Diastereodifferentiating photocyclodimerization of 2-anthracenecarboxylates tethered to a cyclic tetrasaccharide scaffold: critical control of photoreactivity and stereoselectivity.

From a complex mixture of mono- and di-2-anthracenecarboxylic acid (AC) esters of cyclic nigerosylnigerose (CNN), two monoesters (2(B) and 6(A)) and four diesters in which AC was introduced on the transannular B/D (2(B)2(D)), adjacent A/B and A/D (6(A)2(B) and 6(A)2(D)), and same B/B (2(B)3(B)) nigerose rings were isolated. Possessing two ACs at distant positions, 2(B)2(D) and 6(A)2(D) showed negative Cotton effects for the (1)Bb band, the intensities of which were stronger than that of 6(A). 2(B)2(D) and 6(A)2(D) slowly photocyclodimerized to give HH dimers 3* and 4 with 57% and 81% HH selectivity, respectively, which were appreciably higher than that for 6(A) (34%), while the enantiomeric excesses (ee's) of anti-HH dimer 3* were 2% and -18%, respectively. In contrast, 6(A)2(B) and 2(B)3(B) carrying two ACs on adjacent A and B rings or at vicinal positions on the B ring, respectively, exhibited strong positive CD couplets, the amplitudes of which amounted to 97 and 409 M(-1) cm(-1), respectively. Upon irradiation, 6(A)2(B) afforded 3* with -62% ee and 4 in 96% combined yield, whereas 2(B)3(B) gave almost exclusively 3* with -99% ee in 96% yield, likely as a result of the introduction of two ACs at the vicinal positions of the rigid CNN scaffold.

[A case of advanced gastric cancer with esophageal invasion treated by neoadjuvant S-1/CDDP chemotherapy].

A 75-year-old man was found, by endoscopic examination, to have type 2 advanced gastric adenocarcinoma with esophageal invasion in the cardia. Endoscopy and other modalities revealed observable esophageal invasion. To minimize surgical intervention, we treated him with S-1 and cisplatin as neoadjuvant therapy. Treatment was as follows: S-1(80mg/m2)was administered orally for 3 weeks followed by 2 weeks of rest, and cisplatin(60mg/m2)was administered by intravenous drip on day 8. Two courses of treatment resulted in marked shrinkage of the primary lesion and improvement of the esophageal invasion. Total gastrectomy with splenectomy, and D2 lymph node dissection were performed with an adequately long proximal margin, without thoracotomy. Pathological efficacy was Grade 2. At present, 1 year after the operation, the patient presents no evidence of a recurrence. We concluded that through neoadjuvant chemotherapy for advanced gastric cancer with esophageal invasion, thoracotomy could be avoided, thereby reducing risks associated with surgery.

Strictly diastereocontrolled photocyclodimerization of 2-anthracenecarboxylates tethered to cyclic tetrasaccharides.

Photocyclodimerization of 2-anthracenecarboxylate tethered to a cyclic nigerosylnigerose scaffold gave a single chiral cyclodimer (out of two achiral and two chiral stereoisomers) in 99% optical and 96% chemical yields, achieving the ultimate stereocontrol of the supramolecular photochirogenesis in aqueous solution at 25 °C.

Supramolecular photochirogenesis with novel cyclic tetrasaccharide: enantiodifferentiating photoisomerization of (Z)-cyclooctene with cyclic nigerosylnigerose-based sensitizers.

Isophthalic and terephthalic acid monoesters of cyclic nigerosyl-(1→6)-nigerose (CNN), a cyclic tetrasaccharide composed of four d-glucopyranosyl residues connected by alternating α-1,3- and α-1,6-linkages, were synthesized as novel chiral supramolecular sensitizers for enantiodifferentiating photoisomerization of (Z)-cyclooctene (1Z) to planar chiral (E)-isomer (1E). Despite the saucer-shaped shallow cavity of CNN that does not immediately guarantee strong ground-state interactions with 1Z, the sensitizer-appended CNNs afforded optically active 1E in such enantiomeric excesses that are much improved than those obtained with an α-cyclodextrin analog and comparable with those obtained with a ß-cyclodextrin analog. Interestingly, the enantiomeric excess values obtained were a critical function of temperature and solvent to show an inversion of the product chirality by changing the environmental variants. Nevertheless, all of the differential activation parameters calculated from the temperature-dependent enantiomeric excesses gave an excellent compensatory enthalpy-entropy relationship, indicating an operation of a single enantiodifferentiating mechanism in the present chiral photosensitization with modified CNNs.

[Successful withdrawal from disseminated intravascular coagulation caused by disseminated carcinomatosis of bone marrow originated from gastric cancer treated by sequential therapy consisting of MTX and 5-FU and palliative radiotherapy].

