α-Glucosidase and Pancreatic Lipase Inhibitory Activities of Diterpenes from Indian Mango Ginger (Curcuma amada Roxb.) and Its Derivatives.

Enzymatic inhibitions of crude extracts and their constituents from Zingiberaceae against both rat intestinal α-glucosidase and porcine pancreatic lipase were investigated. Structure-activity relationships using their derivatives were also investigated. The rhizomes extract of mango ginger, Curcuma amada showed remarkable inhibitory activity in the screening test. Two natural labdane diterpenes 1 and 2 and a drimane sesquiterpene 3 were major constituents isolated from this hexane extract. Among them, (E)-labda-8(17),12-diene-15,16-dial (1) was the most prominent compound and showed inhibitory activity against both α-glucosidase and lipase. Derivatives 4-10 from compound 1 were prepared and evaluated using inhibitory assays with these enzymes. The reduced derivative 4 maintained α-glucosidase inhibitory activity, but had decreased pancreatic lipase inhibitory activity compared with parent compound 1. Other tested derivatives of compound 1, including acetates 5-7 and oxidative derivatives 8-10, had very weak α-glucosidase inhibitory activity. Most of these compounds showed moderate pancreatic lipase inhibitory activity. However, only sesquiterpene albicanal (3) showed drastically decreased pancreatic lipase activity compared with 1. These findings suggested that molecular size was essential for enzymatic inhibitory activities of these compounds. These results demonstrated that mango ginger may be useful for the prevention of obesity and being overweight.

[A Case of Trigeminal Neuralgia Treated with Microvascular Decompression 10 years after Gamma Knife Radiosurgery].

We report a case of trigeminal neuralgia treated with microvascular decompression 10 years after We report a case of trigeminal neuralgia treated with microvascular decompression 10 years after Gamma Knife radiosurgery was performed. The patient was a 65-year-old female. The root entry zone of the trigeminal nerve received irradiation:a 4-mm shot, with a maximum dose of 80 Gy. The symptoms improved following treatment, however pain recurred five and a half years later. The pain gradually increased over time, to the point where the patient was unable to eat solid food. Carbamazepine was prescribed and the dosage increased. However, side effects such as dizziness and drowsiness manifested. Microvascular decompression was performed, revealing that the trigeminal nerve was markedly atrophied and being pressed upon by the superior cerebellar artery. The superior cerebellar artery was transpositioned with Teflon braided tape to the cerebellar tent. There were no abnormal findings such as arachnoid thickening, adhesions between vessels and nerves, or atherosclerotic plaque in the affected vessels. Pain completely abated following surgery, and side effects such as numbness of the face have not been observed at the time of writing this report.

[Extended Sandwich Patch Technique through Right Ventriculotomy in Patient with Septal Perforation Developed after Off-Pump Coronary Artery Bypass Grafting;Report of a Case].

A 72-year-old diabetic man was diagnosed with acute myocardial infarction of the anterior wall and underwent emergency off-pump coronary artery bypass grafting. He was diagnosed with ventricular septal perforation(VSP) 3 days after the operation. We urgently performed surgical repair of VSP with "extended sandwich patch technique through right ventriculotomy". There was no shunt recurrence. This technique is considered to offer safe, simple and leak-free repair even in an acute phase of VSP.

Antimalarial and Antileishmanial Activities of Phytophenolics and Their Synthetic Analogues.

Thirty-seven phytophenolics and their synthetic analogues were evaluated for activity against two protozoal pathogens, Leishmania donovani and Plasmodium falciparum (D6 and W2 clones), respectively. 4,6-Dimethoxyaurone demonstrated the highest activity with IC50 values of 13.2 and 16.9 µm against L. donovani and P. falciparum (W2 clone), respectively, without undesired cytotoxicity against VERO cells. The moiety having two benzene rings was critical to maintain the antiprotozoal activities based on the observation that both coumaranones and chromones were inactive while other test compounds, including coumarans and aurones, remained active. There was no correlation between antiprotozoal activities and previously evaluated insect antifeedant activity against common cutworms (Spodoptera litura). Flavonoids, including aurones, pterocarpans, and lignan like dihydrobenzofurans, structural analogues of coumarans, are abundant in fruits and vegetables, so these phytophenolics may act as natural antiprotozoal agents in humans.

