Chronic kidney disease on hemodialysis is associated with decreased serum PCSK9 levels.

OBJECTIVES: Serum low density lipoprotein-cholesterol (LDL-C) correlates positively with serum PCSK9 in the general population, consistent with PCSK9 being a determinant of LDL-C levels. Patients with chronic kidney disease (CKD) on hemodialysis (HD) have lower total cholesterol (TC) and LDL-C compared to the general population. Serum PCSK9 and its relationship with serum lipids have not been reported in CKD patients on HD (CKD-HD). METHODS: We measured serum PCSK9 by ELISA and lipid levels in 66 CKD-HD patients and compared them to 178 non-CKD subjects. Since statins increase serum PCSK9 levels, CKD-HD patients were separated into those not on statin therapy (HD-NS, n = 32) and those taking statins (HD-S, n = 34). No control subjects were on statin therapy. RESULTS: Serum PCSK9, TC, LDL-C and HDL-C levels were significantly lower in the CKD-HD group (n = 66) compared to the control group. HD-NS patients showed lower PCSK9, TC and LDL-C levels than control subjects and PCSK9 levels correlated with TC and LDL-C levels (r = 0.35, p = 0.050; r = 0.423, p = 0.0158 respectively) as well as TG levels (r = 0.413, p = 0.0188). In HD-S patients, PCSK9 levels were not significantly different from the non-CKD group. There was no correlation between PCSK9 levels and TC and LDL-C levels in the HD-S group. CONCLUSION: Our data are the first quantitative analysis of serum PCSK9 levels in CKD-HD patients. We show that serum PCSK9 in HD-NS patients is decreased and it retains a positive correlation with LDL-C, suggesting that PCSK9 may remain a significant determinant of LDL-C in CKD-HD subjects. We also show that statin therapy disrupts the correlation between LDL-C and PCSK9 in CKD-HD patients. These data suggest that the regulation of LDL-C by PCSK9 remains intact in CKD-HD patients. PCSK9 may also play a role in the metabolism of triglyceride-rich lipoproteins in CKD-HD patients.

[Autoimmune pancreatitis and IgG-positive sclerosing cholangitis]. / Autoimunitní pankreatitida a IgG pozitivní sklerotizující cholangitida.

Sclerosing cholangitis is a heterogenous disease. Sclerosing cholangitis with an unknown cause is abbreviated PSC. PSC affects extra- as well as intra-hepatic bile ducts and since this is a permanently progressing fibrous condition, it leads to liver cirrhosis. The disease is often associated with a development of cholangocarcinoma and idiopathic intestinal inflammation. Causal therapy does not exist; liver transplantation is indicated. IgG4 cholangitis differs from PSC in a number of features. This form is, unlike PSC, linked to autoimmune pancreatitis (AIP) as well as other IgG4 sclerosing diseases. Anatomically, distal region of ductus choledochus is most frequently involved. Icterus is, unlike in PSC, a frequent symptom of AIP. There also is a distinctive histological picture--significant lymphoplasmatic infiltration of the bile duct wall with abundance of IgG4 has been described, lymphoplasmatic infiltration with fibrosis in the periportal area and the presence of obliterating phlebitis is also typical. However, intact biliary epithelium is a typical feature. IgG4 can be diagnosed even without concurrent presence of AIP. IgG4 sclerosing cholangitis is a condition sensitive to steroid therapy. At present, there is no doubt that IgG4 sclerosing cholangitis is a completely different condition to primary sclerosing cholangitis. From the clinical perspective, these diseases should be differentiated in every clinician's mind as (a) AIP is treated with corticosteroids and not with an unnecessary surgery, (b) IgG4 sclerosing cholangitis is mostly successfully treated with corticosteroids and the disease is not, unlike PSC, a risk factor for the development of cholangiocarcinoma.

[Incidence of pancreatic carcinoma in persons with chronic pancreatitis]. / Incidence pankreatického karcinomu u osob s chronickou pankreatitidou.

