Treating with an implant: BMS or DES?

As the minimal invasive procedures for the treatment of peripheral arterial disease grow at exponential rates, interventional radiologists and vascular surgeons are more often faced with the difficult decision of which devices are the most appropriate to bring the desired results. Under the light of the newest studies and always having in mind the concept of "leaving no metal behind", when focusing on the lesions within the superficial femoral artery and popliteal arteries, we try to answer the question: treating with an implant, bare metal stents or drug eluting stents?

CAS: which stent for which lesion.

Current carotid stent designs and their attributes like scaffolding to reduce plaque prolapses and embolization, flexibility, adaptability and conformability to the vessel vary largely. Knowing that differences in behaviour due to stent design exist, especially due to the open cell design (which show high flexibility and therefore adaptability to the vessel but allows in theory easy particle penetration due to open structure) and closed cell designs (which show low flexibility and therefore low adaptability to the vessel but show high resistance to particle penetration due to closed cell design and high scaffolding), physicians have to be aware of these differences when planning carotid artery stenting procedures. The individual characteristics of each stent device may make it an attractive choice in one circumstance but render it less desirable in other situations; in approximately 75% of all procedures, all types of stents will achieve similar outcomes, making adequate device selection unnecessary; for the remaining quarter, careful preoperative screening is mandatory. The aim of this article was to review different stents with regard to latest designs intended for carotid stenting with regard to topics as mentioned above highlighting latest developments in specific designs especially developed for carotid lesion treatment.

Refined food addiction: a classic substance use disorder.

Overeating in industrial societies is a significant problem, linked to an increasing incidence of overweight and obesity, and the resultant adverse health consequences. We advance the hypothesis that a possible explanation for overeating is that processed foods with high concentrations of sugar and other refined sweeteners, refined carbohydrates, fat, salt, and caffeine are addictive substances. Therefore, many people lose control over their ability to regulate their consumption of such foods. The loss of control over these foods could account for the global epidemic of obesity and other metabolic disorders. We assert that overeating can be described as an addiction to refined foods that conforms to the DSM-IV criteria for substance use disorders. To examine the hypothesis, we relied on experience with self-identified refined foods addicts, as well as critical reading of the literature on obesity, eating behavior, and drug addiction. Reports by self-identified food addicts illustrate behaviors that conform to the 7 DSM-IV criteria for substance use disorders. The literature also supports use of the DSM-IV criteria to describe overeating as a substance use disorder. The observational and empirical data strengthen the hypothesis that certain refined food consumption behaviors meet the criteria for substance use disorders, not unlike tobacco and alcohol. This hypothesis could lead to a new diagnostic category, as well as therapeutic approaches to changing overeating behaviors.

Efficacy of a novel calcium/potassium salt of (-)-hydroxycitric acid in weight control.

The weight-loss efficacy of a novel, water-soluble, calcium-potassium salt of (-)-hydroxycitric acid (HCA-SX) was re-examined in 90 obese subjects (BMI: 30-50.8 kg/m2). We combined data from two previously reported randomized, double-blind, placebo-controlled clinical studies in order to achieve a better statistical evaluation based on a larger population. This re-examination of data also allowed us to reflect more intensely on various aspects of weight loss studies. Subjects were randomly divided into three groups: group A received a daily dose of HCA-SX 4, 667 mg (providing 2,800 mg HCA per day); group B was given a daily dose of a combination of HCA-SX 4,667 mg, niacin-bound chromium (NBC) 4 mg (providing 400 microg elemental chromium), and Gymnema sylvestre extract (GSE) 400 mg (providing 100 mg gymnemic acid); and group C received a placebo in three equally divided doses 30-60 min before each meal. All subjects were provided a 2,000 kcal diet/day and participated in a supervised walking program for 30 min/day, 5 days/week. Eighty-two subjects completed the study. At the end of 8 weeks, in group A, both body weight and BMI decreased by 5.4%, low-density lipoprotein and triglycerides levels were reduced by 12.9% and 6.9%, respectively, while high-density lipoprotein levels increased by 8.9%, serum leptin levels decreased by 38%, serotonin levels increased by 44.5% and urinary excretion of fat metabolites increased by 32-109%. Group B demonstrated similar beneficial changes, but generally to a greater extent. No significant adverse effects were observed. The combined results confirm that HCA-SX and, to a greater degree, the combination of HCA-SX plus NBC and GSE reduce body weight and BMI, suppress appetite, improve blood lipid profiles, increase serum leptin and serotonin levels and increase fat oxidation more than placebo. We conclude that dosage levels, timing of administration, subject compliance and bioavailability of HCA-SX significantly affect results and that when taken as directed, HCA-SX is a highly effective adjunct to healthy weight control.

