Stereoselective oxidation of phenoxathiin-based thiacalix[4]arenes - stereomutation of sulfoxide groups.

A phenoxathiin-based macrocycle represents an inherently chiral building block, well accessible in two steps from the starting thiacalix[4]arene. The oxidized derivatives bearing one sulfoxide group and three sulfonyl groups were found to exhibit unexpected stereochemical preferences of the sulfoxide group during transformations. The sulfoxide moiety is always pointing out of the cavity (SO out), while the opposite (SO in) configuration was never obtained by direct oxidation. In order to achieve full oxidation to sulfone, the configuration of the sulfoxide group must first be changed by a photochemical inversion before the final oxidation occurs. The phenomenon of stereomutation of the sulfoxide group in the thiacalixarene series was studied using a combination of experimental (NMR and single crystal X-ray analysis) and theoretical (DFT) approaches.

RHEOPHERESIS IN THE TREATMENT OF AGE-RELATED MACULAR DEGENERATION.

PURPOSE: Evaluation of the long-term effect of rheopheresis treatment of dry form of age-related macular degeneration (AMD). MATERIALS AND METHODS: The treatment group consisted of 65 patients and 55 patients in the control group, with a minimum follow-up period of 60 months. The basic treatment consisted of 8 rheopheresis procedures, and the additional treatment (booster therapy) of 2 rheopheresis procedures 1.5-2 years after the basic treatment. We evaluated changes in best corrected visual acuity, anatomical effect, electrical activity of the retina, haematological, biochemical and immunological parameters. RESULTS: Rheopheresis treatment contributed significantly: 1) to stabilisation of best corrected visual acuity of the treated patients, which initially showed an insignificant increased during the 2-years follow-up period, and then slightly decreased. By contrast, visual acuity decreased in the control group, to an insignificant degree up to 4 years, then statistically significantly. 2) to an improvement of the morphological findings in 62.4% of treated patients compared to 7.5% in the control group, while disease progression to stage 3 (neovascular form of the disease or geographic atrophy) with a significant decrease of visual acuity occurred in only 7.1% of treated patients, versus 37.0% in the control group. 3) to regression, even to the attachment of drusenoid pigment epithelial detachment (DPED). To a reduction of the area of DPED in 80.4% of treated patients, in contrast with an steaincrease in the area of DPED in 47.1% of patients in the control group, and the development of new DPED in only 2 eyes of treated patients compared with 16 eyes of patients in the control group. 4) to a preservation of the integrity of the ellipsoid layer in the fovea in 68.2% of the treated patients, while by contrast we found a damaged ellipsoid layer in the fovea in 66.6% of the control patients. 5) to a stabilisation of the activity of ganglion cells, the pineal system and the activity of the central area of the retina, with eccentricity between 1.8° and 30° in the treated patients, compared to alteration in the control group manifested mainly after 3.5 years of the follow-up period. 6) to a statistically significant improvement in rheological parameters, thereby increasing flow in microcirculation and positively influencing the metabolism in the retina. Also to a positive effect on the classical, alternative and lectin pathway of complement activation, a reduction in the level of proprotein convertase subtilisin kexin 9 (PCSK9), and thus also the level of LDLcholesterol, and 7) Additional treatment with 2 RHF procedures (so-called "booster therapy") seems to be a safe and suitable method of prolonging the stabilisation phase, or even improving visual acuity, anatomical and functional findings. CONCLUSION: We demonstrated positive changes in anatomical, functional and humoral parameters upon rheopheresis treatment of AMD. Their correlation provides a real possibility to identify patients at risk and to manage an individualised regime of rheopheresis therapy. This method of treatment is effective and safe, with a low percentage of non-serious adverse effects.

Unexpected cleavage of upper rim-bridged calix[4]arenes leading to linear oligophenolic derivatives.

Regioselective meta-mercuration followed by Pd-catalysed intramolecular bridging gave birth to a novel type of calixarene bearing a single bond bridge between the meta positions of the neighboring aromatic subunits. These bridged derivatives possess extremely distorted cavities that imply possible amended properties over common calix[4]arenes. This new type of calixarene reactivity can be documented by acid-/electrophile-mediated cleavage of the basic macrocyclic skeleton leading to open oligomeric structures-the behavior of which has never been observed before in classic calix[4]arenes bearing alkoxy groups on the lower rim.

Application of RDC enhanced NMR spectroscopy in structural analysis of thiacalix[4]arene derivatives.