INTRODUCTION: Pancreatic carcinoma is one of the diseases which mostly fail to be diagnosed on a timely basis, and there is no way to effectively screen patients for pancreatic carcinoma either. An option for the diagnosis of the "early glandular carcinoma" therefore resides in identification and systematic screening of patients with risk of pancreatic carcinoma. METHOD: We monitored 223 patients with chronic pancreatitis on a systematic basis from 1992 to 2005. During this 14-year period, we monitored the number of cigarettes smoked per year in addition to standard parametres measured by biochemical methods, endosonography, CT and ERCP exams, and assigned the alcoholic form of chronic pancreatitis to patients consuming more than 80g of alcohol per day on a systematic basis for more than 5 years in the case of men, and 50 g of alcohol per day in the case of women, and classed the patients according the TIGARO classification. RESULTS: Alcoholic etiology was proven in 73.1% of the examined patients, chronic obstructive form of pancreatitis was diagnosed in 21.5% of patients, and only 5.4% of patients were classified into the idiopathic pancreatitis group. Pancreatic carcinoma in the region of chronic pancreatitis was found in 13 patients (5.8%); stomach carcinoma was diagnosed in 3 patients with chronic pancreatitis, and oesophageal carcinoma in 1 patient of the total of patients monitored. Malignant pancreatic disease was diagnosed primarily in patients with alcoholic pancreatitis (4.5%). During the period of 14 years, 11 patients died, 8 of the deaths being associated with pancreatic carcinoma. CONCLUSION: Both pancreatic and extrapancreatic carcinoma in gastrointestinal location is a serious complication of protracted chronic, non-hereditary pancreatitis. Systematic identification and treatment of patients with chronic pancreatitis is therefore necessary for timely diagnosis ofgastrointestinal and pancreatic malignancies.

Epidemiology of canine urolithiasis in the Czech Republic from 1997 to 2002.

OBJECTIVES: To compare data on the epidemiology of canine urolithiasis in the Czech Republic with that from other countries. METHODS: The records from the Centre for Mineralogical Analysis from 1997 to 2002 were reviewed. The data were obtained from mineralogical analysis of 1366 canine uroliths obtained from patients in the Czech Republic. These included 396 females and 629 males. RESULTS: Sixty-eight breeds plus crossbreeds were identified. Eight breeds plus the crossbreeds accounted for 71.3 per cent of all cases. Males were affected more frequently than females (61.4 per cent versus 38.6 per cent). Struvites significantly predominated in females, while in males calcium oxalates, brushites and cystines were the most common stones. Most of the uroliths (48.9 per cent) were 5 mm or less in dimension. By 2001, struvite was the most frequent (38.5 to 44.1 per cent) urolith, followed by calcium oxalate (26.5 to 32.0 per cent). In 2002, calcium oxalate became the most frequent calculus, followed by struvite, mixed calculi and others. CLINICAL SIGNIFICANCE: Comparison of these results with studies by other authors showed that for most of the monitored parameters there was agreement with respect to the proportions of different breeds within the populations of dogs in different geographical areas.

Amplification and overexpression of HER-2/neu in invasive ductal carcinomas of the pancreas and pancreatic intraepithelial neoplasms and the relationship to the expression of p21(WAF1/CIP1).

Overexpression of HER-2/neu was described in pancreatic intraepithelial neoplasia (PanIN) and in invasive ductal adenocarcinoma of pancreas in a variable proportion of cases. The effects of HER-2/neu overexpression on mitogenic signalling and cell cycle progression were studied in breast luminal epithelial cells and mitogen activated protein kinase-dependent induction of p21(WAF1/CIP1) was found to be necessary for G1 phase progression. Overexpression of p21(WAF1/CIP1) was described as an early event in the development of PanIN by Biankin et al. (2001) and this finding was supported by our previous study that, moreover, did not confirm the possible role of activating K-ras mutations in the induction of p21(WAF1/CIP1) overexpression. Relationship between p21(WAF1/CIP1) expression and HER-2/neu status in PanIN lesions and ductal adenocarcinoma of the pancreas was investigated in our study. Expression levels of p21(WAF1/CIP1) and HER-2/neu were examined imunohistochemically and the amplification of HER-2/neu gene was evaluated by fluorescence in situ hybridisation in HER-2/neu overexpressing adenocarcinomas. Fourty nine pancreatic resection specimens from patients with invasive adenocarcinoma were included into the study. A large spectrum of PanIN lesions adjacent to the structures of infiltrating adenocarcinoma was also examined. The possible role of HER-2/neu in an induction of p21(WAF1/CIP1) overexpression was not confirmed and p21(WAF1/CIP1) overexpression seems to be HER-2/neu independent in pancreatic ductal adenocarcinoma according to our results. Increasing levels of HER-2/neu expression were demonstrated in pancreatic intraepithelial neoplasia and in 18.75% of pancreatic adenocarcinoma. The only 2 from 9 HER-2/neu overexpressing adenocarcinomas showed the amplification of HER-2/neu gene. Based on these results, the overexpression of HER-2/neu in pancreatic adenocarcinoma seems to be a result of increased transcription rather than gene amplification. Therefore HER-2/neu represents a good target for therapy of pancreatic adenocarcinoma only in isolated cases.

