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Aims: To examine the chemistry of two California Lycium species and evaluate the possible use of California Lycium species as dietary supplements especially for age related macular degeneration. Study Design: This exploratory analytical research used samples of Lycium andersonii and Lycium cooperi collected in the field and analyzed in the lab. Place and Duration of Study: University of Southern California School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA USA 90089. Methodology: Plant extracts were analyzed by high pressure liquid chromatography mass spectrometry with ultraviolet photodiode array detection in order to identify the chemical characteristics of compounds found in the plants. Results: Several known compounds were found in extracts of Lycium cooperi and Lycium andersonii foliage and fruit including: zeaxanthin, zeaxanthin monopalmitate and β-cryptoxanthin. The various California species of Lycium are discussed as possible alternatives to Chinese Lycium barbarum. Conclusion: California Lycium berries may be suitable substitutes for Chinese Lycium berries.

BackgroundStudies of mammalian CSF dynamics have been focused on three things: paravascular flow, pressure and pulsatility, and “bulk” flow; and three (respective) potential motive forces have been identified: vasomotor, cardiac, and ventilatory. There are unresolved questions in each area, and few links between the different areas. The American alligator (Alligator mississippiensis) has pronounced plasticity in its ventilatory and cardiovascular systems. This study was designed to test the hypothesis that the greater cardiovascular and ventilatory plasticity ofA. mississippiensiswould result in more variation within the CSF dynamics of this species.MethodsPressure transducers were surgically implanted into the cranial subarachnoid space of 12 sub-adult alligators; CSF pressure and pulsatility were monitored along with EKG and the exhalatory gases. In four of the alligators a second pressure transducer was implanted into the spinal subarachnoid space. In five of the alligators the CSF was labeled with artificial microspheres and Doppler ultrasonography used to quantify aspects of the spinal CSF flow.ResultsBoth temporal and frequency analyses of the CSF pulsations showed highly variable contributions of both the cardiac and ventilatory cycles. Unlike the mammalian condition, the CSF pressure pulsations in the alligator are often of long (~ 3 s) duration, and similar duration CSF unidirectional flow pulses were recorded along the spinal cord. Reduction of the duration of the CSF pulsations, as during tachycardia, can lead to a “summation” of the pulsations. There appears to be a minimum duration (~ 1 s) of isolated CSF pulsations. Simultaneous recordings of cranial and spinal CSF pressures reveal a 200 ms delay in the propagation of the pressure pulse from the cranium to the vertebral canal.ConclusionsMost of the CSF flow dynamics recorded from the alligators, are similar to what has been reported from studies of the human CSF. It is hypothesized that the link between ventilatory mechanics and CSF pulsations in the alligator is mediated by displacement of the spinal dura. The results of the study suggest that understanding the CSF dynamics ofAlligatormay provide unique insights into the evolutionary origins and functional regulation of the human CSF dynamics.

This study compared the pre-sacral intervertebral joints of the American alligator (Alligator mississippiensis) with those from specimens of Varanus. These two taxa were chosen because they have similar number of pre-sacral vertebrae and similar body weights; however, Varanus can move bipedally and has diarthrotic intervertebral joints, whereas Alligator has intervertebral discs and cannot move bipedally. This study consisted of three objectives: (1) to document the anatomy of the intervertebral joint, (2) to quantify the compressive biomechanics of the intervertebral joints and explore which features contributed to compression resistance, and (3) to quantify the impact of compression on the intervertebral foramen and spinal nerves in these two taxa. The experimental results revealed that the diarthrotic intervertebral joints of Varanus were significantly (4x) stiffer than the intervertebral disc of Alligator, and that a significant component of this increased stiffness arose from the facet joints. Compressing the intervertebral joints of the two taxa caused a reduction in foraminal area, but the magnitude of this reduction was not significantly different. We hypothesize that the main factor preventing spinal nerve impingement in Varanus during gravitational compression is the relatively small size of the spinal ganglion/ nerve relative to the foraminal area.

