A pilot study of the modulation of sirtuins on arylamine -acetyltransferase 1 and 2 enzymatic activity

Arylamine -acetyltransferase (NAT; E.C. 2.3.1.5) enzymes are responsible for the biotransformation of several arylamine and hydrazine drugs by acetylation. In this process, the acetyl group transferred to the acceptor substrate produces NAT deacetylation and, in consequence, it is susceptible of degradation. Sirtuins are protein deacetylases, dependent on nicotine adenine dinucleotide, which perform post-translational modifications on cytosolic proteins. To explore possible sirtuin participation in the enzymatic activity of arylamine NATs, the expression levels of NAT1, NAT2, SIRT1 and SIRT6 in peripheral blood mononuclear cells (PBMC) from healthy subjects were examined by flow cytometry and Western blot. The activity of the sirtuins on NAT enzymatic activity was analyzed by HPLC, in the presence or absence of an agonist (resveratrol) and inhibitor (nicotinamide) of sirtuins. We detected a higher percentage of positive cells for NAT2 in comparison with NAT1, and higher numbers of SIRT1+ cells compared to SIRT6 in lymphocytes. NAT2 activity in the presence of NAM inhibitors was higher than in the presence of its substrate, but not in the presence of resveratrol. In contrast, the activity of NAT1 was not affected by sirtuins. These results showed that NAT2 activity might be modified by sirtuins.

The relationship of pancreatic exocrine function with the staging and the size of tumor in the patients with pancreatic cancer / 中华胰腺病杂志

Objective To investigate the relationship of pancreatic exocrine function with the pancreatic cancer staging and the size of tumor. Methods N-benzoyl-tryrosyl para-aminobenzoic acid (NBT- PABA) test was used to measure the pancreatic exocrine function of 39 pancreatic cancer patients, 46 chronic pancreatitis patients and 20 normal subjects. In pancreatic cancer group, the relationship of pancreatic exocrine function with the size of tumor (TS) and JPS classification (T factor) was analysed. Results The rate of NBT-PABA excretion in normal subjects, chronic pancreatitis patients were (78.9±15.9)%, (58.6± 19.3)%, respectively; in mild, moderate, severe chronic pancreatitis patients, the values of NBT-PABA were (75.5±23.6)%, (57.9±21.5)%, (45.5±16.7)% ; respectively. The rate of NBT-PABA excretion in pancreatic cancer patients was (47.6±18.3)%, and the rate of NBT-PABA excretion in patients with T3+T4 stage was (42.2±21.70%, and was obviously less than (64.8±11.2)% of T1+T2 stage (P<0.05). Tthe rate of NBT-PABA excretion in patients with TS3+TS4 was (34.8±17.2)%, and was significantly lower than (55.6±23.5)% of TS1+TS2(P<0.05). The rate of NBT-PABA excretion in patients with pancreatic head cancer was (42.5±16.4)%, which was significantly lower than (71.8±9.6)% of the pancreatic body and tail (P<0.05). In the 33 patients with pancreatic head cancer, the rate of NBT-PABA excretion in patients with main pancreatic duct stricture was (54.2±14.1) %, which was significantly higher than (37.6± 14.1)% of patients with main pancreatic duct interruption (P<0.05). There was no significant difference in pancreatic exocrine function between pancreatic cancer and moderate or severe chronic pancreatitis.Conclusions The pancreatic exocrine function was related to the pancreatic cancer staging and the size of tumor to some degree,but it was affected by mass location,and it was also affected by degrees of the pancreatic duct obstruction. The pancreatic exocrine function can not be used to differentiate pancreatic cancer from moderate or severe chronic pancreatitis.

Clinical application of fecal elastase test in patients with pancreatic disease / 中华消化杂志

Objective To evaluate the clinical application of fecal elastase test in exocrine insufficiency of pancreatic disease. Methods The fecal elastase 1 was detected by ELISA method in 55 patients with chronic pancreatitis, 21 with pancreatic cancer and 25 with nonpancreatic digestive disease, and the urine BT PABA was measured by DACA method simultaneously. Results The fecal elastase 1 and urine BT PABA excretion in patients with chronic pancreatitis and pancreatic cancer were much lower than those in patients with nonpancreatic disease ( P

CLINICAL APPLICATION OF FECAL ELASTASE TEST IN PATIENTS WITH CHRONIC PANCREATITIS / 解放军医学杂志

The aim of this study was to evaluate the clinical application of fecal elastase test in exocrine insufficiency of chronic pancreatitic patieats. The fecal elastase 1 was detected by ELISA method in 55 cases with chronic pancreatitis(CP) and 25 cases with nonpancreatic digestive disease, and the urine BT PABA was measured by DACA method simultaniously.The results showed that the fecal elastase 1 and urine BT PABA excretion in patients with CP were much lower than those in patients with nonpancreatic disease ( P

