RESUMEN
Clinical investigations on patients suffering from halitosis clearly reveal that in the vast majority of cases the source for an offensive breath odor can be found within the oral cavity (90%). Based on these studies, the main sources for intra-oral halitosis where tongue coating, gingivitis/periodontitis or a combination of the two. Thus, it is perfectly logical that general dental practitioners (GDPs) should be able to manage intra-oral halitosis under the conditions found in a normal dental practice. However, GDPs who are interested in diagnosing and treating halitosis are challenged to incorporate scientifically based strategies for use in their clinics. Therefore, the present paper summarizes the results of a consensus workshop of international authorities held with the aim to reach a consensus on general guidelines on how to assess and diagnose patients' breath odor concerns and general guidelines on regimens for the treatment of halitosis.
Asunto(s)
Odontólogos , Halitosis/diagnóstico , Halitosis/terapia , Pruebas Respiratorias , Humanos , Anamnesis , Examen Físico , Olfato/fisiología , Terminología como AsuntoRESUMEN
There is disagreement about a possible relationship between Helicobacter pylori (H. pylori) infection and objective halitosis, as established by volatile sulfur compounds (VSCs) in the breath. Many studies related to H. pylori used self-reported halitosis, a subjective and unreliable method to detect halitosis. In this study a possible relation between H. pylori and halitosis was evaluated, using an objective method (gas chromatography, GC) to detect the VSCs, responsible for the halitosis. The levels of the VSCs hydrogen sulfide (H(2)S), methyl mercaptan (MM) and dimethyl sulfide (DMS) were measured in mouth breath and in stomach air of 11 H. pylori positive patients and of 38 H. pylori negative patients, all with gastric pathology. Halitosis was also established by organoleptic scoring (OLS) of mouth-breath. The levels of H(2)S, MM and DMS in the mouth-breath and stomach air of the H. pylori positive patients did not differ significantly from those of the H. pylori negative patients. OLS of the mouth-breath resulted in 9 patients with halitosis, 1 out of the H. pylori positive group and 8 out of the H. pylori negative group, which is not statistically different. The concentrations of the VSCs in stomach air were in nearly all cases below the thresholds of objectionability of the various VSCs, indicating that halitosis does not originate in the stomach. The patients with gastric pathology were also compared with control patients without gastric pathology and with normal volunteers. No significant differences in VSCs in mouth breath were observed between these groups. Thus, in this study no association between halitosis and H. pylori infection was found. Halitosis, as established by GC and OLS, nearly always originates within the oral cavity and seldom or never within the stomach.
Asunto(s)
Halitosis/diagnóstico , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori , Boca/química , Pruebas Respiratorias/métodos , Cromatografía de Gases , Femenino , Humanos , Masculino , Boca/microbiología , Estómago/microbiología , Compuestos de Azufre/análisisRESUMEN
Halitosis can be subdivided into intra-oral and extra-oral halitosis, depending on the place where it originates. Most reports now agree that the most frequent sources of halitosis exist within the oral cavity and include bacterial reservoirs such as the dorsum of the tongue, saliva and periodontal pockets, where anaerobic bacteria degrade sulfur-containing amino acids to produce the foul smelling volatile sulfur compounds (VSCs), especially hydrogen sulfide (H(2)S) and methyl mercaptan (CH(3)SH). Tongue coating is considered to be the most important source of VSCs. Oral malodor can now be treated effectively. Special attention in this overview is given to extra-oral halitosis. Extra-oral halitosis can be subdivided into non-blood-borne halitosis, such as halitosis from the upper respiratory tract including the nose and from the lower respiratory tract, and blood-borne halitosis. The majority of patients with extra-oral halitosis have blood-borne halitosis. Blood-borne halitosis is also frequently caused by odorous VSCs, in particular dimethyl sulfide (CH3SCH3). Extra-oral halitosis, covering about 5-10% of all cases of halitosis, might be a manifestation of a serious disease for which treatment is much more complicated than for intra-oral halitosis. It is therefore of utmost importance to differentiate between intra-oral and extra-oral halitosis. Differences between intra-oral and extra-oral halitosis are discussed extensively. The importance of applying odor characterization of various odorants in halitosis research is also highlighted in this article. The use of the odor index, odor threshold values and simulation of bad breath samples is explained.