American alligators (Alligator mississippiensis) held inverted exhibit tonic immobility, combining unresponsiveness with flaccid paralysis. We hypothesize that inverting the alligator causes a gravitationally promoted increase in right aortic blood flowing through the foramen of Panizza, with a concurrent decrease in blood flow through the primary carotid, and thereby of cerebral perfusion. Inverting the alligator results in displacement of the liver, post-pulmonary septum, and the heart. EKG analysis revealed a significant decrease in heart rate following inversion; this decrease was maintained for approximately 45 s after inversion which is in general agreement with the total duration of tonic immobility in alligators (49 s). Doppler ultrasonography revealed that following inversion of the alligator, there was a reversal in direction of blood flow through the foramen of Panizza, and this blood flow had a significant increase in velocity (compared to the foraminal flow in the prone alligator). There was an associated significant decrease in the velocity of blood flow through the primary carotid artery once the alligator was held in the supine position. Tonic immobility in the alligator appears to be a form of vasovagal syncope which arises, in part, from the unique features of the crocodilian heart.

Sesquiterpene compounds are widely known for their numerous pharmacological activities. Herein the focus of the authors was on α-Santonin, a sesquiterpene lactone from the Artemisia genus: the aim was to determine whether α-Santonin could be considered in the treatment of inflammation and pain. To this purpose, a small series of derivatives was designed and screened in silico against the enzyme COX-2 along with the parent compound. Drug-likeness parameters were also assessed. The compounds were eventually synthesized, and few were tested to determine their efficacy in the inhibition of COX-2 activity and expression. Overall, compound A2 was the only one with a detectable inhibitory potential of COX-2 activity whilst two of its ether derivatives demonstrated improved ability in the inhibition of COX-2 expression.

Clinical trials of drugs for Alzheimer’s disease have called into question the role of amyloid in the disease. The reasons several drugs recently failed clinical trials for Alzheimer’s disease are presented. An alternative approach with a traditional plant medicine is discussed. The pharmacology of the phytochemicals found in the plant medicine is provided.

The crocodilian naris is regulated by smooth muscle. The morphology of this system was investigated using a combination of gross, light microscopic, and micro-CT analyses, while the mechanics of narial regulation were examined using a combination of Hall Effect sensors, narial manometry, and electromyography. Alligator mississippiensis, like other crocodilians, routinely switches among multiple ventilatory mechanics and does not occlude the nares during any portion of the ventilatory cycle. In a complex that is unique among vertebrates, a single block of smooth muscle functions in dilation when active, and in constriction when passive. The alligator nares may include one of the best examples of a muscle that functions in "pushing" as well as "pulling." The central muscle for narial regulation, the dilator naris, can legitimately be viewed as its own antagonist.

Disorders of the volume, pressure, or circulation of the cerebrospinal fluid (CSF) lead to disease states in both newborns and adults; despite this significance, there is uncertainty regarding the basic mechanics of the CSF. The suboccipital muscles connect to the dura surrounding the spinal cord, forming a complex termed the “myodural bridge;” this study tests the hypothesis that the myodural bridge functions to alter the CSF circulation. The suboccipital muscles of American alligators were surgically exposed and electrically stimulated simultaneous with direct recordings of CSF pressure and flow. Contraction of the suboccipital muscles significantly changed both CSF flow and pressure. By demonstrating another influence on CSF circulation and pulsatility, the present study increases our understanding of the mechanics underlying the movement of the CSF.

A three-part mechanism is proposed for the induction of Alzheimer’s disease: (1) decreased blood lactic acid; (2) increased blood ceramide and adipokines; (3) decreased blood folic acid. The age-related nature of these mechanisms comes from age-associated decreased muscle mass, increased visceral fat and changes in diet. This mechanism also explains why many people do not develop Alzheimer’s disease. Simple changes in lifestyle and diet can prevent Alzheimer’s disease. Alzheimer’s disease is caused by a cascade of events that culminates in damage to the blood–brain barrier and damage to neurons. The blood–brain barrier keeps toxic molecules out of the brain and retains essential molecules in the brain. Lactic acid is a nutrient to the brain and is produced by exercise. Damage to endothelial cells and pericytes by inadequate lactic acid leads to blood–brain barrier damage and brain damage. Inadequate folate intake and oxidative stress induced by activation of transient receptor potential cation channels and endothelial nitric oxide synthase damage the blood–brain barrier. NAD depletion due to inadequate intake of nicotinamide and alterations in the kynurenine pathway damages neurons. Changes in microRNA levels may be the terminal events that cause neuronal death leading to Alzheimer’s disease. A new mechanism of Alzheimer’s disease induction is presented involving lactic acid, ceramide, IL-1β, tumor necrosis factor α, folate, nicotinamide, kynurenine metabolites and microRNA.

