PMID- 3377812
OWN - NLM
STAT- MEDLINE
DCOM- 19880629
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 37
IP  - 10
DP  - 1988 May 15
TI  - In vivo effects of beta-lactam antibiotics and heterocyclic thiol compounds on 
      vitamin K-dependent carboxylation activity and blood coagulation factors in 
      vitamin K-deficient rats.
PG  - 2091-5
AB  - The in vivo effects of heterocyclic thiol compounds, corresponding to the 
      3'-position substituents of several beta-lactam antibiotics, on blood coagulation 
      factors and on liver microsomal gamma-glutamylcarboxylation (gamma-carboxylation) 
      activity were evaluated in rats maintained on a vitamin K-deficient diet. These 
      rats, when compared to normal control animals, exhibited hypoprothrombinemic 
      changes: prolongation of both prothrombin time and activated partial 
      thromboplastin time, decreases in factor VII and plasma prothrombin, and 
      increases in PIVKA II (descarboxyprothrombin) both in plasma and liver. They also 
      displayed a marked increase in liver microsomal gamma-carboxylation activity. 
      These blood coagulation variables could be altered markedly by administering 
      various heterocyclic thiol compounds to the vitamin K-deficient rats, although 
      these compounds did not inhibit gamma-carboxylation activity in an assay system 
      using phylloquinone. A similar pattern of alteration was observed when some 
      beta-lactam antibiotics were administered. Increased microsomal 
      gamma-carboxylation activity in antibiotic-treated vitamin K-deficient rats was 
      normalized by the administration of vitamin K, concomitant with the recovery of 
      blood coagulation variables to the normal range. The results indicate that 
      antibiotic-induced hypoprothrombinemia in vivo is not caused by inhibition of 
      enzymes of the gamma-carboxylation system, such as vitamin K reductase and 
      gamma-glutamylcarboxylase, but is related to the endogenous vitamin K level.
FAU - Oka, T
AU  - Oka T
AD  - Kanzakigawa Laboratory, Shionogi & Co., Ltd., Osaka, Japan.
FAU - Touchi, A
AU  - Touchi A
FAU - Harauchi, T
AU  - Harauchi T
FAU - Takano, K
AU  - Takano K
FAU - Yoshizaki, T
AU  - Yoshizaki T
FAU - Matsubara, T
AU  - Matsubara T
LA  - eng
PT  - Journal Article
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Blood Coagulation Factors)
RN  - 0 (Sulfhydryl Compounds)
RN  - 0 (beta-Lactams)
RN  - 12001-79-5 (Vitamin K)
RN  - EC 6.- (Ligases)
RN  - EC 6.4.- (Carbon-Carbon Ligases)
RN  - EC 6.4.- (glutamyl carboxylase)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/*pharmacology
MH  - Blood Coagulation Factors/*analysis
MH  - *Carbon-Carbon Ligases
MH  - Hypoprothrombinemias/chemically induced
MH  - Ligases/*antagonists & inhibitors
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Sex Factors
MH  - Sulfhydryl Compounds/*pharmacology
MH  - Vitamin K/*pharmacology
MH  - Vitamin K Deficiency/blood/*enzymology
MH  - beta-Lactams
EDAT- 1988/05/15 00:00
MHDA- 1988/05/15 00:01
CRDT- 1988/05/15 00:00
PHST- 1988/05/15 00:00 [pubmed]
PHST- 1988/05/15 00:01 [medline]
PHST- 1988/05/15 00:00 [entrez]
AID - 0006-2952(88)90561-8 [pii]
AID - 10.1016/0006-2952(88)90561-8 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1988 May 15;37(10):2091-5. doi: 10.1016/0006-2952(88)90561-8.