Drug-Induced Cutaneous Toxicity

The skin is the largest organ in the body and is continually exposed to external stimuli, such as chemical and environmental substances. Cutaneous toxicity can be broadly classified according to the mechanism of onset, namely: contact dermatitis, i.e., damage resulting from contact with a substance (irritant dermatitis, allergic contact dermatitis, chemical burns); photosensitivity, i.e., caused by combined effects of a substance and ultraviolet light (phototoxic dermatitis, photoallergic contact dermatitis); contact urticaria; chemical-induced acne; pigmentary disturbance; drug rash; hair disturbance; nail disturbance; or tumor-induced. This review outlines the function and structure of the skin, outlining characteristics of these types of cutaneous toxicity. In recent years, advances have been made in the development of pharmaceutical products targeting specific molecules or genes and nanotechnology-based pharmaceutical products, raising concerns about the onset of toxicity by novel mechanisms involving new pharmaceutical products. Therefore, it is important to understand the basic toxicity-related changes described herein

N -Ethyl- N -Nitrosourea Induces Retinal Photoreceptor Damage in Adult Rats

Seven-week-old male Lewis rats received a single intraperitoneal injection of N-ethyl-N-nitrosourea (ENU) (100, 200, 400 or 600 mg/kg), and retinal damage was evaluated 7 days after the treatment. Sequential morphological features of the retina and retinal DNA damage, as determined by a TUNEL assay and phospho-histone H2A.X (γ-H2AX), were analyzed 3, 6, 12, 24 and 72 hr, 7 days, and/or 30 days after 400 mg/kg ENU treatment. Activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) was analyzed immunohistochemically by poly (ADP-ribose) (PAR) expression in response to DNA damage of the retina. All rats that received ≥ 400 mg/kg of ENU developed retinal degeneration characterized by the loss of photoreceptor cells in both the central and peripheral retina within 7 days. In the 400 mg/kg ENU-treated rats, TUNEL-positive signals were only located in the photoreceptor cells and peaked 24 hr after ENU treatment. The γ-H2AX signals in inner retinal cells appeared at 24 hr and peaked at 72 hr after ENU treatment, and the PAR signals selectively located in the photoreceptor cell nuclei appeared at 12 hr and peaked at 24 hr after ENU treatment. However, degeneration was restricted to photoreceptor cells, and no degenerative changes in inner retinal cells were seen at any time points. Retinal thickness and the photoreceptor cell ratio in the central and peripheral retina were significantly decreased, and the retinal damage ratio was significantly increased 7 days after ENU treatment. In conclusion, ENU induced retinal degeneration in adult rats that was characterized by photoreceptor cell apoptosis through PARP activity

Early uptake and continuous accumulation of thallium-201 chloride in a benign mixed tumor of soft tissue: Case Report

A case of benign mixed tumor of the soft tissue in a 64-year-old Japanese male is presented. He noticed a painless, elastic hard mass sized 3 cm in the right knee, which gradually grew larger and harder in the last 5 years. Magnetic resonance imaging demonstrated a mass lesion embedded in the subcutaneous tissue with low and high signal intensity at T1- and T2-weighted images, respectively. Tl-201 scintigraphy showed an early uptake of Tl-201 within the lesion at 10 minutes after injection, which was slightly decreased but still continued at 2 hours later. The patient underwent a resection of tumor, and the pathological diagnosis was a benign mixed tumor of soft tissue without high vascularity, characterized by histological features similar to pleomorphic adenomas in the salivary glands. Immunohistochemical study proved expression of Na(+)/K(+)-ATPase of tumor cells. Overexpression of Na(+)/K(+)-ATPase of the tumor might be responsible for the early uptake of Tl-201, and poor vascular structure in this tumor might lead to continuous accumulation. The Tl-201 scintigraphic features of mixed tumor of soft tissue are assessed to resemble those of malignant soft tissue tumors

Assessment of bone healing and hypoesthesia in the upper lip after Le Fort I osteotomy with self-setting α-tricalcium phosphate and absorbable plates

