Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome associated with anticonvulsant drugs is a rare but potentially life-threatening disease that occurs in response to arene oxide producing anticonvulsant such as phenytoin and carbamazepine. There have been many reports of cross reactivity among the anticonvulsants upon first exposure to the offending drugs. However, there has been few data describing the development of DRESS syndrome after switching medication from previously well-tolerated phenytoin to carbamazepine, and the induction of hypersensitivity to phenytoin by DRESS to carbamazepine. We experienced a case of a 40-yr-old man who had uncontrolled seizure that led to the change of medication from the long-term used phenytoin to carbamazepine. He developed DRESS syndrome after changing the drugs. We stopped carbamazepine and restored phenytoin for seizure control, but his clinical manifestations progressively worsened and he recovered only when both drugs were discontinued. Patch tests with several anticonvulsants showed positive reactions to both carbamazepine and phenytoin. Our case suggests that hypersensitivity to a previously tolerated anticonvulsant can be induced by DRESS to another anticonvulsant, and that the patch test may be a useful method for detecting cross-reactive drugs in anticonvulsant-associated DRESS syndrome.
Syndrome ; Skin/drug effects/immunology/pathology ; Phenytoin/immunology ; Male ; Humans ; Drug Hypersensitivity/*immunology ; Drug Eruptions/etiology/*immunology ; Carbamazepine/*adverse effects ; Anticonvulsants/adverse effects ; Adult

PURPOSE: Cutaneous lymphocyte-associated antigen (CLA)-expressing CD8+T cells have been known to play an important role in the pathogenesis of atopic dermatitis (AD). However, the mechanisms underlying the loss of self-tolerance remain unclear. Regulatory T cells (Tregs) play a key role in the development of homeostasis in the immune system. We, therefore, hypothesized that a reduced ability of Tregs to inhibit autologous CD8+CLA+T cells might be underlying mechanism in AD. MATERIALS AND METHODS: CD8+CLA+T cells and Tregs were obtained from the peripheral blood of AD patients and control volunteers. The frequencies of CD8+CLA+T cells were evaluated. The proliferative responses of CD8+CLA+T cells were assessed by flow cytometry, and the levels of transforming growth factor-beta1 (TGF-beta1) and interleukin-10 (IL-10) in culture supernatants were detected by enzyme-linked immunosorbent assay. RESULTS: Our results revealed higher frequency and increased expression of perforin and granzyme-B in peripheral CD8+CLA+T cells in AD, and lower inhibitory ability of Tregs on proliferation of CD8+CLA+T cells in AD. Meanwhile, the levels of TGF-beta1 produced by Tregs were significantly lower in AD, and anti-TGF-beta1 abolished such suppression. CONCLUSION: The attenuated inhibitory ability of Tregs on hyper-activated autologous CD8+CLA+T cells, mediated by TGF-beta1, plays an important role in the pathogenesis of AD.
Adult ; Aged ; CD8-Positive T-Lymphocytes/drug effects/*immunology ; Case-Control Studies ; Cell Proliferation ; Cell Separation ; Dermatitis, Atopic/*immunology/pathology ; Female ; Granzymes/metabolism ; Humans ; Interleukin-10/metabolism ; Lymphocyte Count ; Male ; Perforin/metabolism ; Skin/*immunology/pathology ; T-Lymphocytes, Cytotoxic/drug effects/immunology ; T-Lymphocytes, Regulatory/drug effects/*immunology ; Transforming Growth Factor beta1/pharmacology

