin with resistance inducibility and that TAAA duplication enabled the control region to express the downstream methylase gene at a drastically increased level.     

Synthesis of phosphoramide mustard analogues of daunomycin and carminomycin

New phosphoramide mustards (6-8) have been prepared from the antibiotics 2 and 3, and from 5. The mixture of cyclophosphamides could be separated by preparative layer and column chromatography. The assignments of configuration to the isomeric phosphoramidates was based on the magnetic anisotropy of the P = O bond. The synthesized compounds 6a,b-8a,b (mixture of isomers) were tested for inhibitory activity on the [3H]-thymidine incorporation into the DNA of tumor cells, using ovarian carcinoma cell line.     

Ultrastructural features of cystic and merogonic stages of Hepatozoon sipedon (Apicomplexa: Adeleorina) in northern leopard frogs (Rana pipiens) and northern water snakes (Nerodia sipedon) from Ontario, Canada

This article describes the long-term consequences of successful cardiovascular disease (CVD) prevention and its influence on premature mortality in Finland, with special reference to North Karelia. Active community-based CVD prevention began in 1972 in the province of North Karelia (population, 180,000). Since 1977, active preventive work has been carried out nationwide, taking advantage of the experience from North Karelia, which continued as a demonstration area for integrated prevention of noncommunicable diseases. Comprehensive community-based interventions as part of WHO interhealth and CINDI programmes in North Karelia and nationwide aimed at changing the target risk factors and health behaviours (serum cholesterol, blood pressure, smoking, diet) at the population level. Age-adjusted mortality rates for CVD, coronary heart disease (CHD), cerebrovascular disease, all cancers, lung cancer, accidents and violence, and all causes in the population aged 35-64 years from the pre-programme period (1969-71) to 1995 were the main measures of the outcome. Among men there was a great reduction in deaths from CHD, CVD, cancer, and all causes in the whole country. From 1969-71 to 1995 the age-standardized CHD mortality (per 100,000) decreased in North Karelia by 73% (from 672 to 185) and nationwide by 65% (from 465 to 165). The reduction in CVD mortality was of the same magnitude. Among men, CHD mortality decreased in the 1970s, as did lung cancer mortality in the 1980s and 1990s, significantly more in North Karelia than in all of Finland. Among women there was a great reduction in CVD (including CHD and stroke) mortality and all-causes mortality, but only a small reduction in cancer mortality. These results show that a major reduction in CVD mortality among the working-age population can take place in association with active reduction of major risk factors, with a favourable impact on cancer and all-causes mortality.     

A qualitative assessment of the referral system at district level in Zimbabwe: implications on efficiency and effective delivery of health services

This exploratory study describes the nature and magnitude of the problem of health referrals, health-seeking behavior, perceptions, and knowledge at the district level in Zimbabwe. Data were obtained from focus groups with 159 persons in Tsholotsho and 132 persons in Murewa; from discussions with health personnel from the 6 health centers in Murewa and the 2 rural hospitals in Tsholotsho; and from records among a systematic sample of 400 new outpatients during October 1993 and March 1994 in Murewa district. Findings indicate that 71.8% in outpatient departments at Murewa Hospital had no access to a health center. 24.3% by-passed the health center for treatment at the hospital. 3.8% were referred by health centers. The absolute number of referrals did not change during 1991-93. However, the number directly accessing services from outside the district rose. Focus group participants reported their intention to use the nearest clinic for an illness. In Tsholotsho, people initially used the village community worker/headman. If illness was perceived as serious, patients would go to a hospital. For minor illness, people used traditional herbal remedies. If illness did not change after remedies, the clinic was consulted. Some illnesses were perceived as outside the realm of medicine. Most distinguished between a health center and a hospital, but were unaware of the important, superior functions of the health center. Most did not understand the logic behind the referral system, but appreciated referrals and not the cost of hospital treatment or transportation. The community was unaware of Ward Health Teams. Many did not understand the new fee policy introduced in 1994.     

Fluorescence studies of the location and membrane accessibility of the palmitoylation sites of rhodopsin

Fluorescent fatty acid labels have been incorporated into the palmitoylation sites of rhodopsin and used to probe the membrane accessibility and location of these sites. The fluorescence properties of anthroyloxy and pyrenyl fatty acids bound to rhodopsin were investigated in a reconstituted vesicle system. Collisional quenching of fluorescence by stearic acid (DSA) labeled with doxyls in the 16, 12, and 5 positions was used to determine the membrane accessibility and disposition of the modifying fatty acids. To properly determine the membrane concentration of these quenchers, the dependence of the Stern-Volmer parameters on both quencher and vesicle concentration was determined. An analysis of these dependences provided a correction for partitioning of the quencher between the aqueous phase and the membrane. After this correction, the relative effectiveness of doxyl quenchers was 16-DSA > 12-DSA > 5-DSA. Parallel studies on free anthroyloxy and pyrenyl fatty acids incorporated into the reconstituted system showed the same dependence on quencher position. These results indicate that the labels at the palmitoylation sites of rhodopsin are situated in the membrane much as a free fatty acid. This anchoring of the palmitates in the membrane results in the formation of a fourth cytoplasmic loop.     

The adaptive capacities of patients with panic disorders (a psychophysiological study)

Contingent-negative deviation (CND) and orientational reaction (OR) were studied in 9 women suffering from typical (according to DSM-III-R) panic disorders (PD) and 12 healthy females. CND recording was made after giving neutral (70 dB, 1000 Hz) and stress (120 dB, 2000 Hz) pairs of sounds. Patients with PD were divided in two groups depending upon CND amplitudes. The first group (4 patients) was distinguished from healthy individuals by high CND amplitude (which significantly decreased after reaction on stress sound), by delay of extinction of cutaneogalvanic reaction (CGR) and by higher electromyogram amplitude. The second group (5 patients with more severe course of PD) was characterized by low amplitudes of CND and electromyogram, by absence of changes in CND after stress sound, by delay of extinction of CGR and nonspecific response. Above-mentioned data were evidence of psychophysiological heterogeneity of typical PD. The results were interpreted from a position of adaptive abilities of patients with PD, using ineffective and immature psychophysiological strategies of overcoming stress.     

Dens invaginatus--a pathway to pulpal pathology: a literature review

Dens invaginatus is the most common dental anomaly in a group of dental anomalies, related by their embryologic development and by the fact that their defects provide a potential pathway for bacteria to cause pulpal pathology. It occurs when the inner enamel epithelium invaginates into the dental papilla prior to calcification. It exists in erupted teeth as an enamel-lined tract, which either ends in a blind sac inside the crown or root or exits into the periodontal ligament. The lining may be incomplete in areas and may not protect the pulp. Methods of providing preventive treatment for teeth with dens invaginatus are described. When pulpal pathosis occurs, the dens may displace the pulp and complicate access cavity preparation and subsequent endodontic treatment, adversely affecting the prognosis. The learning objective of this article is to present treatment planning considerations and suggestions.