THE IN VITRO PENETRATION OF FLUOCINONIDE THROUGH HUMAN SKIN FROM DIFFERENT VOLUMES OF DMSO

Summary.— The penetration of fluocinonide from solution in DMSO across human abdominal skin in vitro has been examined. Different volumes of solution, ranging from 0.025 ml to 0.75 ml, were studied.
The results show that better penetration is achieved in this in vitro situation from smaller volumes than from larger volumes. Possible mechanisms that might account for this phenomenon are discussed. A possible explanation considers that the flux of water into the DMSO solution causes an increase in the thermodynamic activity of the drug and hence in the penetration rate of the drug into and through the skin.     

A Murine Model of Genetic Susceptibility to Lead Bioaccumulation

Previous reports have shown that blood lead levels in humansare associated with a polymorphic form of -aminolevulinate dehydratase(ALAD), an enzyme of heme biosynthesis that binds and is inhibitedby lead. We hypothesized that ALAD levels may influence thedistribution and accumulation of lead in the blood and targetorgans. To assess this, we studied strains of mice that differin the numbers of copies of the ALAD gene. Our findings showedthat mice with a duplication of the ALAD gene (DBA) accumulatedtwice the amount of lead in their blood and had higher leadlevels in kidney and liver than mice with a single copy of thegene (C57) exposed to the same oral doses of lead during adulthood.Hybrid animals showed intermediate blood lead levels. Levelsof blood zinc protoporphyrin (ZPP) increased with lead exposurein C57 animals while they were not affected in DBA mice, suggestingprotection from production of this abnormal enzyme in mice witha duplication of the gene. Except for these protective effectsin the formation of ZPP in DBA animals, duplication of the ALADgene was found to increase lead accumulation. We conclude thatalthough these mouse strains do not precisely replicate thepolymorphism observed in humans, they may be used as a modelto study genetic influences in lead bioaccumulation. Understandinggenetic factors that affect susceptibility to lead-induced intoxicationcould have important implications for public health and interventioninitiatives. These mouse strains may represent a useful modelfor future study of the role of ALAD in lead intoxication.     

SYSTEMIC LUPUS ERYTHEMATOSUS AND RIGHT RECURRENT LARYNGEAL NERVE PALSY

A 52-year-old woman presenting with systemic lupus erythematosus(SLE) and a right recurrent laryngeal nerve palsy is described.The symptoms and signs resolved within days of initiating steroidtherapy. This is the first reported case of recurrent laryngealnerve palsy associated with SLE in the absence of pulmonaryhypertension or laryngeal lupus. KEY WORDS: Laryngeal nerve palsy, Systemic lupus erythematosus     

RAPID DEVELOPMENT OF CEREBRAL ATROPHY IN SYSTEMIC LUPUS ERYTHEMATOSUS

A 21-year-old female is described who developed severe cerebrallupus 9 months after the onset of her disease. A dramatic changein her CT brain scan from normal to gross cerebral atrophy wasobserved in the month following onset of her cerebral disease. This patient developed hepatitis during the course of her hospitalization.This is an unusual manifestation of systemic lupus. The patient'sserum also contained anti-Sm antibodies. This is a relativelyinfrequent finding in the serum of lupus patients outside theUnited States. KEY WORDS: Systemic lupus erythematosus, Cerebral disease, Sm antibodies     

Immune Disturbances in Treatment-Resistant Depression: Modulation by Antidepressive Treatments

Recently, there were some reports that major depression is accompanied by significant alterations in the percentage and number of peripheral blood mononuclear cells (PBMCs), such as increased number of CD4⁺ T cells, B cells (e.g. CD19⁺, CD21⁺), number of leukocytes, monocytes and neutrophils and an increased CD4⁺/CD8⁺ T-cell ratio. The aims of the present study were to examine the number and percentage of PBMCs in major and treatment-resistant depressed (TRD) patients and the effects of antidepressant treatments on those PBMCs. Major depression was characterized by a significantly higher number of leukocytes and CD4⁺ T-cells, a higher percentage of CD2⁺ T cells and CD4⁺ T cells, and a higher CD4⁺/CD8⁺ T-cell ratio than normal controls. Patients with TRD had a significantly higher percentage of CD4⁺ T cells and CD4⁺/CD8⁺ T-cell ratio, and a significantly lower percentage of CD8⁺ T cells than non-TRD patients and normal controls. There were significant negative correlations between the length of the index episode or duration of illness and number or percentage of monocytes. Subchronic treatment with antidepressants significantly reduced the number of leukocytes and neutrophils, but had no effect either on the absolute number of the other PBMCs or on the CD4⁺/CD8⁺ T-cell ratio. The results suggest that (i) the higher CD4⁺/CD8⁺ T-cell ratio in major depression is a trait marker of that illness and of treatment resistance; (ii) the increased numbers of leukocytes and neutrophils are state markers of depression and are reduced by ‘subchronic’ antidepressant therapy; (iii) the number and percentage of monocytes decrease with respect to duration of illness and length of the index depressive episode. © 1997 by John Wiley & Sons, Ltd.     

Influence of biofilm formation in the susceptibility of Pseudomonas aeruginosa from Brazilian patients with cystic fibrosis

Ferreira AG, Leão RS, Carvalho‐Assef APD, Folescu TW, Barth AL, Marques EA. Influence of biofilm formation in the susceptibility of Pseudomonas aeruginosa from Brazilian patients with cystic fibrosis. APMIS 2010; 118: 606–12. Biofilms play a key role in the occurrence of lung infections by Pseudomonas aeruginosa in patients with cystic fibrosis (CF). In this study, we examined 40 isolates of P. aeruginosa from CF patients according to their capacity to form biofilm. We also compared their in vitro response to antimicrobials according to different modes of growth (planktonic vs biofilm) and performed molecular typing. All isolates proved capable of forming biofilm. However, there was no difference in biofilm development according to the mucoid and nonmucoid phenotypes and among isolates obtained at different periods of the chronic infection. All isolates tested for antimicrobial susceptibility in the biofilm state (BIC) were consistently more resistant to antibiotics than the same isolate tested in the planktonic state. The molecular typing indicates a considerable clonal diversity among isolates. We identified five patients harboring the same strain over different periods. These strains, however, displayed different levels of biofilm formation and BIC values for antibiotics tested. The results of the present study demonstrate that there is a marked difference in the susceptibility profile according to the mode of growth of CF P. aeruginosa, as cells tested in the biofilm state proved consistently more resistant to antibiotics.