Mitochondrial uncoupling proteins--facts and fantasies.

Instead of a comprehensive review, we describe the basic undisputed facts and a modest contribution of our group to the fascinating area of the research on mitochondrial uncoupling proteins. After defining the terms uncoupling, leak, protein-mediated uncoupling, we discuss the assumption that due to their low abundance the novel mitochondrial uncoupling proteins (UCP2 to UCP5) can provide only a mild uncoupling, i.e. can decrease the proton motive force by several mV only. Contrary to this, the highly thermogenic role of UCP1 in brown adipose tissue is not given only by its high content (approximately 5 % of mitochondrial proteins) but also by the low ATP synthase content and high capacity respiratory chain. Fatty acid cycling mechanism as a plausible explanation for the protonophoretic function of all UCPs and some other mitochondrial carriers is described together with the experiments supporting it. The phylogenesis of all UCPs, estimated UCP2 content in several tissues, and details of UCP2 activation are described on the basis of our experiments. Functional activation of UCP2 is proposed to decrease reactive oxygen species (ROS) production. Moreover, reaction products of lipoperoxidation such as cleaved hydroperoxy-fatty acids and hydroxy-fatty acid can activate UCP2 and promote feedback down-regulation of mitochondrial ROS production.

[Solid pseudopapillary tumor of the pancreas: 5 case reports]. / Solidní pseudopapilární tumor pankreatu: soubor peti prípadu.

Solid pseudopapillary tumor of pancreas belongs to rare tumors of exocrine pancreas, which typically affects young women. In a retrospective study the authors reviewed their experience obtained with five cases of this tumor from 1994 until the present time. The group included four women (from 16 to 47 years, mean age 25 years) and one man (43 years old). Clinical symptoms were characterized by abdominal pain in three cases, two years lasting domed belly and an incidental finding in another case. The palpation examination of epigastrium revealed a palpable tumor, visible in sonographic examination and CT. All patients underwent surgical resection of the tumor. The tumor affected cauda of the pancreas (pancreatic tail) in four cases and head of the pancreas in one case. Histopathological examination established the diagnosis of solid pseudopapillary tumor of pancreas in four cases and solid pseudopapillary carcinoma in one case. A typical immunophenotype of tumorous cells was demonstrated and in four cases there was positivity of progesterone receptor. The progesterone and estrogen receptors were negative in the male patient. Solid pseudopapillary tumor of pancreas is the tumor of low malignancy with excellent prognosis. Correct diagnosis and surgical removal of the tumor results in curing up in most cases.

[Apoptosis and expression of bcl-2 protein in invasive ductal adenocarcinoma of the pancreas]. / Apoptóza a exprese bcl-2 proteinu u invazivního duktálního adenokarcinomu pankreatu.

Apoptosis plays a central role in the development and/or progression of cancer. There are several methods for detection of apoptotic cells in tissue sections including light and electron microscopy, in situ nick end-labeling (ISEL), TdT-mediated dUTP nick-end labeling (TUNEL) and immunohistochemical detection of proteins associated with apoptosis. Apoptosis was assessed by the monoclonal antibody M30 CytoDEATH (M30), which is specific for neo-epitope in cytokeratin 18 that becomes available at an early caspase cleavage during apoptosis. Expression of bcl-2 protein was evaluated, because bcl-2 protein plays an important role in the regulation of apoptosis. Twenty-six invasive ductal adenocarcinomas of the pancreas were studied immunohistochemically with antibodies M30 and bcl-2. The mean apoptotic index (AI, the percentage of apoptotic cells of the total tumor cells number) was 2.75%. High AI (> 10%) was observed in 4 cases of the 26 pancreatic carcinomas (15%). Protein bcl-2 was expressed in 3 cases (11.5%). The AI did not correlate with the expression of protein bcl-2. In conclusion, the detection of neo-epitope in cytokeratin 18 by monoclonal antibody M30 can be used for quantification of apoptotic cells with immunohistochemical techniques in tissue sections. It is a new approach to evaluate apoptosis in pancreatic carcinomas. The low positivity of bcl-2 expression in pancreatic adenocarcinomas suggests that bcl-2 protein does not play a central role in pancreatic tumorigenesis and cancer progression.

