N-acetyl-beta-D-hexosaminidase and its isoenzymes A and B in blood serum and urine, as a potential colon cancer markers.

BACKGROUND/AIMS: Evaluation of N-acetyl-beta-D-hexosaminidase (HEX), and its isoenzymes A (HEX A) and B (HEX B) activity in blood serum and urine as potential markers of colorectal cancer. METHODOLOGY: The study was performed in blood serum and urine of 32 patients with adenocarcinoma, 6 with adenocarcinoma mucinosum of the colon, and 20 healthy people. The activity of HEX, HEX A and HEX B was determined in blood serum and urine by spectrophotometric method of Marciniak et al. The concentration of CEA was determined in blood serum by immunoenzymatic method (MEIA). The concentration of protein was assessed by the Lowry method, whereas the concentration of creatinine in urine by the Jaffe method (without deproteinization). RESULTS: A significant increase in the concentration of HEX, HEX A and HEX B activity was proved in serum and urine of patients with colon adenocarcinoma. In patients with colon adenocarcinoma mucinosum, the higher activity of HEX was revealed in blood serum compared to healthy people, and the significantly higher activity of HEX and HEX B expressed as pKat/mg of creatinine, was found in urine. We observe a significant increase in the activity of HEX, HEX A and HEX B expressed in pKat/mg of creatinine was found in urine of patients bearing tumor of diameter 6.0-7.0 cm in comparison to patients with tumor of diameter 4.0-5.0 cm. CONCLUSIONS: The present study results suggest that determination of HEX, HEX A and HEX B activity in blood serum and urine may be used to detect colon cancer in its early stages. However, the use of HEX, HEX A and HEX B activity in oncological diagnostics requires further studies on a larger group of patients.

Colon cancer releases alpha-tocopherol from its O-glycosides better than normal colon tissue.

BACKGROUND/AIMS: Free radicals, in a colon, may damage DNA, make difficult DNA repair and change course of post-translational modifications of regulatory proteins, which promote tumor initiation and progression. Therefore risk of colon cancer is closely related to diet and other lifestyle factors. Dietary antioxidants, such as vitamin E, should reduce the levels of harmful oxidation products. However vitamin E is not soluble in water, which decreases its bioavailability. As O-glycosides of alpha-tocopherol are better soluble in water and penetrate to tissues easier than free alpha-tocopherol, the aim of our work was to investigate the rate of release the free tocopherol from its O-glycosides in colon cancer, in comparison to human healthy colon tissue. METHODOLOGY: The activities of enzymes catalysing hydrolysis of alpha-tocopheryl glucoside (1a) and mannoside (1b) as well as p-nitrophenyl beta-glucoside (2a) and mannoside (2b) in cancer and healthy human colon tissues, were determined according to the modified method described by Zwierz et al. RESULTS: The alpha-tocopherol and p-nitrophenol were significantly better released from the respective glucosides and mannosides in cancer tissue than in "healthy" human colon tissues, with p = 0.000947 for la, p = 0.033024 for 1b; p = 0.0028 for 2a, and p = 0.0033 for 2b, respectively. CONCLUSION: Alpha-tocopherol and p-nitrophenol are released from the O-glycosides of glucose and mannose in significantly higher amount in colon cancer than in healthy tissues. The alpha-tocopherol O-glycosides can be considered as prodrugs in prevention and treatment of the colon cancer.

Lysosomal exoglycosidases in serum and urine of patients with colon adenocarcinoma.

BACKGROUND/AIMS: The aim of this study is to evaluate the usefulness of determination the activity of lysosomal exoglycosidases: N-acetyl-beta-D-hexosaminidase (HEX - E.C. 3.2.1.30), beta-D-galactosidase (GAL - E.C. 3.2.1.23), alpha-L-fucosidase (FUC - E.C. 3.2.1.51) and alpha-D-mannosidase (MAN - E.C. 3.2.1.24) in blood serum and urine in diagnostics of colon adenocarcinoma. METHODOLOGY: The activity of lysosomal exoglycosidases was determined by the method of Marciniak et al. adapted to serum and urine of patients with adenocarcinoma of the colon. RESULTS: A significant increase in concentration of the activity of HEX, GAL and FUC was found in blood serum, as well as HEX and GAL in urine, of patients with colon adenocarcinoma, in comparison with healthy people. With the method of Marciniak et al. for determination the activity of HEX, GAL and FUC in blood serum as well as HEX and GAL in urine, the cases of colon adenocarcinoma were significantly differentiated from healthy people. CONCLUSIONS: The high diagnostic value, sensitivity and specificity of the method of Marciniak et al., suggests the possibility of its use for determination of the activity of HEX, FUC and GAL in blood serum as well as HEX and GAL in urine, in the diagnostics of colon adenocarcinoma.

