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Title
Microbial desulfonation.
Author
Cook AM; Laue H; Junker F
Source
FEMS Microbiol Rev, 1998 Dec, 22:5, 399-419
Abstract
Organosulfonates are widespread compounds, be they natural products
of low or high
molecular weight, or xenobiotics. Many commonly found compounds
are subject to
desulfonation, even if it is not certain whether all the corresponding
enzymes are widely
expressed in nature. Sulfonates require transport systems to
cross the cell membrane, but
few physiological data and no biochemical data on this topic
are available, though the
sequences of some of the appropriate genes are known. Desulfonative
enzymes in aerobic
bacteria are generally regulated by induction, if the sulfonate
is serving as a carbon and
energy source, or by a global network for sulfur scavenging (sulfate-starvation-induced
(SSI) stimulon) if the sulfonate is serving as a source of sulfur.
It is unclear whether an SSI
regulation is found in anaerobes. The anaerobic bacteria examined
can express the
degradative enzymes constitutively, if the sulfonate is being
utilized as a carbon source, but
enzyme induction has also been observed. At least three general
mechanisms of
desulfonation are recognisable or postulated in the aerobic catabolism
of sulfonates: (1)
activate the carbon neighboring the C-SO3- bond and release of
sulfite assisted by a
thiamine pyrophosphate cofactor; (2) destabilize the C-SO3- bond
by addition of an oxygen
atom to the same carbon, usually directly by oxygenation, and
loss of the good leaving
group, sulfite; (3) an unidentified, formally reductive reaction.
Under SSIS control, different
variants of mechanism (2) can be seen. Catabolism of sulfonates
by anaerobes was
discovered recently, and the degradation of taurine involves
mechanism (1). When
anaerobes assimilate sulfonate sulfur, there is one common, unknown
mechanism to
desulfonate the inert aromatic compounds and another to desulfonate
inert aliphatic
compounds; taurine seems to be desulfonated by mechanism (1).
Title
Mucin secretion by the human colon cell line LS174T is regulated
by bile salts.
Author
Klinkspoor JH; Mok KS; Van Klinken BJW; Tytgat GNJ; Lee SP; Groen
AK
Source
Glycobiology, 1999 Jan, 9:1, 13-9
Abstract
We recently reported that bile salts play a role in the regulation
of mucin secretion by
cultured dog gallbladder epithelial cells. In this study we have
examined whether bile salts
also influence mucin secretion by the human epithelial colon
cell line LS174T. Solutions of
bile salts were applied to monolayers of LS174T cells. Mucin
secretion was quantified by
measuring the secretion of [3H]GlcNAc labeled glycoproteins.
Both unconjugated bile salts
as well as taurine conjugated bile salts stimulated mucin secretion
by the colon cells in a
dose-dependent fashion. Hydrophobic bile salts were more potent
stimulators than
hydrophilic bile salts. Free (unconjugated) bile salts were more
stimulatory compared with
their taurine conjugated counterparts. Stimulation of mucin secretion
by LS174T cells was
found to occur at much lower bile salt concentrations than in
the experiments with the dog
gallbladder epithelial cells. The protein kinase C activators
PMA and PDB had no
stimulatory effect on mucin secretion. We conclude that mucin
secretion by the human
colon epithelial cell line LS174T is regulated by bile salts.
We suggest that regulation of
mucin secretion by bile salts might be a common mechanism, by
which different epithelia
protect themselves against the detergent action of bile salts,
to which they are exposed
throughout the gastrointestinal tract.
Title
Hepatic and serum bile acid compositions in patients with biliary
atresia: a microanalysis
using gas chromatography-mass spectrometry with negative ion
chemical ionization
detection.
Author
Abukawa D; Nakagawa M; Iinuma K; Nio M; Ohi R; Goto J
Address
Department of Pediatrics, Tohoku University School of Medicine,
Sendai.
dabukawa@cd.mbn.or.jp
Source
Tohoku J Exp Med, 1998 Aug, 185:4, 227-37
Abstract
Hepatic and serum bile acids in five patients with biliary atresia
were preoperatively
determined by microanalysis using gas chromatography-mass spectrometry
with negative
ion chemical ionization detection. The hepatic content of total
bile acids was markedly
elevated (3079+/-711 nmol/g protein), most of which were primary
bile acids.
