Verapamil-digoxin interaction in chronic hemodialysis patients

Verapamil increases the serum-digoxin concentration (SDC) in digoxin treated normals due to a compromised renal and extrarenal clearance. In chronic hemodialysis patients (CHD-patients) treated with digoxin where the renal elimination is diminished, verapamil has been shown to cause substantial increases of SDC with risk of digoxin intoxication. The effect of verapamil treatment on SDC in 8 nearly anephric (Uvol less than 1 l/d) CHD-patients on digoxin treatment was assessed. The patients were continuously treated with verapamil for two periods of two weeks at two dosage levels, 120 mg/d and 240 mg/d, whereafter verapamil was withdrawn. SDC and serum-verapamil were measured weekly. The SDC increased from 1.1 mmol/l to 1.7 mmol/l (p less than 0.05, N = 7) during the first two weeks. Increasing the dose of verapamil to 240 mg/d did not cause a further increment in SDC; on the contrary, the mean SDC decreased. The SDC increments varied between 0 and 200% of baseline values. We conclude that verapamil treatment decreases digoxin clearance in CHD-patients and that the influence of verapamil on SDC in CHD-patients shows great interindividual variation with no close dose dependency and decreases to pretreatment level in 2-3 weeks.     

Effect of ethanol on ascorbate release in the nucleus accumbens and striatum of freely moving rats.

An in vivo voltammetry technique was used to monitor the extracellular ascorbate (AA) concentration in the nucleus accumbens and striatum of unanesthetized, freely moving rats. A single injection of ethanol, 1.0 g/kg intraperitoneally (IP), induced a significant increase in extracellular AA concentration in both the nucleus accumbens and striatum. This effect was dose dependent within a dose range from 0.5-2.0 g/kg. 4-Methylpyrazole (50 mg/kg, IP), which inhibits alcoholdehydrogenase, could not prevent the increase in AA concentration, evoked by ethanol. Furthermore, systemic administration of acetaldehyde (20 mg/kg, IP), the main metabolite of ethanol, did not have any effect on the level of AA in the nucleus accumbens or striatum. These results show that ethanol can alter the brain extracellular AA levels and that this effect seems to be attributed to ethanol itself and not to acetaldehyde. Consequently, these results indicate that a role for AA in the action of ethanol in the brain should be considered.     

Longitudinal relationship between incisal tooth wear and periodontal condition

The purpose of the study was to examine the relationship between the longitudinal development of incisal tooth wear and periodontal conditions in 51 persons. Stone casts obtained at the ages of 15 and 27 yr were used to assess incisal wear according to a graded scale, the Incisal wear Index (Iwl). The wear increase after 12 yr, ΔIwI, was related to the various health index scores at the age of 15 yr, including the Plaque Index (PII) and Gingival Index (GI) systems. The chi-square tests showed a statistically significant association between AIwI and periodontal condition in 15-yr-olds. Thus, relatively low P1I and GI values were accompanied by relatively high AIwI values. It was concluded that in 15-yr-olds, P1I and GI levels are clinical predictors of future wear (ΔIwI) of maxillary and mandibular central incisors. Pocket depth (PD) was a less valuable clinical predictor of such wear.     

Synthesis and antimalarial activity of new atovaquone derivatives

In this paper we describe the design and synthesis of 18 derivatives of the antimicrobial atovaquone which were substituted at the 3-hydroxy group by ester and ether functions. The compounds were evaluated in vitro for their activity against the growth of Plasmodium falciparum, the malaria causing parasite. All the compounds showed potent activity, with IC₅₀ values in the range of 1.25–50 nM, comparable to those of atovaquone and much higher than chloroquine or quinine.     

Virtual neuropathology: three-dimensional visualization of lesions due to toxic insult

A first-pass approach incorporating high-field magnetic resonance imaging (MRI) was used for rapid detection of neuropathologic lesions in fixed rat brains. This inherently 3-dimensional and nondestructive technique provides high-resolution, high-contrast images of fixed neuronal tissue in the absence of sectioning or staining. This technique, magnetic resonance microscopy (MRM), was used to identify diverse lesions in 2 well-established rat neurotoxicity models. The intrinsic contrast in the images delineated lesions that were identified using a battery of histologic stains, some of which would not be used in routine screening. Furthermore, the MRM images provided the locations of lesions, which were verified upon subsequent sectioning and staining of the same samples. The inherent contrast generated by water properties is exploited in MRM by choosing suitable pulse sequences, or proton stains. This approach provides the potential for a comprehensive initial MRM screen for neurotoxicity in preclinical models with the capability for extrapolation to clinical analyses using classical MRI.     

A multicentre study of loratadine, clemastine and placebo in patients with perennial allergic rhinitis

This multicentre, double-blind, randomized parallel-group study compared 3 weeks' treatment with either loratadine (Clarityn) 10 mg once daily, or clemastine (Tavegyl) 1 mg twice daily, and placebo in outpatients with active perennial allergic rhinitis. 155 patients were evaluated for efficacy and safety. Grading of four nasal and three non-nasal symptoms, rhinoscopy signs, and therapeutic response was performed on treatment days 6, 13, and 20. Patients recorded daily symptoms and possible adverse experiences in a diary, also indicating when symptoms of active rhinitis were relieved. Loratadine and clemastine were statistically significantly superior to placebo throughout the study (P less than 0.05), based on assessment of patients' nasal and eye symptoms, patients' diary scores, rhinoscopy signs of symptoms, and onset of relief. The loratadine group showed a statistically significantly (P less than 0.05) faster onset of relief of symptoms compared with the group treated with clemastine. Concerning nasal stuffiness, loratadine was significantly (P less than 0.05) superior to clemastine after 1 week's treatment. Reports of adverse reactions showed that significantly (P less than 0.05) more patients complained of sedation in the clemastine than in the loratadine group. Regarding other adverse experiences and laboratory tests, the three treatment groups were statistically comparable (P less than 0.05). The study showed that compared with placebo both loratadine and clemastine were effective in relieving nasal and eye symptoms in patients with perennial allergic rhinitis. Loratadine was safe and well tolerated and was significantly less sedative than clemastine; loratadine may therefore possess an advantage in clinical use in the treatment of perennial allergic rhinitis.     

Hürthle cell and mitochondrion-rich papillary carcinomas of the thyroid gland: an ultrastructural and immunocytochemical study

Of 52 consecutive papillary carcinomas of the thyroid, the following cases were included in this study: one Hürthle cell papillary carcinoma, one papillary carcinoma with foci of Hürthle cells, and 10 cases of papillary carcinoma with abundant mitochondria (volumetric density of mitochondria greater than or equal to 20%). All cases were studied by light microscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and immunocytochemistry. Our results showed that papillary carcinomas mainly or exclusively composed of Hürthle cells are very rare; that Hürthle cell papillary carcinomas of the thyroid share the biologic characteristics and blend insidiously with the so-called mitochondrion-rich papillary carcinomas; that TEM and SEM can provide useful evidence for achieving the differential diagnosis between Hürthle cell and so-called mitochondrion-rich papillary carcinomas; and that immunocytochemical studies are useless in the aforementioned differential diagnosis.