Black sage, Salvia mellifera, can be made into a sun tea that is used as a foot soak to treat pain patients. The monoterpenoids and diterpenoids in the preparation penetrate the skin of the feet and stop the pain chemokine cycle, which may be the basis of chronic pain. Several chronic pain patients have reported long-term improvements in their pain after treatment with the preparation.

Inflammatory states are among the most common and most treated medical conditions. Inflammation comes along with swelling, pain and uneasiness in using the affected area. Inflammation is not always a simple symptom; more often is part of a defensive response of the body to an external threat or is a sign that the damaged tissue has not healed yet and needs to rest. The management of the pain associated with an inflammatory state could be a tricky task. In fact, most remedies simply quench the pain, leaving the inflammatory state unaltered. This review focuses on sesquiterpene lactones, a class of natural compounds, that represents a future promise in the treatment of inflammation. Sesquiterpene lactones are efficient inhibitors of multiple targets of the inflammatory process. Their natural sources are often ancient remedies with relevant traditional uses in folk medicines. This work also aims to elucidate how these compounds may represent the starting material for the development of new anti-inflammatory drugs.

Pain is normally treated with oral nonsteroidal anti-inflammatory agents and opioids. These drugs are dangerous and are responsible for many hospitalizations and deaths. It is much safer to use topical preparations made from plants to treat pain, even severe pain. Topical preparations must contain compounds that penetrate the skin, inhibit pain receptors such as transient receptor potential cation channels and cyclooxygenase-2, to relieve pain. Inhibition of pain in the skin disrupts the pain cycle and avoids exposure of internal organs to large amounts of toxic compounds. Use of topical pain relievers has the potential to save many lives, decrease medical costs and improve therapy.

Research joint ventures (RJVs) are projects that combine the research resources of different firms. A sample of RJVs supported by the U.S. Advanced Technology Program shows that the projects yield ...

Adenostoma fasciculatum is used traditionally to treat skin conditions such as eczema. The plant was found to contain monoterpenoids, including hydroquinone and geranial. Other terpenoids were found, including the triterpenoids 7α-hydroxybaruol and glutinol, the diterpenoids thalianol and thaliandiol as well as the steroids suberosol and campesterol. The new compound, 7α-hydroxybaruol, was further analyzed by two-dimensional nuclear magnetic resonance (NMR) imaging, 13C NMR and high-resolution high-performance liquid chromatography combined with mass spectrometry. A balm was made from the plant with olive oil and bees wax. Several patients tried the balm and reported improvements in Adams disease, eczema symptoms and seborrhea within 1 week.

Plants of the Asteraceae family have been used in traditional medicine for centuries due to their main antimicrobial and analgesic activities. A liniment from Artemisia californica has recently been tested on patients affected by either acute pain or chronic pain conditions with great success. The aim of this study was to evaluate the anti-inflammatory activity of sesquiterpene lactones (SLs), representing the majority in the Asteraceae family. Leucodin, α-santonin and sclareolide (three SLs) were chosen to undergo chemical modifications. This pool of molecules underwent molecular modeling experiments using an in-house program, WATGEN, predicting the water network and its contribution to the overall affinity of the enzyme-ligand complex. The anti-inflammatory activity and the ability of compounds to modulate COX-2 expression have been evaluated in LPS-stimulated RAW 264.7 cells and in RIF-1 cells treated according to the Photodynamic Therapy (PDT) protocols using Photoprin (PH) as photosensitizer. Furthermore, commercially available assay kits were used to evaluate the concentration of PGE-2 and the direct inhibition of COX-2. All the tested molecules fit well in the enzyme binding pocket, but to get a substantial inhibition of the expression and activity of the enzyme as well as a reduction in the PGE2 concentration, high concentrations of the compounds are needed. The only exceptions being leucodin itself and FP6, one of the α-santonin derivatives, presenting a CF3 functional group. We believe that this class of compounds has some interesting potential in the treatment of pain and inflammation. Although, the activity seems to be due to a mechanism related to the expression of the COX enzymes rather than on a direct inhibition.

