Search

GABA acts as the major inhibitory neurotransmitter in the mammalian brain, shaping neuronal and circuit activity. For sustained synaptic transmission, synaptic vesicles (SVs) are required to be recycled and refilled with neurotransmitters using an H(+) electrochemical gradient. However, neither the mechanism underlying vesicular GABA uptake nor the kinetics of GABA loading in living neurons have been fully elucidated. To characterize the process of GABA uptake into SVs in functional synapses, we monitored luminal pH of GABAergic SVs separately from that of excitatory glutamatergic SVs in cultured hippocampal neurons. By using a pH sensor optimal for the SV lumen, we found that GABAergic SVs exhibited an unexpectedly higher resting pH (∼6.4) than glutamatergic SVs (pH ∼5.8). Moreover, unlike glutamatergic SVs, GABAergic SVs displayed unique pH dynamics after endocytosis that involved initial overacidification and subsequent alkalization that restored their resting pH. GABAergic SVs that lacked the vesicular GABA transporter (VGAT) did not show the pH overshoot and acidified further to ∼6.0. Comparison of luminal pH dynamics in the presence or absence of VGAT showed that VGAT operates as a GABA/H(+) exchanger, which is continuously required to offset GABA leakage. Furthermore, the kinetics of GABA transport was slower (τ > 20 s at physiological temperature) than that of glutamate uptake and may exceed the time required for reuse of exocytosed SVs, allowing reuse of incompletely filled vesicles in the presence of high demand for inhibitory transmission.

The process development of ethyl-(R)-3-amino-2,5-dioxopyrrolidine-3-carboxylate (2), the chiral intermediate for the manufacture of AS-3201 (1), is described. A practical and scalable Shibasaki asymmetric amination that generates the chiral quaternary center was developed and demonstrated on kilogram scale. A safe, convenient, and large-scale hydrogenation of the hydrazine intermediate was also developed.

The cerebellum is a brain region located in the dorsal part of the anterior hindbrain, composed of a highly stereotyped neural circuit structure with small sets of neurons. The cerebellum is involved in a wide variety of functions such as motor control, learning, cognition and others. Damage to the cerebellum often leads to impairments in motor skills (cerebellar ataxia). Cerebellar ataxia can occur as a result of neurodegenerative diseases such as spinocerebellar ataxia. Recent advances in technologies related to pluripotent stem cells and their neural differentiation has enabled researchers to investigate the mechanisms of development and of disease in the human brain. Here, we review recent applications of leading-edge stem cell technologies to the mechanistic investigation of human cerebellar development and neurological diseases affecting the cerebellum.

Heavy metal-associated (HMA) domains bind metal ions at its Cys-x-x-Cys (CxxC) motif and constitute an intracellular network for trafficking of metal ions for utilization and detoxification. We thus expect that novel metalloproteins can be identified by screening proteins interacting with a HMA domain. In this study, we performed yeast two-hybrid screening of the human proteome and found an uncharacterized protein encoded as open reading frame 123 in chromosome 1 (C1orf123) that can interact specifically with the HMA domain of a copper chaperone for superoxide dismutase (CCSdI). Our X-ray structural analysis of C1orf123 further revealed that it binds a Zn2+ ion in a tetrahedral coordination with four thiolate groups from two conserved CxxC motifs. For the interaction between C1orf123 and CCSdI, the CxxC motifs in both C1orf123 and CCSdI were required, implying metal-mediated interaction through the CxxC motifs. Notably, C1orf123 did not interact with several other HMA domains containing CxxC motifs, supporting high specificity in the interaction between C1orf123 and CCSdI. Based upon these results, we further discuss functional and structural significance of the interaction between C1orf123 and CCS.

