Delayed hypersensitivity reaction resulting in maculopapular-type eruption due to entecavir in the treatment of chronic hepatitis B

Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare, for cutaneous ADRs associated with ETV treatment.

Immunosuppressive Activities of Fucoidan from Laminaria japonica

Effects of fucoidan from Laminaria japonica on 2,4 dinitrochlorobenzene induced delayed type hypersensitivity (DTH) reaction and the serum levels of IgG, IgM, complement C3 and C4 were investigated in the present study. Results showed that oral administration of fucoidan at dose of 150 and 300 mg/(kg·d) for 9 days before the hapten challenge significantly inhibited 2,4 dinitrochlorobenzene induced delayed type hypersensitivity reaction; and also inhibited the humoral immunity. Serum C3 and C4 levels were markedly reduced by fucoidan at dose of 150 and 300 mg/kg; and serum IgG and IgM levels were reduced by fucoidan at dose of 300 mg/kg. The inhibitory effects of fucoidan on delayed type hypersensitivity suggested that it may be potential medication for chronic inflammatory diseases in the future.

Reduced capacity of dendritic cells from trauma-hemorrhage mice in initiating delayed-type hypersensitivity to fluorescein isothiocyanate

Objective： To study the role of dendritic cells （DCs） in initiating delayed-type hypersensitivity （DTH） to fluores- cein isothiocyanate （FITC） after trauma-hemorrhage in mice. Methods： Inbred BALB/c mice （6-8 weeks old, male） were epicutaneously sensitized with FITC 12 hours, 1 day, 2 days, 4 days and 7 days after closed bilateral femur fractures combined with hemorrhage. And 5 days after sensitization, DTH was evaluated by ear swelling after a challenge of FITC. Draining lymph node cells were examined for the percentages of FITC-positive cells, cluster of differentiation （CD）11c positive cells and major histocom- patibility complex II （MHC II）-positive cells by means of flow cytometry. In vitro proliferative responses of syngeneic lymphocytes and in vivo passive transfer of DTH to naive recipients induced by isolated DCs from the draining lymph nodes were determined. Results： The time of DTH to FITC decreased more significantly in the mice with trauma-hemorrhage （12 hours to 4 days） than in the mice with sham injury. After sensitization, the relative percentages of FITC^＋ cells, FITC^＋/ CD 11c^＋ cells and FITC^＋/CD 11c^＋/MHC II^＋ cells from the draining lymph nodes were all significantly reduced following injury. And the capacity of DCs from the draining lymph nodes in stimulating proliferative responses of lymphocytes and transferring DTH to naive recipients were also inhibited after injury. Conclusions： Trauma-hemorrhage induces repressive DTH in mice, which may be attributed, at least partially, to the reduced trafficking of DCs into the draining lymph nodes and insufficient maturation during DC migration.

Global Exponential Convergence of Neutral Type Competitive Neural Networks with D Operator and Mixed Delay

The models of competitive neural network(CNN)was in recent past proposed to describe the dynamics of cortical cognitive maps with unsupervised synaptic modifications,where there are two types of memories:Long-term memories(LTM)and short-term memories(STM),LTM presents unsupervised and slow synaptic modifications and STM characterize the fast neural activity.This paper is concerned with a class of neutral type CNN’s with mixed delay and D operator.By employing the appropriate differential inequality theory,some sufficient conditions are given to ensure that all solutions of the model converge exponentially to zero vector.Finally,an illustrative example is also given at the end of this paper to show the effectiveness of the proposed results.

Monoclonal anti-idiotype antibody bearing the internal image of nasopharyngeal carcinoma associated antigen

Objective To generate and characterize anti-idiotypic monoclonal antibody (Ab2) that bears the internal image of nasopharyngeal carcinoma (NPC) associated antigen. Methods Using NPC monoclonal antibody (Ab1) as immunogen, hybridoma cells were obtained by fusion of SP2/0 myeloma cells with immunized murine spleen cells. Positive clones were screened by Sandwich ELISA and a binding inhibition test. To determine whether Ab2 possess the internal image of the original antigen or not, mice were immunized with Ab2. ELISA and the competitive inhibition assay tested anti-anti-idiotypic antibodies (Ab3) in anti-sera. Cell-mediated immunity to tumors induced by Ab2 was investigated by a delayed-type hypersensitivity response and the mouse T-cell proliferation assay. Results Anti-idiotypic monoclonal antibodies against the monoclonal anti-NPC antibodies FC2 and HNL5 were generated that recognize NPC associated antigens. These Ab2, which were designated 2H4 and 5D3, could inhibit the binding of FC2 or HNL5 to NPC cell lines. Anti-sera from the immunized mice, which contained Ab3, could compete with FC2 or HNL5 for binding with NPC cell by a competitive inhibition assay. Mice immunized with 2H4 or 5D3 coupled with keyhole limpet hemocyanin (KLH), showed a positive and specific delayed-type hypersensitivity (DTH) reaction after stimulation by NPC cells. The mouse T cell proliferative assay indicated that there was a significantly higher proliferative response of the splenocytes in the experimental groups than that in control groups. Conclusions Anti-idiotypic antibodies 2H4 and 5D3 are Ab2 beta bearing the internal image of the epitope of NPC associated antigen. Either 2H4 or 5D3 expressing three-dimensional shapes that resemble the structure of natural antigens could induce humoral and cellular immune response.

On generalized impulsive piecewise constant delay differential equations

A variation of parameters formula with Green function type and Gronwall type integral inequality are proved for impulsive differential equations involving piecewise constant delay of generalized type. Some results for piecewise constant linear and nonlinear delay differential equations with impulsive effects are obtained.They include existence and uniqueness theorems, a variation of parameters formula, integral inequalities, the oscillation property and some applications.