Cathepsin D and carcino-embryonic antigen in serum, urine and tissues of colon adenocarcinoma patients.

BACKGROUND/AIMS: Application of neoplastic markers in early diagnosis of colorectal carcinoma has brought fresh hope to millions of sufferers. However such a marker, distinctive for this particular carcinoma and allowing its detection at a sufficiently early stage of development has not yet been found. Cathepsin D (CD) is lysosomal aspartyl proteinase. It is a component of a proteolytic cascade participating actively in neoplastic invasion as well as in metastasis formation. Carcino-embryonic antigen (CEA) is a useful marker in oncological diagnostics of colorectal cancer. CEA undergoes expression in all kinds of adenocarcinoma and is found both intercellularly and extracellularly. High concentrations of CEA in the blood serum confirm neoplastic changes in the digestive tract with high probability. The objective of this study has been to evaluate CD activity in the blood serum, urine and tumor tissues as well as in the colon biopsies which were not changed macroscopically and CEA concentration in the serum of colon adenocarcinoma, considering the extent of spread of cancer (TNM), the grade of the differentiation of cancer cell (G) as well as the tumor size. The possibility of application of CD along with CEA as markers of colon adenocarcinoma has also been examined. METHODOLOGY: The examination included the serum and urine of 21 patients as well as 12 tissues biopsies with histopathologically confirmed colon adenocarcinoma. The reference group for the blood and urine comprised of 17 healthy controls, and for the colon adenocarcinoma tissues- samples collected from 14 people from the sites most distant from the resected tumor on the boundaries which were free of cancer cells. Activity of CD in the blood serum, urine as well as tissues was determined with a modified Greczaniuk et al. method and expressed by the amount of released tyrosine as the concentration of the activity in nmolTyr/mL/6h, whereas the specific activity was expressed in nmol Tyr/mg of protein /6h. The specific activity of CD in the urine was expressed in nmol Tyr/mg of creatinine/6h. CEA concentration in the blood serum was determined by the immunoenzymatic method (MEIA) on Axym Abbot Analyzer and was expressed in ng/mL. The protein concentration was determined by the Lowry method, and the results were expressed in mg/mL. The creatinine concentration in the urine was determined by the Jaffe method (without deproteinization) and was expressed in mg/100mL. RESULTS: CD activity was increased in the blood serum (p < 0.0001) and tissues (p = 0.022) of colon adenocarcinoma patients in comparison to the reference group. CD specific activity (Tyr/mg of protein/6h) was significantly increased in serum but decreased in the urine (p < 0.0001) whereas the specific activity of CD (nmol Tyr/mg of creatinine/6h) was increased in the urine (p = 0.0001). CD specific activity has tendency to increase in colon adenocarcinoma tissues (p = 0.441) as compared to the reference group. By examining data in regard to TNM clinical-histopathological classification, G and the tumor size, it could be concluded that CD activity in serum and urine in colon adenocarcinoma patients depends on progress of cancer in which CD activity increases with TNM. A statistically significant increase in CEA concentration was found in the serum of colon adenocarcinoma patients, which was almost threefold higher than the in reference group. No significant differences in CEA concentration were found depending on TNM, G and tumor size. CONCLUSIONS: The results of this study suggest that examination of CD activity and CEA concentration in serum, as well as CD activity in the urine, might be used in oncological diagnostics of colon adenocarcinoma.

Isoenzymes A and B of N-acetyl-beta-D-hexosaminidase in serum and urine of patients with pancreatic cancer.

