Trends in type 2 diabetes prevalence according to income levels in Korea (1998-2012).

There was no significant association between diabetes prevalence and income levels for either sex in 1998. However, the high income level in men and the low income level in women positively related to the odds of diabetes in 2011-2012. Preventive strategies for diabetes should consider the gender-specific economic discrepancy.

Novel fluoroquinolone antibacterial agents containing oxime-substituted (aminomethyl)pyrrolidines: synthesis and antibacterial activity of 7-(4-(aminomethyl)-3-(methoxyimino)pyrrolidin-1-yl)-1-cyclopropyl-6- fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid (LB20304).

New pyrrolidine derivatives, which bear an alkyloxime substituent in the 4-position and an aminomethyl substituent in the 3-position of the pyrrolidine ring, have been synthesized and coupled with various quinolinecarboxylic acids to produce a series of new fluoroquinolone antibacterials. These fluoroquinolones were found to possess potent antimicrobial activity against both Gram-negative and Gram-positive organisms, including methicillin resistant Staphylococcus aureus (MRSA). Variations at the C-8 position of the quinolone nucleus included fluorine, chlorine, nitrogen, methoxy, and hydrogen atom substitution. The activity imparted to the substituted quinolone nucleus by the C-8 substituent was in the order F (C5-NH2) > F (C5-H) > naphthyridine > Cl = OMe = H against Gram-positive organisms. In the case of Gram-negative strains, activity was in the order F (C5-NH2) > naphthyridine = F (C5-H) > H > Cl > OMe. The advantages provided by the newly introduced oxime group of the quinolones were clearly demonstrated by their comparison to a desoximino compound 30. In addition, the oxime moiety greatly improved the pharmacokinetic parameters of the novel quinolones. Among these compounds, compound 20 (LB20304) showed the best in vivo efficacy and pharmacokinetic profile in animals, as well as good physical properties. The MICs (microgram/mL) of LB20304, compound 30, and ciprofloxacin against several test organisms are as follows: S. aureus 6538p (0.008, 0.031, and 0.13), methicillin resistant S. aureus 241 (4, 16, and 128), Streptococcus epidermidis 887E (0.008, 0.016, and 0.13), methicillin resistant S. epidermidis 178 (4, 32, and 128), Enterococcus faecalis 29212 (0.063, 0.13, and 1), Pseudomonas aeruginosa 1912E (0.25, 0.5, and 0.13), Escherichia coli 3190Y (0.008, 0.016, and 0.008), Enterobacter cloacae P99 (0.008, 0.031, and 0.008), Actinobacter calcoaceticus 15473 (0.063, 0.13, and 0.25). On the basis of these promising results, LB20304 was selected as a candidate for further evaluation.

Synthesis and antimicrobial activity of novel 3-[(aminopyrimidiniumyl)thio]methyl cephalosporins.

A series of novel cephalosporin compounds which have 3-[(aminopyrimidiniumyl)thio]methyl substituents was synthesized. They show high antimicrobial activity against various bacterial species including Pseudomonas aeruginosa. Structure-activity relationships with various thiopyrimidines, thiopyrimidiniums, bicyclic thiotriazolopyrimidiniums, and bicyclic thioimidazolopyrimidiniums as 3'-substituents were also studied; cephalosporins with quarternized pyrimidinium moieties have better antimicrobial activities than neuteral pyrimidine cephalosporins, and stabilization of the positive charge on the pyrimidinium moieties is essential for better activity. According to semiempirical PM3 calculations, amino and alkylthio substituents on the pyrimidinium rings play a major role in charge stabilization and delocalization.

Pharmacological characterization of LB50016, N-(4-amino)butyl 3-phenylpyrrolidine derivative, as a new 5-HT1A receptor agonist.

