Mariola Śliwińska-Mossoń

The impact of smoking on the development of diabetes and its complications

Diabetes is one of the most common metabolic disorders and emerges secondary to an interaction between genetic, environmental and lifestyle factors. This work provides an overview of the impact of smoking on the development of vascular complications in this condition and also provides an overview of the potential role of smoking in predisposition to diabetes. There are many studies documenting the impact of smoking on health (not focused on patients with diabetes), suggesting that the health exposure in these individuals is at least comparable to that observed in the general population. Distinct studies of smoking in patients with diabetes have unambiguously confirmed an increased prevalence and a higher risk of early death associated with the development of macrovascular complications. Smoking is also associated with premature development of microvascular complications and may contribute to the pathogenesis of type 2 diabetes. It has been shown that smoking is a predictor of the progression of glucose intolerance at both the transition from normoglycaemia to impaired glucose tolerance status and the increased risk of developing diabetes. The mechanisms explaining the relationship between smoking and the development of diabetes are not fully understood, although a number of hypotheses have been put forward. Current evidence indicates that smoking cessation is not only important to prevent macrovascular complications in diabetes, but also has a role in limiting microvascular disease and may also facilitate glycaemic management in this condition.

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.

Immunohistochemical localization of metallothionein and p53 protein in pancreatic serous cystadenomas

IntroductionThe 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 MethodsNeoplastic 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.ResultsMetallothionein 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.ConclusionThe 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.

Somatostatin expression in the pancreatic cells of smoking and non- smoking chronic pancreatitis patients with or without diabetes

OBJECTIVES The aim of the analysis is to determine the location and degree of the hormone immunoreactivity in tissues of patients with chronic pancreatitis and diabetes. METHODS The study was performed on 11 non-smoking and 12 smoking patients with chronic pancreatitis (CP) with/without diabetes. The hormone was located in the pancreatic tissues by means of the immunohistochemical method using somatostatin antibodies. The histopathological evaluation of the hormone expression intensity in tissue sections was carried out using the semi-quantitative method and was calculated by means of a digital image analysis. RESULTS The hormones strong immunohistochemical reaction and the modified D-cell location may be a result of the pancreatic tissue fibrosis process prevention in patients with CP. Changes in the intensity of SS immunoreactivity and the D-cell distribution in the pancreas of patients with CP and diabetes may possibly result from the additional hormone compensatory effect in the excessive glucagon secretion inhibition. Smoking patients with diabetes showed significantly higher hormone immunostaining in the pancreas compared to non-smoking patients without diabetes and healthy persons. CONCLUSIONS The severity of histopathological changes in smoking CP patients indicates that the cigarette smoke components may further exacerbate the inflammatory reactions. Patients with CP were found to have a strong immunohistochemical reaction to SS and changes in the distribution of D cells when compared to healthy patients. The strongest immunohistochemical SS reaction has been identified in the pancreatic tissue from smoking patients with diabetes.

Mechanisms of interaction of the N-acetyl-p-aminophenol metabolites in terms of nephrotoxicity.

Abstract Context: Epidemiological studies have demonstrated that chronic use of N-acetyl-p-aminophenol is correlated with the occurrence of renal dysfunction. Objective: Aim of this study was to review the literature on the mechanisms of interaction N-acetyl-p-aminophenol metabolites in terms of nephrotoxicity. Methods: We present a literature review of studies published in English language on the damage effects of N-acetyl-p-aminophenol on the kidneys, accessed through PubMed database. Results: The pathogenesis of drug-induced nephrotoxicity attributed to the action of cytochrome P450 enzymes, prostaglandin endoperoxide synthase (PGES) and N-deacetylase. The metabolism of N-acetyl-p-aminophenol with the participation of PGES more explicit is in the core of kidney, whereas cytochrome P450 enzymes play role in the renal cortex. Due to the action of cytochrome P450 and N-deacetylase, a very reactive N-acetyl-p-benzochinoimine (NAPQI) is formed. The result of the catalytic activity of PGES is p-benzoquinone (PBQI) production. The formation of NAPQI and PBQI is accompanied by the production of free radicals. Metabolites can connect covalently with sulfhydryl groups of renal proteins, what can cause the injury of proximal tubules. N-acetyl-p-aminophenol may initiate the apoptosis process involving activation of caspase-9 and caspase-3, but also caspase-12 as a result of generation of free radicals. Conclusions: The process of NAPQI and PBQI formation can increase oxidative stress that promotes the kidneys damage. The ability of metabolites to produce covalent bonds with sulfhydryl groups of proteins can increase the nephrotoxicity. It was assumed that the induction of apoptosis in renal tubular epithelial cells, and not necrosis underlies the nephrotoxic potential of N-acetyl-p-aminophenol.