A 5 8-year-old man with severe back pain caused by multiple vertebral metastases developed disseminated intravascular coagulation(DIC). We adopted palliative radiotherapy(8 Gy/1 day)for palliation of his back pain as initial treatment. Afterwards, we started sequential chemotherapy consisting of methotrexate(MTX)and 5-fluorouracil(5-FU). After two courses, DIC was resolved, and the patient was discharged in fair condition after five more courses of MTX and 5-FU therapy.

[An effective case of gemcitabine therapy with post-operative peritoneal recurrence of intrahepatic cholangiocarcinoma].

The patient was a 53-year-old man who had undergone left hepatectomy due to intrahepatic cholangiocarcinoma in August 2007. Pathologically, the tumor was diagnosed as a cholangiocellular carcinoma (T2, N0, M0, Stage II). Ascites appeared about one year after surgery and control was difficult using diuretics. Since abdominal CT revealed peritoneal recurrence with massive ascites, we conducted chemotherapy using gemcitabine (GEM) in September 2008. In the outpatient setting, GEM at a dose of 1, 000 mg/body was administered once a week with a 1-week rest as 1 course. The response was assessed as a complete response (CR) because abdominal CT after 7 courses of chemotherapy showed the disappearance of both ascites and the peritoneal nodules. An adverse effect for GEM was grade 3 anemia, but we could continue the chemotherapy until September 2009. At present, CR has been observed, and one year and three months have passed since the peritoneal reccurrence.

Evaluation of lipoxygenase inhibitory activity of anacardic acids.

6-Alkylsalicylic acids inhibit the linoleic acid peroxidation catalyzed by soybean lipoxygenase-1 (EC 1.13.11.12, type 1) competitively and without pro-oxidant effects. This activity is largely dependent on the nature of their alkyl side chains. Inhibitory activities of anacardic acids, viz. 6-pentadec(en)ylsalicylic acids, isolated from the cashew Anacardium occidentale, were initially used for comparison because their aromatic head portions are the same. Consequently, the data should be interpreted to mean that changes in the hydrophobic side chain tail portions of the molecules evaluated correlate with the specific activity determined.

Anacardic acids and ferric ion chelation.

6-Pentadeca(e)nylsalicylic acids isolated from the cashew Anacardium occidentale L. (Anacardiaceae), commonly known as anacardic acids, inhibited the linoleic acid peroxidation catalyzed by soybean lipoxygenase-1 (EC 1.13.11.12, type 1) competitively without prooxidant effects. Their parent compound, salicylic acid, did not have this inhibitory activity up to 800 pm, indicating that the pentadeca(e)nyl group is an essential element to elicit the activity. The inhibition is attributed to its ability to chelate iron in the enzyme. Thus, anacardic acids chelate iron in the active site of the enzyme and then the hydrophobic tail portion slowly begins to interact with the hydrophobic domain close to the active site. Formation of the anacardic acids-ferric ion complex was detected in the ratio of 2:1 as the base peak in the negative ion electrospray ionization mass spectrometry. Hence, anacardic acids inhibit both Eox and Ered forms.

Structures and physiological roles of 13 integral lipids of bovine heart cytochrome c oxidase.

All 13 lipids, including two cardiolipins, one phosphatidylcholine, three phosphatidylethanolamines, four phosphatidylglycerols and three triglycerides, were identified in a crystalline bovine heart cytochrome c oxidase (CcO) preparation. The chain lengths and unsaturated bond positions of the fatty acid moieties determined by mass spectrometry suggest that each lipid head group identifies its specific binding site within CcOs. The X-ray structure demonstrates that the flexibility of the fatty acid tails facilitates their effective space-filling functions and that the four phospholipids stabilize the CcO dimer. Binding of dicyclohexylcarbodiimide to the O(2) transfer pathway of CcO causes two palmitate tails of phosphatidylglycerols to block the pathway, suggesting that the palmitates control the O(2) transfer process.The phosphatidylglycerol with vaccenate (cis-Delta(11)-octadecenoate) was found in CcOs of bovine and Paracoccus denitrificans, the ancestor of mitochondrion, indicating that the vaccenate is conserved in bovine CcO in spite of the abundance of oleate (cis-Delta(9)-octadecenoate). The X-ray structure indicates that the protein moiety selects cis-vaccenate near the O(2) transfer pathway against trans-vaccenate. These results suggest that vaccenate plays a critical role in the O(2) transfer mechanism.

Enlarging retro-odontoid pseudotumor after expanding cervical laminoplasty in the presence of kyphosis.

