Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “BUTYRATES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed1999

Butyrate increases apical membrane CFTR but reduces chloride secretion in MDCK cells.

Sodium butyrate and its derivatives are useful therapeutic agents for the treatment of genetic diseases including urea cycle disorders, sickle cell disease, thalassemias, and possibly cystic fibrosis (CF). Butyrate partially restores cAMP-activated Cl(-) secretion in CF epithelial cells by stimulating DeltaF508 cystic fibrosis transmembrane conductance regulator (DeltaF508-CFTR) gene expression and increasing the amount of DeltaF508-CFTR in the plasma membrane. Because the effect of butyrate on Cl(-) secretion by renal epithelial cells has not been reported, we examined the effects of chronic butyrate treatment (15-18 h) on the function, expression, and localization of CFTR fused to the green fluorescent protein (GFP-CFTR) in stably transfected MDCK cells. We report that sodium butyrate reduced Cl(-) secretion across MDCK cells, yet increased apical membrane GFP-CFTR expression 25-fold and increased apical membrane Cl(-) currents 30-fold. Although butyrate also increased Na-K-ATPase protein expression twofold, the drug reduced the activity of the Na-K-ATPase by 55%. Our findings suggest that butyrate inhibits cAMP-stimulated Cl(-) secretion across MDCK cells in part by reducing the activity of the Na-K-ATPase.

Animals↗
PubMedDate not supplied

Synergistic cytotoxic interactions between sodium butyrate, MG132 and camptothecin in human retinoblastoma Y79 cells.

This paper studies the effects caused in human retinoblastoma Y79 cells by treatment with combinations of sodium butyrate, the inhibitor of topoisomerase I camptothecin and the inhibitor of 26S proteasome MG132. The combination of sodium butyrate and camptothecin resulted in a strong synergistic cytotoxicity, as revealed by combination indices of 0.77 and 0.52 calculated at IC(50) and IC(75). Synergistic interactions were also demonstrated for combinations of sodium butyrate and MG132, camptothecin and MG132 and for a combination of all three compounds. The cytotoxic effects observed after the combined treatments can be considered a consequence of apoptosis, as suggested by the appearance of morphological signals of apoptosis and by the activation of caspase-3 with degradation of poly-ADP ribose polymerase and lamin B. Treatment of Y79 cells with sodium butyrate alone lowered the levels of p53, E2F-1 and Bcl-2. The addition of MG132 to sodium butyrate counteracted the effect on p53 only, while the addition of camptothecin to sodium butyrate counteracted the effect on both p53 and E2F-1. The treatment of Y79 cells with the triple combination increased the level of p53, decreased that of Bcl-2, while the level of E2F-1 was not modified. We suggest that the effects exerted on the levels of these regulatory proteins can explain the synergistic interactions demonstrated between sodium butyrate, camptothecin and MG132.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Butyrate enhances the production of nitric oxide in mouse vascular endothelial cells in response to gamma interferon.

The effect of butyrate, a natural bacterial product of colonic bacterial flora, on nitric oxide (NO) production in murine vascular endothelial cell line END-D in response to IFN-gamma and/or LPS was studied. Butyrate significantly augmented NO production in END-D cells in response to IFN-gamma or IFN-gamma + LPS, but not LPS alone. The NO production was augmented by the addition of butyrate until 6 h after the stimulation with IFN-gamma or IFN-gamma + LPS. The augmentation was abolished by the removal of butyrate from the cultures. Butyrate enhanced the expression of inducible type NO synthase (iNOS) in the stimulated END-D cells. Furthermore, butyrate-enhanced NO production in the presence of various signal inhibitors down-regulating the signal pathways using nuclear factor (NF)-kappaB, mitogen-activated protein (MAP) kinases and Janus tyrosine kinase. The putative mechanism of butyrate-induced augmentation of NO production in response to IFN-gamma or IFN-gamma + LPS is discussed.

Animals↗
PubMed2006

A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies.