The patient-a Jehovah's Witness-was a woman in her 60s, with locally advanced sigmoid colon cancer. She had severe anemia, and a computed tomography scan of her abdomen showed a tumor with abscess formation and perforation that had invaded into the left urinary duct and the left ovary, without distant metastasis. It was difficult to perform curative resections without transfusion; therefore, CapeOX therapy was plannedas the neoadjuvant treatment. After 3 courses of CapeOX therapy, the patient's anemia improved, and the tumor and abscess had shrunk. Subsequently, a sigmoidectomy with D3 lymph node dissection, partial resection of the small intestine, and the left adnexectomy, as a radical surgery, were performed without blood transfusion. In cases of concomitant colon cancer with anemia that are treated with highly invasive surgery, it might be necessary to conduct systematic treatment in order to complete non-transfusion therapy.

Although a superficial circumflex iliac artery perforator (SCIP) flap has recently been widely used owing to its various advantages, reports on its use in the pediatric population are limited. A case of a supermicrosurgical reconstruction of a soft tissue defect of the ankle associated with the congenital deficiency of the tibia using a free sensate SCIP flap in a 1-year-old child has been presented. The correction of the valgus deformity of the ankle resulted in a soft tissue defect, which required flap coverage. The lateral cutaneous branch of the intercostal nerve of the flap was coapted with the deep peroneal nerve for sensory recovery. Postoperative course was uneventful and the flap completely survived. The patient was able to ambulate independently at 7 months after surgery. To the best of our knowledge, this is the youngest case of a SCIP flap transfer in literature. This case showed that young age is not a contraindication for SCIP flap transfer. It is believed that the SCIP flap procedure may be a useful option for free flap reconstruction in children.

We suggest a novel method that uses artificial blood cells (hemoglobin vesicles, Hb-Vs) as photosensitizers in dye laser treatment (at 595-nm wavelength) for port-wine stains (i.e., capillary malformations presenting as red birthmarks) based on the results of animal experiments. As compared with human red blood cells, Hb-Vs have the same absorbance of 595 nm wavelength light and produce the same level of heat following dye laser irradiation. Small sized Hb-Vs (250 nm) distribute in the plasma phase in blood and tend to flow in the marginal zone of microvessels. Intravenous injections of Hb-Vs caused the dilatation of microvessels, and dye laser treatment with Hb-Vs destroyed the vessel wall effectively. Following the intravenous injection of Hb-Vs, the microvessels contained more Hb that absorbed laser photons and produced heat. This extra Hb tended to flow near the endothelial cells, which were the target of the laser treatment. These attributes of Hb-Vs will potentially contribute to enhancing the efficacy of dye laser treatment for port-wine stains. Hemoglobin is a type of porphyrin. Thus, our proposed treatment may have aspects of photodynamic therapy using porphyrin that leads to a cytotoxicity effect by active oxygen.

Frontonasal dysplasia (FND) is a congenital malformation of the central portion of the face, including the eyes, nose, and forehead. Owing to its rarity and wide spectrum of phenotypes, the optimal timing and technique of surgery remain controversial. Here, we report a case of a patient with FND, who presented with respiratory distress. The deformed nostrils were so small that the patient could not normally breathe through the nose immediately after birth. Rhinoplasty using a costochondral graft was performed at 16 months of age. After surgery, the nostrils enlarged and the appearance of the nose improved. Although congenital nasal deformity is frequently corrected during adolescence, surgery at an early stage can be considered when important issues are noted, such as inability to breathe through the nose.

Background:. Less-invasive surgeries, such as lymphaticovenular anastomosis (LVA), are the widely accepted intervention for lymphedema. This study aimed to assess the outcomes of flow-oriented LVA modification on lymphatic malformation (LM). Methods:. We included 19 patients diagnosed with LM mixed type or microcystic type, who came to our clinic from June 2015 to December 2017. Under general anesthesia, all patients were administered an indocyanine green lymphography injection subcutaneously. In the case of a strong inflow, the patient underwent afferent lymph vessel of LM to venous anastomosis (LMVA). Otherwise, the side wall of LMVA was performed to the cysts. Outcomes were classified into the following groups based on the size changes: treatment effect (TE) 4 = >80% reduction rate; TE 3 = 50%–80% reduction rate; TE 2 = 20%–50% reduction rate; and TE 1 = 0%–20% reduction rate. Results:. All cases underwent surgery, with no case having an increased size. The results were as follows: TE 4 = 4 (21%) patients; TE 3 = 6 (32%) patients; TE 2 = 5 (26%) patients; and TE 1 = 4 (21%) patients. No case required study termination due to disease progression. Minor complication occurred in 3 cases. One vesicle increased at the labial mucosa and one wound dehiscence that epithelized within 1 month. Conclusion:. LMVA could be a novel, minimally invasive lymph flow-oriented surgical method for intractable LM.

