Effect D-003 on Intravascular Platelet Aggregation Induced with Collagen in Rats

Vivian Molina,Daisy Carbajal,Lourdes Arruzazabala,Rosa M?s 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.2

D-003 is a mixture of higher aliphatic primary acids purified from sugar-cane (Saccharum officinarumL.) waxthat inhibits platelet aggregation induced ex vivoby addition of agonists to platelet-rich plasma (PRP) of rats, guinea pigs,and healthy human volunteers. Because the ex vivoplatelet aggregation model does not mimic properly platelet aggregationoccurring inside the arteries, since all blood factors regulating the formation of a platelet aggregate or thrombus are not pre-sent in PRP, this work was undertaken in order to investigate the effects of different oral doses of D-003 on platelet aggre-gation induced by collagen in vivoin rats. Effects of single (5, 25, 100, and 200 mg/kg) or repeated doses (1, 5, 25, 100, and200 mg/kg during 10 days) of D-003 on in vivo platelet aggregation in rats were studied. D-003 (5200 mg/kg) orally ad-ministered as single or repeated doses inhibited significantly and dose-dependently collagen-induced platelet aggregation inrats. The minimal dose investigated effective in both single and repeated administration schemes was 5 mg/kg. The highestdose assessed in both cases was 200 mg/kg, causing inhibitions of 61.5% (single doses) and 74.4% (repeated doses). Thus,the effects of repeated doses were more pronounced than those obtained with single administration. The mean 50% effectivedose of D-003 in both schemes was 2.3 mg/kg, which indicates a promising anti-thrombotic potential of D-003.

Effect of D-003, a Mixture of Very-Long-Chain Aliphatic Acids Purified from Sugarcane Wax, on Cerebral Ischemia in Mongolian Gerbils

Vivian Molina,Miriam Noa,Lourdes Arruzazabala,Daisy Carbajal,Rosa M? 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.4

D-003 is a mixture of very-high-molecular-weight aliphatic acids purified from sugar cane wax (Saccharumofficinarum), which inhibits platelet aggregation and lipid peroxidation. The objective of the present study was to evaluatethe effect of D-003 on cerebral ischemia induced by ischemia-reperfusion (I-R) in Mongolian gerbils. Two experimental se-ries were conducted. The first series investigated the effects of D-003 on cerebral edema, neurological symptoms, and mor-tality in Mongolian gerbils with cerebral ischemia induced by I-R, while the second series investigated the effects on histo-logical markers of cerebral injury, such as edema intensity (vacuolization) and cerebral necrosis. Animals were randomlydistributed in five experimental groups: a sham-operated group experiencing surgical handling except the clamping and orallytreated with Tween/water vehicle and four groups subjected to the I-R surgical procedure. One of these groups was treatedwith the same vehicle, and the other three groups received D-003 at 25, 100, and 200 mg/kg, respectively. All treatments wereadministered for 14 days. D-003 (200 mg/kg) significantly reduced the cerebral edema and clinical symptoms provoked by I-R compared with the positive control group, whereas lower doses (25 and 100 mg/kg) were not effective. Positive controlanimals showed an injury profile characterized by swelling (tissue vacuolization) and necrosis of neurons in all areas of thebrain studied (frontal cortex, hippocampus, and striatum). The results of the histological study were consistent with those ob-served by determining cerebral edema and symptoms observation. Thus, D-003 at 200 mg/kg significantly reduced histolog-ical markers of brain injury (swelling and necrosis) compared with the control group. It is concluded that D-003 administeredorally at 200 mg/kg for 14 days protected against cerebral damage caused by bilateral cerebral ischemia in Mongolian ger-bils.

Therapeutic Effect of D-002 (Abexol) on Gastric Ulcer Induced Experimentally in Rats

Vivian Molina,Daisy Carbajal,Lourdes Arruzazabala,Rosa M? 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.1

D-002 is a mixture of higher aliphatic primary alcohols isolated from beeswax, wherein triacontanol is themost abundant alcohol, with antioxidant and anti-ulcer properties. Since compounds with cytoprotective and antioxidant ef-fects can improve healing of gastroduodenal ulcer induced by noxious agents, this work investigated the healing effect of D-002 on acute and chronic gastric ulcers induced with indomethacin and acetic acid, respectively, in rats. Acute gastric ulcerwas induced with single oral doses of indomethacin (20 mg/kg). Treatments with D-002 at 50, 100, and 200 mg/kg or vehi-cle were administered 3 hours after ulcer induction. Three hours later, rats were sacrificed, and the stomach was removed forquantifying the lesions. Chronic gastric ulcer was induced by 50 .L of 80% acetic acid application on the anterior serosalsurface of the glandular stomach during 20 seconds. Twenty-four hours later D-002 at 50, 100, and 200 mg/kg or vehicle wasadministered for 5 days. At the end of the treatment, animals were fasted for 24 hours and sacrificed, the stomachs were re-moved, and the lesions were quantified. D-002 orally administered at 100 and 200 mg/kg acutely significantly healed gastriculcers induced with indomethacin by 39% and 56% compared with positive controls, respectively. Also, D-002 at 200 mg/kg,but not at 50 or 100 mg/kg, administered orally for 5 days after ulcer induction exerted a significant healing effect (65.8%inhibition) in gastric ulcers induced with acetic acid. In conclusion, this work demonstrated that D-002 administered after ul-cer induction induced effective healing of acute and chronic gastric ulcers provoked by, respectively, indomethacin and aceticacid.

