Diabetes mellitus secondary to pancreatic diseases (type 3c): The effect of smoking on the exocrine-endocrine interactions of the pancreas.

The present study was conducted to ascertain how cigarette smoke affects the exocrine-endocrine interactions of the human pancreas with diabetes mellitus secondary to pancreatic diseases (type 3c). Blood has been collected from smoking and non-smoking healthy individuals as well as from patients with diagnosed chronic pancreatitis and diabetes type 3c. The concentrations of interleukin-6, endothelin-1 and insulin in the plasma were determined by enzyme-linked immunosorbent assay (ELISA) tests. The activities of amylase and lipase in the serum, as well as the lipid profile, creatinine, uric acid and urea concentrations, were measured using colorimetric methods. Samples of normal pancreatic tissue and chronic pancreatitis were verified histopathologically and then interleukin-6, endothelin-1, insulin and glucagon were localized by immunohistochemical staining using a monoclonal anti-human antibody. The highest levels of interleukin-6 and endothelin-1 and the lowest levels of insulin and glucagon intensity from the immunostaining were observed in smoking patients with diabetes. In all smoking patients with pancreatitis and diabetes, there was a significant elevation in interleukin-6 and endothelin-1 concentration and amylase and lipase activities, hyperlipidaemia and a lower value of estimated glomerular filtration rate and blood urea nitrogen when compared to non-smokers. Our study confirmed that smoking exerts a pro-inflammatory effect and disturbs the exocrine-endocrine interactions of the pancreas.

The effect of smoking on endothelin-1 in patients with chronic pancreatitis.

The aim of this study is to prove the influence of tobacco smoking on the endothelin-1 (ET-1) level in the plasma and on the immunohistochemical localization in the pancreatic tissues. The blood was collected from 50 healthy individuals and 63 patients with chronic pancreatitis (CP). The ET-1 and cotinine concentrations in the plasma were estimated by ELISA. Samples of tissues of the normal pancreas and CP were verified histopathologically, and then ET-1 was localized by immunohistochemical staining using the monoclonal anti-human ET-1 antibody. The intensity of immunohistochemical reaction was calculated with the semiquantitative Digital Imaging Methodology. The study demonstrated a significant concentration of ET-1 in smoking healthy individuals and in patients with CP when compared with the nonsmoking population (P=0.003 and 0.0005, respectively). A significantly stronger immunohistochemical ET-1 reaction was observed in the tissue of smoking patients with CP than in the normal pancreatic tissue and of nonsmoking CP patients (P=0.001, 0.008, and 0.03, respectively). The presented data evidence that tobacco smoking has a direct effect on the endothelium, leading to an increased level of ET-1.

Plasma endothelin-1 levels in pancreatic inflammations.

BACKGROUND: In inflammatory processes endothelin exerts an important effect on the pancreatic blood vessels and disturbances in pancreatic microcirculation. OBJECTIVES: The aim of the study was to evaluate the usefulness of plasma endothelin-1 (ET-1) levels in determining the severity of pancreatitis, its prognosis and monitoring the course of therapy. MATERIAL AND METHODS: The investigations were carried out on 115 subjects: 85 patients with pancreatitis and 30 persons serving as a control group. All the participants' ET-1 levels were determined by means of an enzymoimmunological test (Endothelin ETA Kit, Catalog No:583151, Cayman Chemical Company, Michigan, USA) on the 1st, 3rd, 5th and 7th days of treatment. In the control group, the mean ET-1 level was 1.37 pg/ml. RESULTS: Acute pancreatitis (AP) was diagnosed in 53 patients, including 36 patients (67.9%) with severe AP. Their Ranson's scores were over 3 points. The highest mean plasma ET-1 levels were observed in 10 patients with severe AP with necrosis (6.37 +/- 1.9pg/ml). (5 to 9 points on Ranson's scale). In 26 patients with severe AP without necrosis, the mean plasma ET-1 level was 3.49 +/- 1.24 pg/ml. In 17 patients with mild AP the mean plasma ET-1 level was 3.48 +/-1.16 pg/ml (3 to 4 points on Ranson's scale). ET-1 levels normalized gradually with successful treatment. An increase in ET-1 levels between the 5th and 7th days was an unfavorable prognostic factor that was observed in all the patients who died. CONCLUSIONS: Measuring plasma ET-1 levels permits early determination of cases with severe AP. ET-1 can be used as a marker for both the progress of the disease and the efficacy of the treatment. An increase in plasma ET-1 level between the 5th and 7th days of treatment may indicate irreversible ischemic lesions in the pancreas and the development of necrotic lesions.

