In Vitro Surface Investigation of Calcium Fluoride-like Precipitation on Human Enamel after Topical Treatment with the Organic Fluoride Nicomethanol Hydrofluoride.

PURPOSE: The topical fluoride treatment of teeth can lead to a formation of CaF2-like material, which is considered to play a significant role in caries prevention. Different types of fluoride sources are applied. The aim of this study was to analyse the in vitro fluoridation effect of the lesser known organic fluoride compound nicomethanol hydrofluoride (NH) regarding fluoride accumulation and morphological changes on dental enamel surfaces. Materials and Methods: The fluoridation effect was investigated by scanning electron microscopy (SEM) and energy dispersive x-ray analysis (EDX) after treatment with fluoride solutions at a concentration of 1350 ppm F - and a pH value of 5.5. NH was tested against inorganic sodium fluoride (NaF) as reference. Fluoridation was done on pellicle-free and pellicle-covered enamel. Results: Formation of globular CaF2-like material was observed for both fluoride types. However, NH led to considerably higher calcium fluoride accumulation on the enamel surface as shown by both EDX and SEM. The globule diameters varied between 0.2 and 0.8 µm. Cross-sectional analysis revealed that the globular precipitates lay directly on the enamel surface; only the very surface-near volume was affected. No statistically significant difference of the fluoridation effect was measured with vs without saliva pre-treatment. Conclusion: The experiments showed a 6 times greater F - surface uptake on dental enamel with NH compared to sodium fluoride, thus suggesting an important role of NH during remineralization phases, fostering equilibrium between de- and remineralization.

A gas chromatography full scan high resolution Orbitrap mass spectrometry method for separation and characterization of 3-hydroxymethyl pyridine ester of fatty acids at low levels.

Fatty acid methyl esters (FAMEs), which are commonly used to characterize lipids, have several limitations to conclude on many structures. 3-Pyridylcarbinol esters (3-PCE) are used to characterize fatty acid structures [1], in particular, to identify ring and double bond positions on the carbon chain. Chromatographic separation of these esters is complex due to their polarity and high boiling points. In this study, we used a column with high resolutive power based on ionic liquids to increase the separation quality in gas chromatography (GC). In addition, we used a high-resolution detector (Orbitrap) to limit non-specific signals and improve the detection limits. This detector could be used with a mass filter at 5 ppm for the rapid determination of 3-PCE from its characteristic ions (m/z = 108.0441 and 92.0495). This filter allowed the identification of derivative fatty acids with good sensibility. Thus, it was possible to characterize 3-PCE by measuring the exact fragment masses to confirm structures such as C19:2n12cycloΔ9.

Effects of nicomethanol hydrofluoride on dental enamel and synthetic apatites: a role for anti-caries protection.

AIM: To analyse the anti-caries properties of nicomethanol hydrofluoride (NH) and the benefit of its combination with siliglycol, a coating agent. METHODS: Fluoride (F) uptake by dental enamel and synthetic apatite treated with NH was measured in vitro and compared to treatment with mineral fluorides. The addition of siliglycol was also tested. The effect of NH (as a mouthwash) on salivary pH was also investigated in healthy human subjects and compared to the effect of a placebo and of nicomethanol alone. RESULTS: In vitro experiments showed a greater and faster F uptake on dental enamel or synthetic apatite treated with NH compared to sodium fluoride. F uptake was improved further by the addition of siliglycol. In healthy human subjects, pH reduction was strongly inhibited 5 min after two mouthrinses with NH. This effect was less pronounced but still statistically significant at 15 and 30 min (p < 0.05). CONCLUSIONS: NH was able to promote the fixation of F ions and strengthen the dental structure. Its combination with siliglycol further improved F uptake by the tooth and the control/inhibition of dental biofilm development.

Enantiomeric separation of pharmaceutically important drug intermediates using a Metagenomic lipase and optimization of its large scale production.