Risk Factors of Nicardipine-Related Phlebitis in Acute Stroke Patients.

BACKGROUND AND PURPOSE: Intravenous nicardipine is generally used to treat hypertension in acute stroke patients but is associated with frequent phlebitis. We aimed to identify the incidence and risk factors of phlebitis in such patients. METHODS: The incidence and risk factors of phlebitis were investigated in 358 acute stroke patients from July 2014 to June 2015. RESULTS: In total, 138 patients received intravenous nicardipine. Of 45 (12.6%) phlebitis patients in 358 acute stroke patients, 42 (93.3%) were administered nicardipine, which was significantly associated with phlebitis occurrence (P < .01). Other candidate risk factors of phlebitis of acute stroke patients in univariate analysis were intracerebral hemorrhage (P < .01), nicardipine injection to paralyzed limbs (P = .023), dilution of nicardipine with normal saline (P < .01), higher maximum flow rate of nicardipine (7.2 ± 4.1 mg/h versus 1.6 ± 3.1 mg/h; P < .01), and higher maximum concentration of nicardipine (271.5 ± 145.0 µg/mL versus 37.6 ± 75.0 µg/mL; P < .01). The only statistically significant independent factor following multivariate logistic regression analysis, according to the optimal cutoff values defined from receiver operating characteristic curve analyses, was the maximum concentration of nicardipine greater than 130 µg/mL (OR 57.9; 95% CI 21.5-156; P < .01). A gradual decline of pH below 4.3 was observed when the concentration of nicardipine solution increased to greater than or equal to 130 µg/mL in vitro. CONCLUSIONS: Nicardipine-related phlebitis is frequently observed in acute stroke patients and is significantly associated with administration of a maximum concentration of nicardipine greater than 130 µg/mL.

Quantitative evaluation for intravascular structures of vertebral artery dissection with a novel zoomed high-resolution black-blood MR imaging.

BACKGROUND: Although non-stroke vertebral artery dissection (VAD) is diagnosed using MRI, detecting the subtle intravascular structure remains challenging. This study aimed to evaluate the validity of quantitative intravascular scanning based on novel zoomed high-resolution black blood (Z-HB) MRI for distinguishing VAD from other vessel pathologies. METHODS: Twenty-one patients with non-stroke VAD and 18 with symptomatic atherosclerotic plaques in their vertebral artery underwent Z-HB MRI and subsequent profile curve processing. Axial Z-HB imaging was obtained from dissected and normal segments in patients with VAD and atherosclerotic plaque in patients with ischemia. We investigated the qualitative categorization of the scanning patterns of the intravascular signals. We also evaluated the quantitative ability of each profile curve to discriminate multiple vessel pathologies by analyzing the receiver operating characteristics curves. RESULTS: Profile curve processing of 140 Z-HB images categorized the intravascular signal patterns into luminal, asymmetrical, and omega types. The asymmetrical type included both dissecting and atherosclerotic vessels, and the omega type included dissecting and normal vessels. In the asymmetrical type, quantitative evaluation successfully distinguished intramural hematomas of VAD from atherosclerotic plaque with an area under the curve of 0.80. The intimal flap of the VAD was distinguished from the blood flow artifact of the normal vessel with an area under the curve of 0.93 in the omega type. CONCLUSIONS: A combination of novel Z-HB MRI and profile curve processing provided an ultra-high-resolution analysis of the intravascular structure of non-stroke VAD and successfully distinguished VAD from normal vessels or atherosclerotic plaques.

Is central repair with coronary artery bypass grafting enough for multi-organ malperfusion in acute type A aortic dissection with coronary malperfusion?