Thiacalix[4]arene spirodienone was rearranged into the corresponding phenoxathiin-based macrocycle. Alkylation of this inherently chiral system to achieve its immobilization led to a mixture of only two (out of four theoretically possible) stereoisomers. As standard NOE and dynamic NMR experiments did not lead to unambiguous determination of the structures we applied the Residual Dipolar Coupling constant (RDC) method. Poly-γ-ethyl-l-glutamate (PELG) and poly-γ-benzyl-l-glutamate (PBLG) were found to be easily applicable lyotropic liquid crystalline alignment media for the conformational analysis of thiacalixarene derivatives. Using these media the 1,2-alternate and the partial cone conformations were determined unequivocally.

Mercuration of thiacalix[4]arenes in the cone and 1,3-alternate conformations.

The first mercuration in the thiacalixarene series using thiacalix[4]arenes immobilized in the cone or 1,3-alternate conformations gave a mixture of two monomercurated regioisomers (meta and para) in approx. 4 : 1 and 2 : 1 ratios, respectively. The organomercurial intermediates show unusual solid-state behaviour, as evidenced by the formation of η(6) complexes, and can be easily transformed into halogen-substituted derivatives, so far inaccessible in thiacalixarene chemistry. This paves the way towards the synthesis of inherently chiral thiacalixarene-based receptors with an unusual substitution pattern.

[Changes in weight and diabetes compensation (HbA1c) in patients with diabetes mellitus type 2 after adding exenatide (Byetta) to the current treatment in 28 diabetology departments in the Czech Republic -  BIBYII study (observations lasting 24 months)]. / Zmeny hmotnosti a kompenzace diabetu (HbA1c) u nemocných s diabetes mellitus 2. typu po pridání exenatidu (Byetta) ke stávající lécbe ve 28 diabetologických ambulancích v CR -  studie BIBYII (sledování 24 mesícu).

UNLABELLED: BIBYII STUDY OBJECTIVE: To obtain experience with longterm (24 months) exenatide treatment (Byetta) in patients with diabetes mellitus type 2 from a common clinical practice of diabetology departments in the Czech Republic. TYPE OF OBSERVATION: Observational study conducted by a randomly selected group of outpatient medical practitioners from 28 diabetology departments in the Czech Republic. OBSERVED AND ASSESSED POPULATION: From the original population of 465 patients, who underwent a minimum of three months Byetta treatment, 169 patients (36.6%) remained during the second prolonged observation after 18 months, and 76 patients completed 24 months of uninterrupted Byetta treatment. The following basic information about the patients was collected: year of birth, sex, age when diabetes mellitus (DM) manifested, height, maximum weight before diabetes and when DM manifested. The study recorded the following values in three- month intervals: weight, waistline, glycated haemoglobin (HbA1c), and DM treatment. The population of the prolonged observation comprised 50.3% women and 49.7 % men, and the average age at the time of DM2 manifestation was 48.0 (20- 73 years). RESULTS: At the beginning of Byetta treatment, the average maximum BMI in the subpopulation observed for 24 months was 38.44; after 3, 6, 9, 12 and 24 months the following levels were measured, respectively: 36.79, 36.22, 35.91, 35.57 and 35.58. The original HbA1c level of 7.44% at the beginning of Byetta treatment decreased after 3, 6, 9, 12 and 24 months to 6.33, 5.98, 5.83, 5.86 and 5.93%. CONCLUSION: Adding Byetta to the currently applied treatment of obese patients with diabetes mellitus type 2 over a period of 24 months has led to an improvement in HbA1c level by 1.51%, and BMI level was reduced by 2.37 after two years of Byetta treatment.

[Changes in weight and diabetes compensation (HbA(1c)) in patients with diabetes mellitus type 2 after adding exenatide (Byetta) to the current treatment in 28 diabetology departments in the Czech Republic - BIBY-I study (observations lasting 3 to 12 months)]. / Zmeny hmotnosti a kompenzace diabetu (HbA(1c)) u nemocných s diabetes mellitus 2. tpu po pridání exenatidu (Byetta) ke stávající lécbe ve 28 diabetologických ambulancích v CR--studie BIBY-I (sledováni 3-12 mesícu).