Effects of a novel formulation of essential oils on glucose-insulin metabolism in diabetic and hypertensive rats: a pilot study.

BACKGROUND: Insulin resistance and its most severe form type 2 diabetes mellitus are rapidly increasing throughout the world. It is generally recognized that natural products with a long history of safety can increase insulin sensitivity. AIMS: The present investigation examined the ability of various combinations of essential oils such as fenugreek, cinnamon, cumin, oregano, etc. to enhance insulin sensitivity. As a first approximation, we examined the effects of these natural products on Zucker fatty rats (ZFRs), a model of obesity and insulin resistance, and spontaneously hypertensive rats (SHRs), a model of genetic hypertension. MATERIAL AND METHODS: Water or essential oils were given orally via droplets, and insulin sensitivity was estimated by systolic blood pressure (SBP) changes and circulating glucose and/or insulin concentrations. RESULTS: We have found that the ability to alter SBP in rat models is the most sensitive early index of insulin sensitivity. The combined essential oils lowered circulating glucose levels and SBP in both ZFRs and SHRs, suggesting that these natural products are enhancing insulin sensitivity. The second series of studies examined two additional combinations of essential oils along with the original formula. The major differences were in the types and proportions of individual oils contributing to a given formula. CONCLUSIONS: Although all the three formulae decreased SBP in ZFRs, one of the formulae was more effective than the others in lowering circulating glucose in the glucose tolerance testing. Accordingly, some essential oils may be added to the long list of natural products that can affect insulin sensitivity.

[Comparison of four digital and one conventional radiographic image systems for the chest in a patient study with subsequent system optimization]. / Vergleich von vier digitalen und einem konventionellen Röntgenaufnahmesystem für den Thorax mittels einer Patientenstudie mit nachfolgender Systemoptimierung.

PURPOSE: Using a patient study to prove the clinical relevance of a comparison of five different radiographic systems for the chest conducted with an anthropomorphic chest phantom. Depending on the results, it was tested whether the performance of a modern digital system with a transparent imaging plate can be improved by changing the post-processing of the image. METHOD: Chest radiographs of patients were taken with a CsI/aSi-flat panel detector (FDR), transparent imaging plate (tDLR), selenium drum detector (DSR), conventional storage phosphor plate (DLR) and asymmetrical screen-film-system (aFFS), and compared using image criteria scoring (ICS) and visual grading analysis (VGA) for anatomical structures (modified criterions of the EUR 16 260 EN guidelines). After optimizing the post processing, the images of the tDLR-system were evaluated once more in a phantom ROC study and patient VGA study. RESULTS: The flat panel detector-system proved to meet best the anatomical image quality criteria, followed by DSR, tDLR, aFFS and DLR. The modified post processing of the tDLR-images resulted in a significantly better detection of simulated pathological lung-structures, but improved the perceptibility of anatomical structures only slightly. CONCLUSIONS: The results of the patient VGA study and the phantom ROC study are similar and considered valid. The new digital imaging systems with flat panel detector and transparent imaging plate provide the best image quality of the tested radiographic devices for chest imaging, assuming that all system components are attuned and optimized for the type of structure to be detected. Image processing is of primary importance for system optimization.

Safety assessment of (-)-hydroxycitric acid and Super CitriMax, a novel calcium/potassium salt.