OBJECTIVES: Acute type A aortic dissection with coronary malperfusion syndrome is rare but associated with high mortality. Multi-organ malperfusion is an independent predictor of acute type A aortic dissection. Coronary malperfusion requires treatment, but it is not feasible to treat all malperfusions. The adequacy of "central repair and coronary artery bypass grafting" for patients with coronary and other organ malperfusion is unknown. METHODS: Of the 299 patients who underwent surgery between 2008 and 2018, 21 patients with coronary malperfusion, who received cental repair with coronary artery graft bypass, were analyzed retrospectively. They were divided; into Group M (n = 13, coronary and other organ malperfusion) and Group O (n = 8, coronary malperfusion only). The patient background, surgical content, details of malperfusion, surgical mortality and morbidity, and long-term outcome were compared. RESULTS: There was no difference in operation time (205 ± 30 vs. 266 ± 88, p = 0.49), but the time from arrival to circulatory arrest tended to be shorter in Group M (81 vs. 134, p = 0.05). Among Group M, cerebral malperfusion was the most common at 92%. Two of the three cases with mesenteric malperfusion died. The mortality of Group M and Group O was 13% and 15% (P = 0.85), respectively. There was no difference in long-term mortality (p = 0.62). CONCLUSIONS: Central repair and coronary artery bypass grafting is a sufficiently acceptable treatment for patients with acute type A aortic dissection and multi-organ malperfusion, including coronary malperfusion.

Deodorant Activity of Black Cumin Seed Essential Oil against Garlic Organosulfur Compound.

The deodorant activity of black cumin (Nigella sativa L.) seed, a spice used to flavor curry and vegetable foods in Southwest Asia, against garlic (Allium sativum L.) organosulfur compounds related to human malodor was evaluated. Black cumin seed essential oil showed remarkable deodorant activity against garlic essential oil. The mode of action of this deodorant activity was presumed to be that black cumin seed essential oil covalently reacted with the organosulfur compounds in garlic. Therefore, thymoquinone, which is a major constituent in black cumin seed essential oil, and allyl mercaptan, which is one of the organosulfur compounds produced by cutting garlic, were reacted in vitro, and the products were purified and elucidated using spectroscopic data. As a result, these substances were identified as different allyl mercaptan adducts to dihydrothymoquinone. This chemical reaction was presumed to play a key role in the deodorant activity of black cumin seed essential oil.

Inhibitory Activities of Sulfur Compounds in Garlic Essential Oil against Alzheimer's Disease-Related Enzymes and Their Distribution in the Mouse Brain.

Alzheimer's disease (AD) is the most common neurodegenerative disease. Garlic reportedly has various physiological effects, including a role in protecting against dementia. However, the action mechanisms of garlic on AD are not entirely clear. In this study, we investigated the inhibitory activity of garlic essential oil (GEO) against AD-related enzymes and evaluated the distribution of active substances in GEO to the brain. We found that several sulfur compounds in GEO significantly inhibited AD-related enzymes. Sulfur compounds were detected in the serum and brain 6 h post administration. The ratios of allyl mercaptan (24.0 ± 3.9%) and allyl methyl sulfide (49.8 ± 15.6%) in the brain were significantly higher than those in GEO, while those of dimethyl trisulfide (0.89 ± 34.8%), allyl methyl trisulfide (0.41 ± 19.0%), and diallyl trisulfide (0.43 ± 72.8%) in the brain were significantly lower than those in GEO. Similar results were observed in the serum, suggesting that the organosulfur compounds were converted to allyl mercaptan or allyl methyl sulfide in the body. Although allyl mercaptan and allyl methyl sulfide are not the main components of GEO, they might be key molecules to understand the bioactivities of GEO in the body.

Chemical Defense of Yacón (Smallanthus sonchifolius) Leaves against Phytophagous Insects: Insect Antifeedants from Yacón Leaf Trichomes.