BACKGROUND/AIMS: Adenocarcinoma is the most frequent malignant tumor of the pancreas. Biochemical diagnostics of pancreatic adenocarcinoma is based on determination of carcinoma antigen (CA 19-9) in the blood. Determination of N-acetyl-beta-hexosaminidase (HEX) in the serum and urine was used in diagnosis of renal and gastric cancers. Therefore the aim of our research was to estimate N-acetyl-beta-hexosaminidase (HEX) and its isoenzymes (HEX A and HEX B) in the serum and urine as potential markers of pancreatic cancer. METHODOLOGY: Serum and urine samples were collected from 15 patients with adenocarcinoma of the pancreas and 15 healthy persons. The activity of N-acetyl-beta-hexosaminidase and its isoenzymes (A and B) was determined by a colorimetric method of Zwierz et al. Absorbancy of the yellow product of the colorimetric reaction was determined on the microplate reader EL(x)800 produced by BIO-TEK. The concentration of HEX, HEX A and B was expressed in pKat/mL, and the specific activity in pKat/mg of protein. Protein concentration was determined in the serum by the biuret and in the urine by the Lowry method, respectively, and expressed in mg/mL. RESULTS: The concentration and specific activity of HEX and its isoenzyme A were significantly higher in the serum and urine of pancreatic cancer patients in comparison with the concentration and specific activity in the serum and urine of healthy people. CONCLUSIONS: The results suggest that the activity of HEX and its isoenzyme A determined in the serum and urine can be used as a potential marker of pancreatic adenocarcinoma.

Alteration of parafollicular (C) cells activity in the experimental model of hypothyroidism in rats.

Our previous study has shown the alteration of C cells activity in rats with experimental model of hyperthyroidism. The aim of the present study was the evaluation of parafollicular cells activity in rats with hypothyroidism evoked by propylthiouracil (PTU) given in drinking water over 21 days. Histological, ultrastructural and immunocytochemical studies using specific antibodies against calcitonin and CGRP were performed on thyroid glands taken from experimental and control groups of rats. Moreover, in all animals the calcitonin plasma levels were evaluated by radioimmunoassay. After chronic administration of PTU, thyroid image showed predominant microfollicular hyperplasia and attenuated density of parafollicular cells. The intensity of immunocytochemical reactions for CT and CGRP were weaker in the majority of C cells in comparison to the control rats, in which strong immunocytochemical reaction was observed. Examination in the electron microscope reveals the features of hypoactivity both in follicular and parafollicular cells, in which the quantity and electron density of secretory granules were smaller in comparison to the control group. These microscopic changes were accompanied by a significant decrease of calcitonin plasma concentration. Alteration of C cells activity in the experimental model of hypothyroidism, accompanied by microfollicular hypertrophy, may point to the mutual cooperation between parafollicular and follicular cells.

[Carcinoma and acute pancreatitis--case reports]. / Rak a ostre zapalenie trzustki--opis przypadków.

The coexistence of pancreatic carcinoma with severe form of acute pancreatitis (AP) is not only an extremely rare phenomenon described in literature but also a real problem in the aspect of differential diagnostics of neoplastic and inflammatory morphological changes in this organ. The study objective was the analysis of clinical material obtained from patients with inflammatory and neoplastic lesions, treated surgically in I Department of General and Endocrinological Surgery, Medical University of Bialystok in the years 1980-2005. Of these patients, 7 had pancreatic carcinoma at various stages of advancement diagnosed in the late postoperative period after severe form of AP. Patients' history, physical examination as well as biochemical tests and imaging diagnostic procedures (ultrasonography, CT) of the abdominal cavity explicitly showed severe form of acute pancreatitis. In every case, CA19-9 antigen values were substantially elevated (mean 780 +/-325 IU/ml, norm 0-37 IU/ml). Histopathological analyses of samples collected during laparotomy revealed the presence of necrotic-purulent tissues. In the late postoperative period, i.e. 3-24 months, all these patients were reoperated on for pancreatic carcinoma or its metastases. Only in one case, radical Whipple surgery was performed. All the remaining patients underwent palliative procedures or samples for histopathological examinations were only collected. In all the seven cases, metastatic carcinoma was diagnosed, including pancreatic carcinoma in 6 patients. These observations seem to indicate that severe AP may be insidiously accompanied by pancreatic carcinoma and that this coexistence should always be taken into consideration.