Malignancies associated with latent Epstein-Barr virus (EBV) are resistant to nucleoside-type antiviral agents because the viral enzyme target of these antiviral drugs, thymidine kinase (TK), is not expressed. Short-chain fatty acids, such as butyrate, induce EBV-TK expression in latently infected B cells. As butyrate has been shown to sensitize EBV(+) lymphoma cells in vitro to apoptosis induced by ganciclovir, arginine butyrate in combination with ganciclovir was administered in 15 patients with refractory EBV(+) lymphoid malignancies to evaluate the drug combination for toxicity, pharmacokinetics, and clinical responses. Ganciclovir was administered twice daily at standard doses, and arginine butyrate was administered by continuous infusion in an intrapatient dose escalation, from 500 mg/(kg/day) escalating to 2000 mg/(kg/day), as tolerated, for a 21-day cycle. The MTD for arginine butyrate in combination with ganciclovir was established as 1000 mg/(kg/day). Ten of 15 patients showed significant antitumor responses, with 4 CRs and 6 PRs within one treatment cycle. Complications from rapid tumor lysis occurred in 3 patients. Reversible somnolence or stupor occurred in 3 patients at arginine butyrate doses of greater than 1000 mg/(kg/day). The combination of arginine butyrate and ganciclovir was reasonably well-tolerated and appears to have significant biologic activity in vivo in EBV(+) lymphoid malignancies which are refractory to other regimens.

Adolescent↗
PubMed2001

Butyrate, a histone deacetylase inhibitor, activates the human IGF binding protein-3 promoter in breast cancer cells: molecular mechanism involves an Sp1/Sp3 multiprotein complex.

Specific cell growth stimulators and inhibitors regulate IGF binding protein-3 (IGFBP-3), where in turn IGFBP-3 mediates their biological effects. The molecular mechanism(s) by which these factors regulate IGFBP-3 are unknown. Sodium butyrate, a histone deacetylase inhibitor causing growth arrest and differentiation, increases IGFBP-3 expression. We investigated the molecular mechanism of this induction using an IGFBP-3 promoter reporter system in MCF-7 and Hs578T breast cancer cells. IGFBP-3 promoter activity was induced up to 40-fold following a 24-h treatment with sodium butyrate and 46-fold in cells treated with trichostatin A, a pure histone deacetylase inhibitor. Deletion analysis of the IGFBP-3 promoter identified key sodium butyrate-responsive element(s) to a 45-bp region containing consensus binding sites for Sp1 and activating protein-2. Sp1 binding to the Sp1 site and Sp3 to the activating protein-2/GA-box played a functional role in sodium butyrate's activation of the IGFBP-3 promoter, however, with no change in binding direct sodium butyrate regulation was attributed to cofactors. The histone acetyltransferase p300 and histone deacetylase-1 were identified in multiprotein complexes containing DNA bound Sp1 and Sp3, with p300 accumulating following sodium butyrate treatment. Taken together, these data suggest that sodium butyrate increases IGFBP-3 expression by activating the IGFBP-3 promoter via an Sp1/Sp3 multiprotein complex, a mechanism that may be important for other key regulators of IGFBP-3.

Base Sequence↗
PubMed2005

Batch and fed-batch production of butyric acid by clostridium butyricum ZJUCB.

The production of butyric acid by Clostridium butyricum ZJUCB at various pH values was investigated. In order to study the effect of pH on cell growth, butyric acid biosynthesis and reducing sugar consumption, different cultivation pH values ranging from 6.0 to 7.5 were evaluated in 5-L bioreactor. In controlled pH batch fermentation, the optimum pH for cell growth and butyric acid production was 6.5 with a cell yield of 3.65 g/L and butyric acid yield of 12.25 g/L. Based on these results, this study then compared batch and fed-batch fermentation of butyric acid production at pH 6.5. Maximum value (16.74 g/L) of butyric acid concentration was obtained in fed-batch fermentation compared to 12.25 g/L in batch fermentation. It was concluded that cultivation under fed-batch fermentation mode could enhance butyric acid production significantly (P<0.01) by C. butyricum ZJUCB.

Bioreactors↗
PubMed2005

Dose-dependent stimulatory and inhibitory effects of luminal and serosal n-butyric acid on epithelial cell proliferation of pig distal colonic mucosa.