Accumulation of unconjugated bile acids (2.93% to 4.62% of the
total) was observed in the
liver tissue of these patients, although only trace amounts were
detected in their sera. The
ratio of glycine-conjugated to taurine-conjugated bile acids
was 0.44+/-0.18 in liver tissue
and 0.79+/-0.52 in serum and these values were significantly
lower than those of controls.
This study has shown that the composition of bile acids in serum
does not reflect that in
liver tissue faithfully. The accumulation of these hydrophobic
bile acids may contribute to
initiating or exacerbating liver injury in infants with cholestatic
liver diseases.
Title
Differences in the metabolism and disposition of ursodeoxycholic
acid and of its
taurine-conjugated species in patients with primary biliary cirrhosis.
Author
Invernizzi P; Setchell KD; Crosignani A; Battezzati PM; Larghi
A; O'Connell NC; Podda M
Address
Division of Internal Medicine, Ospedale San Paolo School of Medicine,
University of
Milan, Italy. pietro.invernizzi@unim i.it
Source
Hepatology, 1999 Feb, 29:2, 320-7
Abstract
The clinical effectiveness of ursodeoxycholate in the treatment
of liver disease may be
limited by its poor absorption and extensive biotransformation.
Because in vitro and in vivo
studies suggest that the more hydrophilic bile acid tauroursodeoxycholate
has greater
beneficial effects than ursodeoxycholate, we have compared for
the first time the absorption,
metabolism, and clinical responses to these bile acids in patients
with primary biliary
cirrhosis (PBC). Twelve female patients with PBC were sequentially
administered
tauroursodeoxycholate and ursodeoxycholate (750 mg/d for 2 months)
in a randomized,
cross-over study. Bile acids were measured in serum, duodenal
bile, urine, and feces by gas
chromatography-mass spectrometry (GC-MS). Biliary ursodeoxycholate
enrichment was
higher during tauroursodeoxycholate administration (32.6% vs.
29.2% during
ursodeoxycholate; P <.05). Lithocholic acid concentration
was consistently higher in all
biological fluids during ursodeoxycholate administration. Fecal
bile acid excretion was the
major route of elimination of both bile acids; ursodeoxycholate
accounted for 8% and 23%
of the total fecal bile acids during tauroursodeoxycholate and
ursodeoxycholate
administration, respectively (P <.05). Tauroursodeoxycholate
was better absorbed than
ursodeoxycholate, and, although it was partially deconjugated
and reconjugated with glycine,
it underwent reduced biotransformation to more hydrophobic metabolites.
This comparative
study suggests that tauroursodeoxycholate has significant advantages
over ursodeoxycholate
that may be of benefit for long-term therapy in PBC.
Title
Mechanisms of diarrhoea in myotonic dystrophy.
Author
Rönnblom A; Andersson S; Danielsson A
Address
Department of Medicine, Central Hospital, Boden, Sweden.
Source
Eur J Gastroenterol Hepatol, 1998 Jul, 10:7, 607-10
Abstract
BACKGROUND: Gastrointestinal (GI) symptoms are common in myotonic
dystrophy
(MD). Diarrhoea is one of the more disabling of these GI complaints.
The mechanisms
behind diarrhoea in MD have not previously been investigated
systematically.
OBJECTIVE: To elucidate the mechanisms behind diarrhoea in MD.
METHODS: Twenty
patients with MD and suffering from diarrhoea were investigated
in order to detect
malabsorption (blood tests and faecal fat excretion) and bile
acid malabsorption
([75Se]selenahomocholic acid-taurine (SeHCAT) retention) and
to study intestinal
morphology (duodenal and rectal biopsies). RESULTS: Two patients
had deficiency of folic
acid and four showed reduced levels of pancreatic isoamylase,
but none of them had
steatorrhoea. Two out of eight patients had abnormal bile acid
breath tests with normal
SeHCAT, indicating small bowel bacterial overgrowth and 12 displayed
reduced SeHCAT
retention. Duodenal biopsies were normal in eight patients and
five out of nine rectal
biopsies displayed slight inflammation. CONCLUSIONS: A possible
mechanism of
diarrhoea in MD could be identified in most of the patients.