BACKGROUND CONTEXT: In cranio-vertebral junction, retro-odontoid pseudotumor without evidence of rheumatoid arthritis is a rare condition. PURPOSE: To discuss the mechanism of enlarging retro-odontoid pseudotumor after expanding cervical laminoplasty as a predictable complication. STUDY DESIGN: We report a rare case of an elderly man with non-inflammatory retro-odontoid pseudotumor after cervical expanding laminoplasty. PATIENT SAMPLE: A 76-year-old man presented with progressive quadriparesis of two week's duration caused by enlarging retro-odontoid soft tissue mass after cervical laminoplasty. OUTCOME MEASURES: Pre- and postoperative image, including X-ray and MRI, and the Japanese Orthopaedic Association scores for cervical myelopathy were assessed. METHODS: The patient subsequently underwent resection of the posterior arch of the atlas and posterior fusion from the occiput to C6 using Olerud system without removal of the retro-odontoid soft tissue mass. RESULTS: One year after surgery, the Japanese Orthopaedic Association scores for cervical myelopathy improved from 1 to 10 points, and postoperative MRI showed a mild reduction in the size of the retro-odontoid soft tissue mass. CONCLUSIONS: The kyphotic stability from C3 to C7 after laminoplasty, leading to a compensatory hyperlordosis at the occipitocervical junction, may cause the development of a degenerative osteoarthritic change, resulting in the production of an enlarging mass. Not only posterior compression of spinal cord due to posterior arch of the hyperextended atlas but also anterior compression of spinal cord due to retro-odontoid pseudotumor probably triggered the severe myelopathy. Laminoplasty may be inappropriate in cervical myelopathy with kyphosis.

Methyl p-coumarate, a melanin formation inhibitor in B16 mouse melanoma cells.

p-Coumaric acid (4-hydroxycinnamic acid) and methyl p-coumarate (methyl 4-hydroxycinnamate) inhibit the oxidation of L-tyrosine catalyzed by mushroom tyrosinase. However, both were oxidized as monophenol substrate analogues at an extremely slow rate. This oxidation was significantly accelerated as soon as catalytic amounts (0.01 mM) of L-3,4-dihydroxyphenylalanine (L-DOPA) became available as a co-factor. Methyl p-coumarate significantly suppressed the melanin formation in B16 mouse melanoma cells, whereas p-coumaric acid did not show this activity.

Prosthetic alignment and sizing in computer-assisted total knee arthroplasty.

We implanted 60 posterior stabilized total knee prostheses (P.F.C. Sigma, DePuy, Warsaw, USA). In 30 cases, we used a CT-free navigation system (Vector Vision, Brain LAB, Heimstetten, Germany), and in 30 matched-paired controls, we used a conventional manual implantation. We compared postoperative long-leg radiographs in the two groups. The results revealed a significant difference in favor of navigation. In addition, we compared the preoperative anteroposterior dimension of the femoral condyle with the postoperative value. While there were no significant differences in the preoperative anteroposterior dimension of the femoral condyle between the two groups, the postoperative value in the navigation group was significantly larger than that of the preoperative value. Therefore, surgeons using navigation systems should guard against the possibility of oversizing when determining the size of the femoral component.

Synergistic effects of anacardic acids and methicillin against methicillin resistant Staphylococcus aureus.

The synergistic effects of 6-alk(en)ylsalcylic acids, also known as anacardic acids, in combination with methicillin against Staphylococcus aureus ATCC 33591 (MRSA) was investigated. The double bond in C15-anacardic acids is not essential in eliciting the antibacterial activity but is associated with increasing the activity. The synergistic effects decreased with increasing the number of double bonds in the alkyl chain. On the other hand, the antibacterial activity of anacardic acids possessing different alkyl chain lengths against the same MRSA strain was found to be a parabolic function of their lipophilicity and maximized with the alkyl chain length of C10 and C12. Notably, the synergistic effects were noted to increase with increasing the alkyl chain length.

Antibacterial action of anacardic acids against methicillin resistant Staphylococcus aureus (MRSA).

The structural and antibacterial activity relationship of 6-alk(en)ylsalicylic acids, also known as anacardic acids, was investigated against Gram-positive bacteria, emphasizing the methicillin resistant Staphylococcus aureus ATCC 33591 (MRSA) strain. The unsaturation in the alkyl side chain is not essential in eliciting activity but is associated with increasing the activity. The antibacterial activity of methicillin against MRSA strains was significantly enhanced in combination with C(12:0)-anacardic acid, and the fractional inhibitory concentration index for this combination was calculated as 0.281. It appears that biophysical disruption of the membrane (surfactant property) is due to the primary response to their antibacterial activity, while biochemical mechanisms are little involved. The compounds possessing the similar log P values exhibit similar activity.