Dominant mutations in FUS/TLS cause a familial form of amyotrophic lateral sclerosis (fALS), where abnormal accumulation of mutant FUS proteins in cytoplasm has been observed as a major pathological change. Many of pathogenic mutations have been shown to deteriorate the nuclear localization signal in FUS and thereby facilitate cytoplasmic mislocalization of mutant proteins. Several other mutations, however, exhibit no effects on the nuclear localization of FUS in cultured cells, and their roles in the pathomechanism of fALS remain obscure. Here, we show that a pathogenic mutation, G156E, significantly increases the propensities for aggregation of FUS in vitro and in vivo. Spontaneous in vitro formation of amyloid-like fibrillar aggregates was observed in mutant but not wild-type FUS, and notably, those fibrils functioned as efficient seeds to trigger the aggregation of wild-type protein. In addition, the G156E mutation did not disturb the nuclear localization of FUS but facilitated the formation of intranuclear inclusions in rat hippocampal neurons with significant cytotoxicity. We thus propose that intranuclear aggregation of FUS triggered by a subset of pathogenic mutations is an alternative pathomechanism of FUS-related fALS diseases.

Background Kasabach-Merritt phenomenon (KMP) is a rare condition and optimal treatments have not yet been established, especially for cases that are unresponsive to first-line therapy. We retrospectively reviewed 11 KMP cases treated over the past 13 years in our institute. Observations With the exception of 1 case, steroids were administered as the first-line therapy. Eight cases required second-line or third-line therapy. The effective salvage therapies include interferon (n=1), radiotherapy (n=1), and chemotherapy (n=5). One case continues to depend upon chemotherapy. Three refractory cases were therapy dependent over 1 year of age, whereas 8 were treated effectively by 6 months of age. Conclusions Chemotherapy seems to be the most effective therapy for steroid-resistant KMP cases.

Background: Most arteriovenous malformations (AVMs) are localized and occur sporadically. However, they also can be multifocal in autosomal-dominant disorders, such as hereditary hemorrhagic telangiectasia and capillary malformation (CM)-AVM. Previously, we identified RASA1 mutations in 50% of patients with CM-AVM. Herein we studied non-RASA1 patients to further elucidate the pathogenicity of CMs and AVMs. Methods: We conducted a genome-wide linkage study on a CM-AVM family. Whole-exome sequencing was also performed on 9 unrelated CM-AVM families. We identified a candidate gene and screened it in a large series of patients. The influence of several missense variants on protein function was also studied in vitro. Results: We found evidence for linkage in 2 loci. Whole-exome sequencing data unraveled 4 distinct damaging variants in EPHB4 in 5 families that cosegregated with CM-AVM. Overall, screening of EPHB4 detected 47 distinct mutations in 54 index patients: 27 led to a premature stop codon or splice-site alteration, suggesting loss of function. The other 20 are nonsynonymous variants that result in amino acid substitutions. In vitro expression of several mutations confirmed loss of function of EPHB4. The clinical features included multifocal CMs, telangiectasias, and AVMs. Conclusions: We found EPHB4 mutations in patients with multifocal CMs associated with AVMs. The phenotype, CM-AVM2, mimics RASA1 -related CM-AVM1 and also hereditary hemorrhagic telangiectasia. RASA1 -encoded p120RASGAP is a direct effector of EPHB4. Our data highlight the pathogenetic importance of this interaction and indicts EPHB4-RAS-ERK signaling pathway as a major cause for AVMs.