UNLABELLED: BIBY STUDY OBJECTIVE: To obtain experience with exenatide treatment (Byetta) in patients with diabetes mellitus type 2 in a common clinical practice ofdiabetology departments. TYPE OF OBSERVATION: Observational study conducted by a randomly selected group of outpatient medical practitioners from 28 diabetology departments in the Czech Republic. OBSERVED AND ASSESSED POPULATION: 465 patients underwent at least three months of Byetta treatment; 347 persons (74.6% ofthe research population) stayed forthe extended observation of 6-12 months. Apart from the basic identification data (year of birth, sex, age when diabetes mellitus manifested, height, maximum patient weight before diabetes and when diabetes mellitus manifested), the following information was recorded in three-month intervals: weight, waistline, glycated haemoglobin (HbA(1c)), and diabetes mellitus treatment The population included 50.3% women and 49.7% men, and the average age at the time of diabetes manifestation was 48 (20-73 years). The period between the diabetes manifestation and the start of exenatide treatment was 8.3 years on average. RESULTS: The average maximum BMI value before the detection of diabetes was 39.05 (+/- 6.73); at the time of the diabetes manifestation 37.88 (+/- 6.40); and at the start of Byetta treatment 39.01 (+/- 6.22). The BMI after three, six, and 12 months of treatment was as follows: 37.86 (+/- 6.12), 37.18 (+/- 6.0), and 36.60 (+/- 6.21); it decreased by > or = 0.5 in 83.3% patients who were under observation for 12 months. HbA(1c) value decreased in the first three months from 7.39% (+/- 1.57) to 6.41% (+/- 1.34), p < 0.0001. In the period of three-six months, the value decreased to 6.22% (+/- 1.34), and after 12 months, HbA(1c) was at 6.04 (+/- 1.20). An improvement in HbA(1c) value of 0.5-2.0% occurred after the first year in 49% of our research population. The waistline was measured on a regular basis in only 267 patients (58.9%). The average initial value of 120.7 cm was reduced within three months of the treatment to 118.3 cm, and within six and 12 months to 117.3 and 112.6 cm respectively. CONCLUSION: Adding Byetta to the currently applied treatment of obese patients with diabetes mellitus type 2 led, in 66.8% of the population, to a statistically significant reduction in HbA(1c) levels in the first three-six months of the treatment; after 12 months of treatment, 25% of the population was still showing an improvement in HbA(1c) of > 2.0%. Of observed patients, 74.4% significantly reduced their BMI (by > 0.5) during the first three months; 39.6% of patients reduced their BMI in the period of three-six months.

Tomentomimulol and mimulone B: two new C-geranylated flavonoids from Paulownia tomentosa fruits.

Two new discovered C-geranylated flavonoids tomentomimulol (1) and mimulone B (2) were isolated from the methanol extract of Paulownia tomentosa (Thunb). Steud. (Paulowniaceae) fruits by exhaustive chromatographic separation together with one known compound tanariflavanone D (3). The identification of compounds and structure elucidation was carried out using 1D and 2D NMR experiments, as well as mass spectroscopy, ultra-violet, infra red and CD experiments.

[The coincidence of the junction layer of inner and outer photoreceptors segments (IS/OS) defects localization on SD OCT and functional defects in case of Stargardt disease--a case report]. / Koincidence lokalizace defektu vrstvy junkce IS/OS fotoreceptoru na SD OCT s funkcními poruchami v prípade Stargardtovy choroby.

Case report of the different visual functions of the right and left eye of 60-years old man with Stargardt disease is presented. The difference in best corrected visual acuity between both eyes is accompanied with corresponding various alteration of the central retinal activity using multifocal electroretinography (mfERG) and asymmetrical defects of the IS/OS photoreceptor junction using HD-OCT.

Determinants of premature atherosclerosis in children with end-stage renal disease.

Cardiovascular disease is a major cause of morbidity and mortality in young adults with end-stage renal disease (ESRD), but its basis is still not well understood. We therefore evaluated the determinants of atherosclerosis in children with ESRD. A total of 37 children with ESRD (with 31 who had undergone transplantation) were examined and compared to a control group comprising 22 healthy children. The common carotid intima-media thickness (CIMT) was measured by ultrasound as a marker of preclinical atherosclerosis. The association of CIMT with anthropometrical data, blood pressure, plasma lipid levels, and other biochemical parameters potentially related to cardiovascular disease was evaluated. Children with ESRD had significantly higher CIMT, blood pressure, and levels of lipoprotein (a), urea, creatinine, ferritin, homocysteine, and serum uric acid as well as significantly lower values of apolipoprotein A. The atherogenic index of plasma (log(triglycerides/HDL cholesterol)) was also higher in patients with ESRD; however, this difference reached only borderline significance. In addition, a negative correlation was found between CIMT and serum albumin and bilirubin in the ESRD group, and this correlation was independent of age and body mass index. In the control group, a significant positive correlation was observed between CIMT and ferritin levels. Factors other than traditional cardiovascular properties, such as the anti-oxidative capacity of circulating blood, may be of importance during the early stages of atherosclerosis in children with end-stage renal disease.