[Molecular diagnosis in pancreatic carcinoma]. / Príspevek k molekulární diagnostice pankreatického karcinomu.

Present diagnostic possibilities virtually do not make it possible to diagnose early stages of pancreatic cancer. Likewise, it is very difficult to differentiate between pancreatic cancer and chronic pancreatitis. The methods of visualization are insufficiently sensitive and the determination of certain genes could enrich our diagnostic opportunities. Considerable attention in this direction has been devoted to the determination and evaluation of the presence of oncogene K-ras. Our initial experience with the determination of K-ras in preparations from patients with pancreatic cancer or with chronic pancreatitis confirmed that K-ras in an oncomarker associated with adenocarcinoma of pancreas, whereas in patients with chronic pancreatitis it occurs in about 10% of the examined samples.

A prospective, randomized trial comparing endoscopic and surgical therapy for chronic pancreatitis.

BACKGROUND AND STUDY AIMS: Invasive treatment for abdominal pain due to chronic pancreatitis may be either surgical or endoscopic, particularly in cases of ductal obstruction. To date, the data published on the effectiveness of these two forms of therapy have been mostly retrospective, and there have been no randomized studies. A prospective, randomized study comparing surgery with endoscopy in patients with painful obstructive chronic pancreatitis was therefore conducted. PATIENTS AND METHODS: Consecutive patients with pancreatic duct obstruction and pain were invited to participate in a randomized trial comparing endotherapy and surgery, the latter consisting of resection and drainage procedures, depending on the patient's individual situation. Patients who did not agree to participation and randomization were also further assessed using the same follow-up protocol. RESULTS: Of 140 eligible patients, only 72 agreed to be randomized. Surgery consisted of resection (80 %) and drainage (20 %) procedures, while endotherapy included sphincterotomy and stenting (52 %) and/or stone removal (23 %). In the entire group, the initial success rates were similar for both groups, but at the 5-year follow-up, complete absence of pain was more frequent after surgery (37 % vs. 14 %), with the rate of partial relief being similar (49 % vs. 51 %). In the randomized subgroup, results were similar (pain absence 34 % after surgery vs. 15 % after endotherapy, relief 52 % after surgery vs. 46 % after endotherapy). The increase in body weight was also greater by 20 - 25 % in the surgical group, while new-onset diabetes developed with similar frequency in both groups (34 - 43 %), again with no differences between the results for the whole group and the randomized subgroup. CONCLUSIONS: Surgery is superior to endotherapy for long-term pain reduction in patients with painful obstructive chronic pancreatitis. Better selection of patients for endotherapy may be helpful in order to maximize results. Due to its low degree of invasiveness, however, endotherapy can be offered as a first-line treatment, with surgery being performed in case of failure and/or recurrence.

[Therapeutic results and changes in prognosis in patients with multiple myeloma in central and northern Moravia over the past 40 years]. / Výsledky lécby a zmena prognózy nemocných s mnohocetným myelomem v období predchozích 40 let v oblasti strední a severní Moravy--rozbor souboru 562 nemocných.