D-003 and Warfarin Interaction on the Bleeding Time and Venous Thrombosis Experimentally Induced in Rats

Mar? Lourdes Arruzazabala,Vivian Molina,Daisy Carbajal,Rosa M? 한국식품영양과학회 2004 Journal of medicinal food Vol.7 No.2

D-003 is a mixture of higher aliphatic primary acids isolated and purified from sugarcane wax, the main component of which is octacosanoic acid. D-003 exhibits a cholesterol-lowering effect as well as antiplatelet and antithrombotic effects in experimental models. Warfarin is a coumarin derivative with anticoagulant activity that acts as a vitamin K antagonist. Since in clinical practice warfarin and D-003 could be administered together, the objective of this study was to evaluate the effects of the simultaneous administration of both drugs on the bleeding time and the venous thrombosis experimentally induced in rats. The combined therapy of minimally effective doses of D-003 and warfarin produced an antithrombotic effect significantly higher than those produced by each monotherapy. Likewise, the prolongation of bleeding time induced by warfarin was increased by the simultaneous administration with D-003, showing a synergistic effect between both drugs.

Effect of D-003 on Isoproterenol-Induced Myocardial Necrosis in Rats

Daisy Carbajal,Miriam Noa,Vivian Molina,Maria Lourdes Arruzazabala,Rosa M?,Sarah?Mendoza,Jorge Gonz?ez 한국식품영양과학회 2003 Journal of medicinal food Vol.6 No.1

D-003 is a mixture of high-molecular-weigh t aliphatic primary acids purified from sugar canewax with antiplatelet and cholesterol-lowering effects. Cardiac lesions induced by isopro-terenol (ISO) are characterized by myocardial necrosis and exudative infiltration. The objec-tive of this study was to determine whether D-003 shows protective effects against ISO-in-duced myocardial necrosis in rats. Effects of orally administered single doses of D-003 (25 40mg/kg) and acetylsalicylic acid (ASA, 30 mg/kg), as well as repeated doses of D-003 (5 20mg/kg), on characteristic markers of ISO-induced myocardial necrosis in rats were investi-gated. D-003 administered as single doses dose-dependen tly decreased necrosis area, percentof infarct area, and the presence of polymorphonuclear cells (PMNs) in myocardial tissue, butonly the reductions induced by 200 and 400 mg/kg were significant. Oral acute treatment withASA also decreased necrosis area and percent of infarct area, but the occurrence of PMNs wasunchanged. D-003 administered repeatedly for 10 days also decreased all myocardial necro-sis indicators in a dose-dependen t maner, with results effective from 25 mg/kg to the high-est dose tested, indicating that the repeated dose scheme was more effective to prevent thedamage. It is concluded that D-003 shows a protective effect on the myocardial necrosis in-duced by ISO in rats.13

Skin electronics from scalable fabrication of an intrinsically stretchable transistor array

Wang, Sihong,Xu, Jie,Wang, Weichen,Wang, Ging-Ji Nathan,Rastak, Reza,Molina-Lopez, Francisco,Chung, Jong Won,Niu, Simiao,Feig, Vivian R.,Lopez, Jeffery,Lei, Ting,Kwon, Soon-Ki,Kim, Yeongin,Foudeh, Ami Macmillan Publishers Limited, part of Springer Nat 2018 Nature Vol.555 No.7694

Skin-like electronics that can adhere seamlessly to human skin or within the body are highly desirable for applications such as health monitoring, medical treatment, medical implants and biological studies, and for technologies that include human–machine interfaces, soft robotics and augmented reality. Rendering such electronics soft and stretchable—like human skin—would make them more comfortable to wear, and, through increased contact area, would greatly enhance the fidelity of signals acquired from the skin. Structural engineering of rigid inorganic and organic devices has enabled circuit-level stretchability, but this requires sophisticated fabrication techniques and usually suffers from reduced densities of devices within an array. We reasoned that the desired parameters, such as higher mechanical deformability and robustness, improved skin compatibility and higher device density, could be provided by using intrinsically stretchable polymer materials instead. However, the production of intrinsically stretchable materials and devices is still largely in its infancy: such materials have been reported, but functional, intrinsically stretchable electronics have yet to be demonstrated owing to the lack of a scalable fabrication technology. Here we describe a fabrication process that enables high yield and uniformity from a variety of intrinsically stretchable electronic polymers. We demonstrate an intrinsically stretchable polymer transistor array with an unprecedented device density of 347 transistors per square centimetre. The transistors have an average charge-carrier mobility comparable to that of amorphous silicon, varying only slightly (within one order of magnitude) when subjected to 100 per cent strain for 1,000 cycles, without current–voltage hysteresis. Our transistor arrays thus constitute intrinsically stretchable skin electronics, and include an active matrix for sensory arrays, as well as analogue and digital circuit elements. Our process offers a general platform for incorporating other intrinsically stretchable polymer materials, enabling the fabrication of next-generation stretchable skin electronic devices.