Purpose: The purpose of this study was to evaluate hypoesthesia of the upper lip and bone formation using self-setting α-tricalcium phosphate (Biopex ®) between the segments following Le Fort I osteotomy with bent absorbable plate fixation. Subjects and methods: The subjects were 47 patients (94 sides) who underwent Le Fort I osteotomy with and without mandibular osteotomy. They were divided into a Biopex ® group (48 sides) and a control group (46 sides). The Biopex ® was inserted into the anterior part of the gap between the segments in the Biopex ® group. Trigeminal nerve hypoesthesia at the region of the upper lip was assessed bilaterally by the trigeminal somatosensory-evoked potential (TSEP) method. The area of the Biopex ® at the anterior part in the maxilla was assessed immediately after surgery and 1 year postoperatively by computed tomography (CT). Results: The mean measurable period and standard deviation were 13.2 ± 18.5 weeks in the control group, 14.5 ± 17.9 weeks in the Biopex ® group, and there was no significant difference in TSEP. The area of the Biopex ® after 1 year was significantly smaller than that immediately after surgery (right side: P = 0.0024, left side: P = 0.0001) and bone defects between the segments could not be found in the Biopex ® group. In the control group, although the areas of bone defect after 1 year were significantly smaller than that immediately after surgery on the right side (P = 0.0133) and left side (P = 0.0469) in the frontal view, complete healing of the bone defects could be seen in 12 of 46 sides after 1 year. Conclusion: This study suggested that inserting Biopex ® in the gap between the maxillary segments was useful for new bone formation and it did not prevent the recovery of upper lip hypoesthesia after Le Fort I osteotomy with absorbable plate fixation. © 2012 European Association for Cranio-Maxillo-Facial Surgery

Maxillary stability after Le Fort I osteotomy with self-setting α-tricalcium phosphate and an absorbable plate

The purpose of this study was to compare retrospectively postoperative differences in maxillary stability after Le Fort I osteotomy and fixation with an unsintered hydroxyapatite (u-HA)/poly-l-lactic acid (PLLA) plate with or without self-setting α-tricalcium phosphate (Biopex ®) as interpositional material. Subjects comprised 45 patients diagnosed with mandibular prognathism with maxillary retrognathism and mandibular prognathism with bimaxillary asymmetry. All patients underwent Le Fort I osteotomy and bilateral sagittal split ramus osteotomy with fixation by uHA/PLLA plates. Patients were divided into 4 groups consisting of 9 maxillary impaction cases with Biopex ® (group 1) to fill the gap between the bone segments, 14 maxillary advancement cases with Biopex ® (group 2), 8 maxillary impaction cases without Biopex ® (group 3) and 14 maxillary advancement cases without Biopex ® (group 4). Changes in cepahalometric parameters at time intervals (1, 3 and 12 months) between the groups were compared. Results showed that stability did not depend on the use or otherwise of Biopex ®. © 2012 International Association of Oral and Maxillofacial Surgeons

CIPRO 2.5: Ciona intestinalis protein database, a unique integrated repository of large-scale omics data, bioinformatic analyses and curated annotation, with user rating and reviewing functionality

The Ciona intestinalis protein database (CIPRO) is an integrated protein database for the tunicate species C. intestinalis. The database is unique in two respects: first, because of its phylogenetic position, Ciona is suitable model for understanding vertebrate evolution; and second, the database includes original large-scale transcriptomic and proteomic data. Ciona intestinalis has also been a favorite of developmental biologists. Therefore, large amounts of data exist on its development and morphology, along with a recent genome sequence and gene expression data. The CIPRO database is aimed at collecting those published data as well as providing unique information from unpublished experimental data, such as 3D expression profiling, 2D-PAGE and mass spectrometry-based large-scale analyses at various developmental stages, curated annotation data and various bioinformatic data, to facilitate research in diverse areas, including developmental, comparative and evolutionary biology. For medical and evolutionary research, homologs in humans and major model organisms are intentionally included. The current database is based on a recently developed KH model containing 36 034 unique sequences, but for higher usability it covers 89 683 all known and predicted proteins from all gene models for this species. Of these sequences, more than 10 000 proteins have been manually annotated. Furthermore, to establish a community-supported protein database, these annotations are open to evaluation by users through the CIPRO website. CIPRO 2.5 is freely accessible at http://cipro.ibio.jp/2.5

CIPRO 2.5: Ciona intestinalis Protein integrated database with large-scale omics data, bioinformatic analyses and curated annotation, with ability for user rating and comments

CIPRO database is an integrated protein database for a tunicate species Ciona intestinalis that belongs to the Urochordata. Although the CIPRO database deals with proteomic and transcriptomic data of a single species, the animal is considered unique in the evolutionary tree, representing a possible origin of the vertebrates and is a good model for understanding chordate evolution, including that of humans. Furthermore, C. intestinalis has been one of the favorites of developmental biologists; there exists a huge amount of accumulated knowledge on its development and morphology, in addition to the recent genome sequence and gene expression data. The CIPRO database is aimed at not only collecting published data, but also presenting unique information, including the unpublished transcriptomic and proteomic data and human curated annotation, for the use by researchers in broad research fields of biology and bioinformatics