Usefulness of examination of some tumor markers in diagnostics of liver cancer.

BACKGROUND/AIMS: Diagnostics of liver cancer is mainly based on imaging methods: which are ultrasound and computer tomography. Determination of tumor markers is an accessory investigation enabling us to detect cancer, to evaluate the effectiveness of its operative and postoperative treatment and to diagnose early cancer relapse or distant metastases. Alpha-fetoprotein (AFP) is a basic well-known marker in diagnostics of liver cancer. Carcinoembryonic antigen (CEA) and cancer procoagulant (CP) are also important in case of metastases to this organ, especially from the colon. The purpose of this study was to evaluate the usefulness of AFP, CEA and CP in detection of liver cancer. METHODOLOGY: The material of the study was the blood serum from 25 patients with liver cancer diagnosed histopathologically and 12 healthy individuals as a control group. The concentrations of AFP and CEP were assessed by immunoenzymatic method (MEIA) in the Axsym analyzer of Abbott and expressed in ng/mL. CP activity was determined by coagulation method worked out by Gordon and Benson and expressed as coagulation time in seconds (s). RESULTS: Based on the results obtained in our study, the concentrations of AFP and CEP were several fold higher in the serum of patients with liver cancer than the relevant values of these markers. CP activity was higher in the serum of patients with liver cancer than the mean values of patients in the control group. The differences found in the study between the groups examined and the control group were statistically significant atp<0.001. CONCLUSIONS: The results confirmed a high diagnostic value of AFP and CEA testing and suggest the possibility of using CP activity to detect liver cancer.

Assessment of proliferative activity of thyroid Hürthle cell tumors using PCNA, Ki-67 and AgNOR methods.

We have undertaken an attempt to compare the application efficacy of the proliferative activity markers in differential diagnosis of thyroid Hürthle cell tumors (HCT) using the PCNA and Ki-67 labeling and AgNOR visualisation techniques. The present work is a retrospective analysis of 78 Hürthle cell tumors: 20 Hürthle cell carcinomas (HCC), 32 Hürthle cell adenomas (HCA) and 26 hyperplastic nodules with Hurthle cell metaplasia (HCM). Five microm sections were stained according to AgNOR technique and labeled with antibodies against PCNA and Ki-67. AgNOR dot count in the nucleus and proliferative index (PI - percentage of cells expressing PCNA and Ki-67) in randomly chosen nuclei (100 in case of AgNOR and over 1000 in case of PI) were evaluated in each slide. The mean values of AgNOR dot count, PI-PCNA and PI-Ki-67 in HCC, HCA and HCM were respectively: 5.1, 61.3 and 54.9; 3.4, 42.4 and 38.6 and 2.5, 39.3 and 34.3. Statistically significant difference was found in all the proliferative activity markers between malignant and benign tumors: HCC:HCA (p<0.01) and HCC:HCM (p<0.001). There was no statistically significant difference between HCA and HCM.

A new diagnostic approach to pancreatic pseudocyst fine-needle puncture: three-dimensional sonography.

BACKGROUND/PURPOSE: We evaluated the usefulness of three-dimensional (3D) sonography in percutaneous fine-needle pancreatic pseudocyst puncture. METHODS: We examined 52 patients diagnosed as having pancreatic pseudocysts on the basis of clinical symptoms and two-dimensional (2D) ultrasonography findings. The decision to qualify certain patients for percutaneous fine-needle aspiration guided by ultrasonography was made on the basis of 2D and 3D scan results. Spiral computed tomography was done when the presence of connections between pseudocyst and pancreatic duct was suspected. In these cases diagnosis was confirmed in operative procedures. 3D sonography was used to monitor the tip of the needle making its way to the pancreatic pseudocyst and later inside the fluid collection. RESULTS: Pancreatic pseudocysts were diagnosed in all 52 cases; 48 patients underwent percutaneous fine-needle biopsies. CONCLUSIONS: 3D presentation can better visualize irregular shapes, local thickenings, and calcification of pseudocyst walls than classical 2D ultrasound scans. The use of subtraction in 3D scans of blood vessels increases the safety in performing biopsies. We have shown that 3D sonography collects extremely useful information about the status of the pseudocyst structure, and it should become a complementary method to classical ultrasonography. This technique when used on a routine basis should help us change the inclusion criteria for guided biopsies.