(-)-Hydroxycitric acid (HCA) is a principle constituent (10-30%) of the dried fruit rind of Garcinia cambogia, a plant native to Southeastern Asia. The dried rind has been used for centuries throughout Southeast Asia as a food preservative, flavoring agent and carminative. Extensive experimental studies show that HCA inhibits fat synthesis and reduces food intake. The objective of this review is to systematically review the available safety/toxicity literature on HCA to determine its safety in-use. The primary mechanism of action of HCA appears to be related to its ability to act as a competitive inhibitor of the enzyme ATP-citrate lyase, which catalyzes the conversion of citrate and coenzyme A to oxaloacetate and acetyl coenzyme A (acetyl-CoA), primary building blocks of fatty acid and cholesterol synthesis. Super CitriMax, a novel calcium/potassium-HCA extract (HCA-SX), is considerably more soluble and bioavailable than calcium-based HCA ingredients. Acute oral toxicity studies in animals demonstrate that CitriMax (50% HCA as calcium salt) has a low acute oral toxicity. In a subchronic study in rats, the gavage administration of HCA-SX at doses up to 2500 mg/kg/day for a period of 90 days caused a significant decrease in body weight and reduction in feed consumption without any adverse effects. The structure, mechanism of action, long history of use of HCA and other toxicity studies indicate that HCA-SX is unlikely to cause reproductive or developmental effects. HCA-SX was not mutagenic in the presence or absence of metabolic activation in Ames genotoxicity assays in strains TA98 and TA102. HCA-SX-induced increases in number of revertants in other strains (TA100 and TA1535 in the absence of metabolic activation and in strain TA1537 in the presence of metabolic activation) but these were not considered as biologically indicative of a mutagenic effect. In several, placebo-controlled, double-blind trials employing up to 2800 mg/day HCA, no treatment-related adverse effects were reported. There is sufficient qualitative and quantitative scientific evidence, including animal and human data suggesting that intake of HCA at levels up to 2800 mg/day is safe for human consumption.

Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extract on weight loss.

AIM: The efficacy of optimal doses of highly bioavailable (-)-hydroxycitric acid (HCA-SX) alone and in combination with niacin-bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA-SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels. METHODS: A randomized, double-blind, placebo-controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21-50, BMI >26 kg/m(2)). Subjects were randomly divided into three groups. Group A was administered HCA-SX 4667 mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30-60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking. RESULTS: At the end of 8 weeks, body weight and BMI decreased by 5-6% in both groups A and B. Food intake, total cholesterol, low-density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non-significant effect was observed in all parameters in group C. CONCLUSION: The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels.

An overview of the safety and efficacy of a novel, natural(-)-hydroxycitric acid extract (HCA-SX) for weight management.

Garcinia cambogia-derived (-)-hydroxycitric acid (HCA) is a safe, natural supplement for weight management. HCA is a competitive inhibitor of ATP citrate lyase, a key enzyme which facilitates the synthesis of fatty acids, cholesterol and triglycerides. Previous studies in our laboratories have demonstrated the superior bioavailability of a novel calcium-potassium salt of HCA derived from Garcinia cambogia (HCA-SX, Super CitriMax). Greater bioavailability of HCA-SX was observed when taken on an empty stomach. HCA-SX was also shown to exhibit concentration-dependent release of serotonin in isolated rat brain cortex, which may explain its appetite suppressive action. Acute oral, acute dermal, primary dermal irritation, primary eye irritation and 90-day chronic toxicity studies, as well as Ames bacterial reverse mutation and mouse lymphoma tests, were assessed to determine the safety of HCA-SX. In the 90-day toxicity study, dose- and time-dependent effects of HCA-SX were assessed on body weight, selected organ weights, hepatic and testicular lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathology in male and female Sprague-Dawley rats. No remarkable toxicity results were detected, demonstrating the safety of HCA-SX. Furthermore, clinical studies to evaluate the safety and efficacy of HCA-SX over a period of eight weeks were conducted in 60 human volunteers. Subjects were given a 2,000 kcal diet/day, participated in a 30 min walking exercise program 5 days/week and given an oral dose of placebo or 4666.7 mg HCA-SX (providing 2,800 mg HCA) in three equally divided doses 30-60 min before meals, Body weight, BMI, lipid profiles, serum leptin, serotonin and excretion of urinary fat metabolites were determined at 0, 4 and 8 weeks of treatment. At the end of 8 weeks, body weight and BMI decreased by 5.4% and 5.2%, respectively. Food intake, total cholesterol, LDL, triglycerides and serum leptin levels were significantly reduced, while HDL and serotonin levels, and excretion of urinary fat metabolites (a biomarker of fat oxidation) significantly increased. No significant adverse effects were reported. These results demonstrate the safety, bioavailability and efficacy of HCA-SX in weight management.