In the present study, efficient enzymatic methods were developed using a recombinant metagenomic lipase (LipR1) for the synthesis of corresponding esters by the transesterification of five different pharmaceutically important secondary alcohols. The recombinant lipase (specific activity=87m6U/mg) showed maximum conversion in presence of ionic liquid with Naphthyl-ethanol (eeP=99%), Indanol and Methyl-4 pyridine methanol (eeS of 98% and 99%) respectively in 1h. Vinyl acetate was found as suitable acyl donor in transesterification reactions. It was interesting to observe that maximum eeP of 85% was observed in just 15min with 1-indanol. As this enzyme demonstrated pharmaceutical applications, attempts were made to scale up the enzyme production on a pilot scale in a 5litre bioreactor. Different physical parameters affecting enzyme production and biomass concentration such as agitation rate, aeration rate and inoculum concentration were evaluated. Maximum lipase activity of 8463U/ml was obtained at 7h of cultivation at 1 lpm, 300rpm and 1.5% inoculum.

Cytotoxic trans-platinum(II) complex with 3-hydroxymethylpyridine: Synthesis, X-ray structure and biological activity evaluation.

To assess the potential cytostatic properties of Pt(II) complexes with 3-hydroxymethylpyridine (3-hmpy) as the only carrier ligand, novel cis-[PtCl2(3-hmpy)2] (1) and trans-[PtCl2(3-hmpy)2] (2) have been prepared. Elemental analysis, FTIR spectroscopy, multinuclear NMR spectroscopy and X-ray crystallography were used to determine their structures. Based on the results obtained with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and clonogenic assay on T24 human bladder carcinoma cells (T24), the most potent compound 2 was further tested for cytotoxicity in human ovarian carcinoma cell lines - cisplatin sensitive (IGROV 1) and its resistant subclone (IGROV 1/RDDP). The cytotoxicity of compound 2 in IGROV 1/RDDP is comparable to cisplatin. Furthermore, compound 2 induced severe conformational changes in plasmid DNA, which resulted in a delayed onset of apoptosis in T24 cells, and higher amounts of Pt in tumours and serum compared to cisplatin. In addition, in vivo antitumour effectiveness was comparable to that of cisplatin with a smaller reduction of animals' body weight, thus demonstrating that it is a promising transplatin analogue which deserves further studies.

Unique odd-chain polyenoic phospholipid fatty acids present in chytrid fungi.

Chytrid fungi are ubiquitous components of aquatic and terrestrial ecosystems yet they remain understudied. To investigate the use of phospholipid fatty acids as phenotypic characteristics in taxonomic studies and biomarkers for ecological studies, 18 chytrid fungi isolated from soil to freshwater samples were grown in defined media and their phospholipid fatty acid profile determined. Gas chromatographic/mass spectral analysis indicated the presence of fatty acids typically associated with fungi, such as 16:1(n-7), 16:0, 18:2(n-6), 18:3(n-3) 18:1(n-9), and 18:0, as well as, a number of odd-chain length fatty acids, including two polyunsaturated C-17 fatty acids. Conversion to their 3-pyridylcarbinol ester facilitated GC-MS determination of double-bond positions and these fatty acid were identified as 6,9-17:2 [17:2(n-8)] and 6,9,12-17:3 [17:3(n-5)]. To the best of our knowledge, this is the first report of polyunsaturated C-17 fatty acids isolated from the phospholipids of chytrid fungi. Cluster analysis of PLFA profiles showed sufficient correlation with chytrid phylogeny to warrant inclusion of lipid analysis in species descriptions and the presence of several phospholipid fatty acids of restricted phylogenetic distributions suggests their usefulness as biomarkers for ecological studies.

F 16915 prevents heart failure-induced atrial fibrillation: a promising new drug as upstream therapy.

Atrial fibrillation (AF) is a common complication of heart failure. The aim of the present study was to investigate the effects of a new pure docosahexaenoic acid derivative called F 16915 in experimental models of heart failure-induced atria dysfunction. The atrial dysfunction-induced AF was investigated (1) in a dog model of tachypacing-induced congestive heart failure and (2) in a rat model of heart failure induced by occlusion of left descending coronary artery and 2 months reperfusion. F 16915 (5 g/day for 4 weeks) significantly reduced the mean duration of AF induced by burst pacing in the dog model (989 ± 111 s in the vehicle group to 79 ± 59 s with F 16915, P < 0.01). This dose of F 16915 also significantly reduced the incidence of sustained AF (5/5 dogs in the vehicle group versus 1/5 with F 16915, P < 0.05). In the rat model, the percentage of shortening fraction in the F 16915 group (100 mg/kg p.o. daily) was significantly restored after 2 months (32.6 ± 7.4 %, n = 9 vs 17.6 ± 3.4 %, n = 9 in the vehicle group, P < 0.01). F 16915 also reduced the de-phosphorylation of connexin43 from atria tissue. The present results show that treatment with F 16915 reduced the heart dilation, resynchronized the gap junction activity, and reduced the AF duration in models of heart failure. Thus, F 16915 constitutes a promising new drug as upstream therapy for the treatment of AF in patients with heart failure.