Asunto(s)
Halitosis , Aminas/análisis , Butiratos , Cromatografía de Gases , Halitosis/etiología , Halitosis/fisiopatología , Humanos , Azufre/análisis , Compuestos Orgánicos Volátiles/análisisRESUMEN
It is now generally accepted that the volatile sulfur compounds (VSCs) hydrogen sulfide, methyl mercaptan and dimethyl sulfide are the main contributors to halitosis when of oropharyngeal origin. Gas chromatography using a specific sulfur detector is the most appropriate method to detect halitosis of different origin (intra-oral and extra-oral halitosis) and should be considered as the gold standard. However, a gas chromatograph is an expensive apparatus and needs trained personnel. The less specific Halimeter is the most used apparatus in halitosis research. In this study a newly developed portable gas chromatograph, the OralChroma™ (Abilit Corporation, Japan), was evaluated for use in the field of halitosis. The results show that the OralChroma is a very sensitive apparatus for measuring VSCs. Just like standard gas chromatography, it can perfectly differentiate between intra-oral and extra-oral blood-borne halitosis, while the Halimeter can only detect intra-oral halitosis. The hardware of the OralChroma meets all the needs for becoming the apparatus of choice in the field of halitosis. However, the software needs a major revision. Sometimes, the concentrations given for the different VSCs are completely incorrect due to a wrong assignment of the place of the VSCs in the chromatogram.
RESUMEN
It is now generally accepted that the volatile sulfur compounds (VSCs) hydrogen sulfide, methyl mercaptan and dimethyl sulfide are the main contributors to halitosis when of oropharyngeal origin. The VSCs hydrogen sulfide and methyl mercaptan are the major causes of bad breath in oral malodour whereas dimethyl sulfide is generally the major cause of bad breath in extra-oral halitosis. To facilitate research in the field of halitosis, it is highly advantageous to be able to preserve breath samples for longer periods of time before measurement of the VSCs, e.g. for sampling patients at home or when studying a large cohort of patients where an immediate measurement of the VSCs is not possible. After testing numerous sample bags, ultimately the foil balloons, coated inside with the synthetic polymer polyethylene, were the preferred ones. All the VSCs in breath remained quite stable for at least 3 days in these balloons. Besides the sampling bags, the use of an appropriate syringe for sampling mouth air and for injecting samples in e.g. a gas chromatograph is also of great importance. Usually, syringes with a rubber barrel seal are used. However, some rubbers quickly adsorb the VSCs in breath. When preserving breath samples for longer periods, the rubber also releases VSCs, especially methyl mercaptan. It was also found that these syringes release a compound which interferes with dimethyl sulfide, when using gas chromatographic measurements with the OralChroma. We now use all-plastic syringes (B/Braun Injekt), made of polypropylene and polyethylene, in which the VSCs in breath remain quite stable for at least 9 h.
RESUMEN
The ratio of deoxycholic acid to chenodeoxycholic acid in the serum of 62 men was inversely related to body mass index and to saturated fat intake after adjustment for body mass index, smoking, and age conversely, this ratio was associated positively with the intake of fibre from grains.