[Chest radiography: ROC phantom study of four different digital systems and one conventional radiographic system]. / Thoraxübersichtsaufnahme: ROC-Phantomstudie an vier verschiedenen digitalen und einemkonventionellen Röntgenaufnahmesystem.

PURPOSE: To compare the diagnostic quality of five different radiographic systems used in chest radiography for visualization of differently configured, clinically relevant pathologic pulmonary structures. MATERIALS AND METHODS: Four digital detector systems using as detection unit a CsI/aSi-based flat panel detector, a transparent imaging plate, a selenium detector and a conventional storage phosphor plate were analyzed for this study, as well as an asymmetrical film-screen system. The analyzed imaging material consisted of radiographs of an anthropomorphic chest-phantom with superimposed simulated pulmonary structures. The images were evaluated for different pathologic structures by a newly developed multiple structure ROC (ms-ROC). RESULTS: The performance of each system was found to have a strong structure-related variability. The flat panel detector system had the best overall performance. The theoretical advantage of the 4k-matrix of the transparent imaging plate over the 3k-matrix of the flat panel detector was only confirmed for reticular structures. CONCLUSIONS: In addition to comparing the image quality of the different systems, this study shows that the performance of a radiographic system depends on the structure to be analyzed. The modified ROC (ms-ROC) provides valid results with less effort.

[Optimized image processing with modified preprocessing of image data sets of a transparent imaging plate by way of the lateral view of the cervical spine]. / Optimierte Bildverarbeitung durch ein modifiziertes Pre-Processing von Bilddatensätzen eines transparenten Speicherfoliensystems am Beispiel der seitlichen HWS-Aufnahme.

PURPOSE: To improve the diagnostic quality of lateral radiographs of the cervical spine by pre-processing the image data sets produced by a transparent imaging plate with both-side reading and to evaluate any possible impact on minimizing the number of additional radiographs and supplementary investigations. MATERIAL AND METHODS: One hundred lateral digital radiographs of the cervical spine were processed with two different methods: processing of each data set using the system-imminent parameters and using the manual mode. The difference between the two types of processing is the level of the latitude value. Hard copies of the processed images were judged by five radiologists and three neurosurgeons. The evaluation applied the image criteria score (ICS) without conventional reference images. RESULTS: In 99 % of the lateral radiographs of the cervical spine, all vertebral bodies could be completed delineated using the manual mode, but only 76 % oft the images processed by the system-imminent parameters showed all vertebral bodies. Thus, the manual mode enabled the evaluation of up to two additional more caudal vertebral bodies. The manual mode processing was significantly better concerning object size and processing artifacts. This optimized image processing and the resultant minimization of supplementary investigations was calculated to correspond to a theoretical dose reduction of about 50 %. CONCLUSION: The introduction of optimized organ programs for the upper and lower cervical spine based on the 12-bit data of the images should improve the evaluation of the lateral radiograph of the cervical spine without reducing the latitude value.

Effects of a water-soluble extract of maitake mushroom on circulating glucose/insulin concentrations in KK mice.

AIM: We examined benefits of a water-soluble extract of maitake mushroom designated as Fraction X (FXM) on the glucose/insulin metabolism of insulin-resistant KK mice, and compared the results of FXM with those of a sulphonylurea, Glipizide. DESIGN: In several acute studies, insulin-resistant KK mice were gavaged with a single dose of varying concentrations of FXM, or a single dose of one concentration of the oral hypoglycaemic drug, Glipizide. In the one chronic study, KK mice were gavaged with FXM, Glipizide, or an equal volume of isotonic saline (baseline control) twice daily. Retro-orbital blood was drawn on the morning of the 4th and 7th days before the early gavage. Blood glucose was measured by routine laboratory procedures, and serum insulin was estimated by a radioimmunoassay (RIA) assay developed specifically for rodents. RESULTS: At a dose of FXM (140 mg/mouse), a statistically significant lowering of circulating glucose concentrations was again seen at 8-12 h and 16-18 h after oral gavage. The lowering approximated 25% of the original concentration. Oral gavage of Glipizide resulted in statistically significantly lower values of circulating glucose (25-37% lower compared with baseline) at 8-24 h post dosing. In the chronic study, the circulating concentrations of glucose and insulin of mice taking 140 mg FXM per day were decreased significantly at days 4 and 7. CONCLUSIONS: FXM, a natural extract obtained from maitake mushroom, favourably influences glucose/insulin metabolism in insulin-resistant KK mice. The lowering of both circulating glucose and insulin concentrations suggests that FXM works primarily by enhancing peripheral insulin sensitivity.