Yacón is a perennial crop with high insect resistance. Its leaves have many glandular trichomes, which may be related to pest resistance. In order to collect the constituents of glandular trichomes, leaves were rinsed using dichloromethane (DCM) to obtain the rinsate, and the plant residues were subsequently extracted by DCM to obtain a DCM extract containing the internal constituents of yacón leaves. Biologic evaluations revealed that insect antifeedant activity was stronger for the rinsate than for the DCM extract against the common cutworm. The major constituents of rinsate were isolated by silica gel flash chromatography and were identified as sesquiterpene lactones (SLs), uvedalin (1) and enhydrin (2) and uvedalin aldehyde (3), collectively known as melampolides. Although SLs 1 and 2 exhibited remarkably strong insect antifeedant activity, SL 3 and reduced corresponding derivatives (4 and 5) of 1 and 2 exhibited moderate insect antifeedant activity. Additionally, the two analogs, parthenolide (6) and erioflorin (7) showed moderate insect antifeedant activity. The results indicate that the substituent patterns of SLs may be related to the insect antifeedant activities. The insect antifeedant activities of SLs 1 and 2 were similar to that of the positive control azadirachtin A (8), and thus these natural products may function in chemical defense against herbivores.

Phytotoxicity of constituents of glandular trichomes and the leaf surface of camphorweed, Heterotheca subaxillaris.

Camphorweed, Heterotheca subaxillaris (Lam.) Britt. & Rusby, has a camphor-like odor, and its leaf surfaces contain glandular trichomes of the type shown to contain high levels of isoprenoids in other species. Borneol (1), the phytotoxic calamenene-type sesquiterpenes (2-5, 9-11), and methylated flavones (12-15) were isolated from the dichloromethane rinsate of camphorweed aerial tissues. The strongest plant growth inhibitor against Agrostis stolonifera and Lactuca sativa seedlings, as well as duckweed (Lemna pausicostata), was 2-methoxy-calamenene-14-carboxylic acid (2). Esterification of calamenene carboxylic acids decreased their biological activity.

Chemical defense against insects in Heterotheca subaxillaris and three Orobanchaceae species using exudates from trichomes.

BACKGROUND: One of the roles of plant trichomes is thought to be reducing feeding damage from herbivores. Among trichomes, glandular trichomes play a role in chemical defense systems in plants by means of stored biologically active phytochemicals. These phytochemicals act as pest repellents. They show antimicrobial and insecticidal activities, and they have also been isolated and identified from wild plants. RESULTS: The Asteraceae species Heterotheca subaxillaris has many glandular trichomes on the leaf surface, and these contain sesquiterpene carboxylates, which show insect antifeedant activity. Because these sesquiterpene carboxylates are major constituents of glandular trichomes, they may act as a chemical defense in H. subaxillaris. The Orobanchaceae species Parentucellia viscosa also has many glandular trichomes on the leaf surface and produces an insect antifeedant clerodane-type diterpene, kolavenic acid, in these trichomes. Additionally, two other Orobanchaceae species, Bellardia trixago and Parentucellia latifolia, also have many glandular trichomes, but the constituents of these glandular trichomes did not show biological activities against test insects. However, the seco-labdane diterpene alcohol trixagol and its hemi-malonate were major constituents in B. trixago, and these terpenes may act as physical defenses against herbivores by interfering with feeding due to their viscosity. CONCLUSION: The secondary metabolites from glandular trichomes of H. subaxillaris and P. viscosa showed insect antifeedant activity, and these secondary metabolites were presumed to act as chemical defenses for these plant species. On the other hand, non-biologically active secondary metabolites produced by two other Orobanchaceae, B. trixago and P. latifolia, were presumed to act as physical defenses due to their viscosity. Defense systems such as these may be applicable to new crop breeding to enhance protection against insect pests. © 2019 Society of Chemical Industry.

Mechanical Thrombectomy in Anterior Circulation Occlusion Could Be More Effective than Medical Management Even in Low DWI-ASPECTS Patients.