Preliminary immunohistochemical investigations of thyroid C cells in an experimental model of hyperthyroidism.

The role of the parafollicular (C) cells, the second most important cells in the thyroid gland, has not hitherto been clarified. They are considered to be disperse neuroendocrine cells of the APUD system and synthesise and release many of the regulatory peptides. Few publications are concerned with the evaluation of the structure and function of C cells in the thyroid gland or the probable relationship between these cells and the follicular cells in physiological and pathological conditions. For this reason immunohistochemical investigations were carried out into the activity of the C cells in rats in an experimental model of hyperthyroidism caused by chronic thyroxine influence. This C-cell activity was then evaluated. Differences in the quantity, distribution and calcitonin immunoreactivity of C cells were observed in hyperthyroid rats in comparison to the control group, together with a significant diminution of plasma TSH and calcitonin levels. Our preliminary study may indicate a functional interaction between follicular and parafollicular cells in the thyroid gland.

An immunohistochemical study of the thyroid parafollicular (C) cells in rats treated with cannabinoids - preliminary investigations.

The purpose of the present study was to evaluate the effect of a single intraperitoneal injection of a stable analogue of endogenous cannabinoid anandamide - R-(+)-methanandamide (2.5 mg/kg) and CP 55,940 (0.25 mg/kg), an egzogenous CB1 receptor-agonist, on the calcitonin (CT) immunoreactivity of the thyroid parafollicular (C) cells. Four hours after injection with both cannabinoids CT immunoreactivity, evaluated with an avidin-biotin peroxidase complex method by means of rabbit antibodies against CT, was seen to be enhanced in the parafollicular cells in comparison to those of the control group. In thyroids taken from cannabinoid-treated rats the majority of follicles, particularly those located peripherally were large in size, and had low epithelium. Moreover, dilatation of the blood vessels was observed. These changes were accompanied by a significant decrease in CT plasma level, without changes in calcium concentrations. This is the first evidence that a single injection of the cannabinoids R-(+)-methanandamide and CP 55,940 significantly decreases the activity of thyroid C cells.

Activity of the thyroid parafollicular (C) cells in simple and hyperactive nodular goitre treated surgically - preliminary investigations.

The aim of this study was to evaluate the significance of measuring calcitonin (CT) plasma concentrations in patients with simple and hyperthyroid goitre treated surgically. Eighty four patients who underwent operations during the years 2000-2002 were analysed. Plasma concentrations of CT were determined by commercially available radioimmunoassay on the day of hospitalisation. Elevated concentrations of CT were found in 8 patients: in 5 out of 26 (19.2%) and in 3 out of 33 (9.0%) patients with Graves' disease and with multinodular goitre, respectively. No major differences in concentrations of CT were observed in patients with simple goitre. Postoperative morphological analysis of pathologically changed hyperactive thyroids showed the presence of enlarged C cells distributed either in small groups or even singly with weakening immunohistochemical reaction for CT. These observations may point to the possibility of a relationship between the functional state of the thyroid gland and the activity of C cells.

Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity in the human pancreas.

Ethanol metabolism in the pancreas occurs predominantly by way of an nonoxidative pathway to fatty acid ethyl esters but oxidative routes to acetaldehyde also may contribute to injury of pancreatic cells. Three metabolic systems are responsible for the oxidative metabolism of ethanol, among which the cytochrome P-4502E1 and alcohol dehydrogenase have been found in the pancreas. The aims of this study were to detect ADH and ALDH in the human pancreas and to assess which ADH isoenzymes are present in this organ. ADH activity was measured by the photometric method and ADH isoenzyme activity was determined using sensitive and specific substrates. ALDH activity was measured by the fluorometric method. We have shown that the activities of ADH and ALDH are present in the pancreas, although the activity of ALDH was not proportionally as low as ADH activity. The class III isoenzyme exhibited the highest activity of all ADH isoenzymes tested and it was about 7 times higher than the activity of class I. The activities of classes II and IV were low. The activities of ADH isoenzymes of classes I, II, and III in the pancreas of men were significantly higher than in women. This study demonstrates that alcohol dehydrogenase and aldehyde dehydrogenase are present in the pancreas.