Copper (II) complexes of the anti-inflammatory drug naproxen and 3-pyridylmethanol as auxiliary ligand. Characterization, superoxide dismutase and catecholase--mimetic activities.

The synthesis and spectral characterization of binary copper (II) complex of the non-steroidal anti-inflammatory drug naproxen (Nap) with formula [Cu(2)(Nap)(4)](n) (1) and its ternary complex with 3-pyridylmethanol (3-pym) of formula [Cu(Nap)(2)(3-pym)(2)](n) (2) were investigated. Complex 1 is polymeric consisting of units of the known paddle-wheel dicopper (II) tetracarboxylates of four naproxenate ions bridging the two copper atoms. The units are axially connected through the neighboring carboxylate oxygen atoms. The X-ray molecular structure measurements of complex 2 showed that it is polymeric consisting of mononuclear units having trans-CuN(2)O(2) + O(2) chromophores which are bridged by 3-pyridylmethanol ligands through their methanolic oxygen atoms. The measured superoxide dismutase (SOD) mimetic activities of the complexes indicated that complexes 1 and 2 are excellent SOD mimics with an IC(50) of 0.30 microM for complex 1 and 0.39 microM for complex 2. The catecholase activities of the complexes toward the aerobic oxidation of 3,5-di-tert-butylcatechol (DTBC) to 3,5-di-tert-butylquinone (DTBQ) showed that both complexes have moderate catalytic oxidase activities.

The role of p53 in the cellular toxicity by active trans-platinum complexes containing isopropylamine and hydroxymethylpyridine.

Despite some initial research that reported a lack of activity of trans geometry, complexes with general formula trans-[PtCl2(L)(L')] exhibit an important cytotoxic activity in cisplatin-sensitive and resistant cell lines. Based on the proposed mechanism of action for the trans-platinum compounds, they might form DNA adducts initiating a DNA-damage response and ultimately ending in the activation of the p53 protein. In the present work, we have studied the biochemical properties of the trans-[PtCl2(isopropylamine)(L)] complexes (where L is 3- or 4-(hydroxymethyl)-pyridine) against several cell lines and the relationship between cytotoxicity and the protein p53. Both complexes showed different antitumoral properties depending on the presence or absence of protein p53 in isogenic colon carcinoma HCT116 cell lines. Cell cycle studies with the complexes in these cell lines were performed to investigate their antitumoral activity. Apoptosis was observed to be launched from G1 or G2/M accumulations. Confocal microscopy showed the different behaviour of isogenic tumoral cell lines treated with the trans-platinum complexes. Our data suggest that small differences in the carrier ligands could play an important role in the overall biological effects. The body of the research regarding structure-activity relationships such as the different position of groups in the carrier ligands will provide new rational basis for the design of new platinum antitumor drugs.

Oxidation of alcohols using a manganese (II) complex based on a pentakis benzimidazole amide ligand.

A pentakis benzimidazole based penta-amide ligand diethylenetriamine-N,N,N',N',N''-pentakis(2-methyl benzimidazolyl)penta-amide [GBDTPA] has been synthesized and utilized to prepare Mn (II) complexes of general composition [Mn(2)(GBDTPA)X(4)], where X is an exogenous anionic ligand (X = Cl(-), NO(3)(-) and Br(-)). The oxidation of alcohols has been investigated using [Mn(2)(GBDTPA)Cl(4)] as the catalyst and TBHP as an alternate source of oxygen. The respective aldehydic products have been isolated and characterized by (1)H NMR.

Equilibria of 3-pyridylmethanol with copper(II). A comparative electron spin resonance study by the decomposition of spectra in liquid and frozen solutions.