[Assessment of concentrations of creatinine, uric acid and urea in non-smoking and smoking patients with chronic pancreatitis]. / Ocena steien kreatyniny, kwasu moczowego i mocznika u niepalacych i palacych pacjentów z przewleklym zapaleniem trzustki.

Cigarette smoking is a major factor for pancreatic dysfunction in patients with chronic pancreatitis (CP). In the course of acute pancreatitis may lead to organ damage resulting in their failure. The chronic renal failure can cause disturbances in the exocrine pancreas. The study population consisted of 51 patients with chronic pancreatitis and 29 healthy subjects classified as the control group. The study population was divided into smokers and non-smokers on the basis of determining the concentration of cotinine (ELISA). It has been shown that the concentration of creatinine in the groups was in the range of reference values, but in non-smoking and smoking control group that is higher in comparison with patients (respectively 0.97 +/- 0.17 and 0.79 +/- 0.14 [mg/dl] , p = 0.0004; 1.00 +/- 0.14 and 0.78 +/- 0.23 [mg/dl], p = 0.0416). It has been shown 1.5 times higher uric acid concentration in the serum of smoking patients with chronic pancreatitis (245.67 +/- 79.73 micromol/l) compared to non-smoking control group (173.67 +/- 50.08 [micromol/l]). There was a significant difference between the mean value of urea nitrogen (BUN) in terms of the concentration of creatinine (index of BUN/creatinine) in the group of non-smoking healthy persons (13.38 +/- 4.53) and the average index of BUN/creatinine ratio in a group of nonsmoking and smoking patients with pancreatitis (respectively, 2.73 +/- 0.56, p < 0.0001 and 2.40 +/- 0.77, p < 0.0001). The results show that cigarette smoking may be an important factor in potential changes in uric acid levels in patients with chronic pancreatitis. In addition, reduced protein catabolism is the result of progressing exocrine pancreatic dysfunction in both smoking and non-smoking patients with chronic pancreatitis.

The effect of smoking on expression of IL-6 and antioxidants in pancreatic fluids and tissues in patients with chronic pancreatitis.

OBJECTIVES: The present study was conducted to ascertain whether cigarette smoke induces oxidative stress in the human pancreas concurrently with inflammation. MATERIALS AND METHODS: The influence of tobacco smoking on the serum level of interleukin-6 (IL-6), on the activities of glutathione peroxidase (GPx) and copper-zinc superoxide dismutase (Cu/Zn SOD) as well as on the metallothionein (MT) level in the pancreatic pseudocyst fluid and its immunohistochemical localization in tissues of non-smoking (n = 9) and smoking (n = 12) patients with diagnosed chronic pancreatitis (CP) was measured. The concentration of interleukin-6 and metallothionein was determined by means of ELISA and the radioisotopic method, respectively. The enzyme activities in the fluid were assayed by the colorimetric method. Samples of tissues of normal pancreas (n = 4) and CP (non-smoking n = 7; smoking n = 12) were verified histopathologically and then IL-6, MT and enzymes were localized by immunohistochemical staining using the monoclonal anti-human antibody. RESULTS: The concentrations of metallothionein and interleukin-6 were significantly higher in smoking patients with CP (as compared with the non-smoking population (p < 0.01; p < 0.001). Interestingly, the ratio of MT/IL-6 in smoking patients with CP was reduced in comparison to non-smoking patients (respectively: 1.1; 5.6). In smoking patients, a significant elevation of the Cu/Zn SOD and GPx activities was revealed as compared with the non-smokers (p < 0.04; p < 0.0007). These studies clearly demonstrate a moderate and strong expression of IL-6 and enzymes in acinar, islet and duct cells of smoking patients. CONCLUSIONS: These observations favor the role of the oxidative stress in the induction of pancreatitis associated with chronic cigarette smoke inhalation.

