Extracts of Momordica charantia suppress postprandial hyperglycemia in rats

Momordica charantia (bitter melon) is commonly known as vegetable insulin, but the mechanisms underlying its hypoglycemic effect remain unclear. To address this issue, the effects of bitter melon extracts on postprandial glycemic responses have been investigated in rats. An aqueous extract (AE), methanol fraction (MF) and methanol insoluble fraction (MIF) were prepared from bitter melon. An oral sucrose tolerance test revealed that administration of AE, MF or MIF each significantly suppressed plasma glucose levels at 30 min as compared with the control. In addition, the plasma insulin level at 30 min was also significantly lower after MF administration than in the control in the oral sucrose tolerance test. By contrast, these effects of bitter melon extracts were not observed in the oral glucose tolerance test. In terms of mechanism, bitter melon extracts dose-dependently inhibited the sucrase activity of intestinal mucosa with IC(50) values of 8.3, 3.7 and 12.0 mg/mL for AE, MF and MIF, respectively. The fraction with a molecular weight of less than 1,300 (LT 1,300) obtained from MF inhibited the sucrase activity most strongly in an uncompetitive manner with an IC(50) value of 2.6 mg/mL. Taken together, these results demonstrated that bitter melon suppressed postprandial hyperglycemia by inhibition of alpha-glucosidase activity and that the most beneficial component is present in the LT 1,300 fraction obtained from MF.     

Wind, Waves, and Wing Loading: Morphological Specialization May Limit Range Expansion of Endangered Albatrosses

Among the varied adaptations for avian flight, the morphological traits allowing large-bodied albatrosses to capitalize on wind and wave energy for efficient long-distance flight are unparalleled. Consequently, the biogeographic distribution of most albatrosses is limited to the windiest oceanic regions on earth; however, exceptions exist. Species breeding in the North and Central Pacific Ocean (Phoebastria spp.) inhabit regions of lower wind speed and wave height than southern hemisphere genera, and have large intrageneric variation in body size and aerodynamic performance. Here, we test the hypothesis that regional wind and wave regimes explain observed differences in Phoebastria albatross morphology and we compare their aerodynamic performance to representatives from the other three genera of this globally distributed avian family. In the North and Central Pacific, two species (short-tailed P. albatrus and waved P. irrorata) are markedly larger, yet have the smallest breeding ranges near highly productive coastal upwelling systems. Short-tailed albatrosses, however, have 60% higher wing loading (weight per area of lift) compared to waved albatrosses. Indeed, calculated aerodynamic performance of waved albatrosses, the only tropical albatross species, is more similar to those of their smaller congeners (black-footed P. nigripes and Laysan P. immutabilis), which have relatively low wing loading and much larger foraging ranges that include central oceanic gyres of relatively low productivity. Globally, the aerodynamic performance of short-tailed and waved albatrosses are most anomalous for their body sizes, yet consistent with wind regimes within their breeding season foraging ranges. Our results are the first to integrate global wind and wave patterns with albatross aerodynamics, thereby identifying morphological specialization that may explain limited breeding ranges of two endangered albatross species. These results are further relevant to understanding past and potentially predicting future distributional limits of albatrosses globally, particularly with respect to climate change effects on basin-scale and regional wind fields.     