Asunto(s)
Índice de Masa Corporal , Ácido Quenodesoxicólico/sangre , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Ácido Desoxicólico/sangre , Fumar/efectos adversos , Adulto , Factores de Edad , Grasas de la Dieta , Estudios Epidemiológicos , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Four pregnancies in a women with moderately severe deficiency of methionine adenosyltransferase I/III (MAT I/III) activity are reported. She is an apparent homozygote for a point mutation in MAT1A, the gene that encodes the catalytically active subunit of MAT I/III. This mutation reduces the activity of her expressed enzyme to some 11% of wild-type. She was the first such individual identified in the United States, and these are the first pregnancies known in anyone with this extent of MAT I/III deficiency. No adverse effects were noted in the mother. Three normal babies resulted, but fetal arrest was detected in one embryo at 10-11 weeks gestation. Plasma methionine concentrations remained virtually constant at their elevated levels of 300-350 micromol/L throughout the pregnancies. Plasma free choline was below the reference range. In view of the evidence that maternal choline delivery to the fetus is important for brain development, it was suggested the patient ingest two eggs daily from gestation week 17. Plasma choline and phosphatidylcholine tended to rise during such supplementation. Plasma cystathionine concentrations rose progressively to far above normal during these pregnancies, but not during pregnancies in control women. This may be explained by delivery of excessive methionine to the fetus, with consequent increased cystathionine synthesis by fetal tissues. Because fetal tissues lack gamma-cystathionase, presumably cystathionine accumulated abnormally in the fetus and was transferred in abnormal amounts back to the mother. Plasma and urinary concentrations of methionine transamination metabolites rose during pregnancy for reasons that remain obscure.
Asunto(s)
Isoenzimas/deficiencia , Metionina Adenosiltransferasa/deficiencia , Complicaciones del Embarazo/metabolismo , Adulto , Cistationina/sangre , Femenino , Humanos , Metionina/metabolismo , Leche Humana/metabolismo , Fosfatidilcolinas/administración & dosificación , Embarazo , Complicaciones del Embarazo/terapia , Resultado del EmbarazoRESUMEN
This report investigated the origin of H(2)S in a newborn boy with sulfhaemoglobin induced cyanosis, who died because of multiple organ failure. Frozen material was collected and studied after death. The results suggest that enzymes had been released from deteriorating organs into the blood and abdominal fluid, and that the reaction of one of these enzymes with sulfur containing amino acids might have resulted in increased H(2)S concentrations. It is hypothesised that this release of enzymes resulted from a haemolysin produced by an invasive haemolytic Escherichia coli that was found in the blood and organs of this patient.
Asunto(s)
Cianosis/metabolismo , Sulfuro de Hidrógeno/metabolismo , Sulfahemoglobina/metabolismo , Infecciones por Escherichia coli/metabolismo , Resultado Fatal , Humanos , Recién Nacido , Masculino , Insuficiencia Multiorgánica/metabolismoRESUMEN
This paper reports clinical and metabolic studies of two Italian siblings with a novel form of persistent isolated hypermethioninaemia, i.e. abnormally elevated plasma methionine that lasted beyond the first months of life and is not due to cystathionine beta-synthase deficiency, tyrosinaemia I or liver disease. Abnormal elevations of their plasma S-adenosylmethionine (AdoMet) concentrations proved they do not have deficient activity of methionine adenosyltransferase I/III. A variety of studies provided evidence that the elevations of methionine and AdoMet are not caused by defects in the methionine transamination pathway, deficient activity of methionine adenosyltransferase II, a mutation in methylenetetrahydrofolate reductase rendering this activity resistant to inhibition by AdoMet, or deficient activity of guanidinoacetate methyltransferase. Plasma sarcosine (N-methylglycine) is elevated, together with elevated plasma AdoMet in normal subjects following oral methionine loads and in association with increased plasma levels of both methionine and AdoMet in cystathionine beta-synthase-deficient individuals. However, plasma sarcosine is not elevated in these siblings. The latter result provides evidence they are deficient in activity of glycine N-methyltransferase (GNMT). The only clinical abnormalities in these siblings are mild hepatomegaly and chronic elevation of serum transaminases not attributable to conventional causes of liver disease. A possible causative connection between GNMT deficiency and these hepatitis-like manifestations is discussed. Further studies are required to evaluate whether dietary methionine restriction will be useful in this situation.