Bile acid malabsorption seems
to be a frequent cause and can be treated successfully.
Title
Cysteine sulfinic acid decarboxylase mRNA abundance decreases
in rats fed a high-protein
diet.
Author
Jerkins AA; Jones DD; Kohlhepp EA
Address
Department of Nutritional Sciences and the Nutritional Sciences
Program, University of
Arizona, Tucson, AZ 85721, USA.
Source
J Nutr, 1998 Nov, 128:11, 1890-5
Abstract
The partitioning of cysteine metabolism between sulfate and taurine
biosynthetic pathways
may be regulated in part by the activity of cysteine sulfinic
acid decarboxylase (CSAD).
CSAD activity is repressed by high-protein feeding, and we have
previously reported that
changes in CSAD activity are correlated with changes in CSAD
protein. We conducted
experiments to determine the relative expression of CSAD mRNA
in rats fed 18 or 60%
casein diets. In rats fed a 60% casein diet for 1 wk, hepatic
CSAD activity and CSAD
protein were 16 and 36%, respectively, of the values measured
in rats fed the 18% casein
diet. CSAD mRNA abundance in rats fed the 60% casein diet was
14% of the CSAD
mRNA abundance in rats fed an 18% casein diet. The time course
of the change in CSAD
activity and mRNA abundance was examined in rats fed 18 or 60%
casein diets for 48 h.
Within 6 h of switching rats to a 60% casein diet, CSAD activity
was decreased by 20% and
after 48 h, activity was decreased 47% compared to activity measured
at baseline. CSAD
mRNA abundance was decreased 54% within 12 h of feeding rats
a high-protein diet and
remained depressed at 48 h. In a parallel group of rats fed the
18% casein diet, CSAD
activity and CSAD mRNA were not significantly different from
baseline values at 48 h. The
decreased expression of CSAD mRNA in rats fed a high-protein
diet is consistent with
decreases in both CSAD enzyme activity and CSAD protein. Our
results suggest dietary
protein may regulate CSAD at the level of mRNA.
Title
Psyllium, not pectin or guar gum, alters lipoprotein and biliary
bile acid composition and
fecal sterol excretion in the hamster.
Author
Trautwein EA; Rieckhoff D; Kunath Rau A; Erbersdobler HF
Address
Institute of Human Nutrition and Food Science, University of
Kiel, Germany.
etrautwein@nutrfoodsc.uni-kiel.de
Source
Lipids, 1998 Jun, 33:6, 573-82
Abstract
Different soluble dietary fibers known to alter cholesterol metabolism
were fed to golden
Syrian hamsters, and their specific impact on lipoproteins, biliary
bile acid profile, and fecal
sterol excretion was evaluated. Semipurified diets containing
20% fat; 0.12% cholesterol;
and 8% of psyllium (PSY); high (hePE) and low (lePE) esterified
pectin; or high (hvGG)
and low (lvGG) viscous guar gum were fed for 5 wk. Compared to
control, PSY caused a
significant reduction in plasma cholesterol (2.9 +/- 0.5 vs.
5.5 +/- 0.5 mmol/L), whereas
hePE, lePE, hvGG, or lvGG had no apparent effect on plasma lipids.
Hepatic total and
esterified cholesterol were substantially decreased with PSY,
pectin and guar gum, whereby
PSY produced the most pronounced effect. Distinctive changes
existed in the bile acid
profile related to the different fibers. In contrast to pectin
and guar gum, PSY caused a
significant increase in the cholate:chenodeoxycholate and the
glycine:taurine conjugation
ratio. Pectin and guar gum did not alter daily fecal neutral
sterol excretion while PSY caused
a 90% increase due to a higher fecal output. Daily fecal bile
acid excretion and total fecal bile
acid concentration were significantly increased by PSY, whereas
hePE, lePE, hvGG, and
lvGG revealed no or only minor effects. Taken together, the disparate
hypocholesterolemic
effects of PSY, pectin, and guar gum on cholesterol and bile
acid metabolism in the hamster
are possibly related to different physicochemical properties,
e.g., viscosity and susceptibility
to fermentation, affecting the fiber-mediated action in the intestine.