More rapid diffusion of science increases technological opportunity and innovation. To measure the diffusion of science, we use the lag between citing and cited scientific papers. With data from 1981 to 1999, the lag averages 6 years, increases with citation delay, and decreases with firm research. Additional data from 1980 to 2010 show that the lag increases with complexity of papers, age of lines of research and fields, and publication-submission lags; decreases with team size; and shows no evidence of strategic delay. Field differences in characteristics help explain field differences in citation lags, but deployment of specialized human capital among sectors also matters.

Background: This study examined the chemistry and safety of Heteromeles arbutifolia, also called toyon or California holly, which is a traditional California Indian food and treatment for Alzheimer’s disease. Methods: Plant extracts were examined by HPLC/MS, NMR and other techniques to identify compounds. Volunteers were recruited to examine the acute safety of the plant medicine using a standard short-term memory test. Results: The plant was found to contain icariside E4, dihydroxyoleanenoic acid, maslinic acid, betulin, trihydroxyoxo-seco-ursdienoic acid, catechin, vicenin-2, farrerol, kaempferide and tetrahydroxyoleanenoic acid. These compounds are anti-inflammatory agents that may protect the blood-brain barrier and prevent inflammatory cell infiltration into the brain. The dried berries were ingested by six volunteers to demonstrate the safety of the medicine. Conclusion: The plant medicine was found to contain several compounds that may be of interest in the treatment of Alzheimer’s disease. The plant medicine was found to be safe.

The incidence of arthritis is increasing every year, as does the need for pain medication. The current work reviews an American Indian liniment that is traditionally used for pain therapy. The chemistry, therapeutic use and safety of the liniment are reviewed. The liniment contains monoterpenoids, sesquiterpenes, flavonoids, alkaloids and other compounds.

Neuropathic pain is a common and very prevalent disorder affecting the citizens of both developed and developing countries. The approved and licensed drugs for neuropathic pain are reported to have associated side effects. Traditional plant treatments have been used throughout the world for the treatment of neuropathic pain. Among the many medications and other alternative medicines, several herbs are known to cure and control neuropathic pain with no side effects. The present paper discusses the plants with neuropathic pain and related beneficial effects originating from different parts of world that are of current interest.

Mugwort has many traditional uses around the world. The Chumash Indians of California use it to treat imbalances that women may suffer such as premenstrual syndrome, dysmenorrhea and menopausal symptoms. The plant contains a sesquiterpene that appears to work through a serotonergic mechanism and may be beneficial for women. Mugwort therapy is safer for menopausal women than hormone replacement therapy. Children affected by attention deficit hyperactivity disorder benefit from mugwort therapy. There is no doubt that mugwort therapy is safer for these children than methylphenidate or amphetamine.

Adams disease is the consequence of overly active transient receptor potential cation channels (TRP). This case report presents a patient suffering from multiple vascular problems and may provide new insights into the causes of venous problems. Endothelial and smooth muscle cells in veins contain TRP. These channels when activated excessively result in calcium accumulation, oxygen radical formation and apoptosis of endothelial and smooth muscle cells. The death of critical cells in vein valves, may lead to varicose veins. The loss of endothelial cells in venules may lead to retinal tears. Damage to vein walls may lead to a deep vein thrombosis. Transient receptor potential cation channels may be new drug targets of interest in the treatment or prevention of these conditions.