A middle mesenteric artery.

In 114 cases of the transverse colon isolated from cadavers (50 male, 64 female), anatomical examinations of the arterial system of the colon were performed. Arteriograms were obtained after dissecting and contrasting the colonic vessels with Mixobar contrast. In one case, on arteriography of the colon with its mesentery isolated from a 55-year-old male cadaver, a rare anatomical variant was found. The third mesenteric artery originated directly from the aorta-halfway between the superior and inferior mesenteric arteries and ascended obliquely in the direction of the hepatic flexure of the colon. Supply area of the artery was typical for the middle colic branch of the superior mesenteric artery: the distal segment of the ascending colon and the transverse colon. Such a variation, although very rare, may have particular impact on diagnosis and even the method and range of surgery.

Immunohistochemical localization of somatostatin and pancreatic polypeptide in smokers with chronic pancreatitis.

Recent studies have demonstrated a significant role of tobacco smoking in the development of chronic pancreatitis. Although there are published papers on the effects of cigarette smoking on insulin secretion in patients, no data are available on the effects of smoking on pancreatic endocrine cells secreting somatostatin and pancreatic polypeptide. The aim of the study was to evaluate the effects of cigarette smoking on endocrine pancreatic function by immunolocalization of somatostatin and pancreatic polypeptide in the pancreas from smokers and non-smoking patients with chronic pancreatitis in comparison with healthy controls. The LSAB2-HRP technique with polyclonal antibodies was used for the immunolocalization of somatostatin and pancreatic polypeptide in histological preparations of the pancreas. The intensity of immunohistochemical reaction was calculated with digital image analysis. The study demonstrated increased numbers of somatostatin (D) secreting cells and pancreatic polypeptide (PP) cells and their altered location in pancreatic islets and parenchyma of smoking patients with chronic pancreatitis, as compared to non-smoking patients and healthy controls. Smoking patients showed significantly higher immunostaining of the hormones in the pancreas compared to non-smoking patients and healthy persons. This study indicates that smoking may play a significant role in the development of endocrine disturbances in the development of chronic pancreatitis.

Duodenal diverticulum mimicking duodenal stromal tumor.

A patient with duodenal diverticulitis who was initially misdiagnosed with stromal tumor of the duodenum is presented. This case is of interest because it illustrates difficulties in the interpretation of auxiliary investigations and the choice of the best treatment option. US and CT images revealed two large ovoid masses of fluid density in the duodenal wall which may have suggested stromal tumor of the duodenum as well as periampullary cystic neoplasm, the more so because intramural tumor of the duodenum was seen in duodenoscopy. A similar picture may also be seen in duodenal diverticula, especially in diverticula which are not filled with gas or a combination of fluid and gas. This case demonstrates one such entity.

Immunohistochemical localization of metallothionein and p53 protein in pancreatic serous cystadenomas.

INTRODUCTION: The objective of this study was to determine the expression levels of metallothionein (MT) and p53 protein, recognized neoplastic transformation markers, in pancreatic serous cystadenomas (SCA) and adenomocarcinomas. MATERIALS AND METHODS: Neoplastic pancreatic tissue was taken from 20 patients with diagnosed benign (SCA: 5 cases) or malignant tumors (adenomocarcinomas: 15 cases) and control pancreatic tissue from healthy persons who had died in car accidents. Sections were stained with hematoxylin-eosin. Immunohistochemical localization of MT and p53 protein was carried out by LSAB2-HRP using specific antibodies against MT and p53. RESULTS: Metallothionein expression was observed only in the epithelial cells of the neoplastic tissue of SCAs. MT expression in the cystadenomas was weaker than in the healthy pancreatic tissue. No tissue was found with p53 protein expression. In the adenomocarcinomas, positive staining for MT was observed in 67% and p53 was positive in the carcinoma cells. CONCLUSION: The weak MT expression and lack of p53 protein expression in pancreatic SCAs confirms the lack of local invasive potential of the neoplastic lesion. Increased expressions of MT and p53 were observed in the less differentiated tumors. Thus the expression of MT may be a potential prognostic marker for tumors.