OBJECTIVE: The objective of the investigation is evaluation of therapeutic results and the development of the prognosis of patients with multiple myeloma (MM) as a result of consecutive changes of therapeutic procedures in patients of central and northern Moravia in the course of the last 40 years. METHODS AND RESULTS: The analyzed group of 562 patients with MM was concentrated at the Ist and IIIrd Medical Clinic of the Faculty Hospital Olomouc in 1959 - 2000, median age 63 (28-91) male/female ratio 1.1: 1.0. From analysis of Kaplan-Meier survival curves and the results of statistical analysis (log rank test p = 0.0000) ensued that during the evaulated period a very substantial change of prognosis occurred with improvement of theraupeutic results and a significant prolongation of survival in general. The first " turning point" was the introduction of chemotheraphy with alkylating substances with Prednisone (1963-1975), leading as compared with the period of symptomatic treatment alone (1959-1063) to a significant prolongation of the media value of general survival (M) from 8 to 19 months (p = 0.0031) and 3-year survival from 4 to 23 % patients, whereby 10-year survival was only 0 % and 1 %. The second "turning point" was the period from 1976 - 1980 with introduction of systematic chemotherapy using conventional doses of polychemotherapeutic (CP) regimes with better opportunities of supporting treatment (M = 40 months, p = 0.0000; 3-year and 10-year survival 55% and 5.5% patients). The therapeutic results acheived during the subsequent 15 years were however an unsatisfactory advance. During the interval between 1976-1995 in a group of 295 patients divided into 5-year sub-periods remission was acheived (R = < 25 % of the baseline value of M-protein) in 10-24 % patients, an inadequate response (NR) = persistence in > 50 % M-protein) in 55-28 %, prolongation of the median of total survival in 232 of the accessble patients for 44 months and long-term survival of 5 - 10 years after establisment of the diagnosis increased from 25 to 36 % and from 5.5 to 16.5 % patients. The third "turning point" was 1996 characterized by the introduction of high-dosage chemotheraphy with transplantation of autologuos peripheral haematopoietic cells ("HD" therapy with ASCT) leading ina group of so far only 33, assessable patients under 65 years to acheived remission in 71 %, to decline of NR in 10 % only and 5 -year suvival so far in 91 % patients ( p = 0.0037). Improvement of therapeutic results and prognosis of the disease as compared with 1976 - 1995 occurred in the whole group of patients also in 1996 - 2000 (CP and "HD"-therapy with ASCT) characterized by remission in 36 %, NR IN 33 % and 5 -year survival in 57 % (p = 0.030). It was reveled that the application of "HD" theraphy with ASCT led in 1995-2000 to the acheivement of more favorable therapeutic results (R - 71 % NR - 10 %. 5-year survival after the interval which elapsed so far 91 %), as compared with 2 similar groups of subjects under 65 years meeting the criteria of "HD" theraphy with ASCT, but treated only by conventional polychemotheraphy (1991 - 1995 and 1996 - 2000: R - 24 and 32 %, NR - 42 and 23 %, 5-year survival 46 and 68 % of the patients). In the group of 148 patients from the period of 1991-2000 the patients had as regards remission (R) more favourable results as compared with patients with NR concerning the prognosis [M 63 vs.22 months, 5-year and 10-year survival 53 vs. 17 % and 17 vs. 0 % of patients (p = 0.0000)]. CONCLUSION: From the submitted analysis ensured that during the period form 1959 - 2000 in patients with mutiple myeloma in central and northern Moravia as a result of the application of modern methods of chemotheraphy and supporting treatment a significant improvements of results of conventional treatment occurred with a more than 5 fold prolongation of so far assessable median values of survival (8 - 44 months) and long-term 10-year survival of almost one sixth of the patients. The real asset of "HD" theraphy with transplantation of ASCT will be revealed by analyses made after a longer time interval.

[Chronic pancreatitis as a risk factor for pancreatic carcinoma]. / Chronická pankreatitida jako rizikový faktor karcinomu pankreatu.

Carcinoma of the pancreas is a very serious disease as regards early diagnosis, effective therapy and screening of the disease. Possible risk factors of development of carcinoma of the pancreas include chronic pancreatitis. In the submitted investigation the authors evaluated 213 patients under long-term (more than 5 years) dispensary care with the diagnosis of chronic pancreatitis. In these patients they proved unequivocally carcinoma of the pancreas on the background of chronic pancreatitis in 11 instances, incl. 71.8% where from the etiological aspect chronic alcoholic pancreatitis was involved. Practically all patients were smokers, incl. 8 who were regular smokers of more than 10 cigarettes per day for a number of years. Carcinoma of the pancreas is a serious disease, patients with long-term chronic pancreatitis are at risk (prevalence of carcinoma 5.1) and within the framework of dispensary care they must be systematically examined with regard to possible malignant growth on the background of chronic pancreatitis.

[Surgical approaches to treatment of chronic pancreatitis]. / Chirurgické prístupy v terapii chronické pankreatitidy.

In the treatment of pancreatitis in recent decades various surgical methods are used. Essentially we can divide them into resection and drainage methods. In the submitted paper the authors review possible surgical treatment of chronic pancreatitis and indications of optimal surgical methods in different forms of chronic pancreatitis. The application of these surgical procedures is demonstrated on a group of patients operated by the authors in 1985-2001. The authors discuss the problem of indication of patients for surgical treatment and selection of the optimal surgical methods for the treatment of chronic pancreatitis.

The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data.

Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.

Monotherapy versus combination therapy as first line treatment of uncomplicated arterial hypertension.