Background: This study presents several anecdotal case reports of chronic pain patients cured with two different plant medicines from the Chumash Indian tradition. Methods: Patients suffering from fibromyalgia, chronic back pain, chronic bursitis, chronic tendinitis and other conditions were treated. California sagebrush (Artemisia californica) was grown by the author and made into a liniment. The liniment was applied to painful sites on the skin. Black sage (Salvia mellifera) was made into a sun tea. Chronic pain patients soaked their feet in the preparation. Results: The liniment provided relief from even severe pain within a minute or so. After daily use for 1 – 7 days, chronic pain was cured in several patients. The sun tea provided pain relief throughout the body within 20 minutes. After 1 – 7 days of once daily use, several chronic pain patients were cured. Conclusions: Both A. californica liniment and S. mellifera sun tea provide pain medicines that can cure chronic pain.

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Chinese and Chumash traditional medical approaches are similar in terms of disease causation, use of acupuncture or healing touch, plants, spiritual and philosophical approaches. This article provides a brief comparison and discussion of Chinese and Chumash traditional medical practices. A table of 66 plants is presented along with Chinese and Chumash uses of each plant. These uses are compared and contrasted.

This review discusses new mechanisms for the induction of Alzheimer's disease, involving lipid toxicity and adipokines. Ceramide induces oxidative stress and the formation of amyloid beta. Visfatin induces oxidative stress, damages the blood brain barrier and increases the attraction of monocytes, neutrophils and other white blood cells. A new mechanism for visfatin/NAD (nicotinamide adenine dinucleotide)-induced oxidative stress is presented involving redox cycling catalyzed by xanthine dehydrogenase and NADH oxidase. These mechanisms are discussed in terms of the treatment of Alzheimer's disease.

In this paper, we define public technology infrastructure to mean public resources that bring new R&D into existence. Examples are public research that yields knowledge spillovers and government contracts that broker new research. Using this definition we explore the effect of public infrastructure on cooperative R&D, especially R&D sourcing and research joint ventures (RJVs). Our findings strongly suggest that public infrastructure promotes cooperative R&D. We begin by studying the role of federal laboratories in R&D sourcing by private laboratories, finding that sourcing increases as a result. Then we examine patents arising from RJVs sponsored by the Advanced Technology Program (ATP). We find that R&D subsidies as well as difficulty and novelty increase patents produced by the RJVs. Contractual oversight by ATP has no direct effect but an indirect effect appears to exist, since firms value ATP oversight more highly for more difficult and novel projects, and these produce more patents.

This paper describes flows of basic research through the U.S. economy and explores their implications for scientific output at the industry and field level. The time period is the late 20th century. This paper differs from others in its use of measures of science rather than technology. Together its results provide a more complete picture of the structure of basic research flows than was previously available. Basic research flows are high within petrochemicals and drugs and within a second cluster composed of software and communications. Flows of chemistry, physics, and engineering are common throughout industry; biology and medicine are almost confined to petrochemicals and drugs, and computer science is nearly as limited to software and communications. In general, basic research flows are more concentrated within scientific fields than within industries. The paper also compares effects of different types of basic research on scientific output. The main finding is that the academic spillover effect significantly exceeds that of industrial spillovers or industry basic research. Finally, within field effects exceed between field effects, while the within- and between industry effects are equal. Therefore, scientific fields limit basic research flows more than industries.

Sirtuins are enzymes that deacetylate proteins at the expense of NAD. The nuclear forms of sirtuins have generated an enormous amount of interest due to their putative regulation of lifespan. Yeast sirtuins and human sirtuins are involved in very different biochemical processes that make extrapolation of yeast results to the human situation difficult. This review critically examines the issues of NAD biochemistry in relation to nuclear sirtuin activity. Putative sirtuin inhibitors and activators are discussed, especially in terms of lifespan extension by sirtuin activators.

Plants were, and still are, widely used for a number of conditions affecting women in California. This article discusses traditional remedies of the Chumash for dysmenorrhea, premenstrual syndrome, feminine hygiene, heavy menstruation, urinary tract infections, parturition, lactation, infant care, menopause, sexually transmitted diseases, fertility, contraception and abortions. Many plants are presented includingArtemisia douglasiana,Paeonia californica,Trichostema lanatum,Salvia apiana,Ephedra viridis,Leymus condensatus,Vitis californica,Eschscholzia californica,Rosa californica,Scirpus acutus,Anemopsis californicaandPhoradendron macrophyllum. By providing the specific uses of plants for specific diseases and discussing chemistry, efficacy and safety concerns for each plant, we hope that this article gives direction to women seeking to use plants in their health care.

