Archana Chatterjee

Physico-chemical properties of a novel (-)-hydroxycitric acid extract and its effect on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological changes over a period of 90 days

Garcinia cambogia-derived (—)-hydroxycitric acid (HCA) is a popular and natural supplement for weight management. HCA is 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) in the cytosol. Acetyl CoA is used in the synthesis of fatty acids, cholesterol and triglycerides, and in the synthesis of acetylcholine in the central nervous system. Studies have demonstrated the efficacy of a novel 60% calcium-potassium salt of HCA derived from Garcinia cambogia(HCA-SX, Super CitriMax) in weight management. Results have shown that HCA-SX promotes fat oxidation, enhances serotonin release and availability in the brain cortex, normalizes lipid profiles, and lowers serum leptin levels in obese subjects. Acute oral, acute dermal, primary dermal irritation and primary eye irritation toxicity, as well as Ames bacterial reverse mutation studies and mouse lymphoma tests have demonstrated the safety of HCA-SX. However, no detailed long-term safety of HCA-SX or any other HCA extract has been previously assessed. We evaluated the dose- and time-dependent effects of HCA-SX in Sprague-Dawley rats on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry over a period of 90 days. Furthermore, a 90-day histopathological evaluation was conducted. The animals were treated with 0, 0.2, 2.0 and 5.0% HCA-SX of feed intake and were sacrificed on 30, 60 or 90 days of treatment. The body weight and selected organ weights were assessed and correlated as a % of body weight and brain weight at 90 days of treatment. A significant reduction in body weight was observed in treated rats as compared to control animals. An advancing age-induced marginal increase in hepatic lipid peroxidation was observed in both male and female rats, while no such difference in hepatic DNA fragmentation was observed as compared to the control animals. Furthermore, selected organ weights individually and as a % of body weight and brain weight at 90 days of treatment exhibited no significant difference between the groups. No difference was observed in hematology and clinical chemistry or the histopathological evaluation. Taken together, these results show that 90 day treatment of HCA-SX results in a reduction in body weight, and does not cause any changes in major organs or in hematology, clinical chemistry, and histopathology.

Dose- and time-dependent effects of a novel (-)-hydroxycitric acid extract on body weight, hepatic and testicular lipid peroxidation, DNA fragmentation and histopathological data over a period of 90 days

Abstract(−)-Hydroxycitric acid (HCA), a natural extract from the dried fruit rind of Garcinia cambogia (family Guttiferae), is a popular supplement for weight management. The dried fruit rind has been used for centuries as a condiment in Southeastern Asia to make food more filling and satisfying. A significant number of studies highlight the efficacy of Super CitriMax (HCA-SX, a novel 60% calcium-potassium salt of HCA derived from Garcinia cambogia) in weight management. These studies also demonstrate that HCA-SX promotes fat oxidation, inhibits ATP-citrate lyase (a building block for fat synthesis), and lowers the level of leptin in obese subjects. Acute oral, acute dermal, primary dermal irritation and primary eye irritation toxicity studies have demonstrated the safety of HCA-SX. However, no long-term safety of HCA-SX or any other (−)-hydroxycitric acid extract has been previously assessed. In this study, we have evaluated the dose- and time-dependent effects of HCA-SX in Sprague-Dawley rats on body weight, hepatic and testicular lipid peroxidation, DNA fragmentation, liver and testis weight, expressed as such and as a % of body weight and brain weight, and histopathological changes over a period of 90 days. The animals were treated with 0, 0.2, 2.0 and 5.0% HCA-SX as feed intake and the animals were sacrificed on 30, 60 or 90 days of treatment. The feed and water intake were assessed and correlated with the reduction in body weight. HCA-SX supplementation demonstrated a reduction in body weight in both male and female rats over a period of 90 days as compared to the corresponding control animals. An advancing age-induced marginal increase in hepatic lipid peroxidation was observed in both male and female rats as compared to the corresponding control animals. However, no such difference in hepatic DNA fragmentation and testicular lipid peroxidation and DNA fragmentation was observed. Furthermore, liver and testis weight, expressed as such and as a percentage of body weight and brain weight, at 30, 60 and 90 days of treatment, exhibited no significant difference between the four groups. Taken together, these results indicate that treatment of HCA-SX over a period of 90 days results in a reduction in body weight, but did not cause any changes in hepatic and testicular lipid peroxidation, DNA fragmentation, or histopathological changes.