Asunto(s)
Metionina/sangre , Metiltransferasas/deficiencia , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Niño , Preescolar , Dieta , Femenino , Glicina N-Metiltransferasa , Hepatomegalia , Humanos , Hígado/patología , Metionina/administración & dosificación , S-Adenosilmetionina/sangre , Sarcosina/sangreRESUMEN
Resistant starch decreases the concentration of secondary bile acids in the feces and the proliferation rate of colonic mucosal cells in healthy volunteers. This may reduce the risk of colon cancer. We investigated 23 patients with recently removed colonic adenoma(s) in a controlled parallel trial. They consumed 45 g of maltodextrin per day as placebo for four weeks and were randomly assigned to either 45 g of native amylomaize starch, containing 28 g of resistant starch type II or 45 g of maltodextrin for another four weeks. No effect on colorectal cell proliferation, fecal wet and dry weights, pH, and short-chain fatty acid excretion was seen. The bile acid concentration in fecal water decreased by 15% (P = 0.048) and the percentage secondary bile acids decreased by 14% (P = 0.002) on resistant starch relative to placebo. Whether this has a substantial role in colon cancer prevention in these patients remains to be established.
Asunto(s)
Adenoma/metabolismo , Neoplasias del Colon/metabolismo , Almidón/metabolismo , Adulto , Anciano , Ácidos y Sales Biliares/análisis , Heces/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
To assess the ability of patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency to perform the reactions of the methionine transamination pathway, the concentrations of the products of this pathway were measured in plasma and urine. The results clearly demonstrate that CBS-deficient patients develop elevations of these metabolites once a threshold near 350 micromol/L for the concurrent plasma methionine concentration is exceeded. The absence of elevated methionine transamination products previously reported among 16 CBS-deficient B6-responsive patients may now be attributed to the fact that in those patients the plasma methionine concentrations were below this threshold. The observed elevations of transamination products were similar to those observed among patients with isolated hypermethioninemia. Plasma homocyst(e)ine did not exert a consistent effect on transamination metabolites, and betaine appeared to effect transamination chiefly by its tendency to elevate methionine. Even during betaine administration, the transamination pathway does not appear to be a quantitatively major route for the disposal of methionine.
Asunto(s)
Cistationina betasintasa/deficiencia , Homocistinuria/sangre , Metionina/sangre , Adolescente , Adulto , Anciano , Aminación/efectos de los fármacos , Betaína/uso terapéutico , Niño , Preescolar , Femenino , Homocisteína/sangre , Homocistinuria/tratamiento farmacológico , Homocistinuria/orina , Humanos , Lactante , Lipotrópicos/uso terapéutico , Masculino , Metionina/orina , Persona de Mediana Edad , Transaminasas/metabolismoRESUMEN
BACKGROUND: Sevoflurane, a potent inhalational anaesthetic agent that is structurally similar to halothane, has some favourable characteristics, but may also be able to trigger malignant hyperthermia (MH) in susceptible patients. The diagnosis of malignant hyperthermia susceptibility relies on the in vitro contracture test on skeletal muscle. The present study was undertaken to investigate whether exposure to sevoflurane of muscles of malignant hyperthermia susceptible (MHS) patients would also cause an abnormal contracture. METHODS: Muscle fascicles obtained from three MHS patients, one malignant hyperthermia non-susceptible (MHN) patient, two control patients and one malignant hyperthermia equivocal (MHE) patient were exposed to sevoflurane instead of halothane in the in vitro contracture test, carried out according to the protocol of the European Malignant Hyperthermia Group. The muscle fascicles were surplus to diagnostic requirements. Sevoflurane concentrations in the testbath were measured using a headspace gas chromatographic technique. RESULTS: The kinetics of sevoflurane concentration in the testbath were similar to those of halothane. An in vitro contracture response of 2 mN or more was seen in all four MHS/MHE patients with sevoflurane but not in the three control/MHN patients. The magnitude of muscle contracture in the sevoflurane test was less than in the conventional halothane test at comparable testbath concentrations. CONCLUSIONS: Sevoflurane can trigger an abnormal contracture in human muscle in vitro. This is indicative of malignant hyperthermia susceptibility. Exposure to sevoflurane should be avoided in patients thought to be susceptible to malignant hyperthermia.