Nipple adenoma is an uncommon proliferative process of the breast and predominantly occurs in women aged 40-50. Its incidence is extremely low in men, and it has not been reported in a boy. Although nipple adenoma is rare and benign, being familiar with it is important because it clinically resembles Paget disease and histologically adenocarcinoma. We report a case of nipple adenoma in a boy.

A styrene-based monomer having a five-membered cyclic dithiocarbonate structure, 4-vinylbenzyl 1,3-oxathiolane-2-thione-5-ylmethyl ether (VBTE), was synthesized from 4-vinylbenzyl glycidyl ether (VBGE) and carbon disulfide in the presence of lithium bromide in 86% yield. Radical polymerization of VBTE in dimethyl sulfoxide by 2,2′-azobisisobutyronitrile was carried out at 60 °C to afford the corresponding the polymer, polyVBTE, in 64% yield. PolyVBTE with number-averaged molecular weight higher than 31,000 was obtained. The glass transition temperature (Tg) and 5 wt % decomposition temperature (Td5) of the polyVBTE were evaluated to be 66 and 264 °C under nitrogen atmosphere by differential scanning calorimetry and thermal gravimetry analysis, respectively. It was confirmed that a polymer consisting of the same VBTE repeating unit could also be obtained via polymer reaction, that is, a lithium bromide-catalyzed addition of carbon disulfide to a polyVBGE prepared from a radical polymerization of VBGE. Copolymerization of VBTE and styrene with various compositions efficiently gave copolymers of VBTE and styrene. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013

Background: Dominant mutations in TDP-43 cause familial ALS. Results: Longer half-lives of mutant TDP-43 proteins correlated with earlier disease onset, and stabilized TDP-43 provoked protein insolubility, cleavage, RNA dysregulation, and cytotoxicity. Conclusion: Increased stability of TDP-43 causes toxicity through abnormal proteostasis and RNA dysregulation. Significance: This is the first TDP-43 cell model based on genotype-phenotype correlation of ALS patients., Abnormal protein accumulation is a pathological hallmark of neurodegenerative diseases, including accumulation of TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis (ALS). Dominant mutations in the TDP-43 gene are causative for familial ALS; however, the relationship between mutant protein biochemical phenotypes and disease course and their significance to disease pathomechanism are not known. Here, we found that longer half-lives of mutant proteins correlated with accelerated disease onset. Based on our findings, we established a cell model in which chronic stabilization of wild-type TDP-43 protein provoked cytotoxicity and recapitulated pathogenic protein cleavage and insolubility to the detergent Sarkosyl, TDP-43 properties that have been observed in sporadic ALS lesions. Furthermore, these cells showed proteasomal impairment and dysregulation of their own mRNA levels. These results suggest that chronically increased stability of mutant or wild-type TDP-43 proteins results in a gain of toxicity through abnormal proteostasis.

AlCl3-mediated cleavage of ethereal methyl–oxygen bond in aroylated 2,7-dimethoxynaphthalene compounds proceeds chemospecifically and regioselectively. The ethereal bond at the β(2)-position of 1-monoaroylated 2,7-dimethoxynaphthalene is cleaved readily and predominantly against the β(7)-position, whereas scission of β-ethereal bonds of 1,8-diaroylated 2,7-dimethoxynaphthalene hardly undergoes like the non-aroylated mother frame compound of 2,7-dimethoxynaphthalene.

The crystal structure and the dynamic feature of molecular structure in solution for 1,8-dibenzoyl-2,7-dimethoxynaph-thalene are revealed by X-ray crystallographic analysis and VT-NMR measurements. In crystal, the molecule of the title compound is located on a twofold rotation axis. The two benzoyl groups are situated in an opposite direction. The dihedral angle between the mean planes of the phenyl ring and the naphthalene ring system is 80.25(6). The benzene ring and carbonyl moiety in each benzoyl group are almost coplanar. The molecular packing is stabilized by weak C–H…O hydrogen bonds and aπ-πstacking interaction between the benzene rings [centroid-centroid and interplanar distances of 3.6383(10) and 3.294 , respectively]. In solution, the temperature-dependent rotation behavior of the C–C bond between the benzene ring and the ketonic carbonyl group has been observed by1H VT-NMR measurements. Furthermore, comparison of the C–C bond rotation behavior between the benzene ring and the carbonyl group with 1-ben-zoyl-2,7-dimethoxynaphthalene has clarified that the C–C bond between the ketonic carbonyl group and the naphthalene ring rotates slower than the 1,8-dibenzoylated homologue.