Antimicrobial effects of antioxidants with and without clarithromycin on Helicobacter pylori

Increasing resistance to currently used antimicrobials has resulted in the evaluation of other agents that have antimicrobial activity against Helicobacter pylori. H. pylori American Type Culture Collection (ATCC) strain 49503 (a toxin-producing strain known to be associated with gastric cancer) was grown, a cell suspension prepared in 2 mL PBS and diluted 10-fold. One hundred μL of this cell suspension was added to vitamin C 0.5%, vitamin E 0.5%, garcinol 100 μg/mL, Protykin® (containing 50% rans-resveratrol) 100 μg/mL and garcinol + Protykin® 100 μg/mL in Lennox broth, and incubated for 16 h under microaerophilic conditions. Three replicates of 10 μL from each 10−7 dilution tube were plated, colonies were counted after 16 h, and growth of H. pylori was confirmed by the CLO® test. These colony counts were compared to control cultures without the addition of any antioxidants. The experiments were then repeated with the addition of 15 μg/mL of clarithromycin to experimental and control samples. Enhanced killing of H. pylori by 37.6% was noted when vitamin C was added, which increased to 66% when clarithromycin was added, compared to controls (p < 0.05). With garcinol and Protykin® alone there was 91.4 and 87% killing of H. pylori, respectively, while a combination of garcinol + Protykin® resulted in 90.8% killing compared to controls (p < 0.05). When clarithromycin was added, there was 76.3% increased killing with garcinol alone, 55.3% with Protykin® alone, and 73.7% with garcinol + Protykin® compared to controls (containing clarithromycin) (p < 0.05). Vitamin E had no effect on H. pylori growth compared to controls. We conclude from this study that some antioxidants such as vitamin C, garcinol and Protykin®, but not vitamin E, may have potential as antimicrobial agents against H. pylori. (Mol Cell Biochem 270: 125–130, 2005)

Safety and toxicological evaluation of a novel, standardized 3-O-acetyl-11-keto-beta-boswellic acid (AKBA)-enriched Boswellia serrata extract (5-Loxin (R))

The novel anti-inflammatory properties of the gum resin derived from Boswellia serrata, also known as Salai guggal in Ayurvedic medicine, are well recognized and highly recommended for human consumption. The active constituents of the gum resin are boswellic acids (BAs). Among the BAs, AKBA potently inhibits 5-lipoxygenase product formation with an IC50 of 1.5 m μM. We developed a novel Boswellia serrata extract (5-Loxin®) enriched with 30% AKBA (US Patent 2004/0073060A1). The genetic basis of the anti-inflammatory effects of 5-Loxin® was explored in a system of TNFα-induced gene expression in human microvascular endothelial cells. 5-Loxin® significantly prevented the TNFα-induced expression of matrix metalloproteinases and adhesion molecules (ICAM-1 and VCAM-1), and inducible expression of the mediators of apoptosis. With such interesting findings, we planned to determine the broad-spectrum safety of 5-Loxin®. Acute oral, acute dermal, primary skin and eye irritation, and dose-dependent 90-day subchronic toxicity studies were conducted. In safety studies, acute oral LD50 of 5-Loxin® was found to be greater than 5,000 mg/kg in both male and female Sprague-Dawley rats. No changes in body weight or adverse effects were observed following necropsy. Acute dermal LD50 of 5-Loxin® was found to be >2,000 mg/kg. Primary skin irritation test was conducted with 5-Loxin® on New Zealand Albino rabbits and 5-Loxin® was classified as nonirritating. Primary eye irritation test was conducted with 5-Loxin on rabbits and 5-Loxin® was classified as mildly irritating to the eye. A dose-dependent 90-day subchronic toxicity study demonstrated no significant changes in selected organ weights individually and as percentages of body and brain weights. 5-Loxin® supplementation did not cause changes in hepatic DNA fragmentation on 30, 60, or 90 days of treatment. Hematology, clinical chemistry, and histopathological evaluations did not show any adverse effects in all organs tested. Taken together, these results demonstrate the broad spectrum safety of 5-Loxin®.