Asunto(s)
Anestésicos por Inhalación/efectos adversos , Hipertermia Maligna/etiología , Éteres Metílicos/efectos adversos , Contracción Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Cafeína/farmacología , Humanos , Técnicas In Vitro , Músculo Esquelético/fisiología , SevofluranoRESUMEN
Bile salts modulate postprandial gallbladder emptying and pancreatic enzyme secretion, possibly by interfering with plasma cholecystokinin (CCK) responses. The regulatory role of bile salts in the absence of nutrients from the gut is poorly understood. Therefore, we studied the effect of intraduodenal sodium chenodeoxycholate on bombesin (BBS)- or CCK-stimulated plasma CCK levels, plasma pancreatic polypeptide levels, gallbladder motility, and pancreatic enzyme secretion. In a crossover design, saline without or with chenodeoxycholate was perfused intraduodenally for 3 hours in healthy volunteers. During the last hour, either BBS (n = 9) or CCK (n = 10) was infused intravenously. Chenodeoxycholate inhibited BBS-stimulated gallbladder emptying from 59% +/- 4% to 34% +/- 6% (P <.05) and intraduodenal bilirubin output from 41 +/- 9 to 21 +/- 5 micromol/h (P <.05), but it increased integrated plasma CCK levels from 157 +/- 19 to 184 +/- 19 pmol/L. 60 min (P =.01). Similarly, chenodeoxycholate administration inhibited gallbladder emptying and bilirubin output in response to intravenous CCK. Chenodeoxycholate also tended to reduce pancreatic polypeptide release and intraduodenal amylase output in response to intravenous BBS or CCK. It is concluded that intraduodenal chenodeoxycholate administration inhibits BBS- or CCK-stimulated gallbladder emptying, probably by diminishing target organ sensitivity to circulating CCK.
Asunto(s)
Conductos Biliares/efectos de los fármacos , Bombesina/farmacología , Ácido Quenodesoxicólico/administración & dosificación , Colagogos y Coleréticos/administración & dosificación , Colecistoquinina/farmacología , Duodeno/fisiología , Páncreas/efectos de los fármacos , Adolescente , Adulto , Ácidos y Sales Biliares/metabolismo , Bilirrubina/metabolismo , Ácido Quenodesoxicólico/farmacología , Colagogos y Coleréticos/farmacología , Colecistoquinina/sangre , Duodeno/metabolismo , Femenino , Vesícula Biliar/anatomía & histología , Vesícula Biliar/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Páncreas/enzimología , Polipéptido Pancreático/sangreRESUMEN
Two isozymes of mammalian methionine adenosyltransferase, MAT I and MAT III, are expressed solely in adult liver. They are, respectively, tetramers and dimers of a single subunit encoded by the gene MAT1A. A third isozyme, MAT II, contains a catalytic subunit encoded by a separate gene, MAT2A, and is expressed in a variety of tissues, including (to a slight extent) adult liver. Based on a recent finding that 2 children with isolated hypermethioninemia and brain demyelination were homozygous for MAT1A mutations predicted to produce severely truncated proteins, and devoid of activity when expressed, it was concluded that complete lack of MAT I/III activity may be associated with neurological symptoms and demyelination. We now report that a 43-year-old man with persistent isolated hypermethioninemia, previously demonstrated to have deficient MAT activity in his liver, has normal brain myelination on MRI and normal neurological function, despite being homozygous for a 539 TG insertion in exon V of MAT1A, so that the gene is predicted to encode a protein of only 184 rather than the normal 395 amino acids. This patient's exon V mutation was demonstrated by SSCP analysis and verified by sequencing. Both parents are heterozygous for the same insertion. This suggests that MAT1A mutations producing severely truncated proteins do not necessarily produce brain demyelination. This finding has relevance to a previously reported 4-year-old girl who was also homozygous for the 539insTG mutation. Finally, our patient's 7% residual hepatic MAT activity, measured at 1 mM methionine, may reflect the hepatic activity of the more ubiquitous enzyme form, MAT II.