The purpose of this study was to investigate whether patients with low preoperative Diffusion-weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) could benefit from mechanical thrombectomy for acute anterior circulation occlusion. This was a retrospective, non-blinded, cohort study. From September 2012 to August 2016, 83 consecutive patients of acute anterior circulation occlusion were treated with thrombectomy using second-generation devices or medical management. The DWI-ASPECTS was scored after the first MRI. Patient characteristics and clinical outcomes were compared between the treatment groups. Significant dependence was defined as a modified Rankin scale score ≥3 at 90 days. As a result, 33 patients underwent mechanical thrombectomy and 50 received medical management. In the mechanical thrombectomy group, the variable of lower DWI-ASPECTS (5, 4-6 vs. 8, 7-8, P < 0.001), especially ≤6, was significantly associated with poor prognosis. However, compared with patients of DWI-ASPECTS ≤ 6 who received medical management, there were significantly fewer patients with poor outcomes in thrombectomy (dependent in 11 of 15 vs. 23 of 23, respectively; P = 0.019). Although patients with lower pretreatment DWI-ASPECTS could benefit less from thrombectomy, their outcomes were still better than medical management. Therefore, mechanical thrombectomy could be considered in some patients with low pretreatment DWI-ASPECTS.

Age-related differences in the properties of the plantar flexor muscles and tendons.

PURPOSE: The purpose of this study was to determine age-related differences in the human plantar flexor muscles and tendon. METHODS: Four age groups--a 20-yr group (20-27 yr, N = 19), 30-yr group (31-38 yr, N = 15), 50-yr group (46-57 yr, N = 10) and 70-yr group (62-77 yr, N = 15)--volunteered to take part in the present study. Muscle thickness, strength, and activation level (using twitch-interpolation technique) of plantar flexor muscles were measured. Elongation of the Achilles tendon was determined using ultrasonography while subjects performed ramp isometric plantar flexion up to the voluntary maximum. RESULTS: No significant difference in relative muscle thickness (to limb length) was observed among the four age groups. Muscle strength and activation level of the 20-yr group were significantly higher than those of the 50- and 70-yr groups (activation levels were not measured in the 70-yr group), and maximal strain (elongation/initial tendon length) of the Achilles tendon decreased with aging. Although there were no differences in muscle strength and activation levels between the 20- and 30-yr groups, maximal strain of the Achilles tendon of the 30-yr group was already lower than that of the 20-yr group (P = 0.062). CONCLUSION: These results suggest that the processes of age-related changes in the muscle and tendon are different. Furthermore, the differences in age-related changes of muscle and tendon might play a role in the frequency of Achilles tendon ruptures among men in their 30s.

Effects of plyometric and weight training on muscle-tendon complex and jump performance.

PURPOSE: The purpose of this study was to investigate the effects of plyometric and weight training protocols on the mechanical properties of muscle-tendon complex and muscle activities and performances during jumping. METHODS: Ten subjects completed 12 wk (4 d.wk(-1)) of a unilateral training program for plantar flexors. They performed plyometric training on one side (PT; hopping and drop jump using 40% of 1RM) and weight training on the other side (WT; 80% of 1RM). Tendon stiffness was measured using ultrasonography during isometric plantar flexion. Three kinds of unilateral jump heights using only ankle joint (squat jump: SJ; countermovement jump: CMJ; drop jump: DJ) on sledge apparatus were measured. During jumping, electromyographic activities were recorded from plantar flexors and tibial anterior muscle. Joint stiffness was calculated as the change in joint torque divided by the change in ankle angle during eccentric phase of DJ. RESULTS: Tendon stiffness increased significantly for WT, but not for PT. Conversely, joint stiffness increased significantly for PT, but not for WT. Whereas PT increased significantly jump heights of SJ, CMJ, and DJ, WT increased SJ only. The relative increases in jump heights were significantly greater for PT than for WT. However, there were no significant differences between PT and WT in the changes in the electromyographic activities of measured muscles during jumping. CONCLUSION: These results indicate that the jump performance gains after plyometric training are attributed to changes in the mechanical properties of muscle-tendon complex, rather than to the muscle activation strategies.

Synthesis and insect antifeedant activity of aurones against Spodoptera litura larvae.