Late postoperative cervical metastasis (LCM) greatly influences prognosis in cases such as squamous cell carcinoma of the tongue. Indications and preferred prophylactic neck dissection of the clinically negative neck (N0) in tongue carcinoma remain controversial and non standardized. We studied adequate neck dissection area, focusing on T2N0, T2N1 and T3N0 tongue carcinoma. We retrospectively analyzed surgical efficacy in 61 cases with stage I-T1N0, stage II-T2N0, stage III-T2N1 and T3N0 and stage IV-T2-3 N2b-c. All were treated initially with surgery alone. In 13 T1N0 cases, tumors were removed with a 15-20 mm surgical margin, showing LCM in 2. In 18 T2N0 cases, resected with the same surgical margin, LCM was seen in 9. In 5 T2N1 cases performed with partial tongue resection and radical neck dissection (RND), no LCM was seen. In 3 of 4 T3N0 cases, including level I resection, LCM occurred. In 9 stage IV pull-through cases and RND, LCM ocurred in 2. In 30% (9/30) of stage II LCM, 44.4% (4/9) was salvaged by RND. Five-year cumulative survival in 61 was 71.1%, 87.5% in stage I, 76.8% in stage II, 65.6% in stage III, and 55.4% in stage IV. We concluded that local resection is feasible (1) in T1N0 and early T2N0, (2) local and level I-III neck dissection in late T2N0 and T2N1, (3) local dissection, pull-through technique and level I-IV neck dissection in T3N0 and (4) local dissection, pull-through and level I-V neck dissection in stage IV.

In the present study, 37 patients with advanced laryngeal carcinoma (stage III and IV) were analyzed, who had been treated at St. Marianna University, School of Medicine between 1996 and 2007, based on the modified TNM classification by the international union against cancer (UICC, 6th edition, 2003). Before the modification of the TNM classification, total laryngectomy (TL) was our strategy of treatment for T3 and T4 patients. Those patients who refused TL received radiotherapy (low-dose concurrent chemoradiotherapy or radiotherapy alone). Five out of 16 cases in T3 who were classified under the 6th edition belonged to T2 under the previous edition, which made the treatment of T3 more difficult. The 5-year cause-specific survival rate of all cases was 63.9%, 81.3% in stage III, 46.8% in stage IV, 90.9% in the glottic type and 50% in the supraglottic type. A particularly significant difference was seen between these latter two types (p

We compared the influences of auditory and visual targets on the vestibulo-ocular reflex (VOR) in healthy adults, to investigate auditory, visual, and vestibular modality integration in location perception. Under head fixed target conditions, VOR gains with visual target decreased, compared with VOR gain in darkness. VOR gains with auditory target were as big as those in darkness. On the other hand, in earth fixed conditions, VOR gains increased and phase delay decreased with both visual and auditory target. These findings suggest that auditory stimuli with relative motion have an influence on the vestibule-ocular system.

Outer membrane-specific lipoproteins of Escherichia coli are released from the inner membrane through the action of Lol-CDE, which leads to the formation of a complex between the lipoprotein and LolA, a periplasmic chaperone. LolA then transfers lipoproteins to LolB, a receptor in the outer membrane. The structures of LolA and LolB are very similar, having an incomplete beta-barrel covered with an alpha-helical lid forming a hydrophobic cavity inside. The cavity of LolA, but not that of LolB, is closed and thus inaccessible to the bulk solvent. Previous studies suggested that Arg at position 43 of LolA is critical for maintaining this closed structure. We show here, through a crystallographic study, that the cavity of the LolA(R43L) mutant, in which Leu replaces Arg-43, is indeed open to the external milieu. We then found that the binding of a fluorescence probe distinguishes the open/close state of the cavity. Furthermore, it was revealed that the hydrophobic cavity of LolA opens upon the binding of lipoproteins. Such a liganded LolA was found to be inactive in the release of lipoproteins from the inner membrane. On the other hand, the liganded LolA became fully functional when lipoproteins were removed from LolA by detergent treatment or transferred to LolB. Free LolA thus formed was inaccessible to a fluorescence probe. These results, taken together, reveal the LolA cycle, in which the hydrophobic cavity undergoes opening and closing upon the binding and release of lipoproteins, respectively.

