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Diabetic neuropathic cachexia associated with malabsorption.

Diabetic neuropathic cachexia is characterized by neuropathic pain and severe weight loss of unknown aetiology. We describe four patients with diabetic neuropathic cachexia who were found to have malabsorption. Four diabetic patients presented with neuropathic pain, anorexia, depression and weight loss of 16 (range 10-21) kg. None complained of diarrhoea. There were three males and one female, median age 54 (46-67) years. A butterfat test showed a serum turbidity difference of 9 (6-10) light scattering units (normal greater than 60 units). The median serum xylose was low and there was delayed urinary xylose excretion. Urinary indicans, small bowel histology, liver function tests, and thyroid and renal function were normal. Ultrasound scans of liver, gall bladder and pancreas, and endoscopic retrograde cholangiopancreatogram were normal. The patients were treated with pancreatic supplements and a high calorie diet. Three have completely recovered and the other patient is improving. Thus these cases of diabetic neuropathic cachexia appeared to be associated with malabsorption which may be due to pancreatic dysfunction. It is suggested that the management of diabetic neuropathic cachexia should include the investigation and treatment of malabsorption.

Aged↗

[Detection of new pigments related to purple urine bag syndrome].

It is well known that participation of two kinds of pigments, indigo blue and indigo red, are concerned with purple urine bag syndrome (PUBS). However, there is no research which describes the participation of other pigments. We separated three new kinds of red pigments, other than indigo blue and indigo red, from four patients with PUBS. One of the pigments was not visible to the naked eye and appeared only when an ultraviolet ray was irradiated. The appearance patterns of indigo blue, indigo red and the three new red pigments were in complete agreement in two cases, but differed in the other two cases. Moreover, bacteria isolated from the urine were cultured in an indican-added alkaline liquid media (pH9), 80% or more bacteria produced purple pigments. In case 1, from deep-colored pigments, each bacterium produced both indigo blue and indigo red, although new pigments could not be observed in the in vitro media.

Aged↗

beta-Glucosidase Activity in Phytopathogenic Bacteria.

Most of 58 isolates of phytopathogenic and related bacteria comprising 24 species in the genera Agrobacterium, Erwinia, Corynebacterium, Pseudomonas, and Xanthomonas exhibited beta-glucosidase activity, especially the gall-nonforming pathogenic pseudomonads and soft rot organisms. The gall-forming pseudomonads and P. fluorescens exhibited no beta-glucosidase activity, with the exception of one isolate of P. savastanoi which showed slight activity on an inorganic nitrogen-arbutin medium. The best medium for demonstrating beta-glucosidase activity contained peptone as the nitrogen source and arbutin. beta-Glucosidase activity in this medium was indicated by either acid production or browning. P. syringae, in contrast to other bacteria tested, produced most beta-glucosidase in a medium containing large amounts of glucose. Chromatographic analyses confirmed that splitting of the glucoside occurred at the glucosidic linkage. Reaction of sonically treated bacterial cells with indican or p-nitrophenyl-beta-D-glucoside proved a rapid method for assaying relative amounts of beta-glucosidase among bacterial species. Harda's paper-strip method of detecting beta-glucosidase also was useful in revealing the distribution and relative amounts of beta-glucosidase in most bacteria, but did not indicate the relatively greater amount of beta-glucosidase in P. syringae.

Journal Article↗

Novel indole S,O-bisdesmoside, calanthoside, the precursor glycoside of tryptanthrin, indirubin, and isatin, with increasing skin blood flow promoting effects, from two Calanthe species (Orchidaceae).

