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Alcohol downregulates hepcidin expression in the liver leading to an increase in intestinal iron transport and liver iron storage. We have previously demonstrated that alcohol-mediated oxidative stress is involved in the inhibition of hepcidin transcription by alcohol in vivo. Kupffer cells and TNF-[alpha] play a key role in alcohol-induced liver injury. The aim of this study was to define their involvement in the regulation of hepcidin expression by alcohol. Kupffer cells were inactivated or depleted by employing gadolinium chloride and liposomes containing clodronate, respectively. Rats pair fed with the alcohol-Lieber-DeCarli diet for 6 wk and mice fed with 20% ethanol in the drinking water for 1 wk were used as experimental models. Interestingly, alcohol downregulated hepcidin expression in the livers of rats and mice independent of gadolinium chloride or clodronate treatment. One week of alcohol treatment was sufficient to induce a significant increase in TNF-[alpha] levels and phosphorylation of NF-[kappa]B subunit p65. The neutralization of TNF-[alpha] by specific antibodies inhibited p65 phosphorylation. However, neither the neutralization of TNF-[alpha] nor the lack of TNF-[alpha] receptor expression reversed alcohol-induced suppression of liver hepcidin expression. The level of alcohol-induced ROS in the liver was also undiminished following Kupffer cell inactivation or depletion. Our results demonstrate that alcohol-induced Kupffer cell activation and TNF-[alpha] signaling are not involved in the suppression of liver hepcidin expression by alcohol-mediated oxidative stress in vivo. Therefore, these findings suggest that alcohol acts within hepatocytes to suppress hepcidin expression and thereby influences iron homeostasis. alcoholic liver disease; iron; liver injury; oxidative stress

A new synthetic method is developed for preparing propargylic alcohols from epoxides and terminal alkynes through 1,2-shifts. The synthetic method is useful for both electron-rich and electron-deficient alkynes with other acid and base-sensitive functional groups because of the mild conditions to pre-activate alkynes with silver nitrate.

Indium promoted coupling of propargyl aldehydes with allyl halides has resulted in the synthesis of propargyl alcohols under aqueous and organic conditions. Oxy-Cope rearrangement of 4-hydroxy-1-ene-5-ynes followed by a secondary addition step under highly basic conditions has led to the formation of lactol.

[Ca.sup.2+] is a universal intracellular messenger that controls a wide range of cellular processes. In pancreatic acinar cells, acetylcholine and cholecystokinin regulate secretion via generation of repetitive local cytosolic [Ca.sup.2+] signals in the apical pole. Bile acids and nonoxidative alcohol metabolites can elicit abnormal cytosolic [Ca.sup.2+] signals that are global and sustained and result in necrosis. Necrosis results from excessive loss of [Ca.sup.2+] from the endoplasmic reticulum, which is mediated by [Ca.sup.2+] release through specific channels and inhibition of [Ca.sup.2+] pumps in intracellular stores, followed by entry of extracellular [Ca.sup.2+]. Reduction of the cellular ATP level has a major role in this process. These abnormal [Ca.sup.2+] signals, which can be inhibited by caffeine, explain how excessive alcohol intake and biliary disease cause acute pancreatitis, an often-fatal human disease in which the pancreas digests itself and its surroundings.

Ethanol strongly augments secretin-stimulated, but not acetylcholine (ACh)-stimulated, fluid secretion from pancreatic duct cells. To understand its mechanism of action, we examined the effect of short-chain n-alcohols on fluid secretion and intracellular [Ca.sup.2+] concentration ([[Ca.sup.2+].sub.i]) in guinea pig pancreatic ducts. Fluid secretion was measured by monitoring the luminal volume of isolated interlobular ducts. [[Ca.sup.2+].sub.i] was estimated using fura-2 microfluorometry. Methanol and ethanol at 0.3-10 mM concentrations significantly augmented fluid secretion and induced a transient elevation of [[Ca.sup.2+].sub.i] in secretin- or dibulyryl adenosine 3',5'-cyclic monophosphate (DBcAMP)-stimulated ducts. However, they failed to affect fluid secretion and [[Ca.sup.2+].sub.i] in unstimulated and ACh-stimulated ducts. In contrast, propanol and butanol at 0.3-10 mM concentrations significantly reduced fluid secretion and decreased [[Ca.sup.2+].sub.i] in unstimulated ducts and in ducts stimulated with secretin, DBcAMP, or ACh. Both stimulatory and inhibitory effects of n-alcohols completely disappeared after their removal from the perfusate. Propanol and butanol inhibited the plateau phase, but not the initial peak, of [[Ca.sup.2+].sub.i], response to ACh as well as the [[Ca.sup.2+].sub.i] elevation induced by thapsigargin, suggesting that they inhibit [Ca.sup.2+] influx. Removal of extracellular [Ca.sup.2+] reduced [[Ca.sup.2+].sub.i] in duct cells and completely abolished secretin-stimulated fluid secretion. In conclusion, there is a distinct cutoff point between ethanol (C2) and propanol (C3) in their effects on fluid secretion and [[Ca.sup.2+].sub.i] in duct cells. Short-chain n-alcohols appear to affect pancreatic ductal fluid secretion by activating or inhibiting the plasma membrane [Ca.sup.2+] channel. intracellular calcium; acetylcholine