A series of aurones were prepared from various phenols via phenoxy acetic acids and coumaranones and evaluated for insect antifeedant activity against the common cutworm (Spodoptera litura). The naturally occurring aurone was most active at an ED50 of 0.12 micromol/cm2. The synthetic precursor, coumaranones, showed that the introduction of methoxyl and methyl groups to the benzene ring increased insect antifeedant activity. Similarly, the tested aurones showed that the introduction of methoxyl group to the A and/or B rings increased the insect antifeedant activity, but 4,5,6- and 3',4',5'-trisubstituted compounds did not show this activity in this test. The hydroxylation of aurones in the B ring should be disadvantageous for insect antifeedant activity against S. litura. Although the melting points did not correlate well with the insect antifeedant activity, compounds that were nearly inactive had high melting points. A significant correlation was noted between biological activity (pED50) and a hydrogen-bonding parameter calculated from the Rf value obtained from SiOH thin-layer chromatography and a lipophilicity parameter (log k) calculated from the retention time in ODS high-performance liquid chromatography. The respective correlation coefficients (r) were -0.83 and -0.70. The introduction of alkoxy and alkyl groups along with adequate hydrogen bonding seems to contribute to the antifeedant activity of the compounds tested.

Electrochemical Synthesis of Dihydrobenzofurans and Evaluation of Their Insect Antifeedant Activities.

Electrochemically synthesized dihydrobenzofurans were evaluated for their insect antifeedant activities against phytophagous insects. They were prepared through the coupling reactions of various alkenes with a phenoxy cation generated by oxidation near the cathode in the electrolytic reaction. The insect antifeedant activities of these synthetic dihydrobenzofurans were evaluated in the common cutworm (Spodoptera litura) and diamond back moth (Plutella xylostella) with the dual choice leaf disk bioassay method. The insect antifeedant activities of most of the acetophenone-type dihydrobenzofurans were strong, while those of derivatives with a t-butyl group were weaker. The biological activities in insect species differed with the structural features of the compounds.

Deodorizing Substance in Black Cumin (Nigella sativa L.) Seed Oil.

A deodorizing substance in black cumin (Nigella sativa L.), a spice for curry and vegetable foods in Southwest Asia, was examined. The essential oil prepared from the seeds of this plant exhibited strong deodorizing activity against methyl mercaptan, which is a main factor in oral malodor. After purification with silica gel column chromatography, the active substance in black cumin seed oil was identified as thymoquinone. This monoterpenic quinone functions as the main deodorizing substance in this oil against methyl mercaptan. Metabolite analysis suggested that the deodorizing activity may be generated by the addition of a reactive quinone molecule to methyl mercaptan. In the present study, the menthane-type quinone and phenol derivatives exhibited deodorizing activities via this mechanism.

Delayed expansion of an intracranial cyst induced by ventriculoperitoneal shunt in a patient with Chiari malformation type 2.

A male neonate was referred to our hospital for the treatment of myelomeningocele and hydrocephalus related to Chiari malformation type 2. After the placement of ventriculoperitoneal (VP) shunt for hydrocephalus, an intracranial cyst, which was asymptomatic at first, expanded and caused clinical symptoms due to increased intracranial pressure. The expansion of the cyst was confirmed dominantly in the right lateral ventricle where the VP shunt was inserted. Intraoperative findings through a neuroendoscope suggested that the expanded cyst was an isolated lesion. The pressure reduction in the lateral ventricle through the shunt tube, not the malfunction of the VP shunt, might have attributed to increased intracranial pressure with the expanded cyst. The authors present this rare case, speculating the cause of the expansion of the cyst.

Inhibitory Activities of Sesame Seed Extract and its Constituents against ß-Secretase.

The need for a preventive agent against dementia led us to screen natural plant resources. Among the herbs and spices tested, sesame seed prepared from Sesamum indicum seeds showed potent ß-secretase inhibitory activity. The active principles were determined to be sesamin and sesamolin, typical lignans in S. indicum. The IC(50) values of sesamin and sesamolin were 257 and 140 µM, respectively. These compounds were investigated in a preliminary absorption experiment. After oral administration, these compounds were detected in an intact form in the brain and serum. These results suggest that consumption of sesame seeds may prevent dementia by sesamin and sesamolin, the constituents in sesame seeds.