Sialylation Determines the Nephritogenicity of IgG3 Cryoglobulins

Monoclonal 6-19 IgG3 anti-IgG2a rheumatoid factor derived from lupus-prone MRL-Fas^lpr mice can induce GN and cryoglobulinemia, but the features that confer nephritogenic potential are not completely understood. Asparagine-linked oligosaccharide chains of 6-19 IgG3 mAb are poorly galactosylated and hardly sialylated, possibly contributing to the pathogenic potential of 6-19 IgG3 rheumatoid factors. Here, we used the 6-19 model of cryoglobulin-associated GN to define the relative contributions of galactosylation and sialylation, in relation to cryoglobulin activity, to the nephritogenic potential of IgG3 antibodies. We generated one highly sialylated and two distinct more galactosylated 6-19 IgG3 rheumatoid factor variants. Although the mere extent of galactosylation had no effect on either the cryogenic and nephritogenic activities of 6-19 IgG3 rheumatoid factor, terminal sialylation attenuated the nephritogenic potential of 6-19 IgG3 by limiting its cryoglobulin activity. These data suggest a protective role of IgG sialylation against the development of cryoglobulin-mediated GN, highlighting the anti-inflammatory activity of sialylated IgG antibodies.Cryoglobulins are a heterogeneous group of Igs that precipitate at temperatures <37°C, with resolution upon warming.^1,2 Most cryoglobulins are either monoclonal Ig or Ig complexes in which one component, usually IgM, has rheumatoid factor (RF) activity.^1,2 Monoclonal cryoglobulins are mainly associated with various lymphoproliferative disorders, whereas mixed cryoglobulins are often found in sera of patients with autoimmune diseases, such as SLE and rheumatoid arthritis, or with chronic infectious diseases. The presence of cryoglobulins can result in a wide range of vascular, renal, and neurologic complications, likely depending on their concentration, their temperature-dependent solubility behavior, and the nature and type of proteins involved.²Antibodies of the IgG3 subclass in humans and mice have the unique physicochemical property that allows them to self-associate via Fc-Fc interactions and to display cryoglobulin activity, independently of their specificities.^3–8 Nucleotide sequence analysis of the variable regions of cryogenic and noncryogenic IgG3 mAbs, in combination with the assessment of mutant antibodies, showed that cryoglobulin activity of IgG3 was associated with the presence of more positively charged amino-acid residues at positions 6 and 23 of the heavy-chain variable domain.^9,10 Moreover, structural analysis of asparagine-linked biantennary complex-type oligosaccharide chains (N-glycans) attached to the CH2 domain of different IgG3 mAbs revealed an inverse correlation between the extent of terminal sialylation and cryogenic activity.¹¹ Thus, the cryoglobulin activity of IgG3 is likely to be determined by the presence of positively charged amino-acid residues in the variable region and of negatively charged sialic-acid residues in N-glycans attached to the Fc region. Notably, several studies reported a marked reduction of sialic-acid content in cryoglobulins from human patients.^2,12–15With regard to cryoglobulin-associated pathology, we previously established that implantation of 6-19 hybridoma secreting IgG3 anti-IgG2a RF mAb derived from lupus-prone MRL-Fas^lpr mice induces lupus-like GN in association with the development of cryoglobulinemia.^16,17 Studies with a panel of anti-IgG2a RF mAbs, including Ig class-switch variants of 6-19 RF, demonstrated that the nephritogenicity of anti-IgG2a RF mAb is dependent on the IgG3 subclass.^18–20 Moreover, the development of identical glomerular lesions in Ig-deficient mice lacking the corresponding IgG2a autoantigens indicated that the direct glomerular localization of IgG3 RF mAb, without the involvement of IgG3-IgG2a immune complex formation, is responsible for the development of such lesions.^21,22 However, because IgG3 complexes self-associating due to Fc-Fc interaction could potentially be sufficient to provoke glomerular injuries, it has been unclear whether cryogenic activity is essential for the nephritogenic potential of IgG3.The structural analysis of N-glycans revealed that 6-19 IgG3 RF mAb is poorly galactosylated and hence hardly sialylated,¹⁰ because the terminal sialylation is dependent on the presence of galactose residues. The same pattern of IgG glycosylation has been observed in MRL-Fas^lpr mice,²³ in which IgG3 cryoglobulin formation correlates with the development of the disease,²⁴ and in patients with rheumatoid arthritis, in parallel with the progression of the disease.^25,26 Although the pathogenic significance of this association remains to be determined, it has been reported that agalactosylated and asialylated IgG could be more pathogenic due to the activation of complement by the lectin pathway and an enhanced interaction of IgG with activating IgG Fc receptors (FcγR).^27–29 Moreover, hyposialylation could specifically enhance the nephritogenic potential of IgG3 mAbs by promoting their cryogenic activity.¹¹Using the 6-19 IgG3 RF model of cryoglobulinemia, we aimed to define the contribution of galactosylation or sialylation of N-glycans, in relation to cryoglobulin activity, to the nephritogenic potential of IgG3 antibodies. To this end, we generated two more galactosylated 6-19 IgG3 RF variants, either established from mice expressing a transgene encoding the 6-19 IgG3 heavy chain or obtained by overexpressing β-galactoside α2,6-sialyltransferase I (ST6GalI), as well as a highly sialylated variant carrying phenylalanine instead of alanine at position 243 (F243A) in the CH2 domain. The analysis of these three different 6-19 IgG3 RF variants revealed that the nephritogenic activity of 6-19 IgG3 RF mAb was dependent on the extent of terminal sialylation that negatively regulated the IgG3 cryoglobulin activity, but independent of the extent of galactosylation per se.     

Obstructive jaundice associated with extrahepatic portal vein obstruction: Report of two cases

We herein report two cases of obstructive jaundice with markedly dilated collateral veins either in or around the bile duct in the setting of extrahepatic portal vein obstruction (EHPO). In the first case, a proximal splenorenal shunt provided relief of biliary stenosis as well as eradication of esophageal varices due to a decompression of portal hypertension. This evidence proved that the markedly extended collateral veins in the hepatoduodenal ligament caused biliary stenosis by compressing the bile duct. In the second case, obstructive jaundice was probably caused by cholangitis and was relieved with biliary drainage. Portal decompressive surgery was not indicated because of the slight degree of esophageal varices. The relationship between cholangitis and EHPO in these patients calls for further investigation. In cases with EHPO manifesting obstructive jaundice associated with risky esophageal varices, portal decompressive surgery is recommended as the procedure of choice.     