The structures of a lipoprotein carrier, LolA, and a lipoprotein receptor, LolB, are similar except for an extra C-terminal loop containing a 3(10) helix and beta-strand 12 in LolA. Lipoprotein release was significantly reduced when beta-12 was deleted. Deletion of the 3(10) helix also inhibited the lipoprotein release. Furthermore, lipoproteins were non-specifically localized to membranes when LolA lacked the 3(10) helix. Thus, the membrane localization of lipoproteins with the LolA derivative lacking the 3(10) helix was independent of LolB whereas LolB was essential for the outer membrane localization of lipoproteins with the wild-type LolA.

Various 2-(2′-hydroxy-4′-methyl-1′-cyclohexylidene) carboxylic acid lactones were synthesised in good yield from carboxylic acids and 4-methylcyclohexanone. For example, mintlactone (VI) and isomintlactone (VII) were prepared from 2-(1′- hydroxy-4′-methylcyclohexan-1′-yl) propanoic acid (III) which was obtained by reaction of propanoic acid (I) with 4-methylcyclohexanone (II) using lithium naphthalenide in the presence of diethylamine. Compound (VI) could be separated from compound (VII) by silica gel column chromatography. Several new 2-(2′- hydroxy-4′-methyl-1′-cyclohexylidene) carboxylic acid lactones which may be used as perfumery materials, were obtained in good yield by this method.

Various 1, 4-diketones were prepared from carboxylic acids via two steps : Grignard reaction with vinylmagnesium chloride and oxidation with Jones reagent catalysed by mercuric propionate. For example, 2, 5-undecanedione was prepared from heptanoic acid via 1-undecen-5-one.

Several, 2,4-dialkyl-2-cycloalkenyl-γ-butyrolactones were synthesised from 2-(cycloalken-1′-yl) carboxylic acids and epoxides using lithium naphthalenide in the presence of diethylamine. From 2-(cyclohexen-1′-yl)propanoic acid and propylene oxide, 4-hydroxy-2-(cyclohexen-1′-yl)-2-methylpentanoic acid was obtained. The latter easily cyclised to give 2-(cyclohexen-1′-yl)-2,4-dimethyl-γ-butyrolactone. Similarly, 2,4-dialkyl-2-(cycloalken-1′-yl)-μ-butyrolactones were prepared from other 3,4-unsaturated carboxylic acids and epoxides. These lactones may be used as perfumery materials.

One mole of propionic acid (I) reacts with 2 mol of 1,2-butylene oxide (II) in the presence of lithium naphthalenide to give 4-hydroxy-2-(2′-hydroxybutyl)-2-methylhexanoic acid (V), which can be easily converted into 2-(2′-hydroxybutyl)-2-methyl-4-ethyl-γ-butyrolactone (VII). Similarly, 2,4-dialkyl- and 2,4,4-trialkyl-2-hydroxyalkyl-γ-butyrolactones were prepared from other carboxylic acids having two hydrogens at 2-position and various epoxides.

3-Hydroxy acids were synthesised in good yield from ketones and carboxylic acids using lithium naphthalenide in the presence of diethylamine. From cyclohexanone and propionic acid, 2-(1′-hydroxycyclohexan-1′-yl) propionic acid (I) was obtained in 98.3% yield. 3-Hydroxy acids were treated with various acidic materials to give 3,4-unsaturated carboxylic acids and γ-butyrolactones. From the reaction of (I) with p-toluenesulphonic acid or potassium bisulphate, 2-(cyclohexen-1′-yl) propionic acid (II) (a 3,4-unsaturated acid) was obtained (yield 98%), and with 97% sulphuric acid 2-(1′-hydroxycyclohexan-1′-yl) propionic acid lactone (III) was formed (93% yield). Several new γ-butyrolactones were obtained in good yield by this method.