Comparative study of bentiromide test and endoscopic retrograde pancreatography in patients with chronic pancreatitis

We performed a bentiromide test in 25 patients with chronic pancreatitis and 7 normal controls to evaluate pancreatic exocrine function, and compared the test results of patients with their endoscopic retrograde pancreatography(ERP) findings. The cumulative 6-hour recovery rate of para-aminobenzoic acid(PABA) in the urine was significantly lower in patients with chronic pancreatitis(55.8 +/- 24.2%) than in controls(82.0 +/- 10.0%). Among 25 patients with chronic pancreatitis, however, 7 patients showed normal recovery rates of PABA. Pancreatograms of the patients represented 4 mild changes, 5 moderate changes, and 16 marked changes. The average 6-hour recovery rates of PABA of the groups were 56.9 +/- 21.6%, 78.4 +/- 10.5%, and 47.2 +/- 23.7%, respectively. Urinary PABA recovery rates were found subnormal as follows: 3(75%) in the mild changes group; 1(20%) in the moderate changes group; and 14(87.5%) in the marked changes group. We found hardly any correlation between the degree of functional impairment and the changes noted by ERP. These findings suggest that both the pancreatic function test and morphologic study are required to evaluate the degree of functional impairment in patients with chronic pancreatitis.

The Effect of Various Topical Agents on Sunburn Cell Formation by Ultraviolet Irradiation / 대한피부과학회지

BACKGROUND: The sunburn cell is an abnormal keratinocyte of the skin induced by ultraviolet (UV) irradiation, and is used as an indicator of cell damage. The sunburn cell is consideredas an apoptotic cell which has been caused by UV irradiation, and many studies have been performed to understand the mechanism of photodamage in relation to apoptosis. The mechanism of photodamage by UV irradiation is still unclear. However, it is suggested that oxygen stress by reactive oxygen species produced by the UV rays may play an important role. OBJECTIVE: This study was a med at evaluating whether various antioxidants and sunscreen can prevent sunburn cell formation. In addition, we studied whether or not the sunburn cell is identical to an apoptotic cell stained using the TUNEL method. METHODS: White mice (ICR strain) were used to test the potency of various topical agents which are used in the prevention of sunburn cell formation; the agents were various antioxidants of L-ascorbic acid, tocopherol, catalase, a reduced form of glutathione (GSH), and sunscreen PABA (para-amino benzoic acid). Each agent was topically applied daily for 5 consecutive days on the dorsal skin of the ears. 300 mJ/cm of UV-B was irradiated on the ears 30 mins after the final applicaion, and skin samples were taken 24 hrs after that. The sunburn cells in the H & E stain were counted per 1 mm under the microscope. Also, the same sections for the sunburn cell study were stained by the TUNEL method using the ApopTag In Situ Apoptosis Detection Kit (Oncor, Inc.). RESULTS: The number of sunburn cells increased in a UV-B dosage-dependent. manner up to 300 mJ/cm2. The potency in the reduction of sunburn cell formation was as follows in order,PABA (0.37 +/- 0,5), GSH (0.87 +/- 0.5), ascorbic acid (1.62 +/- 0.85) and tocopherol (1.75 +/- 1.12). However catalase (2.93 +/- 1.56) did not show any protective effect. Also, the finding that sunburn cells were the same as TUNEL-positive cells confirmed the notion that the sunburn cell is a kind of apototic cell. CONCLUSION: A sunburn cell is a kind of apoptotic cell that may be caused by reactive oxygen species induced by UV-B irradiation, in view of the fact that sunburn cell formation was inhibited by the topical application of various antioxidants. But the result that physical protection by PABA has the most potent protective effect in relation to sun damage suggests that protection using a combined physical and biochemical approach is important in the development of new topical agents which will inhibit sundamage to the skin.

An Evaluation of Sunscreen Efficacy Using Mouse Ear Swelling Reaction / 대한피부과학회지

This study was undertaken to investigate the efficacy of 5% PABA cream using mouse ear swelling reaction(ESR). Mice were exposed to 100mJ/cm of UVB, five times a week for four weeks, on the both ventral aspect of the ear, with application of 5% PABA cream on the right ear. The results were as follows : 1. The intensity of ear swelling reaction of 5% PABA protected group was reduced greater than unproteeted group after the first 3 days of UUR. 2. The intensity of ear swelling reached at peak after 1 week of the ultraviolet radiation. Thereafter it has decreased gradually the following 4 weeks. The difference of ear swelling between the two groups was the greatest after 1 week, and the sunscreening efficacy of 5% PABA cream has remained persisted for 4 weeks. 3. The number of mice which have shown severe inflarnmatory response after ultravioiet radiation was more in unprotected group than that in 5% PABA protected group. 4. Determination of mouse ESR is considered a good method for the evaluation of longterm efficacy of sunscreen preparation.