Asunto(s)
Encéfalo/metabolismo , Hígado/enzimología , Metionina Adenosiltransferasa/deficiencia , Vaina de Mielina/metabolismo , Adulto , Pruebas Respiratorias , Preescolar , Análisis Mutacional de ADN , Disulfuros/orina , Femenino , Homocigoto , Humanos , Isoenzimas/metabolismo , Masculino , Metionina/metabolismo , Metionina Adenosiltransferasa/genética , Análisis de Secuencia de ADN , Eliminación de Secuencia/genética , Sulfuros/análisisRESUMEN
We have determined ammonia in cerebrospinal fluid (CSF) with the indophenol direct method. The results were compared with an enzymatic method. The method is very simple, and precision (coefficient of variation 1.6%) and linearity (r = 0.9999, p < 0.001) of the method are excellent. The recoveries of the method are very good (within-sample recovery: range 88-93, median 93%; between-sample recovery: 88-93, median 91%). In a population of 23 neurological patients not suffering from liver disease, the reference values ranged from 8 to 26, median 18 microM. Males and females did not differ (p = 0.5). The values obtained with the indophenol method were equal to the enzymatic method (range 9-28, median 18 microM, p = 0.6). On storage in the deep freeze (-20 degrees C), there was no change in CSF ammonia concentration for at least 1 mo. When stored at 4 degrees C (refrigerator), ammonia determinations have to be performed within 2 d. CSF storage at room temperature results in artificially elevated ammonia levels and should be avoided.
Asunto(s)
Amoníaco/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Neoplasias Encefálicas/líquido cefalorraquídeo , Trastornos Cerebrovasculares/líquido cefalorraquídeo , Epilepsia/líquido cefalorraquídeo , Humanos , Indicadores y Reactivos , Indofenol , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrofotometría/métodosRESUMEN
A highly sensitive, reproducible, and rapid gas chromatographic method for ethanol determination in various biological specimens (human whole blood, serum, urine, and fecal supernatants) was developed. The method involves direct injection of the biological specimen into the gas chromatograph, without any pretreatment. Contamination of the gas chromatographic column with nonvolatile material was prevented by the use of a glass liner in the injector. This liner, which acted as a precolumn, was partly filled with small glass beads. Injection was performed in between the glass beads. More than 50 injections of the various biological specimens could be done before the liner had to be replaced by a new one. This injection technique between glass beads allows direct injection of large sample volumes up to 10 microL without disturbing the gas chromatographic separation. Injection of these large sample volumes made the method very sensitive. The detection limit for ethanol amounted to 0.1 mg/L (2 mumol/L) when using an injection volume of 5 microL. Attention has also been paid to simultaneously monitoring ethanol, methanol, acetaldehyde, and acetone in blood and urine of control subjects.
Asunto(s)
Cromatografía de Gases/métodos , Etanol/sangre , Etanol/orina , Heces/química , Calibración , Etanol/análisis , Humanos , Inyecciones , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Ursodeoxycholic acid (UDCA) improves liver biochemistry in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Since UDCA acts partly by reducing the intestinal absorption of hydrophobic endogenous bile salts and is poorly absorbed from the intestine, a multiple dose regimen has been advocated. Single dose treatment, on the other hand, may improve compliance. AIM: The effects of a single or multiple dose regimen on liver enzymes and serum and biliary bile salts composition were evaluated. METHODS: Twenty-seven patients (19 PSC, 8 PBC), most with early stage disease, received UDCA (10 mg kg-1 day-1) in a single dose at bed time (n = 13) or in three divided gifts with meals (n = 14) over 3 months. Five patients had both treatment regimens in random order with a 1-month wash-out period in between. RESULTS: Liver biochemistry equally improved in both groups. Biliary enrichment (% UDCA of total bile salts, mean +/- SEM) was 40.1 +/- 2.4 in the single dose group vs 40.8 +/- 2.8 in the multiple dose group (p = NS) and was positively correlated with biochemical improvement (AP: r = 0.47, p = 0.02; GGT: r = 0.58, p = 0.002; ASAT: r = 0.67, p = 0.002; ALAT: r = 0.52, p = 0.01). Biochemical improvement was not correlated with the concentration or %UDCA in serum. Patients participating in the cross-over design had comparable biochemical response and biliary %UDCA during both regimens. CONCLUSION: Single and multiple dose UDCA have similar effects on liver biochemistry and biliary enrichment in cholestatic liver disease. Biochemical improvement appears to be related to biliary (but not serum) enrichment with UDCA.