Title
Lecithin protects against plasma membrane disruption by bile
salts.
Author
Narain PK; DeMaria EJ; Heuman DM
Source
J Surg Res, 1998 Aug, 78:2, 131-6
Abstract
INTRODUCTION: Detergent disruption of epithelial plasma membranes
by bile salts may
contribute to pathogenesis of cholestasis and gastroesophageal
reflux disease. Bile, despite
containing high concentrations of bile salts, normally is not
toxic to biliary or intestinal
epithelia. We hypothesize that lecithin in bile may protect cell
membranes from disruption
by bile salts. METHODS: We studied the interactions of taurine
conjugates of
ursodeoxycholate (TUDCA), cholate (TCA), chenodeoxycholate (TCDCA),
and
deoxycholate (TDCA) with erythrocyte plasma membranes with or
without large
unilamellar egg lecithin vesicles for various times at 23 degreesC.
Release of hemoglobin
was quantified spectrophotometrically. The concentration of bile
salt monomers and simple
micelles in the intermixed micellar aqueous phase (IMMC) was
determined by centrifugal
ultrafiltration. RESULTS: The degree of hemolysis depended on
the hydrophobicity of the
bile salts and was progressive over time. Addition of lecithin
reduced the hemolytic effects
of 20 mM TCA or 2 mM TDCA in a concentration-dependent manner
at both 30 min and 4
h. Increasing the concentration of lecithin progressively reduced
the IMMC of TDCA.
Hemolysis following addition of lecithin to 2 mM TDCA was comparable
to hemolysis
produced by lecithin-free TDCA solutions when diluted to similar
IMMC values.
CONCLUSION: We conclude that lecithin reduces plasma membrane
disruption by
hydrophobic bile salts. This protection may be attributable to
association of bile salts with
vesicles and mixed micelles, reducing the concentration of bile
salt monomers and simple
micelles available to interact with cell membranes. Lecithin
may play a key role in
preventing bile salt injury of biliary and gastrointestinal epithelia.
Copyright 1998 Academic
Press.
Title
Altered serum amino acid profiles in head and neck cancer.
Author
Scioscia KA; Snyderman CH; Wagner R
Source
Nutr Cancer, 1998, 30:2, 144-7
Abstract
Patients who develop squamous cell carcinoma of the head and
neck (SCCHN) are often
malnourished because of poor dietary habits, excessive alcohol
consumption, local tumor
effects, tumor-induced cachexia, and the effects of various therapies.
The composition of the
diet may be a risk factor for the development of head and neck
cancer as well as tumor
progression. This study compares the amino acid profiles in the
banked serum of patients
with and without SCCHN. In comparison to the control group, patients
with SCCHN had
significantly decreased preoperative serum levels of alanine
(p = 0.006), asparagine (p =
0.002), aspartic acid (p = 0.0001), glycine (p = 0.0002), histidine
(p = 0.002),
3-methylhistidine (p = 0.001), ornithine (p = 0.001), phenylalanine
(p = 0.002), serine (p =
0.002), taurine (p < 0.0001), and threonine (p = 0.001). Levels
of cystine were significantly
elevated in the group of cancer patients (p < 0.0001). No
significant differences were noted
on the basis of T stage, N stage, or nutritional status. Serum
levels increased postoperatively
for the majority of the amino acids tested. Postoperative histidine
levels were associated
with tumor recurrence (p = 0.04). Serum amino acid levels may
prove to be useful markers
of disease status and provide prognostic information.
Title
Astrocyte metallothioneins (MTs) and their neuroprotective role.
Author
Aschner M
Source
Ann N Y Acad Sci, 1997 Oct, 825:, 334-47
Abstract
I have briefly detailed in this review the role of astrocytes
in MeHg neurotoxicity,
emphasizing the mechanisms and significance of astrocytic swelling
in neuropathological
conditions. I have also described the functions of brain MTs
and have reported recent
observations on their propensity to attenuate cytotoxicity. While
it is unclear why three
different MT genes are expressed in the brain, this redundancy
should allow for greater
accumulation of MTs under stressful conditions compared to its
accumulation if only a
single gene was present. Another explanation may be that genes
encoding functionally
identical MTs might be regulated independently, thus permitting
cell-specific MT
expression. Finally, each of the three MT isoforms may have distinct
functions. As
discussed herein, astrocytic MTs afford protection from the acute
cytotoxic effects of
MeHg, reversing the effect of this organometal on RVD and inhibition
of taurine release.