The methanolic extracts from Calanthe discolor LINDL. and C. liukiuensis SCHLTR. were found to exhibit hair restoring and skin blood flow promoting activities. Through bioassay-guided separation using the skin blood flow increasing effect, a novel indole S,O-bisdesmoside, calanthoside, was isolated together with three new components, glucoindican, calaliukiuenoside, and calaphenanthrenol, and known compounds such as tryptanthrin, indirubin, isatin, and indican. The structures of the new compounds were determined on the basis of physicochemical and chemical evidence and they showed an activating effect on skin blood flow. In addition, it was found that enzymatic hydrolysis of calanthoside with beta-glucosidase furnished tryptanthrin together with a small amount of indirubin and isatin, whereas indirubin and isatin were obtained from calanthoside by acid hydrolysis. Based on their contents in the fresh and dried plant, calanthoside may be a common genuine glycoside of tryptanthrin, indirubin, and isatin in the plant.

Animals↗

Light quality influences indigo precursors production and seed germination in Isatis tinctoria L. and Isatis indigotica Fort.

Isatis tinctoria L. and Isatis indigotica Fort. are biennial herbaceous plants belonging to the family of Cruciferae that are used as a source of natural indigo and show several morphological and genetic differences. Production of indigo (indigotin) precursors, indican (indoxyl beta-D glucoside) and isatan B (indoxyl ketogluconate), together with seed germination ability were compared in Isatis tinctoria and Isatis indigotica grown under six different light conditions (darkness, white, red, far red, blue, yellow light) at 25 degrees C. Light quality influenced both germination and production of indigo precursors in the two Isatis species. Different responsiveness to far red and blue light was observed. Indeed, a detrimental effect on germination by blue and far red light was found in I. tinctoria only. Different amounts of isatan B were produced under red and far red light in the two Isatis species. In I. tinctoria, the level of main indigo precursor isatan B was maximal under red light and minimal under far red light. Whereas in I. indigotica far red light promoted a large accumulation of isatan B. The photon fluence rate dependency for white and yellow light responses showed that the accumulation of indigo precursors was differently influenced in the two Isatis species. In particular, both white and yellow light enhanced above 40 micromol m(-2) s(-1) the production of isatan B in I. indigotica while only white light showed a photon fluence dependency in I. tinctoria. These results suggest a different role played by the labile and stable phytochrome species (phyA and phyB) in the isatan B production in I. tinctoria and I. indigotica. I. indigotica, whose germination percentage was not influenced by light quality, demonstrated higher germination capability compared with I. tinctoria. In fact, I. tinctoria showed high frequency of germination in darkness and under light sources that establish high phytochrome photoequilibrium (red, white and yellow light). Germination in I. tinctoria was negatively affected by far red and blue light. I. indigotica seeds appear to be indifferent to canopy-like light (far red). Our results provide further insights on the distinct behaviour of I. tinctoria and I. indigotica that belong to two different genetic clusters and different original environments.

Germination↗

[Microecological system and its importance in evaluation of the effectiveness of biologically active supplements and probiotic products].

A possibility to estimate a quality of bioactive supplements and probiotical foods by their influence on microecological system of a gastrointestinal tract are exhibited as a result of multiyear research. The consist and biological activity of micropopulations, including the normalization of level of protective intestinal microflora, the increasing their antibiosis activity, the elimination of potentially pathogenic microorganisms, the excretion of volatile phenols and indican with urine, the content of volatile fatty acids, enzymes, secretory immunoglobulins in feces, destruction in vitro cholic acid and cholesterol etc., are tested as indicators. The reasoned supposal is advanced that the wide spread of disbacteriosis is connected not only with changing of defence mechanisms (reactions) of macroorganism, but also with accumulation of pathogenic features in microorganisms by action of environmental factors.

Bacteria↗

A study of urinary tryptophan metabolites in relation to the phenylalanine content of semi-synthetic diets in a patient with phenylketonuria.

The influence of different phenylalanine (Phe) levels in semi-synthetic diets on the urinary excretion of tryptophan (Try) metabolites was studied in one untreated phenylketonuric (PKU) patient. Low dietary Phe decreased the excretion of indoleacetic acid, indolelactic acid, indican and Try but did not increase 5-hydroxyindoleacetic acid. Under the low Phe diet, the excretion of N-acetyltryptophan, kynurenic and xanthurenic acid are greatly increased in the urine after a Try load. The possible significance of the extensive acetylation of Try and Phe is discussed in relation to the low blood levels of Try and PKU and to the phenomenon of decreasing blood Phe levels in PKU.

