T-cell-mediated drug hypersensitivity represents a significant proportion of immune mediated drug hypersensitivity reactions. In the recent years, there has been an increase in understanding the immune mechanisms behind T-cell-mediated drug hypersensitivity. According to hapten mechanism, drug specific T-cell response is stimulated by drug-protein conjugate presented on major histocompatibility complex (MHC) as it is presented as a new antigenic determinant. On the other hand, p-i concept suggests that a drug can stimulate T cells via noncovalent direct interaction with T-cell receptor and/or peptide-MHC. The drug binding site is quite variable and this leads to several different mechanisms within p-i concept. Altered peptide repertoire can be regarded as an 'atypical' subset of p-i concept since the mode of the drug binding and the binding site are essentially identical to p-i concept. However, the intracellular binding of abacavir to HLA-B*57:01 additionally results in alteration in peptide repertoire. Furthermore the T-cell response to altered peptide repertoire model is only shown for abacavir and HLA-B*57:01 and therefore it may not be generalised to other drug hypersensitivity. Danger hypothesis has been postulated to play an important role in drug hypersensitivity by providing signal 2 but its experimental data is lacking at this point in time. Furthermore, the recently described allo-immune response suggests that danger signal may be unnecessary. Finally, in view of these new understanding, the classification and the definition of type B adverse drug reaction should be revised.
Binding Sites ; Classification ; Drug Hypersensitivity ; Drug-Related Side Effects and Adverse Reactions ; Hand ; Haptens ; HLA Antigens ; Major Histocompatibility Complex ; Receptors, Antigen, T-Cell ; T-Lymphocytes

Observational studies and laboratory research support cardioprotective effects of menopausal hormone treatment (MHT). However, cardioprotective effects of MHT were not confirmed by randomized clinical studies that were made up of subjects who were well-beyond the time of menopausal symptoms and were of advanced chronological age when they began hormone treatment (HT). The differences in study outcomes most likely reflect age-related differences in cardiovascular risk factors such as hypertension and metabolic syndromes. As well, data from the randomized clinical trial (RCT)s confirmed the presence of actual cardiovascular disease (CVD) in many of the RCT subjects prior to beginning HT. Therefore, beginning MHT early seems crucial since older women are at greater risk for the presence of risk factors and sub-clinical CVD. Older women also are possible targets of hormonally related thrombosis because of their underlying vascular disease. The need for early prophylaxis is convenient since most women seek treatment for symptoms within the first few years of menopause. This review addresses issues regarding optimization of the initiation of MHT for cardioprotection.
Aging ; Atherosclerosis ; Cardiovascular Diseases ; Estrogens ; Female ; Humans ; Hypertension ; Menopause ; Risk Factors ; Thrombosis ; Vascular Diseases

Observational studies and laboratory research support cardioprotective effects of menopausal hormone treatment (MHT). However, cardioprotective effects of MHT were not confirmed by randomized clinical studies that were made up of subjects who were well-beyond the time of menopausal symptoms and were of advanced chronological age when they began hormone treatment (HT). The differences in study outcomes most likely reflect age-related differences in cardiovascular risk factors such as hypertension and metabolic syndromes. As well, data from the randomized clinical trial (RCT)s confirmed the presence of actual cardiovascular disease (CVD) in many of the RCT subjects prior to beginning HT. Therefore, beginning MHT early seems crucial since older women are at greater risk for the presence of risk factors and sub-clinical CVD. Older women also are possible targets of hormonally related thrombosis because of their underlying vascular disease. The need for early prophylaxis is convenient since most women seek treatment for symptoms within the first few years of menopause. This review addresses issues regarding optimization of the initiation of MHT for cardioprotection.
Aging ; Atherosclerosis ; Cardiovascular Diseases ; Estrogens ; Female ; Humans ; Hypertension ; Menopause ; Risk Factors ; Thrombosis ; Vascular Diseases

BACKGROUND/AIMS: To investigate the effects of esomeprazole and rebamipide combination therapy on symptomatic improvement in patients with reflux esophagitis. METHODS: A total of 501 patients with reflux esophagitis were randomized into one of the following two treatment regimens: 40 mg esomeprazole plus 300 mg rebamipide daily (combination therapy group) or 40 mg esomeprazole daily (monotherapy group). We used a symptom questionnaire that evaluated heartburn, acid regurgitation, and four upper gastrointestinal symptoms. The primary efficacy end point was the mean decrease in the total symptom score. RESULTS: The mean decreases in the total symptom score at 4 weeks were estimated to be −18.1±13.8 in the combination therapy group and −15.1±11.9 in the monotherapy group (p=0.011). Changes in reflux symptoms from baseline after 4 weeks of treatment were −8.4±6.6 in the combination therapy group and −6.8±5.9 in the monotherapy group (p=0.009). CONCLUSIONS: Over a 4-week treatment course, esomeprazole and rebamipide combination therapy was more effective in decreasing the symptoms of reflux esophagitis than esomeprazole monotherapy.
Esomeprazole* ; Esophagitis, Peptic* ; Heartburn ; Humans

BACKGROUND/AIMS: To investigate the effects of esomeprazole and rebamipide combination therapy on symptomatic improvement in patients with reflux esophagitis. METHODS: A total of 501 patients with reflux esophagitis were randomized into one of the following two treatment regimens: 40 mg esomeprazole plus 300 mg rebamipide daily (combination therapy group) or 40 mg esomeprazole daily (monotherapy group). We used a symptom questionnaire that evaluated heartburn, acid regurgitation, and four upper gastrointestinal symptoms. The primary efficacy end point was the mean decrease in the total symptom score. RESULTS: The mean decreases in the total symptom score at 4 weeks were estimated to be −18.1±13.8 in the combination therapy group and −15.1±11.9 in the monotherapy group (p=0.011). Changes in reflux symptoms from baseline after 4 weeks of treatment were −8.4±6.6 in the combination therapy group and −6.8±5.9 in the monotherapy group (p=0.009). CONCLUSIONS: Over a 4-week treatment course, esomeprazole and rebamipide combination therapy was more effective in decreasing the symptoms of reflux esophagitis than esomeprazole monotherapy.
Esomeprazole* ; Esophagitis, Peptic* ; Heartburn ; Humans