LB50016 was characterized as a selective and potent 5-HT1A receptor agonist and evaluate its anxiolytic and antidepressant activities. It shows high affinity for 5-HT1A receptor, moderate affinity for alpha 2 adrenergic and 5-HT2A receptors and no significant affinity for other receptors tested. Hypothermia and increased serum corticosterone level were observed in LB50016-treated rats, which are mediated mostly by post synaptic 5-HT1A receptor activation. In the mouse forced swim model for depression, LB50016-elicited dose-dependent reductions in immobility time, showing ED50 of approximately 3 mg/kg i.p., which was blocked by pretreatment of NAN-190, 5-HT1A antagonist. In face-to-face test for anxiolytic activity in mice, estimated ED50 was 2 mg/kg, i.p. In isolation-induced aggression test with mice, fifty-fold increases in latency to attack were observed at 30 min and last up to 4 h after LB50016 treatment (3 mg/kg, i.p.). Taken together, LB50016-induced pharmacological activities are mediated by activation of 5-HT1A receptors, offering an effective therapeutic candidate in the management of anxiety and depression in humans.

[Immunosuppressive and cytotoxic effect of the humoral factors from ischemic damaged organs (author's transl)]. / Immunosuppressiver und zytotoxischer Effekt des humoralen Faktors ischämisch geschädigter Organe.

These studies demonstrate the presence of an immunosuppressive and cytotoxic factor in the perfusate of ischemic damaged liver. A BDE rat liver perfusate (LP) was prepared after 6 h warm ischemia by intraportal perfusion with 2 ml/g of Ringer's solution (one time-LP1 or five times-LP5 with the same volume of solution). Protein amount of LP1 and LP5 was 0.9 and 2.8-3.9 mg/ml. In vivo activity of the hepatic perfusates was studied by effect on renal allograft survival time. LEW rats with BDE kidney transplant, treated daily with 2 ml of LP1 for 5 days, starting on the day of grafting, survived 8.9 +/- 1.8 days, significantly longer than control animals (6.5 +/- 0.5 days). After administration of LP5 renal recipients survived 10.3 +/- 1.3 days and when the treatment with LP5 was prolonged to 10 days animals survived 9-34 days (mean 15.3 +/- 7.3 days). The presence of the suppressive factor was also studied in renal, spleen and heart extracts, prepared after 6 h warm ischemia. Protein amount of extracts was adjusted to 3-4 mg/ml by Ringer's solution. Immunosuppressive activity of LP and other organ extracts was tested in vitro by their influence on MLC reaction (LEW and BDE lymphocytes) and on LEW cells in the PHA stimulation assay. Lymphocyte blastogenic response on MLC reaction and in culture with PHA was strongly inhibited by LP but weakly by organ extracts. Hepatic perfusates were cytotoxic against lymphocytes and fibroblasts in a three day cultures. Cytotoxic activity of the organ extracts was lower than LP. Extract of the cold preserved kidneys showed immunosuppressive and cytotoxic effect like extract of ischemically injured kidneys but smaller than LP. After heat inactivation at 70 degrees C the activity of hepatic perfusate decreased. Immunosuppressive organ factor (IOF) seems to be a normal cell component, not a decomposition product of the ischemically damaged hepatic tissue.

[A humoral transfer factor preventing rejection of allotransplanted rat liver? (author's transl)]. / Ist der humorale Transferfaktor für die Reaktionslosigkeit von Rattenleberallotransplantaten verantwortlich?

We grafted orthotopically 11 DA and 20 WiS-livers into LEW. The recipients of DA-livers survived 10.5 +/- 4.3 days; of the 20 recipients of WiS-liver, however, nine survived 18-37 days, and the other 11 survived indefinitely. The cells of recipients who survived more than 4 months showed GvHR of grade III, and their transfer showed no significant immunosuppressive effect. The indefinitely surviving liver recipients could accept specific skin grafts, but normally rejected third party skin. The serum of these recipients was able to prolong the survival of kidney grafts. This transfer factor is in our estimation responsible for the prolonged survival of rats with liver grafts.