Adult↗

Enhancing effect of allopurinol on the induction of bladder cancer in rats by n-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide.

The effects of allopurinol on the induction of bladder cancer by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), excretion of urinary tryptophan metabolites, hepatic nitroreductase activity, and the acid-soluble thiol content of liver and blood in weanling female Fischer rats were investigated. Four groups of rats were given normal diet or normal diet supplemented with 0.005% allopurinol, 0.188% FANFT, or 0.005% allopurinol-0.188% FANFT. Transitional cell carcinomas appeared in 3 of 30 rats (10%) at 15 weeks and in 7 of 44 rats (16%) at 20 weeks in the FANFT-treated group; the carcinomas appeared in 14 of 35 rats (40%) at 15 weeks and in 27 of 50 rats (54%) at 20 weeks in the FANFT-allopurinol-treated group. Growth rate was not affected by allopurinol and FANFT. Allopurinol alone caused no morphological change in the epithelial cells of the urinary bladder but decreased hepatic cytosol nitroreductase activity. FANFT alone had no effect on hepatic cytosol or microsomal nitroreductase activity but increased hepatic and blood acid-soluble thiol content. FANFT increased the urinary excretion of anthranilic acid glucuronide, kynurenine, acetylkynurenine, and 3-hydroxykynurenine and decreased indican and o-aminohippurate excretion. Allopurinol did not alter the effects of FANFT on the acid-soluble thiol content of liver and blood or the excretion of urinary tryptophan metabolites.

Allopurinol↗

Baltic myoclonus.

It has been found that PME without Lafora bodies is more common in Finland than elsewhere. The incidence is 1:20,000. The mode of inheritance is autosomal recessive. At first the children are healthy. Stimulus-sensitive myoclonic jerks and grand mal seizures appear at the age of 6 to 15 years. The EEG shows a generalized disturbance with spike-wave or polyspike-wave paroxysms which increase during photic stimulation. Myoclonic jerks incapacitate the patient. Within 5 years after the onset of the first symptoms, many patients have a disorder of gait and may become confined to bed. Sodium valproate alone or combined with clonazepam is the most effective therapy. However, the course of the disease is progressive. The mean age at death has been 24 years but appears to be increasing. The etiology and pathogenesis of PME without Lafora bodies are unknown. Increased excretion of indican has been noted, suggesting deficient intestinal absorption of L-tryptophan. A loss of Purkinje cells is the most prominent neuropathological feature. No inclusion bodies are present. Finnish PME patients are similar to the patients described by Unverricht from Estonia and by Lundborg from Sweden. Neuropathological data from these patients are not available. Clinically, these patients could form an entity with Finnish patients defined as a Baltic or Nordic type of PME. The gene is enriched in Finland, but elsewhere it is rare.

Adolescent↗

[Effect of antibiotics on intestinal microflora and production of metabolites].

Methodical approaches to detection of relation between intestinal microflora and its metabolites are described. The microbial origin of certain compounds can be asserted by a decrease in their production after exposure to antibacterial drugs or the absence of their production in microbe-free animals. The authors consider that parallel investigation of intestinal microflora and its metabolites after exposure to various agents e.g. narrow spectrum antibiotics or specific substrates is the most accurate methodical approach to detection of their interrelations. Data on the effect of four drugs i.e. kanamycin, metronidazole, cefotaxime and bactrim on production of 10 bacterial metabolites: p-cresol, phenol, indican, acetic, propionic, butyric, isobutyric, valeric, isovaleric and caproic acids in rats are presented. Correlation between the metabolites and the intestinal microflora composition was revealed. It is concluded that detection of microorganisms responsible for production of definite metabolites requires at the maximum: (1) exposure to drugs of different spectra, (2) detection of changes in intestinal microflora by biotope++ and (3) investigation of mucosa microflora which more exactly characterizes metabolism of definite biotops.