Innate elastase inhibitors are known to be putatively involved in the regulation of tissue inflammation by inhibiting polymorphonuclear leukocyte (PMN) derived proteinases. The aim of this study was to evaluate affects of leukocyte elastase suppression and PMN infiltration on wound healing in mouse by administering the recombinant elastase inhibitor guamerin (rEIG) in two different wound models; 1) impaired pin-punctured dorsal mucosa of anterior tongue wound, 60 mice, treated with saline containing rEIG that were fed ad libitum and 2) stable linear excisional cutaneous wound, 40 mice, covered with fibrin sealant containing rEIG. The progress of healing was analyzed by histological methods. The tongue wounds treated with rEIG became edematous around the pin-punctured tongue wound, and influx of inflammatory cells and PMN into the underlying stromal tissue were seen rapidly after wounding and peaked between 2-4 days. Whereas the control mice showed almost no wheal formation in the pin-punctured wound, a far lesser levels of PMN infiltration, and almost complete wound closure in 4 days. In the other model, the liner excisional cutaneous wound treated with fibrin sealant containing rEIG showed early wound constriction, lesser degree of inflammatory cells influx, and complete reepithelialization in 4-5 days, whereas the wound of control mice with the fibrin sealant alone showed contrary delayed reepithelialization, greater degree of inflammatory cell infiltration, and consequencial formation of greater granulation tissue at wound site. Taken together, these data suggest paradoxical effects of rEIG on the wound healing where in the wound exposed to infiltrating milieu of microorganisms in the oral cavity, the rEIG aggravates the wound healing by interfering with other innate defensive factors and extended greater flux of PMNs to inflamed wound site, while in the wound enclosed by fibrin, the rEIG accelerated wound healing by inhibiting the inflammation-generated proteases and the acute inflammatory reaction.
Animals ; Enzyme Inhibitors/*pharmacology ; Female ; Fibrin Tissue Adhesive/pharmacology ; Invertebrate Hormones/analysis/pharmacokinetics/*pharmacology ; Leukocyte Elastase/*antagonists & inhibitors ; Macrophages/immunology ; Mice ; Research Support, Non-U.S. Gov't ; Skin/drug effects/*injuries/pathology ; Tongue/drug effects/*injuries/pathology ; Wound Healing/*drug effects

Cutaneous nocardiosis, which usually manifests in the form of pustules, abscesses, or subcutaneous nodules, is occasionally found in immunocompromised patients. A 59-yr-old Korean man with myasthenia gravis and thymoma developed nodular skin lesions on his trunk. Histopathologically, abscess formation with a dense infiltrate of neutrophils and many cytophagic histiocytes were observed. Numerous filamentous organisms, which turned out to be Nocardia asteroides by culture, were also found. After sulfamethoxazole-trimethoprim therapy, all of the skin lesions rapidly decreased in size, with a marked diminution of the number of cytophagic histiocytes, and cleared up within four months. On reporting a case of cutaneous nocardiosis showing unusual histopathologic findings, we considered that reactive conditions should be included in the differential diagnosis of the cutaneous cytophagocytosis, and that nocardiosis could be one of the diseases showing reactive cytophagocytosis.
Anti-Bacterial Agents/therapeutic use ; Histiocytes/*immunology ; Humans ; Male ; Middle Aged ; Myasthenia Gravis/complications ; Neutrophils/*immunology ; Nocardia Infections/drug therapy/*immunology/microbiology/pathology ; Nocardia asteroides/drug effects/*immunology/isolation & purification ; Phagocytosis/*immunology ; Skin Diseases, Bacterial/drug therapy/*immunology/microbiology/pathology ; Thymoma/complications ; Thymus Neoplasms/complications ; Treatment Outcome ; Trimethoprim-Sulfamethoxazole Combination/therapeutic use

OBJECTIVETo study the anti-tumor and immunity activity of toad coat (Chantui), which is a new officinal part of Bufo bufo gargarizans.

METHODThe tumor weight of S180, H22, Lewis lung cancer cell inoculated in mice were compared between the groups of mice, fed with toad coat, and those which were not (control group). The average longevity of the mice with HCA fed with toad coat was also compared with the control group. The T lymphocyte transformation and NK cell killing activity were tested and compared with the control group. The condition of the mice which were fed with great dosage of Chantui (16 g x kg(-1) x d(-1)) was observed.

RESULTThe tumor weight was remarkably reduced in the groups which were fed with toad coat compared with the control group. Tests show that toad coat can raise the activity of both T lymphocyte and NK cell. There was no obvious side-effect when the mice were fed with great dosage of toad coat.