Effects of orally administered undenatured type II collagen against arthritic inflammatory diseases: a mechanistic exploration.

Arthritis afflicts approximately 43 million Americans or approximately 16.6% of the US population. The two most common and best known types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). A significant amount of scientific research has been done in attempts to explain what initiates forms of arthritis, how it is promoted and perpetuated and how to effectively intervene in the disease process and promote cartilage remodeling. Current pharmacological strategies mainly address immune suppression and antiinflammatory mechanisms and have had limited success. Recent research provides evidence that alterations in the three-dimensional configuration of glycoproteins are responsible for the recognition/response signaling that catalyzes T-cell attack. Oral administration of autoantigens has been shown to suppress a variety of experimentally induced autoimmune pathologies, including antigen-induced RA. The interaction between gut-associated lymphoid tissue in the duodenum and epitopes of orally administered undenatured type II collagen facilitates oral tolerance to the antigen and stems systemic T-cell attack on joint cartilage. Previous studies have shown that small doses of orally administered undenatured type II chicken collagen effectively deactivate killer T-cell attack. A novel glycosylated undenatured type II collagen material (UC-II) was developed to preserve biological activity. The presence of active epitopes in the UC-II collagen is confirmed by an enzyme-linked immunosorbent assay test and distinguishes this form from hydrolyzed or denatured collagen. Oral intake of small amounts of glycosylated UC-II presents active epitopes, with the correct three-dimensional structures, to Peyer's patches, which influences the signaling required for the development of immune tolerance. UC-II has demonstrated the ability to induce tolerance, effectively reducing joint pain and swelling in RA subjects. A pilot study was conducted for 42 days to evaluate the efficacy of UC-II (10 mg/day) in five female subjects (58-78 years) suffering from significant joint pain. Significant pain reduction including morning stiffness, stiffness following periods of rest, pain that worsens with use of the affected joint and loss of joint range of motion and function was observed. Thus, UC-II may serve as a novel therapeutic tool in joint inflammatory conditions and symptoms of OA and RA.

Effects of oral glucosamine and chondroitin sulfate alone and in combination on the metabolism of SHR and SD rats.

Glucosamine (G), often combined with chondroitin sulfate (CS), is a popular natural supplement used widely to treat osteoarthritis. However, use of glucosamine has been linked to development of insulin resistance. To assess the association between glucosamine and insulin resistance more closely, we challenged two rat strains highly sensitive to sugar-induced insulin resistance-Sprague-Dawley (SD) and Spontaneously Hypertensive (SHR) rats. Since elevations of systolic blood pressure (SBP) have been found to be an early and highly sensitive sign of insulin resistance in these two rat strains, we used this parameter as our primary endpoint. Four groups of both rat strains received either no agent (control), G, CS, or a combination of both for 9 weeks. The intake of each agent was calculated to be approximately 3-7 times comparable to human dose. Throughout the study, SBP of both strains consuming the two ingredients alone and in combination were not elevated. Rather, they were significantly lower than control, contrary to what is found in glucose-induced insulin resistance in rats. Over the study period, body weights of the four groups of SD and SHR did not vary significantly. Furthermore, no consistent trends in circulating glucose concentrations were found among the four different groups in the two strains after oral challenge with glucose. Finally, no significant histological differences were found in hearts, kidneys, and livers among the various groups of SHR and SD. From the above result, we conclude that glucosamine and chondroitin sulfate given alone or together do not produce insulin resistance or other related perturbations in two rat strains highly sensitive to sugar-induced insulin resistance.

Long-term effects of chromium, grape seed extract, and zinc on various metabolic parameters of rats.