Animals↗

Improved reagent for detection of allantoin in thin-layer chromatographic method for urine stains on foods and packaging.

Ten detection reagents known to react with either primary amine groups or indole derivatives were tested to improve sensitivity for allantoin (ALN) and indican (IND) in the official AOAC thin-layer chromatographic method for urine metabolites (44.175-44.177). The lowest levels found using the official method were 500 ng ALN and 6 ng IND. The best reagent was p-dimethylaminocinnamaldehyde (pDMAC), which yielded intensely colored spots with both compounds. The lowest amounts consistently found were 125 ng ALN and 13 ng IND. pDMAC was also used as an overspray for ALN after the spray specified in the official method, p-dimethylaminobenzaldehyde (pDMAB), was applied. This resulted in a detection limit of 250 ng. The overspray procedure was incompatible with IND detection, but provided an easy way to gain slightly greater sensitivity for ALN when use of pDMAB gave negative or borderline results. The combined use of pDMAC for ALN, and the official sprays (pDMAB and sodium acetate) for IND, maximized sensitivity for both compounds.

Allantoin↗

[Dynamic study of plasma and urine amino acid patterns after an oral load of tryptophan. Application to a patient with a complex deficiency syndrome].

The aim of this work was to show that the dynamic study of the amino acid pattern in plasma and urine following an oral load of tryptophan might confirm anomalies suggested by inconsistent clinical data and below-normal biological values. Such oral loads were administered to five control subjects and one patient who had recovered from a celiac condition but was suffering from a complex deficiency syndrome associating a polyneuritis due to a lack of folic acid and the excretion of blue-colored transpiration. Thirty minutes following the load a slowing in the rate of tryptophan absorption was observed (p less than 0.05) and, during the first 6 hours, increased urinary excretion of tryptophan (p less than 0.01) and indican (p less than 0.05). Similarly, changes in the metabolism of other amino acids were either revealed or accentuated by this oral load test (ornithine, glycine, lysine, phenylalanine). It is probable that in this patient a problem of tubular re-absorption led to tryptophan being less available for metabolization along the kynurenine pathway, accounting for the increase in urinary excretion of the amino acids concerned. The diagnosis put forward is that of an unexpressed form of Hartnup's disease in association with a folic acid deficiency.

Adult↗

Phenol sulfotransferases.

Two phenol sulfotransferases have been purified from rat liver by conventional techniques coupled with affinity chromatography on Affi-Gel blue and ATP-agarose. Both enzymes are homogeneous by the criterion of sodium dodecyl sulfate gel electrophoresis. Each enzyme has a molecular weight of approximately 65,000 and consists of two subunits of apparently equal size. The enzymes are also similar in specificity and in their kinetic parameters but differ in amino acid composition and in their elution from DEAE-cellulose. With adenosine 3'-phosphate 5'-phosphosulfate as donor, a large variety of phenolic compounds serve as sulfate acceptor; sterols, simple alcohols, bile acids, and hydroxamates do not serve as substrates. The transferases may be considered as detoxification enzymes which catalyze the conjugation of xenobiotics containing a phenol group or of phenolic compounds generated by endogenous oxidation. The enzymes act on 3-hydroxyindole to yield indican, suggesting that their in vivo function may include the production of this normal tryptophan metabolite.

Amino Acids↗

Value of small intestinal bile acid analysis in the diagnosis of the stagnant loop syndrome.

