On the interaction between anthralin and DNA: a revision.

The interaction between anthralin and DNA in vitro was examined. According to our data, there is no evidence for a specific interaction between these substances. However, we found that the addition of small quantities of DNA or albumin significantly enhanced the stability of aqueous solutions of anthralin and markedly affected the rate of anthralin decomposition.

Determination of partition coefficients of glucocorticosteroids by high-performance liquid chromatography.

Two high-performance liquid chromatographic (HPLC) techniques have been used for the determination of the lipophilicity of 50 glucocorticosteroids. For a log P range of 1 to 3, we used a persilylated octadecylsilane phase saturated with 1-octanol, which was eluted with 1-octanol saturated phosphate buffer (pH = 7). For log P values greater than or equal to 3.00, the same phase was used without 1-octanol saturation and was eluted with different methanol-buffer mixtures. These two procedures allowed the determination of log P values ranging from 1.00 to greater than 5.00. Good agreement was found between these procedures and others described in the literature. The effect of different structural changes in the glucocorticosteroid molecule on the lipophilicity is discussed.

High-pressure liquid chromatographic determination of anthralin in ointments.

Anthralin concentration was determined in different ointments by high-pressure liquid chromatography, and results were compared with those of the USP assay technique. Significant differences existed between the claimed and the actual levels of anthralin in some preparations. Varying quantities of anthralin breakdown products were found, and their concentrations appear to be related to the nature of the formulation.

Anthralin: chemical instability and glucose-6-phosphate dehydrogenase inhibition.

The chemical stability of the antipsoriatic drug, anthralin (1,8-dihydroxy-9-anthrone), in solution has been studied using high-performance liquid chromatographic analysis. The time course for decomposition in solution has been correlated with that of the inhibition of glucose-6-phosphate dehydrogenase, one of the most widely documented biochemical properties associated with anthralin. Solutions of anthralin in aqueous buffer (37 degrees, pH 7.5, under light protection) completely within 4 hr giving the 10,10'-dimer (40%), no detectable 1,8-dihydroxy-9,10-anthraquinone, and a greatly increased potency of inhibition of glucose-6-phosphate dehydrogenase. This increased inhibitory potency could not be explained by formation of the dimer which, like anthralin and its quinone, were shown to be only weak inhibitors of the enzyme. In acetone solution exposed to light and air, anthralin decomposed completely within 4 days, in part via the dimer as intermediate. The final solution had the characteristic color of anthralin-brown, contained the quinone (20%), and like decomposed aqueous solutions of anthralin, completely inhibited glucose-6-phosphate dehydrogenase. The results show that neither anthralin, nor either of its two identified decomposition products, is the potent toxic species against glucose-6-phosphate dehydrogenase.

Glucocorticoids: binding affinity and lipophilicity.

The relative binding affinity of 35 steroids for the glucocorticoid receptor was determined in experiments in which the competition of various unlabeled steroids with either [6,7-3H]dexamethasone or [1,2-3H]hydrocortisone for the cytosolic glucocorticoid receptor of cultured human keratinocytes was measured. The data obtained were correlated with steroid lipophilicity, measured as the partition coefficient of the steroid between 1-octanol and pH 7.4 aqueous buffer. The introduction of various substituents on the steroid molecule induced changes in the binding affinity and was associated in some cases with concomitant changes in steroid lipophilicity. The substitution by a 17 alpha-OH or 21-OH group leads in all cases to a decrease in steroid lipophilicity and to an increase in affinity. In contrast, 17 alpha-OAc and especially 21-OAc substitution on hydrocortisone and betamethasone causes a decrease in the steroid affinity for the receptor and an increase in steroid lipophilicity. The elongation of the ester chain from acetate to valerate in both position C-17 and C-21 leads to the increase in both the binding affinity for the receptor and the lipophilicity of steroids. However, all 21-esters showed lower binding affinity than the parent alcohol. The binding affinity of the highly lipophilic 17 alpha, 21-diester was found to be lower than that of the 17 alpha-ester but higher than that of the 21-ester or of the parent alcohol. Only in the series of 17 alpha- and 21-esters is there a correlation between the binding affinity of steroids for the glucocorticoid receptor and their lipophilicity.

Differential penetration of skin by topical metronidazole formulations.

This in vitro study compared the release and penetration of various metronidazole formulations: 0.75% gel, 0.75% cream, and a new 1% cream. Six skin samples from each of six women (28 to 58 years of age) were used to test the three formulations, for a total of 12 samples per formulation. A 10-mg target dose of each metronidazole formulation (75 micrograms of 0.75% gel and 0.75% cream, 100 micrograms of 1% cream) was applied to a skin surface of 1 cm2 per cell. The randomized application schedule controlled for variability in skin origin, individual cell thickness, and formulations. Seven fluid samples were collected over a 15-hour period. Metronidazole concentrations were measured in both the skin samples and through the fluid from a dynamic diffusion system with the use of high-performance liquid chromatography method with ultraviolet detection. Cutaneous penetration of metronidazole was significantly greater with the 0.75% gel and cream formulations than with the 1% cream. These results suggest that the delivery vehicle may be more important than the active drug concentration in cutaneous delivery of metronidazole.