Progressive insulin resistance may contribute to both enhanced glycosylation of proteins and nucleic acids and augmented free radical damage commonly associated with aging. Accordingly, ingestion of chromium and antioxidants which improve insulin sensitivity and/or lessen free radical formation could theoretically ameliorate these basic disorders and lessen signs and symptoms of chronic age-related disorders. However, this supposition is based primarily upon acute rather than chronic data. Therefore, we divided 104 F344/BN rats into 2 groups: a control group receiving a basic diet and a test group receiving the same diet with added chromium polynicotinate (5 ppm), zinc monomethionine (18 ppm elemental zinc), and a grape seed extract high in flavonoids (250 ppm). Initial mean systolic blood pressures (SBP) of both control and test groups were 122 mm Hg. Over the first 7 months, the SBP of the control animals steadily increased to 140 mm Hg and remained at this level for the next 7-8 months. In contrast, the SBP of the test animals initially decreased over the first 4 months to as low as 110-114 mm Hg. The SBP then increased over the following months, essentially reaching the starting value of 120 mm Hg. This was still significantly lower than control (p < 0.001). In 12 control and 12 test rats, hepatic TBARS formation, an estimate of lipid peroxidation/free radical formation, was significantly lower after 1 year ingesting the test diet (p < 0.04); and HbA1C was also statistically significantly lower in the test group (5.4 vs. 4.8%, p < 0.003). Circulating levels of cholesterol, HDL, and triglycerides were similar between the two groups. Body, kidney, and liver weights were not different after 1 year ingesting the different diets; but epididymal fat pad weight was less in the group receiving supplements. We conclude that after prolonged supplementation a combination of agents known to sensitize insulin response and act as antioxidants (chromium polynicotinate, grape seed extract, and zinc monomethionine) can markedly lower SBP in normotensive rats, lessen oxidative damage to fats as suggested by decreased TBARS formation, and lower HbA1C without showing signs of toxicity.

Influence of a combination of herbs on appetite suppression and weight loss in rats.

AIM: We evaluated the ability of a Chinese herbal formulation previously associated with weight loss to influence appetite and weight loss in a carefully controlled laboratory study performed on rats. As a secondary gain, results with this herbal formulation were compared with those from a commonly available phenylpropanolamine (PPA) compound. DESIGN: Eight rats were placed in each arm of a three-arm study, a total of 24 rats. All rats were gavaged with a 2-ml fluid volume containing no addition (control) or the two test substances (combined herbs or PPA) for the first 4 days of the week over 6 consecutive weeks; no gavages were given over weekends. Rats in the two-test groups were given a relatively low dose of the test substance for 3 weeks, followed by a higher dose over the next 3-week periods. Food and water intake were measured for 24-h periods over the ensuing week days. The average daily values for food and water intake for an individual rat were calculated on the basis of collected data over each 3-week period. The mean values for each rat obtained over the low- and high-dose periods comprised results from averaging at least 10 measurements. RESULTS: Average daily food intake was decreased only with the herbal formulation, not the PPA compound at the low and high doses. Both the PPA compound and the herbal formulation lowered water intake significantly at the low and high doses. Rats ingesting the herbal formulation at the lower dose had statistically significant lower daily body weight changes over the 3 weeks than those ingesting the PPA compound. At the higher dose, body weight changes for both agents were significantly less than the control, but not significantly different from each other. No evidence of toxicity was seen in the blood chemistries or after histopathological examination. CONCLUSIONS: Data collected on rats suggest that the herbal formulation examined might be a useful and safe combination to overcome the overweight state and obesity.

Wild garlic has a greater effect than regular garlic on blood pressure and blood chemistries of rats.

When groups of 10 Spontaneously Hypertensive Rats (SHR) were fed diets containing either 1% w/w regular garlic (Allium sativum) (AS) or 1% w/w wild garlic (Allium ursinum) (AU) for 45 days, the final mean systolic blood pressure (SBP) was reduced significantly compared to control (C) (C 189; AS 175; Au 173 mm Hg). Compared to C, body weight and circulating glucose and triglyceride levels were not significantly different; but circulating insulin was significantly higher (C 23.6; AS 33.9; AU 29.5 uIU/dl), and total cholesterol was significantly lower (C 133; AS 115; AU 117 mg/dl) in the two groups consuming AS or AU. HDL rose in the two garlic groups, but the differences from C were statistically significant only for the AU group. In a second study, the effects of a lower dose of dietary AS and AU (0.1% w/w) on SBP and various blood chemistries were compared head-to-head in 80 SHR-40 control and 40 test rats. Both AS and AU decreased SBP significantly compared to a control group of 10 SHR followed simultaneously. However, AU at this lower concentration produced a significantly greater SBP-lowering effect compared to the AS group. In addition, AU decreased total cholesterol significantly and tended to increase HDL compared to AS. Accordingly, the results suggest that AU has a greater therapeutic benefit compared to AS at a given concentration.