The copper(II)-3-pyridylmethanol (L) system was investigated in aqueous solution by two-dimensional ESR evaluation at 298 K, and computer simulation of the individual anisotropic spectra at 77 K. The data revealed that the paramagnetic copper(II) complexes [CuL] (2+), [CuL 2] (2+), [CuL 3] (2+), and [CuL 4] (2+) are formed up to pH approximately 7 at a moderate or high excess of ligand. As compared with chelating ligands, two differences were observed for the complexation of 3-pyridylmethanol with copper(II): (1) In contrast with the well-resolved spectra in frozen solution, considerable line-broadening and distortion of the spectral shapes were seen at 298 K, which was interpreted in terms of isomeric equilibria and the medium-rate interconversion of various complexes on the ESR time-scale. (2) At low temperature, there were dramatic changes in the concentration distribution, the minor complexes with higher numbers of coordinating ligands ([CuL 3] (2+) and in particular [CuL 4] (2+)) becoming strongly favored. This phenomenon is explained by the significant differences in the formation enthalpy values of various species, shifting the equilibria according to the van't Hoff equation, and a significant undercooling in the course of fast freezing of the solution, which enhances the changes of the concentration distribution.

Enzymatic oxidation of NADP+ to its 4-oxo derivative is a side-reaction displayed only by the adrenodoxin reductase type of ferredoxin-NADP+ reductases.

We have previously shown that Mycobacterium tuberculosis FprA, an NADPH-ferredoxin reductase homologous to mammalian adrenodoxin reductase, promotes the oxidation of NADP(+) to its 4-oxo derivative 3-carboxamide-4-pyridone adenine dinucleotide phosphate [Bossi RT, Aliverti A, Raimondi D, Fischer F, Zanetti G, Ferrari D, Tahallah N, Maier CS, Heck AJ, Rizzi M et al. (2002) Biochemistry41, 8807-8818]. Here, we provide a detailed study of this unusual enzyme reaction, showing that it occurs at a very slow rate (0.14 h(-1)), requires the participation of the enzyme-bound FAD, and is regiospecific in affecting only the C4 of the NADP nicotinamide ring. By protein engineering, we excluded the involvement in catalysis of residues Glu214 and His57, previously suggested to be implicated on the basis of their localization in the three-dimensional structure of the enzyme. Our results substantiate a catalytic mechanism for 3-carboxamide-4-pyridone adenine dinucleotide phosphate formation in which the initial and rate-determining step is the nucleophilic attack of the nicotinamide moiety by an active site water molecule. Whereas plant-type ferredoxin reductases were unable to oxidize NADP(+), the mammalian adrenodoxin reductase also catalyzed this unusual reaction. Thus, the 3-carboxamide-4-pyridone adenine dinucleotide phosphate formation reaction seems to be a peculiar feature of the mitochondrial type of ferredoxin reductases, possibly reflecting conserved properties of their active sites. Furthermore, we showed that 3-carboxamide-4-pyridone adenine dinucleotide phosphate is good ligand and a competitive inhibitor of various dehydrogenases, making this nucleotide analog a useful tool for the characterization of the cosubstrate-binding site of NADPH-dependent enzymes.

Determination of the site of glucuronidation in an N-(3,5-dichlorophenyl)succinimide metabolite by electrospray ionization tandem mass spectrometry following derivatization to picolinyl esters.

Derivatization using 3-pyridylcarbinol coupled with liquid chromatography electrospray ionization tandem mass spectrometry (LC/MS/MS) was used to characterize a novel Phase II metabolite of the nephrotoxic agricultural fungicide, N-(3,5-dichlorophenyl)succinimide (NDPS). A glucuronide conjugate of N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA) was identified in the urine from a rat dosed with [14C]NDPS. However, 2-NDHSA contains an aliphatic hydroxyl group and a carboxylic acid group, both of which are potential sites for glucuronidation. Mass spectrometry alone was unable to distinguish between these possibilities. Since the position of glucuronidation may be important in the mechanism of NDPS-induced nephrotoxicity, chemical derivatization in conjunction with mass spectrometry was used to characterize the glucuronide. The 2-NDHSA glucuronide conjugate was isolated from rat urine, derivatized with 3-pyridylcarbinol, and the derivatized metabolite was then analyzed by LC/MS/MS. Two known NDPS metabolites, 2-NDHSA and N-(3,5-dichlorophenyl)succinamic acid (NDPSA), were also isolated from rat urine and derivatized similarly. 3-Pyridinylcarbinol reacted rapidly with the carboxylic acid groups and formation of the picolinyl esters increased the ionization potential under positive ion conditions. The urinary glucuronide of 2-NDHSA was identified as an alcohol-linked glucuronide by examination of the molecular ions and the collision-induced dissociation (CID) product ion spectra of the derivatized products. When used in combination with mass spectrometry, derivatization of carboxylic acids with 3-pyridylcarbinol provided useful mass fragmentations and is a rapid way to obtain structural information about the position of glucuronidation of NDPS metabolites.