Even though there is a large body of information concerning the harmful effects of alcohol on different organisms, the mechanism(s) that affects developmental programs, at a single-cell level, has not been clearly identified. In this respect, the spore-forming bacterium Bacillus subtilis constitutes an excellent model to study universal questions of cell fate, cell differentiation, and morphogenesis. Here, we demonstrate that treatment with subinhibitory concentrations of alcohol that did not affect vegetative growth inhibited the initiation of spore development through a selective blockage of key developmental genes under the control of the master transcription factor Spo0A~P. Isopropyl-[beta]-o-thiogalactopyranoside-directed expression of a phosphorylation-independent form of Spo0A (Sad67) and the use of an in vivo mini-Tn10 insertional library permitted the identification of the developmental SinR repressor and RapA phosphatase as the effectors that mediated the inhibitory effect of alcohol on spore morphogenesis. A double rapA sinR mutant strain was completely resistant to the inhibitory effects of different-C-length alcohols on sporulation, indicating that the two cell fate determinants were the main or unique regulators responsible for the spo0 phenotype of wild-type cells in the presence of alcohol. Furthermore, treatment with alcohol produced a significant induction of rapA and sinR, while the stationary-phase induction of sinI, which codes for a SinR inhibitor, was completely turned off by alcohol. As a result, a dramatic repression of spo0A and the genes under its control occurred soon after alcohol addition, inhibiting the onset of sporulation and permitting the evaluation of alternative pathways required for cellular survival.

The synthesis of different stereospecifically deuterium-labeled and isotopically tagged palmitic acid probes needed to decipher the stereospecifically course of the T. pityocampa delta(super 11) desaturase is described. The synthesis of probes is carried out by a chemoenzymatic route, in which the key step is the kinetic lipase-catalyzed resolution of racemic mixtures of secondary propargyl alcohols.

Research has been conducted on the omega-alkynals that yield macrocyclic (S)-allylic alcohols. The ligand type, reproducibility and the size and nature of the macrocycle have been investigated to study the macrocyclization methodology.

Research has been conducted on beta-azido alcohols. Enzymatic resolution of these alcohols in combination with ruthenium-catalyzed alcohol isomerization has been investigated.

Research has been conducted on the methyl group deprotonation on silicon group. The methodology for this deprotonation based on the intramolecular pyridyl group coordination is discussed.

Research has been conducted on the silylketene dithiocetal reaction with aldehydes. The reaction resulting in deoxygenation divinylation products in the presence of Lewis acid is described.

The polymer-supported proline-based diamine catalyst efficiently resolves the racemic mixtures of secondary alcohols with products separated chromatographically. The reactions are fully automatable without an aqueous workup and the catalyst can be recovered and reused.

Results show that molecular oxygen oxidizes primary and secondary alcohols at ambient temperature using N-hydroxyphthalimide and cobalt(II) ion as the catalyst. Data indicate that this reaction is economical and environmentally sound for the conversion of alcoholic functions to carbonyl groups.

Research describes a method for reduction of primary alcohols and ethers with hydrosilane aided deprotection of aryl alkyl ethers in the presence of B(C(sub)6F(sub)5)(sub)3. The mechanistic aspects of the reaction are presented.

Research points out that simple amino acids can be used as ligands in the ruthenium(II)-catalyzed transfer hydrogenation of aryl alkyl ketones. The bicyclic beta-amino alcohols are obtained by simple aza-Diels-Alder adduct formation between cyclopentadiene and iminium ion and adduct's subsequent reduction.

Research describes the synthesis of N,S-chelates that function as ligands for the iridium-(I)-catalyzed transfer hydrogenation of prochiral ketones. Data indicate that the aminosulfide is the best ligand for controlling asymmetric iridium-catalyzed transfer hydrogenation of prochiral ketones.