Computer-assisted three-dimensional gait analysis of amphotericin-induced carpal lameness in horses.

Motion of 6 clinically sound horses trotting at a speed of 4 m/s on a treadmill was captured by video cameras before and 9, 16, and 23 days after amphotericin-induced lameness to determine the quantitative variables of three-dimensional computer-assisted image analysis that objectively describe carpal lameness. Amphotericin-B was used to induce lameness, and phenylbutazone (2.2 mg/kg of body weight, PO, once) and butorphanol tartrate (0.1 mg/kg IM, q 6 h, to effect) were used to control discomfort. Four 60-Hz cameras were symmetrically placed around the treadmill to capture 6 seconds of images from retro-reflective spheres taped to the trotting horses. Images were transferred to a video-based digitizer and a computer work station, where 4 files of two-dimensional data were reduced to 1 file of three-dimensional data. The effect of lameness on motion analyzed was assessed by use of two-way ANOVA. Differences between means were assessed, using the Student-Newman-Keul's test (P < or = 0.05). Head and withers excursions, (dorsal vertical displacement of head and withers targets, respectively) during the sound forelimb support phase were increased significantly during all lameness measurement periods. Head excursion, but not withers excursion, during the lame forelimb support phase, was decreased significantly during all lameness measurement periods. Computer determinations of stride length swing phase, stance phase, forelimb abduction, and carpal and fetlock ranges of motion did not consistently characterize the lameness. It was concluded that three-dimensional computer-assisted image analysis could be used for objective lameness evaluation in horses and that head and withers excursions were the most consistent variables for assessing equine carpal lameness.

[Cerebral form of Degos's disease]. / Maladie de Degos à forme cérébrale.

The writers report on a new anatomical and clinical observation of Degos' disease with neurological complications. A highly fluctuating meningoencephalitic syndrome took place in a young man 17 years old with a fatal outcome in 2 months. It was a general examination which revealed the lesions of atrophic papulosis typical of the disease. A histological examination confirmed the skin arteriolar, intestinal, and hemispheric lesions. It drew attention to the very abundant similar venular lesions, thus leading to a reconsideration of the physiopathology of this disorder, in which the oft demonstrated autoimmunity and arterial involvement are perhaps only symptoms of the disease.

[Lumbosacral dysraphia and "long spinal cord" of delayed appearance (9 cases)]. / Dysraphie lombo-sacrée et "moelle longue" de révélation tardive (neuf observations).

Urinary disorders, deformities of the feet, and sensory of trophic disturbances appearing during, or increasing in severity at adolescence, were observed in 9 patients. In seven cases there appeared to be an abnormality of the teguments of the lumbosacral region, and in all cases, as shown by straight radiological examination of a spina bifida of L5 or S1, a sacral dehiscence and wide sacral canal, and a subjacent nervous tissue abnormality was suspected. Radiculography showed the presence of a "long spinal cord" terminating in the sacrum by a tumor mass. Examination of this mass in the seven operated cases demonstrated that the tumor was an intradural lipoma with a wedge-shaped penetration into the end of the medulla, fixing the cord in the sacrococcygial region, in the absence of the filum terminale and cauda equina. The etiology of this "long spinal cord" is discussed, and it appears to be the consequence of a dysraphia, which is also the cause of the lipoma. Mechanical factors appear later and produce neurological signs.

[Water intoxication after polydipsic episodes. (8 cases)]. / Les intoxications par l'eau après accès polydipsiques. (Huit observations).

Eight cases of convulsive coma by water intoxication without predisposing disease in the majority of instances in psychiatric patients, added to 25 cases from the literature make it possible to describe a stereotyped picture of "psychogenic" water intoxication. This includes episodes of polydipsia preceding convulsions and altered conscious level, accompanied by severe hyponatraemia. Cure occurs spontaneously after an acute hypotonic polyuric phase. Study of free water clearances and dynamic ADH suppression tests demonstrate hypovasopressinism which is difficult to inhibit, with "lower osmoreceptor reset". This abnormality is transient and sometimes relapsing.

[Juvenile distal cerebral ischemia: value of pulp biopsy]. / Ischémie cérébrale distale juvénile: intérêt de la biopsie pulpaire.