Gender-related differences in hepatic activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in humans.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are most abundant in the liver, are the main enzymes involved in ethanol metabolism in humans. Gender-related differences in total liver ADH and ALDH activity among different animal species have been observed in many studies. We measured total ADH and ALDH activity, and the activity of class I-IV ADH in the livers of male and female patients. Total ADH and class I and II ADH activities were significantly higher in males than in females (P=0.0052, P=0.0074, P=0.020, respectively). Class III and IV ADH and total ALDH activities were not significantly different between the genders (P=0.2917, P=0.0590, P=0.2940, respectively). The results of our study clearly show that there is a difference in enzymatic activity between male and female patients for those isoenzymes that actively participate in ethanol oxidation in the liver (class I and II ADH), although the main form of ADH in this organ is class III ADH.

Antioxidant potential in esophageal, stomach and colorectal cancers.

BACKGROUND/AIMS: The gastrointestinal tract is particularly susceptible to reactive oxygen species attack which lead to carcinogenesis. An important role in defense strategy against reactive oxygen species is played by antioxidants. The present study aims at examining antioxidant parameters and malondialdehyde--the product of lipid peroxidation as well as the marker of cancer progression--and cancer procoagulant in esophageal, gastric and colorectal cancer patients. METHODOLOGY: The activity of superoxide dismutase, catalase, glutathione peroxidase and reductase and the level of glutathione, vitamin C, malondialdehyde and cancer procoagulant were determined in tumors and normal mucous from 18 patients with esophageal cancer, 18 patients with stomach tumor and 62 patients with colorectal cancer. RESULTS: In esophageal tumor the activity of all enzymes has been increased compared with normal mucous. Stomach tumor has been also characterized by an increase in antioxidant enzymes activity except glutathione peroxidase and reductase whose activities have been decreased. However in colorectal tumor the activity of enzymes has been increased apart from catalase. In all cases the glutathione level has been increased while the vitamin C content has been significantly decreased. Tumor malondialdehyde level was significantly increased, too. The level of cancer procoagulant also increased in cancer tissues as well as in the serum. CONCLUSIONS: Antioxidant potential in all cases of gastrointestinal tract cancer has been unbalanced which has lead to increase in reactive oxygen species action and enhancement of lipid peroxidation and cancer procoagulant generation.

Prolidase activity disregulation in chronic pancreatitis and pancreatic cancer.

BACKGROUND/AIMS: One of the consequences of inflammatory diseases and neoplastic transformation is disregulation in metabolism of collagen and its interaction with cell surface integrin receptors. Although extracellular collagenases initiate the breakdown of tissue collagen the final step of collagen degradation is mediated by prolidase (E.C.3.4.13.9). We investigated whether prolidase activity may reflect disturbances of collagen metabolism in human pancreatitis and pancreatic cancer. METHODOLOGY: Ten human samples of advanced chronic pancreatitis and pancreatic cancer and ten samples of normal pancreas were compared in respect to prolidase activity and expression (western immunoblot), collagen content (hydroxyproline determination), collagenolytic activity (zymography) and beta 1 integrin subunit expression (western immunoblot). RESULTS: In pancreatitis tissue, an increase in collagen content, collagenolytic activity and beta 1 integrin expression were accompanied by significant decrease (about 2-fold) in prolidase activity and marked decrease in its expression, compared to normal pancreas. Pancreatic cancer tissue, compared to normal pancreas showed insignificant increase in collagen content, dramatic increase of collagenolytic activity and undetectable beta 1 integrin expression. These phenomena were accompanied by over 10-fold decrease in prolidase activity and marked decrease in prolidase expression. CONCLUSIONS: The results suggest that prolidase activity may reflect the extent of disturbances in tissue collagen metabolism during pancreatic diseases and the level of its activity may serve as a marker of chronic pancreatitis and pancreatic cancer.

