Dietary Supplements, Isotretinoin, and Liver Toxicity in Adolescents: A Retrospective Case Series.

Isotretinoin is the most effective acne therapy available, but has the potential for a number of adverse side effects, including transaminitis. The iPLEDGE isotretinoin program recommends avoiding some herbals and supplements due to potential side effects. However, little is known about the effects of protein supplements on the liver, particularly in patients taking isotretinoin. We designed a retrospective chart review to evaluate the symptoms, diagnosis, treatment, and outcome of patients on or preparing to take isotretinoin therapy who were concurrently ingesting protein or herbal supplementation and who developed transaminitis. In 100% (8/8) of cases, dietary supplementation was determined to be at least a possible cause of elevated liver transaminases. In 75% (6/8) of cases, dietary supplement appears to be the most likely cause at some point in their evaluation. Most of our patients' elevations in aspartate aminotransferase and/or alanine aminotransferase were likely caused by supplementation with protein, creatine, or herbal extracts, rather than prescribed isotretinoin or tetracycline antibiotics for acne. Hence, dietary supplementation may cause liver function abnormalities. As supplement usage appears common in teenagers, clinicians should consider counseling their patients to avoid these products, particularly when prescribing known hepatotoxic drugs.

Innate immunity and the role of the antimicrobial peptide cathelicidin in inflammatory skin disease.

Cathelicidin antimicrobial peptide is an important mediator of the innate immune response. In addition to its potent antimicrobial activity, cathelicidin has been shown to have chemoattractant and angiogenic properties. Recent research has demonstrated that, in addition to its aforementioned functions, cathelicidin plays an important role in the complex pathogenesis of several chronic inflammatory skin diseases. This review will present a concise overview of the role of cathelicidin in infection and in the development of atopic dermatitis, psoriasis, and rosacea. This understanding will direct future research efforts to identify therapeutic approaches that use cathelicidin as a novel drug itself, or aim to modify its expression and regulation.

Immunochemical characterization of inhibitory mouse cortical neurons: three chemically distinct classes of inhibitory cells.

The cerebral cortex has diverse types of inhibitory neurons. In rat cortex, past research has shown that parvalbumin (PV), somatostatin (SOM), calretinin (CR), and cholecystokinin (CCK) label four distinct chemical classes of GABAergic interneurons. However, in contrast to rat cortex, previous studies indicate that there is significant colocalization of SOM and CR in mouse cortical inhibitory neurons. In the present study we further characterized immunochemical distinctions among mouse inhibitory cortical neurons by double immunochemical labeling with chemical markers. We found that, PV, SOM, and vasointenstinal peptide (VIP) reliably identify three nonoverlapping distinct subpopulations, as there was no overlap of immunoreactivity between PV and all the other chemical markers tested, and SOM and VIP did not show any overlap in labeled neurons in all the cortical areas. In comparison, there was significant overlap in combinations of other chemical markers. With some laminar and regional variations, the average overlap of SOM/CR (percentage of SOM+ cells expressing CR) and SOM/neuropeptide tyrosine (NPY) across all examined layers and cortical regions was 21.6% and 7.1%, respectively. The average overlap of VIP/CR, VIP/NPY, and CR/NPY was 34.2%, 9.5%, and 10%, respectively. We quantified and assessed the percentages of marker-positive GABAergic cells, and showed that the nonoverlapping subpopulations (i.e., PV+, SOM+ and VIP+ cells) accounted for about 60% of the GABAergic cell population. Taken together, our data reveal important chemical distinctions between mouse inhibitory cortical neurons and indicate that PV, SOM, and VIP can differentially label a majority of mouse inhibitory cortical neurons.

Mouse cortical inhibitory neuron type that coexpresses somatostatin and calretinin.

Mammalian cortex contains a diversity of inhibitory neuron types, each with distinct morphological, immunochemical, and/or physiological properties. In rat cortex, chemical markers distinguish at least four distinct and nonoverlapping neuron classes based on expression of parvalbumin (PV), somatostatin (SST), calretinin (CR), and cholecystokinin (CCK). It has generally been assumed that these classifications should also apply to other rodent species. In mouse cortex, however, we found significant colocalization of SST and CR in inhibitory neurons; about 30% of SST-positive cells contained CR, and about 33% of CR-positive cells contained SST across frontal, somatosensory (S1), and visual cortex (V1). The SST and CR colocalized cells were concentrated in layer 2/3. We further characterized morphological and physiological properties of the mouse cortical inhibitory neuron types that express SST by using "GIN" transgenic mice, in which GFP is expressed in a subset of SST inhibitory neurons (see Oliva et al. [2000] J Neurosci 20:3354-3368). Generally, both SST/CR+ cells and SST/CR- cells exhibited morphological features of Martinotti cells as described in rat cortex, and they also had similar accommodating spike-firing patterns. However, they differed significantly in quantitative comparisons of morphology and spike shapes. SST/CR+ cells had more horizontally extended dendritic fields and more primary process than did SST/CR- cells; and SST/CR- cells had narrower action potential widths and faster afterhyperpolarization than did SST/CR+ cells. Thus, our data show an important species difference in the chemical distinction of inhibitory neuron subtypes, and indicate that colocalization of CR in SST cells correlates with different morphological and physiological features.