Asunto(s)
Colagogos y Coleréticos/administración & dosificación , Colangitis Esclerosante/tratamiento farmacológico , Cirrosis Hepática Biliar/tratamiento farmacológico , Ácido Ursodesoxicólico/administración & dosificación , Adulto , Fosfatasa Alcalina/sangre , Ácidos y Sales Biliares/sangre , Ácido Quenodesoxicólico/uso terapéutico , Colangitis Esclerosante/sangre , Colangitis Esclerosante/complicaciones , Cromatografía de Gases , Estudios Cruzados , Ácido Desoxicólico/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Cirrosis Hepática Biliar/sangre , Cirrosis Hepática Biliar/complicaciones , Masculino , Persona de Mediana Edad , Análisis de Regresión , Transaminasas/sangre , Resultado del Tratamiento , gamma-Glutamiltransferasa/sangreRESUMEN
Homozygotes for homocystinuria due to cystathionine synthase (CS) deficiency accumulate homocysteine and methionine in their blood and tissues. High-dose pyridoxin, folic acid, vitamin B12, or betaine are therapeutical options to lower the elevated homocysteine concentration. These compounds stimulate the transsulfuration or remethylation of homocysteine. Despite such treatment, elevated blood homocysteine concentrations may persist in many homocystinurics. Therefore, it is warranted to study alternative regimen to reduce the blood homocysteine concentration in homocystinurics. Apart from entering the transsulfuration pathway, methionine can be catabolized via the transamination pathway, by conversion into 4-methylthio-2-oxobutyrate (MTOB), followed by oxidative decarboxylation of MTOB to 3-methylthiopropionate. Thiamine pyrophosphate, the active form of thiamine, is a cofactor of the supposed rate-limiting oxidative decarboxylation in the transamination of methionine. The effect of thiamine administered in 2 or 3 daily doses of 25 mg orally, was studied in nine homozygote CS deficient patients. Methionine levels decreased in 6 out of 9 patients. In 8 out of 9 patients, however, the levels of plasma homocysteine remained virtually unchanged, as did the serum transamination metabolites in all patients. We conclude that vitamin B1 cannot be used as an additional homocysteine-lowering treatment in most homozygotes for homocystinuria.
Asunto(s)
Homocistinuria/terapia , Tiamina/uso terapéutico , Cistationina betasintasa/deficiencia , Homocisteína/sangre , Homocistinuria/genética , Homocigoto , HumanosRESUMEN
The objective of this study was to describe diarrhoea as a dominating symptom of cerebrotendinous xanthomatosis (CTX), a lipid storage disease, and investigate its cause. Two children with chronic diarrhoea as the dominating symptom of CTX are presented. Before and after therapy with orally administered chenodeoxycholic acid (15 mg kg-1 24 h, in three divided doses) bile alcohol excretion in urine, serum cholestanol level, serum bile acid patterns and faecal bile acids were measured. All routine gastro-intestinal investigations before therapy were normal. Diarrhoea ceased immediately after starting treatment with chenodeoxycholic acid. Abnormal bile alcohol excretion in urine decreased rapidly during the first days and elevated serum cholestanol level normalized in 2 years. We postulate the presence of bile alcohols in the lumen of the gut as most likely cause for diarrhoea in CTX, since the rapid decrease of bile alcohol excretion is associated with prompt cessation of diarrhoea after starting treatment with chenodeoxycholic acid.