We have studied simple methods of analysing bile acids in human small intestinal aspirates, in order to assess their suitability for the routine clinical investigation of patients with steatorrhoea. Following extraction into methanol, samples were analysed qualitatively for bile acid deconjugation by thin-layer chromatography and quantitatively by the 3-alpha-hydroxysteroid dehydrogenase enzyme assay. These methods were found to give good recoveries, and to be sensitive, accurate, and specific, in addition to being sufficiently simple and rapid for routine diagnostic purposes. This diagnostic procedure was applied to the identification of patients with steatorrhoea due to the stagnant loop syndrome, and was compared with other tests for this condition, viz, study of the small intestinal bacterial flora, urinary indican excretion, and the Schilling test with added intrinsic factor. Three groups of subjects were studied; group I consisted of nine patients with steatorrhoea due to the stagnant loop syndrome; group II (disease control group) of six patients with an anatomical stagnant loop that was not causing steatorrhoea; and group III (normal control group) of 11 subjects with no known gastrointestinal disease. The screening of postprandial upper jejunal samples for bile acid deconjugation proved the most useful diagnostic test, being positive in eight out of nine patients from group I, but in none of those from groups II and III. At lower levels of the small intestine, bile acid deconjugation was found in subjects from groups II and III. The other three diagnostic tests discriminated poorly between subjects from group I and those from group II.

Adult↗

Liquid-chromatographic study of fluorescent materials in uremic fluids.

Using reversed-phase "high-performance" liquid chromatography with fluorescence detection, we separated and identified some naturally fluorescent compounds in uremic serum and hemodialysate from patients with chronic renal disease. Several of the naturally fluorescent compounds were identified as indole derivatives by co-chromatography with authentic standards. In one specific case, the identity was confirmed by an enzymic peak-shift method. Compounds identified included indican, kynurenic acid, tryptophan, and 5-hydroxy-indole-3-acetic acid. Comparison of normal and uremic serum showed that the fluorescent materials are present in significantly greater concentrations in samples from uremic patients.

Chromatography, High Pressure Liquid↗

[Urinary excretion of blastomogenic tryptophan metabolites in tubazide- and phthivazid-treated patients].

The levels of tryptophan metabolites in the urine of 30 isoniazid--and phthivazid--treated patients with tuberculosis and 25 healthy subjects were determined by paper chromatography. The urine of healthy subjects was found to contain tryptophan, indican, tryptamine and urea, while that of tuberculosis patients--tryptophan metabolites, including 3-hydroxykynurenine, known as carcinogen. Administration of pyridoxine does not eliminate metabolic disturbances caused by anti-tuberculosis of preparations, while thiamine may inhibit pyridoxine enzymes, thus aggravating these disorders.

Carcinogens↗

Endogenous accumulation products and serum protein binding in uremia.

A number of compounds known to accumulate in the blood of uremic patients were added to serum from healthy normal volunteers. It was observed that both hippuric acid and indican were capable of increasing substantially the serum f of both diazepam and warfarin. Furthermore, a mixture of nine different accumulation products (many of which did not measurably increase f when added alone) caused an even greater increase in the f of diazepam. Serum from uremic patients and from normal volunteers, with and without the addition of the compounds known to accumulate in uremia, wee treated by standard procedures (i.e., prolonged dialysis, charcoal treatment, pH alteration) to remove associated small molecules. The results of such treatments suggest that at least part of the diminished binding of drugs seen in the presence of uremia is due to the accumulation of low-molecular-weight endogenous competitors.

Blood Proteins↗

[Granulated carrots (Daucus carota) in dog nutrition].

In feeding and balance trials with dogs (4) dried, ground carrots were tested in addition (30%) to a basic dry food (rice, corn gluten, fish meal and supplements). The palatability of both mixtures was good: fecal water losses were increased after feeding the carrots. Apparent digestibilities of organic and inorganic matter, especially sodium and potassium (not phosphorus), decreased. Digestibility of carrots was calculated to reach 70% with 1.2 MJ of digestible energy per 100 g dry matter. Reduced fecal pH (6.9-->6.1), higher lactate concentrations and increasing excretion of volatile fatty acids were seen as results of the stimulated bacterial metabolism in the colon. Diurnal pattern of breath hydrogen exhalation was similar in both periods: renal excretions of phenol, indican, and nitrogen were significantly reduced after supplementation with carrots as compared to control period.

Animal Feed↗