Large bowel bacteria convert various carbohydrates into short-chain fatty acids (SCFA). SCFA stimulate epithelial cell proliferation of the large intestine in vivo and inhibit that of various cells in vitro. Supposing that too high concentration of SCFA on the serosal side is responsible for their inhibitory effect in vitro, we studied effects of luminal and serosal n-butyric acid (0, 0.1, 1, or 10 mmol/L, adjusted to neutral pH) on the epithelial cell proliferation rate of pig colonic mucosa in organ culture taking crypt cell production rate (CCPR) as the measure of proliferative activity. With 0 or 0.1 mmol/L n-butyric acid on the serosal side, luminal n-butyric acid increased CCPR at 1.0 mmol/L, and decreased CCPR at 10 mmol/L when compared to the luminal 0 mmol/L control. With 1.0 or 10 mmol/L serosal n-butyric acid, luminal n-butyric acid depressed CCPR dose-dependently. The above results indicated that n-butyric acid stimulated colonic epithelial cell proliferation at low concentration and inhibit it at high concentration with interaction effect to enhance the inhibitory action. The stimulatory effect of a low dose of serosal n-butyric acid may be responsible for the distant trophic effect of SCFA.

Animals↗
PubMed2002

[In vitro expression of human factor VIII gene induced by sodium butyrate].

OBJECTIVE: To explore the effect and mechanism of sodium butyrate on expression of human clotting factor VIII in vitro. METHODS: Mouse NIH/3T3 cell line was transfected with recombinant plasmid vector pRC/RSV-BDD-hFVIII, which enclosed B-domain deleted (760aa approximately 1 639aa) human factor VIII cDNA (BDD-hFVIII cDNA). Then cells were incubated in Dulbecco's modification of Eagle's medium (DMEM) containing sodium butyrate for 24 hours, hFVIII: C and hFVIII: Ag in the cell culture medium were measured by ELISA assay and one-stage method, respectively. In addition, the effect of sodium butyrate on transcription of cDNA encoding the whole hFVIII, heavy and light chain of hFVIII was also investigated by means of run-on assay. RESULTS: After stimulation of sodium butyrate, the levels of hFVIII: C and hFVIII: Ag increased 70% than those of control. Run-on assay showed that sodium butyrate enhanced the transcription of cDNA which encoded heavy chain of hFVIII. CONCLUSION: Sodium butyrate can improve the expression of hFVIII through enhancing the transcription of hFVIII heavy chain encoding cDNA. It demonstrated that sodium butyrate had potential utility in inducing the expression of hFVIII in vitro.

3T3 Cells↗
PubMedDate not supplied

The elevated serum interleukin-6 correlates with the increased serum butyrate level in patients with nasopharyngeal carcinoma.

We investigated the clinical significance and regulation of serum interleukin-6 (IL-6) in patients with nasopharyngeal carcinoma (NPC). Serum IL-6 levels of 314 NPC patients and 202 healthy individuals were determined. Of the NPC patients, 69.1% (217/314) showed higher IL-6 levels than that of normal average (2.76+/-2.06 pg/ml). Elevation of IL-6 correlated with the advanced disease and the adverse prognosis of NPC patients. By employing in situ hybridization technique, IL-6 mRNA was detected in the tumor cells of NPC patients with high serum IL-6 levels. Concurrently, serum levels of butyrate were determined in 147 NPC patients and 52 healthy individuals by gas chromatography. Patients with elevated serum butyrate concentrations (4.2+/-2.2 micro M) also had significantly higher IL-6 levels (29.14+/-5.17 pg/ml). No detectable serum butyrate was measured in the healthy individuals. In order to investigate the direct relationship between butyrate and IL-6, n-sodium butyrate (n-BT) was added to the NPC cells in an in vitro study, and marked increase of IL-6 expression was detected in n-BT-treated cells. Our results suggested that tumor cells could be an important source of elevated serum IL-6 in patients with NPC and that IL-6 level in NPC patients was proportional to the serum butyrate concentration. In vitro, IL-6 expression in NPC cells could be up-regulated by butyrate.

Biomarkers, Tumor↗
PubMed2003

[Investigation of the effect of Na-butyrate on TNBS induced rat colitis].

