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By D. Ugolf. John F. Kennedy University. 2018.

These are probably not equivalent to the products on which trials have been published buy 40mg cialis professional with mastercard erectile dysfunction in young adults, and may not therefore produce the same therapeutic effect generic cialis professional 20mg amex erectile dysfunction youtube. Nevertheless, manufacturers rely on the publicity associated with the trialed Table 1 Examples of standardization parameters for herbal products. The issue of achieving bioequivalence in herbal products has been discussed in a 14 review by Loew and Kaszkin. This is relevant where trials have been conducted on a particular branded product, and other companies wish to demonstrate that their products will be equally efficacious. However, if the active components are not known, then data on selected chemical substances within an extract may not be sufficient to prove bioequivalence in terms of therapeutic effect, although the information may be useful to ensure repeatability of the production process. The authors suggest that equivalence should be shown in a range of aspects including pharmaceutical equivalence (chemical standardization), biopharmaceutical equivalence (in vitro dissolution rate) and comparable biological effects (in vitro, animal or clinical studies). A number of studies comparing the bioequivalence of different brands of a particular product have been reported. Several silymarin preparations (derived from Silybum marianum or milk thistle) from the German market showed a two-fold difference in 15 bioavailabilty (in vitro dissolution) between products. Examination of a variety of 16 ginkgo products available in the USA showed clear differences in both the content of marker compounds and in vitro dissolution rates. Flavone glycosides ranged from 24 to 36%, the terpene lactones from 4 to 11% and ginkgolic acids from <500 to 90000ppm. The majority of products achieved the required dissolution rate of over 75% in 30 min. However, several fell short of this standard, one product achieving less than 25% Botanicals—quality, efficacy, safety and drug interactions 17 dissolution after an hour. Thus, even with the required chemical content, these products may fail to achieve therapeutic equivalence. Garlic showed dose-dependent effects in an 17 in vitro enzyme assay—the inhibition of adenosine deaminase. The authors suggested that this may be a useful test to demonstrate bioequivalence between products. Adapted from references 18 and 19 Ash insoluble in hydrochloric acid (to measure inorganic impurities) Foreign matter (to identify botanical and nonbotanical contaminants) Stomata and stomatal index (to identify leaves) Swelling index (to assess the polysaccharide content of gel-forming botanicals) Water in essential oils Foreign esters in essential oils Fatty and resinified oils in essential oils Odor and taste of essential oils Residue on evaporation of essential oils Solubility in alcohol of essential oils Assay of 1,8-cineole in essential oils Determination of essential oils in vegetable drugs Pesticide residues QUALITY CONTROL METHODS FOR BOTANICAL PRODUCTS The analytical control of botanical products should ideally be based on approved methods and standards that are found in official monographs in pharmacopeias or other standards that have been validated. The standard or quality of an herbal product is determined, as mentioned earlier, by performing analytical tests to establish the identity of the plant material and/or its active principles, the content of active principles or characteristic marker compounds by assay and the purity of the product by exclusion of specific adulterants or contaminants. The methods employed for 18 these aspects have been reviewed in detail by Forte and Raman and are summarized here. Some of these methods are unique to the evaluation of botanical products (Table 18,19 2 ). More specific chromatographic and spectroscopic techniques, Complementary therapies in neurology 18 e. DNA fingerprinting has also been suggested as a means of identification, for example to distinguish between Korean 22 ginseng (Panax ginseng) and American ginseng (Panax quinquefolius). In terms of determining the content of constituents, natural variation of crude drugs and the influence of processing make standardization more difficult than with synthetic compounds. Quantitative chromatography (HPLC or GC) is one of the most popular and effective means of quantifying compounds in crude drugs and their preparations. This may be combined with mass spectrometry to obtain more detailed information on the 23 identity of the constituents analyzed. Several other analytical methods may be used to 24 quantitate herbal constituents including separation and weighing of active constituents, titration, physical tests, quantitative spectroscopy, radioimmunoassay, enzyme- 25 immunoassay and biological assays based on an appropriate therapeutic activity. The analytical basis of the assay of a particular herbal product depends on the type of 9 preparation and the state of knowledge about its active constituents. Where the therapeutically relevant constituents are known, the product is standardized to that 9 particular substance. Alternatively, standardization may be based on a group of related constituents, all of which are known to contribute to therapeutic efficacy. An example here would be the measurement of total hydroxyanthracene glycosides in senna (Cassia angustifolia or acutifolia) fruit, as these compounds collectively provide the laxative effects of the botanical.