On the neuronal origin of the afferents to the ciliary ganglion in cat

The histological constitution of the oculomotor nuclear complex and the surrounding structures of cat was re-examined, and it was found that the so-called Edinger-Westphal (EW) nucleus and the anteromedian nuclei consisted of oval cells of small sizes and polygonal cells of medium sizes. The latter cells were scattered in the peripheral portions of the EW and the anteromedian nuclei, and were frequently intermingled with cells of the same type scattered in the central gray and the medial portion of the ventral tegmental area (VTA). Horseradish peroxidase (HRP) was injected into the ciliary ganglion, in order to locate the cells of origin of afferents to this ganglion. The cells labeled by an injection into the ganglion were these polygonal cells of medium sizes scattered in the injected side of midbrain. They weremainly distributed in the VTA, the central gray, and the caudal half of the anteromedian nucleus. The peripheral portion of the EW and the anteromedian nuclei also contained some labeled cells, but these were considered to be cells which had migrated from the central gray and the VTA. Most of the cells in the EW and the anteromedian nuclei were labeled by the injection into the spinal cord. Hence, it was concludedthat the main sources of the afferents to the ciliary ganglion were polygonal cells of medium sizes scattered in the VTA and the central gray, and some of these intermingled with the cells of peripheral boundaries of the EW and the anteromedian nuclei. By contrast, the greater part of the EW and the anteromedian nuclei had a connection with the spinal cord, but not with ciliary ganglion.     

Results of esophageal transection for esophageal varices: Experience in 100 cases

The results of transthoracic esophageal transection in 100 patients with esophageal varices are described. There were 11 operative deaths in this series, and the majority of patients died from hepatic failure. Esophageal varices disappeared completely in 81 percent of the patients and faded in 18 percent. Post-transection rebleeding was observed in six cases. There were 16 late deaths, caused mainly by hepatic failure and hepatoma. The 3 year and 5 year survival rates including operative deaths were 70 and 58 percent, respectively. Based on the low operative mortality rate, the efficacy in eliminating varices and the sufficient survival rate, it is presumed that esophageal transection is the most suitable operation for esophageal varices, even in poor risk patients.     

Polymerization of anhydro sugar derivatives. Cationic polymerization of 5,6-anhydro-1,2-O-isopropylidene-α-D-glucofuranose and structure of the polymer

The cationic polymerization of 5,6-anhydro-1,2-O-isopropylidene-α-D -glucofuranose ( 1 ), containing an oxirane ring, gave a polymer whose structure was found to be poly(5,6-anhydro-1,2-O-isopropylidene-α-D -glucofuranose) ( 2 ). Polymerizations with phosphorus pentafluoride, boron trifluoride etherate, stannic chloride, or antimony pentachloride below 10°C for 0,04 to 240h gave yields of 51,7 to 97,5% of polymers with M?_n in the range of 1290 to 9500. Polymerization above 20°C produced insoluble gels. The specific rotations of the polymers changed with the polymerization conditions, being in the range of ?31,6° to ?15,0°. The mechanism of the epoxide polymerization of the 5,6-anhydro sugar derivatives is discussed.     

In vitro susceptibilites to levofloxacin and various antibacterial agents of 11,475 clinical isolates obtained from 52 centers in 2002

The susceptibilities of bacteria to fluoroquinolones (FQs), especially levofloxacin, and other antimicrobial agents were investigated using 11,475 clinical isolates collected in Japan during 2002. Methicillin susceptible staphylococci, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, the family of Enterobactericeae, Haemophilus influenzae and Acinetobacter spp. exhibited stable and high susceptibilities to FQs. The rate of FQs-resistant MRSA was 80 approximately 90%, being markedly higher than that of FQs-resistant MSSA. The FQs-resistance rate of MRCNS was also higher than that of MSCNS, however, it was lower than that of MRSA. No FQs-resistant clinical isolates of Salmonella spp. were detected in any of the surveys. Thirteen of Escherichai coli 696 isolates, 8 of Klebsiella pneumoniae 630 isolates and 33 of Proteus mirabilis 373 isolates produced extended-spectrum beta-lactamase (ESBL), furthermore 6 of 13 in E. coli, 1 of 8 in K. pneumoniae and 14 of 31 ESBL-producing isolates, and in P. mirabilis were FQs resistant. Attention should be focused in the future on the emergence of ESBL in relation to FQs resistance. The rate of FQs-resistant P. aeruginosa isolated from urinary tract infection (UTI) was 40 approximately 60%, while 15 approximately 25% of isolates from respiratory tract infection (RTI) were resistant. IMP-1 type metallo beta-lactamase producing organisms were found in 49 of P. aeruginosa 1,095 isolates, 7 of S. marcescens 586 isolates and 4 of Acinetobacter spp. 474 isolates, respectively. Glycopeptide-resistant enterococci or S. aureus was not found.