Influence of powder characteristics of bulk substance with pharmaceutical processing.

The physicochemical properties of crystals can vary with the crystallization procedure employed in their isolation and purification. Moreover, the success of any direct-tableting procedure is directly effected by the quality of the crystals used in this process. We examined the conventional crystallization method employed in the isolation and purification of octotiamine crystals, the active component of the pharmaceutical compound Neuvita. Our objective was to determine under what crystallization conditions (i.e., supersaturation ratio [pH], temperature, impeller speed) octotiamine crystals with excellent direct-tableting potential could be obtained. Our results indicated that modifications in pH level (from 4.3 to 4.0), i.e., a reduction in the supersaturation ratio, and in impeller speed (from 100 to 78 rpm) are necessary to obtain octotiamine crystals with superior flowability and compressibility compared to the use of the conventional crystallization method. Thus, with these modifications in the conventional crystallization method, octotiamine crystals can be made that show dissolution rates similar to those of the conventionally made crystals, yet which can be manufactured into tablets using a simpler method (i.e., direct tableting). Also, the tableting powder made from the new crystal type proved to be less adhesive than the conventionally made crystal powder. This property attributed to the new crystal type will allow for more stable automated manufacturing than the conventional crystal type would allow.

Purification and kinetic characterization of Haemophilus parasuis malate dehydrogenase.

Haemophilus parasuis malate dehydrogenase ((S)-malate:NAD+ oxidoreductase; EC 1.1.1.37) isolated from cell sonicates was purified 584-fold to electrophoretic homogeneity with a 19% recovery and a specific activity of 222 units/mg protein. SDS-polyacrylamide gel electrophoresis and molecular exclusion chromatography indicated the purified enzyme to be a dimer composed of 34,600 molecular weight subunits. Kinetic parameters for all four substrates in the forward and reverse reactions indicated a sequential mechanism for this enzymic process. Product and dead-end inhibition studies were consistent with an ordered bi-bi mechanism in which NAD is the first substrate bound to the enzyme and NADH the second product released. Protection against thermodenaturation of the enzyme by NAD and not by malate was supportive of this mechanism. A pronounced product inhibition by NADH (K(i) = 9.0 microM) was observed. Although NADP did not serve as a coenzyme, a number of analogs of NAD structurally altered in the nitrogen base moieties were observed to function as coenzymes in the oxidation of malate catalyzed by the purified malate dehydrogenase. Coenzyme-competitive inhibition of the malate dehydrogenase was observed with five adenosine derivatives and six structural analogs of NAD. Of the NAD analogs studied as inhibitors, 3-pyridylcarbinol adenine dinucleotide was the most effective (K(i) = 18 microM). Although inhibition of growth of H. parasuis by this analog was observed, it was less effective (K(i) = 136 microM) than the inhibition of the purified dehydrogenase.

Determination of nicotine and its main metabolites in urine by high-performance liquid chromatography.

Nicotine and its main metabolites (cotinine, trans-3'-hydroxycotinine, trans-3'-hydroxycotinine glucuronide, nicotine-1'-N-oxide and 3-pyridylcarbinol) were analysed in urine after liquid-liquid extraction by high-performance liquid chromatography using norephedrine as internal standard, ultraviolet detection at 260 nm and scanning ultraviolet spectra with a photodiode-array detector. The conjugated trans-3'-hydroxycotinine was determined after enzymatic hydrolysis. Specific determination of 3-pyridylcarbinol was also carried out. Owing to its good selectivity, sensitivity and reproducibility, the method was applied to the analysis of urine samples from smokers and non-smokers. The results obtained suggest that the urinary markers used to assess active smoking or exposure to environmental tobacco smoke must be not only nicotine and cotinine, but also their main free and conjugated metabolites.

Resistance to insulin mediated glucose disposal in obese subjects: respective effect of lipid metabolism and glycemia.