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We addressed this issue by exploring the response of neurons in M1 during reaching with and without velocity-dependent (viscous) loads applied to the shoulder or elbow joints order cialis professional 20 mg fast delivery erectile dysfunction drugs trimix. A third load condition generic cialis professional 40 mg free shipping lovastatin causes erectile dysfunction, where viscous loads were applied to joints simultaneously (viscous both [VB]), allowed us to examine how mechanically dependent loads with common features or characteristics are repre- sented neurally. We found that many cells changed their activity for one, two, and in some cases all three load conditions as compared to their activity during unloaded reaching. The representation of VS and VE loads were not completely independent, but demonstrated at least a partial overlap across the cell population in M1. Of the 51 cells that responded to either loading condition, 27 were sensitive only to VE, 9 were sensitive only to VS, and 15 showed significant changes in discharge for both VS and VE (p < 0. There was a highly consistent relationship between how a cell responds in VS and VE. Cells that increase discharge for VS also tend to increase discharge for VE, while decreases in discharge for VS are likewise associated with discharge decreases in VE. Perhaps the most important observation was that there was considerable overlap in the representations of VB and either VS or VE. Almost all neurons that changed their activity for VB as compared to unloaded movements, also showed significant changes of activity related to VE or VS. We found that almost all cells showed similar signs of change across all three load conditions. If a neuron increased its discharge for a given loading condition, its response to any other load condition would also be an increase in discharge. If a neuron decreased its discharge for a load condition, responses to other loads would also tend to be a reduction in discharge. With regard to whether the brain uses a single internal model or multiple internal models for different mechanical contexts, the present results illustrate that neural activity in M1 appears to reflect a single internal model for both these single- and multiple-joint loads. However, other regions of the brain, such as the cerebellum, may use separate internal models for these different contexts. Further, because only velocity-dependent loads were used in this study, it is quite possible that neural representations for different types of mechanical loads (i. This mechanical segregation allowed us to illustrate that load-related activity for some neurons was limited to loads at only one of the two joints, whereas other neurons responded to loads applied to either joint. These results suggest that there is some separation, but not a complete separation, in neurons responding to loads at different joints, reflecting a course somatotopic map within M1. The present data on neural responses for single- and multiple-joint loads allow us to ask how information related to different joints is integrated together. We tested two possible models, one in which load-related activity related to each joint is linearly summed across all joints. However, we found this model consistently over- estimated the response of neurons to multiple-joint loads. We examined a second model that assumed that the response of a neuron reflected vector summation of its response to loads at each joint. This vector summation model assumes that activity Copyright © 2005 CRC Press LLC related to each joint can be treated as orthogonal vectors and that multiple-joint loads reflect the vector sum of these single-joint loads. Our data illustrated that the response of neurons tended to follow this simple rule. We are presently assessing whether this integrative feature of multiple-joint loads reflects an inherent feature of cortical processing or simply parallels the activity of shoulder and elbow muscles for these movement-dependent loads. Another of our recent studies examined the response of neurons to constant- magnitude (bias) loads applied to the shoulder or elbow as the monkey maintained its hand at a central target. Load-sensitive cells again responded to both multiple-joint loads and at least one of the two single- joint loads so that there was no segregation between neural responses to single- and multiple-joint loading conditions. Further, the response of neurons to multiple-joint loads again could be predicted using a vector summation model from the response of neurons to single-joint loads. A key feature of both of these studies was that we could load the shoulder and elbow joints independently.

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