OBJECTIVE: To observe the effect of Na-butyrate on trinitrobenzene sulfonic acid (TNBS) induced rat colitis and discuss its mechanism. METHODS: 0.85 ml of 50% ethanol enema containing 30 mg TNBS was instillated into rat colon to produce distal colitis. On the 5th day after TNBS enema, the rats were divided into 3 groups and were given respectively 100 mmol/L Na-butyrate, 100 mg/kg SASP or 0.9% saline enema daily. On the 19th day, macroscopical, histological injury scores of colonic mucosa and tissue myeloperoxidase (MPO) activity were evaluated, and the mitotic index in Na-butyrate group was compared with that in SASP group. RESULTS: Diarrhea was apparently improved, weight gain was not apparently different, the scores of macroscopical and histological injury and MPO activity decreased in the SASP group and the Na-butyrate group, compared with the control (P < 0.05). However, there was not obvious difference between the Na-butyrate group and SASP group (P > 0.05). Mitotic index in Na-butyrate group was higher than that in SASP group (P < 0.05). CONCLUSION: Na-butyrate enema can expedite the restoration of the experimental colitis, and its therapeutic effect is as good as that of SASP.

Administration, Rectal↗
PubMed2003

[Selective apoptosis in HeLa cells induced by sodium butyrate and its mechanism].

OBJECTIVE: To investigate apoptosis induced by sodium butyrate in cervix cancer cell line HeLa and primary human embryo lung fibroblasts and its mechanism. METHODS: Cell apoptosis was assessed by morphology, cell viability, DNA fragmentation, the percentage of sub-G1 cells and phosphatidylserine (PS) externalization. The effects of sodium butyrate on transcription of Bax and Bcl-2 was analyzed by RT-PCR. RESULTS: Sodium butyrate inhibited proliferation in a time and dose-dependant manner. The inhibition of proliferation in HeLa cells was more significant than that in primary human embryo lung fibroblasts. DNA fragmentation, sub-G1 peak and AnnexinV/PI by flow cytometry showed very high apoptosis rates in HeLa cells 72 hours after treated with sodium butyrate, while pretty low in primary human embryo lung fibroblasts. RT-PCR showed sodium butyrate had little effects on transcription of Bax and Bcl-2 in HeLa cells. CONCLUSION: Sodium butyrate can induce apoptosis in HeLa cells without changing the expression of Bax and Bcl-2. Sodium butyrate comparatively has little effects on fibroblasts.

Antineoplastic Agents↗
PubMedDate not supplied

Quantification of p21 gene expression in Caco-2 cells treated with sodium butyrate using real-time reverse transcription-PCR (RT-PCR) assay.

Butyric acid, a short chain fatty-acid derived from bacterial fermentation of complex carbohydrates in the large intestine has been shown to be a growth inhibitory in many colon cancer cell lines. Butyrate induced inhibition of cellular proliferation is considered to result from the induction of P21 gene expression through the activation of this gene transcription. P21 is an inhibitor of cyclin-dependent protein kinases that are required for the cells to enter the DNA synthesis phase. In the present study the kinetics of the changes of the P21 transcription in Caco-2 colon adenocarcinoma cells treated with various concentrations of sodium butyrate was determined using a novel real-time quantitative RT-PCR (TaqMan) technique. Beta-actin mRNA and GAPDH mRNA levels were used as the endogenous references. Colonocytes were incubated with sodium butyrate at concentrations of 5 mM, 10 mM and 20 mM for 3, 6, 12, 24 and 48 h. The results of this study indicated that butyrate strongly induced P21 gene expression as early as 3 h after treatment. Characteristic patterns of time-dependent changes of the target gene expression were observed. The increases in P21 mRNA level were generally more pronounced at higher butyrate concentrations. Because Caco-2 cells are lacking the wild allele of the P53 gene, the present results support the hypothesis that butyrate induces P21 gene expression by P53-independent mechanism.

Butyrates↗
PubMed1991

Pharmacokinetics of butyric acid derivative with xylitol.

