Probing structure-function relationships of serine hydrolases and proteases with carbamate and thiocarbamate inhibitors.

Benzene-1,3-di-N-n-octylcarbamate (1), benzene-1-hydroxyl-3-N-n-octylcarbamate (2), benzene-1,3-di-N-n-ocztylthiocarbamate (3), and benzene-1-hydroxyl-3-N-n-octylthiocarbamate (4) are synthesized from 1,3-benzene-diol and are characterized as the pseudo-substrate inhibitors of acetylcholinesterase, butyrylcholinesterase, cholesterol esterase, lipase, trypsin, and chymotrypsin. For these six enzyme inhibitions by 1-4, the pKi values are linearly correlated with their log ki values - Brønsted plots. Therefore, 1-4 inhibit these enzymes through a common mechanism. Moreover, both pKi and log ki values for the inhibitions by 1,3, and 4 are linearly correlated with both pKi and log ki values for the inhibitions by 2, respectively. Thus, the pKi values for the inhibitions by 2 are defined as the nucleophilicity constants of these enzymes (nenzyme). The log k2 values for the inhibitions by 1-4 are also linearly correlated with the nenzyme values. Therefore, the nucleophilicity for serine hydrolases and proteases toward 1-4 also applies the Swain-Scott correlations.

[The factors of diagnosis and treatment delay in the late stage of cancers in pharynx, larynx and oral cavity].

Cancers of pharynx, larynx and oral cavity (CPLOC) are the tumors can be easily found by patients themselves. Unfortunately, the diagnosis and treatment delay in CPLOC is very severe in our country. The study was based on the data collected through questionnaire from 100 patients with CPLOC in late stages. The causes of diagnosis and treatment delay in those patients were evaluated. The study reveals that traffic and financial difficulties are not the principal factors causing the delay. Instead, limited knowledge which the patients learned from television and newspapers, and sometimes bias cancer knowledge play major role in the delay. When the symptoms developed, 64% of the patients either did not pay attention to their symptoms, or took some improper medical treatments according to their own diagnosis. It took them 207 days on average from having the symptoms to consulting a doctor, about 108 days on average from consulting a doctor to getting a right suggestion. The latter delay was often caused by ambiguous and improper suggestion from doctors. However, if a patient receives a proper suggestion from a doctor, the major reason for diagnosis delay was that patients felt their symptoms were not severe or the examinations required too much time. Even if patients were confirmed to have cancer, treatment delay is still not avoidable as they often turned to Chinese herb doctors, took herb drugs, or feared of receiving an operation. Therefore, the best way of reducing treatment delay in CPLOC is to enhance medical knowledge and education, and to correct the image that traditional Chinese herbs are effective in curing CPLOC.