[The effect of donorspecific antigen type for active enhancement of renal-allografts in the histoincompatible inbred rats (author's transl)]. / Der Effekt der spenderspezifischen Antigen-Typen auf aktives Enhancement der Rattennierenallotransplantate bei histoinkompatibilen Inzucht-Ratten

49 kidneys of male LBNF1-rats were transplanted into male Lewis-rats. BN-rats were used as a source of antigen. Control animals survived 16.1 +/- 1.8 days. 5 recipients were preteated with donorspecific living cells, 7 with semisoluble and 5 with low dosage of soluble antigen. The living cell-pretreatment showed the best effect for the active enhancement, the soluble antigen the least. The pretreatment with 6 mg protein/kg bw. caused the sensibilization of recipients. At the time of transplantation lymphcytotoxic antibody titers were detected in all recipients with pretreatment of living cells, but no titer in other groups. Renal allografts with elevated postopertive titer were rejected rapidly.

In vitro and in vivo activities of LB10522, a new catecholic cephalosporin.

In vitro activity of LB10522 was compared with those of cefpirome, ceftazidime, ceftriaxone, and cefoperazone against clinical isolates. Against gram-positive bacteria, LB10522 was most active among the compounds tested. It was fourfold more active than cefpirome against methicillin-susceptible Staphylococcus aureus and Enterococcus faecalis. LB10522 was highly effective against most members of the family Enterobacteriaceae tested. Ninety percent of isolates of Escherichia coli, Klebsiella oxytoca, Proteus vulgaris, Proteus mirabilis, and Salmonella spp. were inhibited at a concentration of < or = 0.5 micrograms/ml. These activities were comparable to those of cefpirome. Against Pseudomonas aeruginosa, LB10522 with a MIC at which 90% of the isolates are inhibited of 2 micrograms/ml was 16- and 32-fold more active than ceftazidime and ceftazidime against systemic infections caused by Staphylococcus aureus giorgio, Streptococcus pneumoniae III, Pseudomonas aeruginosa 1912E, Escherichia coli 851E, Proteus mirabilis 1315E, Serratia marcescens 1826E, and Acinetobacter calcoaceticus Ac-54. LB10522 was very resistant to hydrolysis by various beta-lactamases such as TEM-3, TEM-7, SHV-1, FEC-1, and P-99. LB10522 did not induce beta-lactamase in Enterobacter cloacae 1194E, although most of the reference cephalosporins acted as inducers of beta-lactamase in this strain. Time-kill study showed that LB10522, at concentrations of two or four times the MIC, had a rapid bactericidal activity against Staphylococcus aureus 6538p, Escherichia coli 851E, and Pseudomonas aeruginosa 1912E.

In-vitro and in-vivo antibacterial activity of LB10517, a novel catechol-substituted cephalosporin with a broad antibacterial spectrum.

LB10517 is a new injectable cephalosporin with a broad spectrum of antibacterial activity against Gram-positive and Gram-negative bacteria. LB10517 inhibited 90% of methicillin-susceptible Staphylococcus aureus (MSSA) at 0.25 mg/L (MIC90), and was 8-fold more active than cefpirome. LB10517 was two- or four-fold more active than cefpirome against methicillin-susceptible Staphylococcus epidermidis (MSSE), Streptococcus pyogenes and Enterococcus faecalis. Both methicillin-resistant S. aureus (MRSA) and methicillin-resistant S. epidermidis (MRSE) were highly resistant to all compounds. LB10517 activity against most Enterobacteriaceae was comparable to or greater than that of cefpirome, and it also showed high activity against Pseudomonas aeruginosa. In a mouse septicaemia model, LB10517 exhibited excellent protective effects. In a respiratory tract infection model, the protective effect of LB10517 was comparable to that of cefpirome and ceftazidime. It was highly stable to hydrolysis by beta-lactamases, showing better physiological efficiency for TEM-9 than the other test compounds. LB10517 had the most potent antibacterial activity against beta-lactamase producing resistant strains. LB10517 did not induce beta-lactamase production in Enterobacter cloacae 1194E.