CONCLUSIONThe results show that toad coat has a strong inhibitory activity against tumors inoculated in mice and a strong enhancement of immune activity, so it could be viewed as a new valuable safe medicinal source.

Animals ; Antineoplastic Agents ; administration & dosage ; Bufo bufo ; Cell Line, Tumor ; Female ; Killer Cells, Natural ; immunology ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasms ; drug therapy ; immunology ; pathology ; Random Allocation ; Skin ; chemistry ; T-Lymphocytes ; immunology ; Tumor Burden ; drug effects

We examined the effect of class II transactivator (CIITA) down-modulation on allograft rejection. To inhibit the function of CIITA, we constructed a series of CIITA mutants and found one exhibiting the dominant-negative effect on the regulation of major histocompatibility complex (MHC) class II expression. To test whether the CIITA dominant-negative mutant reduces immunogenecity, CIITA-transfected melanoma cells were injected into allogeneic host and assessed for immune evading activity against host immune cells. We demonstrated that the CIITA dominant-negative mutant allowed tumor nodules to develop earlier in the lung than control by this tumor challenge study. Furthermore, skin grafts deficient for CIITA also survived longer than wild-type in allogeneic hosts. Both the tumor challenge and skin graft studies suggest the inhibition of CIITA molecules in donor tissue would be beneficial to the control of allo-response.
Transplantation, Homologous ; Transfection ; Trans-Activators/genetics/*immunology/metabolism ; Trans-Activation (Genetics)/genetics/immunology ; Skin Transplantation ; Nuclear Proteins/genetics/*immunology/metabolism ; Mutation ; Mice, Transgenic ; Mice, Knockout ; Mice, Inbred C57BL ; Mice, Inbred BALB C ; Mice ; Melanoma, Experimental/genetics/immunology/pathology ; Male ; Interferon Type II/pharmacology ; Humans ; Histocompatibility Antigens Class II/genetics/*immunology/metabolism ; Graft Survival/genetics/immunology ; Graft Rejection/genetics/*immunology ; Genes, MHC Class II/genetics/immunology ; Flow Cytometry ; DNA, Complementary/genetics ; Cell Proliferation/drug effects ; Cell Line, Tumor ; Animals

This study investigated whether trinitroglycerine (TNG) as nitric oxide (NO) releasing agent had anti-leishmanial effects and mediated pathology in BALB/c mice infected with Leishmania major. Cutaneous leishmaniasis (CL), a zoonotic infection caused by leishmania protozoa is still one of the health problems in the world and in Iran. NO is involved in host immune responses against intracellular L. major, and leishmania killing by macrophages is mediated by this substance. Moreover, application of CL treatment with NO-donors has been recently indicated. In our study, TNG was used for its ability to increase NO and to modify CL infection in mice, in order to evaluate NO effects on lesion size and formation, parasite proliferation inside macrophages, amastigote visceralization in target organs, and NO induction in plasma and organ suspensions. Data obtained in this study indicated that TNG increased plasma and liver-NO, reduced lesion sizes, removed amastigotes from lesions, livers, spleens, and lymph nodes, declined proliferation of amastigotes, hepatomegaly, and increased survival rate. However, TNG reduced spleen-NO and had no significant effects on spelenomegaly. The results show that TNG therapy reduced leishmaniasis and pathology in association with raised NO levels. TNG had some antiparasitic activity by reduction of positive smears from lesions, livers, spleens, and lymph nodes, which could emphasize the role of TNG to inhibit visceralization of L. major in target organs.
Animal Structures/parasitology ; Animals ; Antiprotozoal Agents/chemistry/*therapeutic use ; Female ; Leishmania major/*drug effects/immunology ; Leishmaniasis, Cutaneous ; Macrophages/parasitology ; Mice ; Mice, Inbred BALB C ; Nitric Oxide/blood/metabolism/*pharmacology ; Nitroglycerin/*analogs & derivatives/*therapeutic use ; Severity of Illness Index ; Skin/pathology ; Survival Analysis