The short chain fatty acids, especially butyric acid salts have interesting biological properties. In some cases, transformed cells can recover a normal phenotype and in animal, butyrate salts increase antitumor resistance. Butyrate may be considered as possibly useful for antitumor therapy. But these products exhibit two essential disadvantages which restrict their clinical use in man: high concentrations required to achieve therapeutic effects and rapid excretion with short half life. In order to optimize the clinical use of butyrate, we studied a n-butyric acid ester obtained with xylitol selected for its physiological and metabolic inertia. Structure determination of tributyryl xylitol was carried out by mass and NMR spectrometry (MW = 344). The low toxicity and the antitumor effects of this ester, especially in association with Corynebacterium parvum and interferon, confirm its therapeutic interest. The slow excretion of this prodrug should make butyrate clinical use easier by preventing extensive systemic metabolism and metabolic side-effects due to cations of butyrate salts.

Animals↗
PubMed1987

Ultrastructural localization of gamma amino butyric acid immunoreactivity in B cells of the rat pancreas.

The purpose of this study was to determine the ultrastructural localization of gamma amino butyric acid (GABA) within the B cell of isolated rat islets, particularly with respect to the B cell secretion granules. GABA immunoreactivity was localized ultrastructurally, with colloidal gold, in the B cells and absent in the A cells and D cells. Quantitative analysis of the colloidal gold particle distribution in the B cell revealed 29.5 +/- 5.2 gold particles/micron 2 in the nuclei, 29.3 +/- -6.9 gold particles/micron 2 in the mitochondria and 4.9 +/- 1.0 gold particles/micron 2 in the secretion granules. Particle density in the remainder of the cytoplasm was 41.9 +/- 4.1 particles/micron 2. The paucity of gamma amino butyric acid in the B cell secretion granules differs from observations on gamma amino butyric acidergic neurons, where there is an accumulation of gamma amino butyric acid within the neurosecretory vesicles. These findings indicate that if gamma amino butyric acid is released from the islet, then it is by a nongranular mechanism. In addition, the results are compatible with the hypotheses that gamma amino butyric acid within the B cell functions in the regulation of insulin biosynthesis, and/or functions as an alternative energy source for the B cell through the gamma amino butyric acid shunt.

Animals↗
PubMed2002

Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone butyrate ointment in adult patients with atopic dermatitis.

BACKGROUND: Vehicle-controlled studies have demonstrated the efficacy and safety of tacrolimus ointment for patients with atopic dermatitis. OBJECTIVE: This study was undertaken to compare 0.03% and 0.1% tacrolimus ointment with 0.1% hydrocortisone-17-butyrate ointment, a midpotent to potent topical corticosteroid, in the treatment of adult patients with moderate-to-severe atopic dermatitis. METHODS: Patients applied ointment twice daily to all affected areas for 3 weeks in this multicenter, randomized, double-blind, parallel-group study. The primary endpoint was the modified eczema area and severity index (mEASI) mean area under the curve as a percentage of baseline. RESULTS: Five hundred seventy patients were randomized and received treatment. Discontinuations included 22 of 193 patients from the 0.03% tacrolimus group, 22 of 191 patients from the 0.1% tacrolimus group, and 17 of 186 patients from the hydrocortisone butyrate group. The median mEASI mean area under the curve as a percentage of baseline was 47.0%, 36.5%, and 36.1% for patients who received 0.03% tacrolimus, 0.1% tacrolimus, and 0.1% hydrocortisone butyrate, respectively. There was no statistically significant difference between 0.1% tacrolimus and 0.1% hydrocortisone butyrate; however, the lower improvement in mEASI for 0.03% tacrolimus was statistically significant when compared with 0.1% tacrolimus (P <.001) or hydrocortisone butyrate (P =.002). Skin burning and pruritus at the application site showed a higher incidence in the tacrolimus treatment groups than in the hydrocortisone butyrate group (P <.05). Laboratory parameters showed no treatment differences and no marked changes over time. CONCLUSIONS: The efficacy of 0.1% tacrolimus ointment was similar to that of 0.1% hydrocortisone butyrate ointment and was lower for 0.03% tacrolimus ointment. No serious safety concerns were identified.

Administration, Topical↗
PubMed1988

Product inhibition of butyrate metabolism by acetate and hydrogen in a thermophilic coculture.