Interleukin-18 promoter polymorphisms in type 1 diabetes.

Type 1 diabetes is believed to be a Th1 lymphocyte-mediated disease, and both environmental and genetic factors play a role in its pathogenesis. It was recently found that interleukin (IL)-18 acts as a proinflammatory cytokine and, in synergy with IL-12, promotes development of Th1 lymphocyte response by induction of gamma-interferon production. The aim of our study was to evaluate the frequency of known polymorphisms in the IL-18 promoter in patients with type 1 diabetes in comparison with healthy control subjects, since higher levels of IL-18 were recently reported in the subclinical stage of type 1 diabetes. We studied two recently described single-nucleotide polymorphisms of the promoter of IL-18 gene at the position -137 and -607, which have been suggested to cause differences in transcription factor binding and have an impact on IL-18 gene activity. The genotype distribution differed significantly between patients with type 1 diabetes and control subjects. The difference reflected an increase in the GC genotypes and a decrease in GG genotypes at position -137 in the promoter of IL-18 gene. AA genotype at position -607 was found only in the control group. The results also demonstrated that the contribution of -137GC genotypes to genetic susceptibility to type 1 diabetes differs depending on the combination of IL-18 promotor gene haplotypes. Our study suggests the first evidence of an association between type 1 diabetes and polymorphisms in the promoter of IL-18 gene.

[Surgical treatment of primary and secondary hyperparathyroidism]. / Chirurgiczne leczenie pierwotnej i wtórnej nadczynnosci przytarczyc.

Primary hyperparathyroidism is a systemic disease, more and more frequently recognised--concerning 1 to 3% of the population. Statistically appears in 1 of 1000 adults, with significant advantage of women. In Poland every year about 30 new cases are noticed and incidence of it increases with an age. In spite of significant advance of the knowledge, it still makes a lot of diagnostic troubles. It appears to be non-specific illness, characterised by just one symptom, mainly urolithiasis, sometimes chronic ulcer disease, chronic pancreatitis, arterial hypertension, disorders of the movement or psychic disorders. Parathyroid adenoma which is the main reason of the disease is usually single and small, multiple and bigger ones are found exceptionally. In about 2% of cases they are localised in mediastinum. In the comparison to primary hyperparathyroidism the secondary one appears as an effect of the other general disorders. Our material contains 12 patients, 9 with primary and 3 with secondary hyperparathyroidism. All of them were diagnosed and prepared to the operation in the departments of internal diseases. We have not observed any serious complications during the operations and in the postoperative period. In the article the basic symptoms, diagnostic and therapeutic problems of primary and secondary hyperparathyroidism were shown, especially concerning surgical treatment which is safe, radical and efficacious method when performed by experienced surgical team.

Ultrastructural observations of intermediate cells in chronic pancreatitis.

BACKGROUND/AIMS: The intermediate cells exhibiting both exo- and endocrine features occur in small numbers in the normal and pathologic pancreas of many animal species. In human pathology their presence has been reported in children with hyperinsulinemia, in hypoglycemia, and chronic hypergastrinemia. METHODOLOGY: Fragments of the pancreas collected from 27 patients operated on for chronic pancreatitis of various intensity fibrosis (I degree-IV degree) was subjected to ultrastructural analysis. RESULTS: All chronic pancreatitis cases revealed the presence of intermediate cells that were found outside Langerhans islets, separately or in small groups. They were more common in III degree and IV degree chronic pancreatitis. All forms of chronic pancreatitis with I degree-IV degree fibrosis showed, apart from undamaged cells, numerous intermediate cells with features of destruction. Some intermediate cells contained fibrillate cytoplasm inclusion bodies. Intermediate cells took part in the formation of acini and were also found among ductural cells. CONCLUSIONS: The presence of intermediate cells both within the acinar texture and among proliferating ductular cells confirms the common origin of these cellular elements of the pancreas. In chronic pancreatitis intermediate cells appear during pancreatic texture regeneration, being rather abnormal cell forms produced in this process than an intermediate stage in precursor cell differentiation.