Juvenile distal cerebral ischemia has been attributed to small artery atherosclerosis (Arnold, Benoit, Merlen, Dobbelaere, Delandsheer, 1979), based on clinicopathologic findings in one male patient and results of big toe pulp biopsy in three other cases. Pathological findings were obstruction of small artery lumens by hypertrophic endothelium and loose fibrocellular bands, their origin being the result possibly of partial intimalization of media by elastic neogenesis. Appearances were similar to those described by Dahl in human cerebral atherosclerosis in 1976, and approached those of the initial stages of experimental atheroma (Ross, Glomset, 1976). Arterial exiguity was also present in the 4 cases. Results of biologic, metabolic, inflammatory and immunologic examinations were negative. The present study concerns 4 additional cases of juvenile distal encephalic ischemia. One case in a female patient not on oral contraceptives confirmed the hypothesis of intimalization of media of arterioles of big toe pulp. Elastic neogenesis was present in the tunica media in areas where there was a change of direction of myocytes, and was apparent at a distance from the internal elastic layer. The latter was fragmented, sometimes doubles and of variable color. In another case, a woman taking oral contraceptives, there was almost total obstruction of the pulp arteriolar lumens with a very thin tunica media. Elastic neogenesis encircled two very narrow lumens in the center of the vessel and there were also elastic changes common to both.(ABSTRACT TRUNCATED AT 250 WORDS)

[Refsum's disease. Epidemiologic, clinical and biological correlation. 6 cases]. / La maladie de Refsum. Corrélations épidémiologiques, cliniques et biologiques. Six cas.

Nine patients with symptoms and signs of Refsum's disease are reported. In 6 a systemic accumulation of phytanic acid was demonstrated, together with low phytanic acid oxidase activity in skin fibroblasts in 5 of them. In 3, no disorder of phytanic acid metabolism was demonstrated. In 3, the diagnosis was made during the pre-clinical period. The disease seems more frequent in Northern France, which agrees with the hypothesis of a genetic mutation which would have taken place in Scandinavia some centuries ago and was subsequently spread by the Vikings. The effects of a dietary treatment on serum phytanic acid levels and clinical disorders are reported. The general condition of the patients improved remarkably but only partially. The diet is unpalatable and in some patients the level of serum phytanic acid increased, due to the mobilization of body fat. Patients with very high levels of phytanic acid might be initially treated by plasmapheresis. For the same reason, the diet should supply enough calories to keep body weight unchanged, and body weight loss whatever its cause should be avoided.

[Meadows syndrome. A case history (author's transl)]. / Le syndrome de Meadows. A propos d'une observation.

The authors, having studied a case of Meadows syndrome, confirm that this cardiomyopathy is a specific entity in pregnancy and the puerperium. They point out the difficulties in diagnosis, as Meadows syndrome seems to be diagnosis of elimination. They point out that a paraclinical balance has to be drawn up very fully on the biological and haemodynamic planes to confirm this condition. Finally, after a short discussion about the therapy, they tackle the problem of the prognosis for life and for future childbearing in these patients, which is determined by the persistence or absence of cardiac enlargement.

[Orthopedic problems of the lower extremities excluding the hips, in meningomyelocele]. / Problèmes orthopédiques concernant les membres inférieurs à l'exclusion des hanches dans les myéloméningocèles.

Four types of problems relating to the lower limbs, hips excluded are reviewed in connection with myelomeningocele. These are essentially deformities and instability. Deformities follow three patterns: prenatal due to uterine pressure on paralyzed limbs, postnatal either postural or secondary to muscular imbalance. Various means of preventing these deformities are exposed. Lower limb stabilization by means of more or less extensive bracing according to the level of the initial lesion is described. Emphasis is put on early weight bearing and gait training in these patients. Problems of skin lesions and of spontaneous fractures are mentioned.

[Lamellar rotation osteotomy of the tibia in children]. / Ostéotomies lamellaires de dérotation du tibia chez l'enfant.

The authors describe the technique and results obtained by a derotation osteotomy of the tibia in children. The method is simple, reliable and does not require internal fixation. It is suitable for dealing with deformity following poliomyelitis, and may also be used to treat tibial torsion which fails to correct with growth in children who are otherwise healthy.

Reduced levels of histidine and urocanic acid in suction blister fluids from patients with psoriasis.

Metabolites of histidine were determined by high performance liquid chromatography in suction blister fluids from lesions and normal appearing skin of patients with psoriasis and from healthy subjects. There was a significant decrease in the levels of histidine and urocanic acid in the samples obtained from patients with psoriasis as compared to healthy subjects. Virtually only the E-isomer of urocanic acid was detected.

Differential thermal analysis of human sebum as a new approach to rheological behaviour.

Synopsis The oily aspect of a hair is not only the consequence of an excessive lipidic production on the scalp; the quality of the fatty mixture should also be considered. Differential scanning calorimetry (DSC) is a useful tool for qualitative examination of human sebum. The melting curves recorded using this technique characterise the seborrhoeic state of the subject, their profile being related to the clinical appreciation. Data from DSC are correlated with other physico-chemical characteristics of sebum, especially with the proportion of unsaturated fatty acids in the whole fatty acids fraction. The straight chain monoenic acids have been more closely examined. A number of positional isomers can be seen; the distribution of the C(18) isomers varies according to the seborrhoeic state of the subject.