[Neuropeptides Y, YY, PP and their clinical significance].

peripheral nervous system. Considering the structure and evolutionary origin, neuropeptide Y (NPY) is a peptide of the same family as peptide YY (PYY) and pancreatic polypeptide (PP). These proteins were discovered relatively recently, however, knowledge about them is deepened. They are 36-amino acid peptide acting through G-protein coupled receptors, Y1, Y2, Y3, Y4, Y5 and Y6. The diverse structure C-terminus of the peptide and protein binding to receptors affect the biological activity and the physiological effects on the digestive system, blood vessels, and the center of hunger and satiety in the hypothalamus. Peptides have anorexic properties, they regulate appetite and food intake mainly through the intestinal cerebrospinal axis and the hypothalamus. These substances represent an important potential target of new drugs in the long-term treatment and prevention of obesity. Furthermore, neuropeptide Y affects many processes depending on the central nervous system modifies ethanol consumption, affect circadian rhythms, memory processes, anxiety behavior. Peripherally NPY affects smooth muscle contraction of the blood vessels, blood pressure, and atherogenic processes. Conducted more thorough research trying to define the role and participation of various neuropeptides in the development of diseases of the pancreas and the gastrointestinal tract, cardiovascular system and use it for diagnosis.

Influence of oral contraceptives on lipid profile and paraoxonase and commonly hepatic enzymes activities.

The aim of the study was to verify the influence of oral contraceptives (OCs) on lipid profile and the arylesterase, lactonase and phosphotriesterase activities of paraoxonase 1 (PON1). Also commonly hepatic enzymes: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ‐glutamyltranspherase (GGT) were measured.

The effect of occupational exposure on pro/antioxidant balance in the blood of non-smoking and smoking smelters with diabetes

Arsenic, lead and cadmium, potent environmental toxicants have been reported to induce diabetes mellitus, but their potential biological mechanism(s) have not been much investigated. The present study was designed to correlate parameters of pro/antioxidant balance with occupational exposure on heavy metals and smoking in smelters with diabetes compared on control group. The results showed a significant increase in the concentration of arsenic, cadmium and lead in the blood and urine of smelters, while smoking caused a further increase in the concentration of these metals. Increasing γ-glutamyltransferase activity and lead concentration due to occupational exposure in copper foundry, tobacco smoke and co-existing diabetes were observed. Also these factors have synergistic effects on metallothionein and glutathione concentrations as well as glutathione dependent enzymes activities. Our data suggests that sub-chronic arsenic, lead and cadmium exposure induces diabetic condition which may be mediated due to increased oxidative stress in blood.

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.

Distribution of Pancreatic Polypeptide-secreting Endocrine Cells in Nondiabetic and Diabetic Cases.

The aim of the study was to demonstrate the effects of cigarette smoking and ongoing inflammation in chronic pancreatitis on the functioning of pancreatic polypeptide (PP)-secreting cells and to determine the relationship between the occurrence of an increased number of PP cells in the pancreas, the change in their location, and the intensity of their inflammatory changes in the course of pancreatitis and diabetes. Samples of tissues from healthy persons and from patients were verified histopathologically, and then PP was localized by immunohistochemical staining using the monoclonal anti-human PP antibody. The histopathologic evaluation of the hormone expression intensity in tissue sections was carried out using the semiquantitative method and was calculated with digital image analysis. The present study showed a very strong PP expression in the pancreatic tissue (especially in the head of the pancreas) derived from smoking patients with diabetes. The increase in the percentage of cells in the PP islets, between the acinar cells in smoking patients with diabetes and a statistically significant increase in the expression of PP, indicates a pancreatic endocrine dysfunction and suggests that cigarette smoking has a negative impact on the organ’s efficiency. Because of its properties, the PP appears to be a useful marker of the endocrine insufficiency of the pancreas and a specific prognostic parameter of developing diabetes due to chronic pancreatitis.