Studies on product inhibition of a thermophilic butyrate-degrading bacterium in syntrophic association with Methanobacterium thermoautotrophicum showed that a gas phase containing more than 2 x 10 atm (2.03 kPa) of hydrogen prevented growth and butyrate consumption, while a lower hydrogen partial pressure of 1 x 10 to 2 x 10 atm (0.1 to 2.03 kPa) gradually inhibited the butyrate consumption of the coculture. No inhibition of butyrate consumption was found on the addition of 0.75 x 10 atm (76 Pa) of hydrogen to the gas phase. A slight inhibition of butyrate consumption by the coculture occurred at an acetate concentration of 16.4 mM. Inhibition gradually increased with increasing acetate concentration up to 81.4 mM, when complete inhibition of butyrate consumption occurred. When the culture contained an acetate-utilizing methanogen in addition to M. thermoautotrophicum, the inhibition of the triculture by acetate was gradually reversed as the acetate concentration was lowered by the aceticlastic methanogen. The results show that optimal growth conditions for the thermophilic butyrate-degrading bacterium depend on both hydrogen and acetate removal.

Journal Article↗
PubMed1983

Laidlomycin butyrate--an ionophore with enhanced intraruminal activity.

The polyether ionophore, laidlomycin, and several acyl derivatives were tested for their ability to favorably alter fermentation in two types of in vitro rumen fluid incubations. Dose response data were used to estimate the concentration (microgram/ml) of each ionophore required for either 50% maximal enhancement of propionic acid production (EC50) or 50% maximal inhibition of lactic acid production (IC50). Acylation of laidlomycin with straight-chain acyl groups from two to 12 carbon atoms tended to improve the potency of laidlomycin, especially for inhibiting lactic acid production. Comparative incubations using laidlomycin butyrate, laidlomycin and monensin indicated that both laidlomycin butyrate (EC50 = .3) and monensin (EC50 = .7) were more potent enhancers of propionic acid production than laidlomycin (EC50 = 2.0; P less than .05). Laidlomycin butyrate (IC50 = .3) was a more potent inhibitor of lactic acid production than either laidlomycin (IC50 = 1.8) or monensin (IC50 = 1.3; P less than .05). In a continuous culture experiment, three chemostats each received laidlomycin butyrate or monensin at the rate of .5 micrograms/ml of effluent/d while two flasks remained as control. Propionic acid production was increased (P less than .01) from 22.9 mmol/d in control flasks to 30.5 and 33.7 mmol/d in flasks treated with monensin and laidlomycin butyrate, respectively. Concomitant decreases in production rates of acetic, butyric and isovaleric acids also were observed (P less than .01). Thirty-six steers were used in a 56-d trial to evaluate effects of laidlomycin butyrate and monensin, at 33 mg/kg of diet, on feedlot performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

alpha-Amino butyric acid cannot reactivate the silenced gamma gene of the beta locus YAC transgenic mouse.

Butyric acid, a naturally occurring fatty acid, has been shown to increase fetal hemoglobin in BFUe cultures, in primates, and in patients with beta chain hemoglobinopathies. The precise mechanism of gamma gene induction by butyrate is unknown. Butyrate may induce fetal hemoglobin production in vivo by reactivation of silenced gamma globin genes, by inhibiting the silencing of gamma genes, or by both mechanisms. We examined the effects of butyrate on gamma gene expression in transgenic mice carrying three types of constructs: microLCRA gamma mice, which continue to express the gamma gene in the adult stage of development at a level of one-third to one-fifth of the expression in the fetus; microLCRA gamma psi beta delta beta mice, which display correct developmental regulation of gamma and beta human globin genes and have low level gamma globin expression in the adult; and beta locus YAC mice, which display correct developmental regulation of epsilon, gamma, and beta globin genes and have a totally silenced gamma gene in the adult stage. Animals were treated with a continuous infusion of alpha-amino butyric acid (alpha-ABA) for 7 days. In microLCRA gamma mice alpha-ABA produced up to a 43-fold induction of gamma and 9-fold induction of mouse alpha globin genes. In contrast, butyrate did not induce gamma globin expression in the beta locus YAC mice. However, the gamma globin genes of beta locus YAC mice were activated after administration of 5-azacytidine (5-azaC), and the level of gamma globin expression was further increased by administration of alpha-ABA. These results suggest that butyrate cannot reactivate a totally silenced gamma gene and that induction of fetal hemoglobin by this compound may require the presence of preactivated gamma globin genes.

Aminobutyrates↗