This paper presents new evidence on the practice of industrial Research and Development (R&D), especially its allocation between learning and internal research, and the role of outside knowledge in reshaping this allocation. The evidence describes the sources of outside knowledge, portrays the flow of that knowledge into firms, and interprets the channels by which outside knowledge influences R&D. In this way, the paper illustrates R&D's value in dealing with disequilibria. The empirical work is based on a sample of 220 R&D laboratories owned by 115 firms in the US chemical, machinery, electrical equipment, and motor vehicle industries. The findings are consistent with the view that universities and firms generate technological opportunities in R&D laboratories. In addition to partnerships that define rather strict channels of opportunity, the paper uncovers broader effects of R&D spillovers. The results also suggest that academic spillovers drive learning about universities and that industrial spillovers...

This note addresses the identification and California distribution of Psorothamnus fremontii (A. Gray) Barneby s.l. and P. arborescens (A. Gray) Barneby s.l. Both plants are generically known as indigo bush. Psorothamnus fremontii, sometimes called Fremont's indigo bush, can only be distinguished from P. arborescens by analysis of the seed pods, which differ in size, arrangement and exudates of their glands. The distribution of P. fremontii is very limited in California, restricted to the Grapevine Mountains, in Death Valley National Park, near the Nevada border, and the Providence Mountains, California State Recreation Area and nearby Lavic. Psorothamnus arborescens is much more common in California and occurs throughout the Mojave Desert and barely into the Great Basin Desert, from near Mount San Jacinto to the White Mountains.

This paper explores recent trends in the size of scientific teams and in institutional collaborations. The data derive from 2.4 million scientific papers written in 110 top U.S. research universities over the period 1981–1999. The top 110 account for a large share of published basic research conducted in the U.S. during this time. We measure team size by the number of authors on a scientific paper. Using this measure we find that team size increases by 50% over the 19-year period. We supplement team size with measures of domestic and foreign institutional collaborations, which capture the geographic dispersion of team workers. The time series evidence suggests that the trend towards more geographically dispersed scientific teams accelerates beginning with papers published at the start of the 1990s. This acceleration suggests a sharp decline in the cost of collaboration. Our hypothesis is that the decline is due to the deployment of the National Science Foundation's NSFNET and its connection to networks in Europe and Japan after 1987. Using a panel of top university departments we also find that private universities and departments whose scientists have earned prestigious awards participate in larger teams, as do departments that have larger amounts of federal funding. Placement of former graduate students is a key determinant of institutional collaborations, especially collaborations with firms and with foreign scientific institutions. Finally, the evidence suggests that scientific output and influence increase with team size and that influence rises along with institutional collaborations. Since increasing team size implies an increase in the division of labor, these results suggest that scientific productivity increases with the scientific division of labor.

Chumash Healers used breathing therapy and counseling to keep patients involved in daily life and to avoid depression. Heat therapy, massage and pain medications were used to help with pain. Another primary function of the Healer was to help the patient sleep as normally as possible, possibly using mugwort or momoy. Nutrition was considered by Healers in treating their patients. The overall concern of the Healer was to help maintain the daily routine of village life during the normal process of the death of a village member.

Chumash healing has been practiced in California for ∼13 000 years. Chumash healers treat their patients with prayer, laughter, dreaming, phytotherapy, aromatherapy, healing ceremonies and other techniques. Healing involves first healing the spirit, then healing the body. Chumash people still maintain their unique identity. Chumash Healers still practice the ancient healing arts in California. This lecture is a brief introduction to Chumash Healing.

This article discusses the importance of the spirit and mind in health and well-being among Chumash people. Prayer was the first step in healing since prayer invites the participation of God. Initiation practices are discussed that encouraged young people to develop the maturity and spiritual strength to become productive members of society. Pictographs were used in healing usually not only as a relaxation therapy, but also as a mode of education. A supportive environment was an important factor in Chumash health care, since the support of friends helps, comforts and relieves anxiety that is detrimental to healing.