The reaction of isoprene with phenol, catalysed by nickelocene and phenylmagnesium bromide, yields 2,2-dimethylchroman, 2-(3′-methyl-2′-buten-1′-yl)phenol, 4-(3′-methyl-2′-buten-1′-yl)phenol, 2,2-dimethyl-8-(3′-methyl-2′-buten-1′-yl)chroman and 2,2-dimethyl-6-(3′-methyl-2′-buten-1′-yl)chroman. Reactions with other phenols were examined.

The oligomerisation of isoprene catalysed by nickel naphthenate and isoprene magnesium was studied under various conditions. The use of various phosphites as donors gives cyclic dimers containing dimethyloctadiene (about 90%); in particular 1,1,1-trishydroxymethylpropane phosphite gives trimethylcyclo-dodecatriene selectively. The use of triphenylphosphine gives a linear isoprene trimer containing farnessene.

5-Cyclohexadecenone is prepared from cyclododecanone via four new steps: chlorination, Grignard reaction with vinylmagnesium chloride and rearrangement with aluminium isopropoxide, revinylation with vinylmagnesium chloride and oxy-Cope rearrangement.

New cyclohexenyl alkenyl ketones are prepared by the reaction of various methyl cyclohexenyl carboxylates and vinylmagnesium chloride; for example, 1-(4′-methyl-3′-cyclohexene-1′-yl)-1-oxo-4-pentene is obtained from methyl 4-methyl-3-cyclohexene-1-carboxylate and vinylmagnesium chloride.

The reaction of vinylmagnesium chloride with an aromatic carboxylic acid gives a vinyl ketone. From benzoic acid, 5-oxo-5-phenyl-1-pentene is obtained. Similarly, from aliphatic carboxylic acid, a mixture of vinyl ketone and divinyl carbinol is obtained. From pentanoic acid, a mixture of butyl divinyl carbinol and 5-oxo-1-nonene is obtained.

It was found that lithium naphthalenide can be prepared from metallic lithium cuttings and naphthalene in non-ethereal solvents, such as benzene–N,N,N′,N′-tetramethylethylenediamine (TMEDA) or benzene-N,N,N′,N′-tetramethyldiaminopropane (TMDAP), under ultrasonic irradiation. Secondary amines reacted with conjugated olefins, such as isoprene or myrcene, using lithium naphthalenide in such non-ethereal solvents to give allylic amines. The yields of products were higher than in the reaction using lithium naphthalenide in tetrahydrofuran. From diethylamine (I) and isoprene (II), a mixture of N,N-diethyl-3-methyl-2-butenylamine (IV) and N,N-diethyl-2-methyl-2-butenylamine (V) (IV:V = 79:21) was obtained in 77% yield, and from diethylamine (I) and myrcene (III), N,N-diethylgeranylamine (VI) and N,N-diethylnerylamine (VII) (VI:VII = 88:12) were produced in 72% yield. These terpenic amines, VI and VII, are used as starting compounds for the preparation of perfumery materials.

Various 2-alkyl-3-methyl-2-cyclopentenones were prepared via 2-alkyl-4-penten-2-ols serving as common intermediates from carboxylic acids or methylketones. For example, dihydrojasmone was prepared from heptanoic acid as follows: Grignard reaction of heptanoic acid (I) with allylmagnesium chloride gave 1-decen-4-one (II) and re-Grignard reaction of (II) with methylmagnesium iodide produced 4-methyl-1-decen-4-ol (IV). 4-Methyl-1,4-decanediol (V) was obtained by hydroboration of (IV). Oxidation of (V) with chromium trioxide gave 4-hexyl-4-methyl-4-butanolide (VI). Dihydrojasmone may be prepared by dehydration of (VI) with polyphosphoric acid. Several new 2-alkyl-3-methyl-2-cylopentenones were obtained by this method.