The present study was designed to assess the respective effect of altered lipid metabolism and hyperglycemia on glucose metabolism in vivo in obese subjects. Six young obese non-diabetic volunteers were studied on four occasions during hyperinsulinemic clamp, twice during euglycemia and twice during hyperglycemia, with or without the infusion of beta-pyridylcarbinol, an inhibitor of lipid metabolism. Glucose oxidation was calculated from continuous respiratory exchange measurements, and glucose storage was obtained as the difference between total glucose disposal and glucose oxidation. Two-way analysis of variance (with interaction term) demonstrated (i) a significant increase for total glucose disposal with beta-pyridylcarbinol but no significant effect of hyperglycemia and no interaction between the two treatments, and (ii) an important increase of beta-pyridylcarbinol to enhance glucose storage but no significant effect of hyperglycemia and no interaction between the two treatments. These results show that obese people, at physiological insulinemia, enhance their glucose disposal and glucose storage when lipid oxidation is artificially lowered. This suggests that enhanced lipid oxidation is related to insulin resistance in these patients. However, hyperglycemia in these patients failed to compensate for defective glucose disposal or storage.

Interaction of lipid and carbohydrate metabolism after infusions of lipids or of lipid lowering agents: lack of a direct relationship between free fatty acid concentrations and glucose disposal.

The present work was planned to study the effects of changes in lipid metabolism irrespective of FFA concentrations (FFA) on the regulation of oxidative and nonoxidative disposal of a glucose infusion during hyperinsulinaemia. Fifteen normal volunteers participated in the 3 protocols, in which 1) Intralipid 2) beta-pyridylcarbinol or 3) isotonic saline were infused during 2 hours. Thereafter, these infusions were discontinued and a two-hour euglycaemic hyperinsulinaemic clamp was performed. All three studies were carried out in combination with indirect calorimetry to measure glucose uptake, and oxidative and nonoxidative glucose disposal (corresponding essentially to glucose storage). Plasma FFA concentrations were 508 +/- 34, 601 +/- 43 and 546 +/- 45 mumol/l in the basal state during the Intralipid, beta-pyridylcarbinol and control protocols. It increased to 960 +/- 71 mumol/l after the Intralipid infusion, fell to 246 +/- 17 mumol/l after the beta-pyridylcarbinol infusion, vs 600 +/- 48 mumol/l in the control. At the end of the glucose-insulin clamp the values were low in the 3 protocols: 263 +/- 17, 233 +/- 19 and 204 +/- 14 mumol/l. Intralipid infusion prior to the clamp protocol induced a suppression of both insulin-mediated glucose uptake (4.91 +/- 0.46 (Intralipid) vs 6.83 +/- 0.63 mg.kg-1.min-1 (saline)) and storage (1.61 +/- 0.34 vs 2.99 +/- 0.53 mg.kg-1.min-1) while beta-pyridylcarbinol infusion induced an increased insulin-mediated glucose uptake (8.58 +/- 0.37 mg.kg-1.min-1) and in glucose storage (4.29 +/- 0.31 mg.kg-1.min-1) (p less than 0.5 vs Intralipid). These changes occurred even though FFA plasma concentrations were similar in the 3 experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ocular side effects of beta-pyridylcarbinol]. / Okuläre Nebenwirkungen von beta-Pyridylcarbinol.

Derivatives of nicotinic acid such as beta-pyridylcarbinol play an important role in the therapy of lipoprotein disorders. In 1973, J.D. Gass reported the development of cystoid macular edema provoking metamorphosia during the course of nicotinic acid treatment. The aim of this study was to determine subtle changes in ocular function induced by beta-pyridylcarbinol. We investigated 16 patients prior to and after 6 months of beta-pyridylcarbinol treatment and compared the results of clinical and color vision tests in 9 patients after 2-25 years of continuous beta-pyridylcarbinol treatment. After 6 months, significant blue-yellow color vision changes (total error scores within normal ranges) were detected by the Farnsworth-Munsell 100 hue tests in all patients. One patient demonstrated macular edema. Fluorescein angiography, however, showed no evidence of fluorescein leakage. Beta-pyridylcarbinol treatment lasting for years led to diffuse color vision disturbances (total error score = 195). To the best of our knowledge neither macular edema nor color vision disturbances following beta-pyridylcarbinol treatment have been reported so far.