Hepatoprotective ability of a novel botanical formulation on mild liver injury in rats produced by acute acetaminophen and/or alcohol ingestion.

Medicinal herbs have been used for centuries in an attempt to overcome hepatic dysfunctions emanating from ingestion of hepatotoxic substances. However, the vast majority of information concerning their use is anecdotal. Well-performed animal studies would lend credence to the concept that some medicinal herbs may prevent or, at least ameliorate, hepatic dysfunction arising from drug-induced toxicity. The present investigation examined the potential for a combination of medicinal herbs to favorably influence the course of mild/moderate acute hepatic injury induced in rats by the oral intake of acetaminophen and/or ethyl alcohol. We performed four separate studies using elevations of liver enzymes [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] as our primary biomarkers of hepatotoxicity. In the first study, the ability of orally administered acetaminophen at different doses to produce acute hepatotoxicity was examined. In the second and third studies, the ability of a combination of medicinal herbs (a novel botanical formulation) was assessed to ameliorate the acetaminophen-induced hepatotoxicity. In the last series of studies, we used acute alcohol ingestion to cause liver perturbations and examined the ability of medicinal herbs to overcome hepatotoxicity. We also evaluated the ability of the medicinal herb combination to overcome acetaminophen-induced hepatotoxicity in rats simultaneously challenged with ethyl alcohol ingestion. Hepatotoxicity, estimated by increased levels of AST and ALT, was produced by a 2.0 mg/Kg oral dose of acetaminophen but not by lesser doses. Treatment with a combination of medicinal herbs (a novel botanical formulation) significantly ameliorated acetaminophen-induced toxic response. The combination of medicinal herbs also decreased the hepatic toxicity produced by acute ethyl alcohol ingestion. We conclude that oral ingestion of a novel botanical formulation (a combination of medicinal herbs) is effective in lessening drug-induced hepatotoxicity produced by acetaminophen and/or ethyl alcohol in an animal model.

Acute and long-term safety evaluation of a novel IH636 grape seed proanthocyanidin extract.

Grape seed proanthocyanidins are known to possess a broad spectrum of pharmacological, medicinal and therapeutic properties. Previous studies in our laboratories have demonstrated the various protective abilities of a novel IH636 grape seed proanthocyanidin extract (GSPE) against various pathologic conditions. However no extensive safety studies have been conducted on grape seed proanthocyanidins to date. This study demonstrates the acute and chronic safety studies on GSPE. Acute oral toxicity, dermal toxicity, dermal irritation and eye irritation studies have been conducted. The LD50 of GSPE was found to be greater than 5000 mg/kg when administered once orally via gastric intubation to fasted male and female albino rats. The LD50 of GSPE was found to be greater than 2000 mg/kg when administered once for 24 hr to the clipped, intact skin of male and female albino rats. In addition, 2000 mg/kg was found to be the no-observed-effect level (NOEL) for systemic toxicity under the conditions of the study. In a dermal irritation study, GSPE received a descriptive rating classification of moderately irritating. Extensive chronic studies were also conducted. We have assessed the effects of chronic administration of 100 mg GSPE/kg/day for twelve months and its effect on seven vital target organs, namely, brain, heart, intestine, kidney, liver, lung and spleen, and on serum chemistry changes in male B6C3F1 mice. Furthermore, the dose-dependent chronic effects of GSPE in female B6C3F1 mice were evaluated. Mice were fed 0, 100, 250 or 500 mg GSPE/kg/day for six months and the effects of GSPE exposure were examined on brain, duodenum, heart, kidney, liver, lung, pancreas and spleen, and on serum chemistry changes in female mice. These acute studies demonstrated that GSPE is safe and did not cause any detrimental effects in vivo under the conditions investigated in this study.