Neoparamoeba branchiphila n. sp., and related species of the genus Neoparamoeba Page, 1987: morphological and molecular characterization of selected strains.

A total of 18 Neoparamoeba strains were characterized both morphologically and using the SSU rRNA gene sequences as molecular markers. Nine were isolated from gills of farmed Atlantic salmon, Salmo salar L., six from sediments sampled in areas of sea-cage farms and three from net material of sea-cages. The newly obtained sequences extended substantially the dataset of Neoparamoeba strains available for phylogenetic analyses, which were used to infer taxonomic relatedness among 32 strains morphologically assigned to this genus. In addition to the N. pemaquidensis and N. aestuarina clades, phylogenetic analyses clearly distinguished a third clade with sequences from six strains. Members of this clade are characterized as representatives of a new species, N. branchiphila n. sp. The diagnostic primers for the identification of this species are introduced.

Somatostatin: beneficial effects on remission in young adult patients with newly diagnosed diabetes mellitus type 1.

To assess a possible influence of short-term administration of somatostatin on remission development in adult patients with newly diagnosed diabetes mellitus type 1, the somatostatin analog octreotide was given for two weeks after the establishment of the diagnosis at the daily dose of 150 microg subcutaneously in addition to the regular insulin and metabolic therapy. When compared to the control group, the remission was achieved earlier in the octreotide group (6+/-4 weeks vs. 11+/-12 weeks in the control group, p 0.05) and its duration was longer (99+/-49 weeks vs. 49+/-31 weeks in the control group, p 0.05). Moreover, remission also appeared in patients from the octreotide group with lower endogenous residual secretion of insulin (basal C peptide at the time of diagnosis in patients who later entered remission was 0.23+/-0.16 nmol/l vs. 0.34+/-.18 nmol/l in the control group, p<0.05). The increase of 24-h urine excretion of C-peptide after the therapy with octreotide was predictive for remission development. It can thus be concluded that octreotide administration in adults with newly diagnosed diabetes mellitus type 1 positively influences both the onset and duration of remission.

Synthesis and cytostatic activity of substituted 6-phenylpurine bases and nucleosides: application of the Suzuki-Miyaura cross-coupling reactions of 6-chloropurine derivatives with phenylboronic acids.

The Suzuki-Miyaura reaction of protected 6-chloropurine and 2-amino-6-chloropurine bases and nucleosides with substituted phenylboronic acids led to the corresponding protected 6-(substituted phenyl)purine derivatives 6-9. Their deprotection yielded a series of substituted 6-phenylpurine bases and nucleosides 10-13. Significant cytostatic activity (IC(50) 0.25-20 micromol/L) in CCRF-CEM, HeLa, and L1210 cell lines was found for several 6-(4-X-substituted phenyl)purine ribonucleosides 12 (X = H, F, Cl, and OR), while the 6-phenylpurine and 2-amino-6-phenylpurine bases 10 and 11, as well as 2-amino-6-phenylpurine ribosides 13, were entirely inactive against these cell lines.

Structure-antiviral activity relationship in the series of pyrimidine and purine N-[2-(2-phosphonomethoxy)ethyl] nucleotide analogues. 1. Derivatives substituted at the carbon atoms of the base.