5-Methyl-2-isopropyl-4-hexenoic acid, dihydrolavandulic acid (III), was synthesised in 65% yield from 3-methylbutanoic acid and isoprene with sodium naphthalenide in the presence of N,N,N′,N′-tetramethylethylenediamine. Reduction of III with lithium aluminum hydride gave 5-methyl-2-isopropyl-4-hexen-l-ol, dihydrolavandulol (IV) (85% yield). Oxidation of IV with pyridinium chlorochromate gave 5-methyl-2-isopropyl-4-hexenal, dihydrolavandulyl aldehyde (V) (81 % yield).

Various 2,3-dialkyl parasorbic acids were prepared from carboxylic acids. For example, 2-methyl-5-pentyI parasorbic acid was prepared from hexanoic acid and propanoic acid as follows: Grignard reaction of hexanoic acid (I) with allylmagnesium chloride gave l-nonen-4-one (II) and the reaction of (II) with propanoic acid (III) with lithium naphthalenide in the presence of diethylamine produced 3-allyl-3-hydroxy-2-methyloctanoic acid (IV). From the reaction of (IV) with 97% (v/v) sulphuric acid, 2-methyl-3-pentyl parasorbic acid was formed. Several 2,3-dialkyl parasorbic acids were obtained by this method. These products may be used as perfumery materials.

Various oxo-dimethylallyl compounds were prepared from intermediates which are obtained by the reaction of allylic Grignard reagents with carboxylic acid derivatives. For example, the reaction of prenylmagnesium chloride with ethyl hexanoate gave 3,3–dimethyl-4–prenyl-1-nonen-4–ol (1) in 92% yield. The thermolysis of 1 at the temperature of 693 K gave 2–methyl-2–decen-5–one (2) in 81% yield. Furthermore, 3,3–dimethyl-1-alken-4–ones (E) were prepared by the methylation of 1-alken-4-ones (C), which are obtained by the reaction of allylmagnesium chloride with carboxylic acids (A).

3,4-Unsaturated acids were condensed with paraformaldehyde in boiling acetic acid containing a small amount of aluminium chloride to afford 2,3-unsaturated-δ-lactones. For example, from 2-(cyclohexen-1′-yl)caprylic acid (I) and paraformaldehyde, 2′-hydroxymethyl-2-cyclohexylidenecaprylic acid lactone (II) was obtained in up to 93% yield. Several 2,3-unsaturated-δ-valerolactones were obtained in good yield by this new method. These lactones may be used as perfumery materials.

This review article describes preparations and properties of various types of water-soluble cutting fluids additives derived from various materials. It is concerned with synthetic additives classified according to their functional groups: carboxylic acids, esters, dibasic acids, ethers, amides, substituted fatty acids and others for iron materials. Testing methods for water-soluble cutting fluids are described on ways for laboratory and practical tests for factory.

Although a superficial circumflex iliac artery perforator (SCIP) flap has recently been widely used owing to its various advantages, reports on its use in the pediatric population are limited. A case of a supermicrosurgical reconstruction of a soft tissue defect of the ankle associated with the congenital deficiency of the tibia using a free sensate SCIP flap in a 1-year-old child has been presented. The correction of the valgus deformity of the ankle resulted in a soft tissue defect, which required flap coverage. The lateral cutaneous branch of the intercostal nerve of the flap was coapted with the deep peroneal nerve for sensory recovery. Postoperative course was uneventful and the flap completely survived. The patient was able to ambulate independently at 7 months after surgery. To the best of our knowledge, this is the youngest case of a SCIP flap transfer in literature. This case showed that young age is not a contraindication for SCIP flap transfer. It is believed that the SCIP flap procedure may be a useful option for free flap reconstruction in children.

A number of derivatives of thiocarboxylic acid were prepared from the reaction of 3-mercaptopropionic acid and alkyl halides, and screened for anti-rust properties in water-soluble metalworking fluids. Aqueous metalworking fluids containing octylthiopropionic acid or hexylthioacetic acid showed excellent anti-rust properties for water-soluble metalworking fluids.