Immunohistochemical localization of interleukin-6 in human pancreatitis.

The aim of the study was to identify immunohistochemically the localization of interleukin (IL)-6 in normal pancreas and in chronic pancreatitis (CP). Samples of tissues of normal pancreas (n=5) and CP (n=16), were verified histopathologically and then IL-6 was localized by immunohistochemical staining using the monoclonal antihuman IL-6 antibody and test LSAB2-HRP to visualize IL-6/Ab complexes. In slices of the pancreas, derived from patients with CP, a much stronger immunohistochemical reaction was noticed as compared with controls specimens. IL-6 was localized in exocrine, islet cells and ducts cells of the pancreas. Interestingly, this cytokine was detected in cytoplasm and very close to nucleus. Moreover, in cases of CP with inflammatory infiltration, there were a markedly stronger IL-6 expression, than that observed in specimens without infiltrate. In conclusion, the results presented herein clearly demonstrated a moderate and strong expression of IL-6 in exocrine and endocrine cells of patients with CP. These observations provide further support for the existence of local immune-pancreatic interactions.

Dysfunction of the pancreas in healthy smoking persons and patients with chronic pancreatitis.

OBJECTIVES: The aim of the study was to assess the effect of cigarette smoking on the endocrine pancreatic function by determining the levels of serum glucose and plasma insulin as well as by defining immunohistochemical localization of insulin and glucagon in tissue specimens of the pancreata derived from healthy persons and smoking and nonsmoking patients with diagnosed chronic pancreatitis (CP). METHODS: The oxidative method was used to measure fasting glycemia in blood plasma and the method enzyme-linked immunoassay to determine the level of insulin in plasma. Immunohistochemical localization of hormones in paraffin tissue specimens of the pancreas was performed using the LSAB2-HRP visual test with polyclonal insulin and glucagon antibodies. The intensity of immunohistochemical reaction was calculated with digital imaging methodology. RESULTS: The study revealed a substantially higher level of serum glucose in smoking CP patients and in healthy persons compared with nonsmoking patients and healthy persons, whereas insulin concentration in smoking patients was statistically lower than in nonsmokers. Smoking patients showed significantly lower expression of insulin and glucagon in the pancreas compared with nonsmoking patients and healthy persons. CONCLUSIONS: Impairment of the endocrine function of beta and alpha cells in the pancreatic islets is frequently manifested by complications in pancreatitis resulting among others from long-term smoking.

Blood plasma antioxidant defense in patients with pancreatitis.

OBJECTIVES: The aim of this study was to establish the main determinants of plasma antioxidant potential in different types of human pancreatitis: chronic pancreatitis (CP, n = 19), chronic pancreatitis exacerbated (CPE, n = 16), and acute pancreatitis (AP, n = 8). METHODS: We measured the plasma thiobarbituric acid reactive substances (TBARS), total peroxyl radical trapping potential (TRAP), and the levels of antioxidants such as uric acid (UA), SH groups (SH), ascorbic acid (AA), and bilirubin (BIL). RESULTS: In comparison to healthy volunteers (HV, n = 22) the average levels of TBARS in all types of pancreatitis were significantly higher (by 50%-90%), and plasma SH groups were lower (approximately 30%). In the multivariate regression models, the variability of plasma TRAP was explained in the HV group through UA only (36%), in the CP group through UA, AA, and BIL together (75%), and in CPE group through UA and AA together (81%). Plasma SH concentration did not enter the regression models in all groups. The AP group revealed "paradoxically" high concentrations of AA and TRAP and a negative, linear correlation between the level of TRAP versus UA concentration (R = -0.87). CONCLUSIONS: The multivariate regression analysis points to different structures of antioxidant defense in healthy people and those with pancreatitis: they were much the same in the CP and CPE groups but fundamentally different in the AP group. AP may activate unidentified antioxidant defenses as an adaptive response against oxidative stress.