A series of dialkyl esters of purine and pyrimidine N-[2-(phosphonomethoxy)ethyl] derivatives substituted at position 2, 6, or 8 of the purine base or position 2, 4, or 5 of the pyrimidine base were prepared by alkylation of the appropriate heterocyclic base with 2-chloroethoxymethylphosphonate diester in the presence of sodium hydride, cesium carbonate, or 1,8-diazabicyclo[5,4, 0]undec-7-ene (DBU) in dimethylformamide. Additional derivatives were obtained by the transformations of the bases in the suitably modified intermediates bearing reactive functions at the base moiety. The diesters were converted to the corresponding monoesters by sodium azide treatment, while the free acids were obtained from the diester by successive treatment with bromotrimethylsilane and hydrolysis. None of the PME derivatives in the pyrimidine series, their 6-aza or 3-deaza analogues, exhibited any activity against DNA viruses or retroviruses tested, except for the 5-bromocytosine derivative. Substitution of the adenine ring in PMEA at position 2 by Cl, F, or OH group decreased the activity against all DNA viruses tested. PMEDAP was highly active against HSV-1, HSV-2, and VZV in the concentration range (EC50) of 0.07-2 microg/mL. Also the 2-amino-6-chloropurine derivative was strongly active (EC50 = 0.1-0. 4 microg/mL) against herpes simplex viruses and (EC50 = 0.006-0.3 microg/mL) against CMV and VZV. PMEG was the most active compound of the whole series against DNA viruses (EC50 approximately 0.01-0.02 microg/mL), though it exhibited significant toxicity against the host cells. The base-modified compounds did not show any appreciable activity against DNA viruses except for 7-deazaPMEA (IC50 approximately 7.5 microg/mL) against HIV-1 and MSV. The neutral (diisopropyl, diisooctyl) diesters of PMEA were active against CMV and VZV, while the corresponding monoesters were inactive. The diisopropyl ester of the 2-chloroadenine analogue of PMEA showed substantially (10-100x) higher activity against CMV and VZV than the parent phosphonate. Also, the diisopropyl and diisooctyl ester of PMEDAP inhibited CMV and VZV, but esterification of the phosphonate residue did not improve the activity against either MSV or HIV.

Towards regioselective synthesis of oligosaccharides by use of alpha-glucosidases with different substrate specificity.

alpha-Glucosidase from two microbial sources, Bacillus stearothermophilus and Brewer's yeast, has been used to catalyze transglycosylation reactions and a comparative study was carried out to determine the regioselectivity of this reaction. Bacterial alpha-glucosidase exhibited higher transfer activity with maltose and was able to synthesize tri- and tetrasaccharides in high yield (27%). In the case of yeast enzyme, only trisaccharides were synthesized in lower yield. Structure analysis of transglycosylation products by means of GC-MS and NMR spectroscopy revealed a correlation between the hydrolytic substrate specificity and the regioselectivity of transglycosylation reaction. Higher substrate specificity of bacterial enzyme, however, influenced its transglucosylation activity toward other saccharide acceptors.

[Importance of short-term administration of low doses of somatostatin analog in the development and remission of type 1 diabetes mellitus in adult patients]. / Význam krátkodobého podání malých dávek analogu somatostatinu pro vznik a vývoj remise u dospelých nemocných s cerstvým diabetem I. typu.

The objective of the presented work was to evaluate the short-term administration of octreotide on the development, onset and persistence of remission in recent insulin-dependent diabetics. The importance of remission means for the patient a clinically favourable condition with satisfactory metabolic compensation and a greater metabolic stability during the subsequent course of the disease. The period of remission is important from the aspect of prevention of late organ complications. Two-week treatment with octreotide, 150 micrograms/day, administered during the first month after establishment of the diagnosis was not associated with serious undesirable effects. Treatment with octreotide led to more frequent development of remission, partial and complete, as compared with a control group. In the majority of diabetics in the intervened group remission started immediately after administration of octreotide. The serum value of peptide-C as part of the glucagon test made at the time of diagnosis had a predictive value for the development of induced and spontaneous remission. Octreotide administration increased the probable development of remission even in patients with a substantially lower peptide C value at the time of diagnosis as compared with controls. The preliminary results indicate also a protraction of the remission period.

Acyclic nucleotide analogs derived from 8-azapurines: synthesis and antiviral activity.

Reaction of phosphoroorganic synthons with 8-azaadenine, 8-aza-2, 6-diaminopurine, and 8-azaguanine using cesium carbonate yielded regioisomeric 8-azapurine N7-, N8-, and N9-(2-(phosphonomethoxy)alkyl) derivatives. This reaction followed by deprotection afforded isomeric 2-(phosphonomethoxy)ethyl (PME), (S)-(3-hydroxy-2-(phosphonomethoxy)propyl) [(S)-HPMP], (S)-(3-flouro-2-(phosphonomethoxy)propyl) [(S)-FPMP], (S)-(2-(phosphonomethoxy)propyl) [(S)-PMP], and (R)-(2-(phosphonomethoxy)propyl) [(R)-PMP] derivatives. 13C NMR spectra were used for structural assignment of the regioisomers. None of the 8-isomers exhibited any antiviral activity against herpesviruses, Moloney murine sarcoma virus (MSV), and/or HIV. 9-(S)-HPMP-8-azaadenine (23) and PME-8-azaguanine (65) were active against HSV-1, HSV-2, and CMV at 0.2-7 micrograms/mL, VZV at 0.04-0.4 microgram/mL, and MSV (at 0.3-0.6 microgram/mL). PME-8-azaguanine (65) and (R)-PMP-8-azaguanine (71a) protected MT-4 and CEM cells against HIV-1- and HIV-2-induced cytopathicity at a concentration of approximately 2 micrograms/mL.