Whether other vital cellular functions are protected by MTs will
have to await future studies,
as will the mechanisms associated with MT-induced cellular protection.
That the resistance
to heavy metal toxicity is closely related to the cellular ability
to synthesize MTs, raises
interesting questions regarding the potential involvement of
heavy metals in
neurodegenerating (amyotrophic lateral sclerosis, Parkinson's
disease, Alzheimer's disease)
under conditions of compromised MT synthesis. Future studies
on the expression and
regulation of MT genes are likely to culminate in novel strategies
for manipulating
intracellular MT levels, providing insight to their role in both
health and disease.
Title
Selective use of calcium chelators enhances the yield of calcium-tolerant
myocytes from
adult heart.
Author
Nair P; Nair RR
Source
Indian J Exp Biol, 1997 May, 35:5, 451-6
Abstract
Isolation of viable and functional cells from adult heart remains
an intriguing problem for
investigators who choose to use the cardiomyocyte model for experimental
studies. With a
few modifications of the existing procedures we have been able
to improve the yield of
ventricular myocardial cells from the adult rat heart. Sarcolemmal
damage leading to
hypercontracture due to Ca2+ loading appears to be the major
hindrance to the successful
isolation of sufficient number of viable cells. The two crucial
steps are found to be the
pre-enzymatic perfusion for Ca(2+)-depletion and the final step
of Ca(2+)-repletion in
extracellular medium for the isolation of Ca(2+)-tolerant myocytes.
Inclusion of EGTA and
taurine during the initial perfusion of Ca(2+)-free medium and
of trypsin during
reintroduction of Ca2+ led to a considerable increase in the
yield of Ca(2+)-tolerant
myocytes. The contraction amplitude and speed of shortening and
relaxation of isolated cells
were measured using an edge detection device. Selective use of
calcium ion chelators
appears to have a beneficial effect on the isolation of Ca(2+)-tolerant
myocytes.
Title
Neutrophil antioxidant capacity during the respiratory burst:
loss of glutathione induced by
chloramines.
Author
Ogino T; Packer L; Maguire JJ
Source
Free Radic Biol Med, 1997, 23:3, 445-52
Abstract
Low-molecular weight antioxidants in rat peritoneal neutrophils
undergo rapid redox
recycling, so measurements were made of their initial content
and subsequent changes
during the respiratory burst, when superoxide formation is maximized.
Endogenous
vitamin E, ascorbate and total glutathione (reduced + oxidized)
were not significantly
changed during 30 min of respiratory burst, which was stimulated
by phorbol 12-myristate
13-acetate (PMA). When de novo synthesis of glutathione was inhibited
by
buthionine-[S,R] sulfoximine (BSO), the glutathione content rapidly
decreased in activated
neutrophils but not in resting cells. The lost total glutathione
was recovered neither from the
incubation medium nor as a protein-bound form, which suggests
that irreversible oxidation
of glutathione occurs. Furthermore, the glutathione loss continues
even 30 min after PMA
stimulation, when the respiratory burst has almost ceased. The
decrease of glutathione was
prevented by added catalase, or by addition of NaN3 or KCN which
inhibits
myeloperoxidase (MPO). Superoxide dismutase had no protective
effects. These findings
suggest the involvement of an MPO-H2O2-halide system in the accelerated
consumption of
glutathione during the respiratory burst. Additional studies
showed that neutrophil-derived
chloramines found in the extracellular medium could lead to intracellular
glutathione loss.
Incubation of resting cells with chemically produced membrane
permeable monochloramine
in the presence of BSO resulted in a decrease of glutathione,
whereas
membrane-impermeable taurine-chloramine was less effective. We
conclude that
chloramines are responsible for accelerated glutathione turnover
in neutrophils during the
respiratory burst. Permeable extracellular chloramines derived
from the respiratory burst
activity, such as monochloramine, can reenter cells and react
with thiols. |
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