Mild to moderate hypertension still remains poorly controlled. This relates to multiple factors including low antihypertensive efficacy of single drug therapies reluctance of primary care physicians to modify/titrate initially chosen therapy to obtain target blood pressure, and poor compliance with medication. Several guidelines for the treatment of high blood pressure now include combination therapy with low doses of 2 drugs as one of the strategies for the initial management of mild/moderate arterial hypertension. Evidence discussed in this article points to superior control of blood pressure by combinations of low doses of 2 drugs as compared with monotherapy in regular doses. This superior effectiveness of combined therapy relates to a better antihypertensive efficacy and higher response rates in the low range of doses as the result of complementary mechanisms of antihypertensive effects, better tolerance as a result of a lower rate of adverse effects in the low dose range, improved compliance from better tolerance and simple drug regimen, and lower cost. Whether increased use of fixed low dose combination therapies would translate to better control of arterial hypertension in the population and thereby further reduction of cardiovascular/cerebrovascular morbidity and mortality caused by hypertension remains to be assessed.

Central sympathoinhibitory effects of calcium channel blockers.

It is generally assumed that the arterial vasodilation induced by inhibition of Ca(2+) influx into vascular smooth muscle cells represents the main mechanism for the hypotensive effect of dihydropyridine calcium channel blockers. Increases in sympathetic tone have been related to activation of the arterial baroreflex by rapid lowering of blood pressure. This review highlights new findings in two areas. First, in animal studies, direct central administration of dihydropyridines such as nifedipine or amlodipine lowers sympathetic nerve activity and thereby blood pressure. Peripheral administration of nifedipine or amlodipine at low rates appears to result in gradual accumulation of drug in the central nervous system, and also causes lowering of sympathetic nerve activity and thereby lowering of blood pressure (rather than by arterial vasodilation). Second, in hypertensive humans treated with long-acting dihydropyridines and presumably little activation of the arterial baroreflex, some studies have demonstrated lowering of sympathetic activity (as assessed by plasma norepinephrine), but others reported increases (as assessed by plasma norepinephrine or microneurography). This sympathoexcitatory response may be due to activation of the renin-angiotensin system, particularly at higher doses.

Natural and azido fatty acids inhibit phosphate transport and activate fatty acid anion uniport mediated by the mitochondrial phosphate carrier.

The electroneutral P(i) uptake via the phosphate carrier (PIC) in rat liver and heart mitochondria is inhibited by fatty acids (FAs), by 12-(4-azido-2-nitrophenylamino)dodecanoic acid (AzDA) and heptylbenzoic acid ( approximately 1 microm doses) and by lauric, palmitic, or 12-azidododecanoic acids ( approximately 0.1 mm doses). In turn, reconstituted E. coli-expressed yeast PIC mediated anionic FA uniport with a similar pattern leading to FA cycling and H(+) uniport. The kinetics of P(i)/P(i) exchange on recombinant PIC in the presence of AzDA better corresponded to a competitive inhibition mechanism. Methanephosphonate was identified as a new PIC substrate. Decanephosphonate, butanephosphonate, 4-nitrophenylphosphate, and other P(i) analogs were not translocated and did not inhibit P(i) transport. However, methylenediphosphonate and iminodi(methylenephosphonate) inhibited both electroneutral P(i) uptake and FA cycling via PIC. AzDA analog 16-(4-azido-2-nitrophenylamino)-[(3)H(4)]-hexadecanoic acid ((3)H-AzHA) bound upon photoactivation to several mitochondrial proteins, including the 30- and 34-kDa bands. The latter was ascribed to PIC due to its specific elution pattern on Blue Sepharose and Affi-Gel. (3)H-AzHA photolabeling of recombinant PIC was prevented by methanephosphonate and diphosphonates and after premodification with 4-azido-2-nitrophenylphosphate. Hence, the demonstrated PIC interaction with monovalent long-chain FA anions, but with divalent phosphonates of short chain only, indicates a pattern distinct from that valid for the mitochondrial uncoupling protein-1.

[Benign tumors of the pancreas]. / Benigní nádory pankreatu.

The contemporary incidence of the tumours of the pancreas is approximately 3.5% in the Czech Republic. Benign tumours represent only about 2% of them. We have found 7 such patients (2.3%) in our population of 303 patients operated for pancreatic tumours. This paper summarizes our experience with the diagnostics and surgical treatment of these patients.

[Complications of esophageal stents used in benign esophageal stenoses]. / Komplikace jícnových stentu uzitých u benigních stenóz jícnu.

Oesophageal stents are used in the treatment of stenosis of the oesophagus in the last 10 years. The application of the stent in benign stenosis should be exceptional because it is associated with high morbidity and mortality. Two cases with severe complications treated by operation are demonstrated. Types of stents for the treatment of the oesophageal stenosis are presented.