[Immunohistochemical localization of p53 protein in smoking patients with chronic pancreatitis]. / Immunohistochemiczna lokalizacja bialka p53 u palacych pacjentów z przewleklym zapaleniem trzustki.

Epidemiological studies show that smokers are at a significantly higher (70%) risk of getting affected by chronic pancreatitis and tumours of pancreas than non-smokers. The aim of the study was to assess the effect of cigarette smoking on the expression of gene p53 in pancreas by defining immunohistochemical localization of p53 protein in tissue specimens of the pancreases derived from healthy persons and smoking and non-smoking patients with diagnosed chronic pancreatitis (CP). Patients underwent surgery in which tissue material was collected. Immunohistochemical localization of 53 protein in paraffin tissue specimens of the pancreas was performed using the LSAB2-HRP visual test (DAKO K0673) with monoclonal p53 protein (DAKO N1581) antibodies. Exposure to tobacco smoke was assessed by determining cotinine in the patients' serum using the ELISA method. The study revealed a expression of p53 protein in smoking CP patients. In non-smoking patients and healthy persons wasn't showed expression of protein. Smoking patients above the twenty cigarettes for day showed significantly higher expression of p53 protein in the pancreas compared to smoking patients less. Cigarette smoking increases the expression p53 protein in pancreas of smoking patients with chronic pancreatitis. Impairment of the gene p53 in pancreas is frequently manifested by complications in pancreatitis resulting among others from long-term smoking, and conducted by tumour proliferation.

Immunohistochemical localization of metallothionein in chronic pancreatitis.

Metallothionein (MT) is a low-molecular weight intracellular protein, rich in sulfhydryl residues, and able to bind bivalent metals. MT, like Zn, is a component of the diversified elements of antioxidant system. Recent studies have shown that reactive oxygen species play a role in the pathogenesis and development of chronic pancreatitis. The aim of the study was to identify immunohistochemically (LSAB2-HRP; DAKOCytomation) the localization of metallothionein and to determine MT expression in 9 patients with chronic pancreatitis. Our studies confirm that MT is present in exocrine and endocrine cells of patients with chronic pancreatitis and chronic pancreatitis with concomitant diabetes. They also indicate increased expression of MT, particularly in acinar cells of the pancreas. This suggests that MT is greatly involved in homeostasis of the pancreas and synthesis of pancreatic hormones.

[Effect of tobacco smoking on amylase activity in patients with pancreatitis]. / Wplyw palenia papierosów na poziom amylazy u pacjentów z procesem zapalnym trzustki.

The pancreas is one of the first organs pathologically affected by the tobacco smoking. However, the mechanism of development of these changes is not eventually recognised. It has been demonstrated that nicotine influences exogenous function of pancreas. The aim of this study is to prove the influence of tobacco smoking on amylase activity in serum and urine of smoking and non-smoking patients with diagnosed acute (AP), chronic (CP) and chronic exaggerated pancreatitis (CEP). Serum and urine has been collected from 57 patients with AP, CP and CEP. The activity of enzyme has been determined using the colorimetric method with ethylidene-G7-PNP (4,6-ethylidene-p-nitrophenyl-alpha,D-malthoheptozyde). The nicotine metabolites has been assayed with the immunoenzymatic method (ELISA) using rabbit polyclonal antibodies against cotinine. The highest amylase activity in serum and urine has been observed in smoking patients with CEP. Much higher differences in amylase activity has been estimated in urine of patients with CP and AP (CP: in non-smoking patients more than three times lower activity than in smoking patients; AP: in non-smoking patients more than two times lower activity than in smoking patients). It has been revealed that the differences in amylase activity in both serum and urine in smoking patients in comparison with non-smoking patients with pancreatitis may prove a significant influence of tobacco smoking on exocrine function of pancreas.