Synthesis of 2'-aminomethyl derivatives of N-(2-(phosphonomethoxy)ethyl) nucleotide analogues as potential antiviral agents.

A series of purine and pyrimidine N-(2-(phosphonomethoxy)ethyl) derivatives bearing aminomethyl, (dimethylamino)methyl, morpholinomethyl, and (trimethylammonio)methyl groups at the 2'-position were synthesized. The compounds were prepared by alkylation of the heterocyclic bases with appropriately substituted (aminoalkyl)oxiranes followed by condensation of the resulting intermediates with dialkyl ((p-tolylsulfonyl)oxy)methanephosphonate and subsequent treatment of the obtained diester with bromotrimethylsilane. 9-(3-Amino-2-(phosphonomethoxy)propyl)adenine (2a) proved active against varicella zoster virus (VZV), cytomegalovirus (CMV), and Moloney murine sarcoma virus (MSV) in the concentration range of 7-35 micrograms/mL. None of the other aminoalkyl derivatives demonstrated significant antiviral activity against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2), VZV, (CMV), vaccinia virus (VV), MSV, and human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2).

Antiviral activity of selected acyclic nucleoside analogues against human herpesvirus 6.

Human herpesvirus 6 (HHV-6) was examined in vitro for its sensitivity to a broad range of nucleoside analogues, including acyclovir (ACV), ganciclovir (GCV), penciclovir (PCV), buciclovir (BCV), brivudin (BVDU), the N7-isomer of 6-deoxyganciclovir (S2242), foscarnet (phosphonoformic acid, PFA), and several acyclic nucleoside phosphonate (ANP) analogues such as (S)-HPMPA, (S)-HPMPC, PMEA and PMEDAP. Antiviral efficacy was monitored microscopically by the inhibitory effect of the compounds on HHV-6-induced cytopathic effect in human T-lymphoblastoid HSB-2 cells. In addition, a newly developed immunofluorescence/flow cytometric assay (FACS) was used to determine HHV-6-specific antigen expression. A close correlation was observed between the antiviral data obtained by the microscopic assay and the flow cytometric assay. Marked antiviral efficacy was noted for S2242, PFA and the ANP analogues (S)-HPMPA, (S)-HPMPC, (S)-cHPMPC, (S)-3-deaza-HPMPA, (S)-3-deaza-cHPMPA, (S)-HPMPG and (R)-HPMPG. Also, PMEA and PMEDAP proved highly active against HHV-6 infection, whereas (S)-FPMPA and (R)-PMPDAP were inactive. ACV was only slightly protective against HHV-6, and no activity was found for GCV, PCV, BCV and BVDU. Overall, the efficacy of the nucleoside analogues against HHV-6 appeared to correlate with their efficacy against human cytomegalovirus (HCMV).

An adapted program of colorectal cancer screening--7 years experience and cost-benefit analysis.

The Czech program of colorectal cancer screening differs from most foreign programs in a number of points. The age interval of screened population was limited to 45 to 60 years. Screening was multicentric, with one reference center. More than 95% of the subjects screened were asymptomatic employees of various factories, boards and institutions. Total colonoscopy was the primary procedure in all Haemoccult-positive subjects. Some 109,213 subjects received 3 Haemoccult slides. Compliance was 83.1%, and Haemoccult was positive in 2.92% of the subjects. The diagnostic program revealed 347 (13.1%) cancers, 763 adenomas in 592 (22.2%) subjects, and other bleeding conditions in 1043 (39.2%) persons. Dukes A or B colorectal cancer was found in two-thirds of the screened subjects and in only one-third of non-screened symptomatic patients. Average diagnostic and therapeutic costs were almost the same in both groups. Gross national product savings realized by one asymptomatic subject were 315,540 Czechoslovak Crowns (approximately 18,560 US-dollars at the 1989 exchange rates). The adapted program was found to be effective, and its use in a population with a high incidence of colorectal neoplasia deserves consideration.