Vaccine and Immunization Resources on the World Wide Web

Abundant information regarding immunizations and vaccines is available on the World Wide Web. This report was prepared as a guide to reliable Internet sources for health care providers, researchers, and patients or parents interested in gaining Web-based information on these topics. I describe comprehensive Web sites about immunizations, meetings on immunizations, and clinical trials on vaccines and for journals and publications on vaccines, organizations providing immunization information, and pharmaceutical companies and vaccine manufacturers.

Endocarditis Due to Kingella kingae: A Patient Report

Infections due to Kingella kingae most frequently occur as septic arthritis1,2 followed by osteomyelitis, endocarditis, bacteremia, pneumonia, and ophthalmic or central nervous system infections.1,3,4 While the majority of K. kingae infections have excellent prognoses, K. kingae endocarditis is accompanied by significant morbidity and mortality.5 The increased frequency of recognition of K. kingae as a pathogen in recent years, has been attributed to increased awareness of the organism and improvements in bacterial identification techniques.6 Our literature review reveals 15 reported cases of pediatric K. kingae endocarditis.1,2,7 We report on a 20month-old female with K. kingae endocarditis and no history of previous cardiac disease or valvular malformation. Patient Report

Impact of Surveillance Rounds on Adherence to Infection Control Policies and Procedures at a Children's Hospital

Adherence to written infection control policies and procedures was studied and on-site education was provided for 1 year at a childrens hospital. There was significant improvement in sharp objects disposal, hazardous waste handling, availability of personal protective equipment, isolation precautions, and staff knowledge regarding location of the exposure control plan.

Cytokine expression due to Helicobacter pylori in a tissue culture model

Helicobacter pylori, in recent years, has been recognized as the major causative agent in chronic gastritis and peptic ulcer disease in humans. H. pylori is a ubiquitous organism, with at least half of the world’s population infected. Of those individuals with peptic ulcer disease, it is estimated that 90% of cases are caused by H. pylori. Currently, the efficacy of therapies is starting to decline due to increasing resistance rates, especially towards clarithromycin. Due to this, new therapies are needed to combat this bacterium. It is hypothesized that cytokine release (especially interleukin-1β, -6, -8, and TNF-α) due to H. pylori infection and the subsequent influx of inflammatory cells causes a massive release of reactive oxygen species (ROS) during the inflammatory reaction. The ROS then cause the pathologic changes seen in the infected tissues. In this study, human gastric adenocarcinoma cell line ATCC 1739 (a cell line not previously evaluated) was examined for its production of interleukin-1β, -6, -8, and TNF-α when cocultured in a ratio of 10:1 H. pylori to adenocarcinoma cells, to determine its value as a model to demonstrate the inflammatory response. Results from this study indicated that ATCC 1739 cells only reliably produced IL-8 when cocultured with H. pylori and stimulated with TNF-α. The production of IL-1β, IL-6, and TNF-α by the ATCC 1739 cells was no different in H. pylori-exposed cells than non-exposed cells. It was concluded that the ATCC 1739 cell line is not suitable to study the effects of coculture with H. pylori on cytokine production.

Safety Assessment of a Novel Niacin-Bound Chromium-Based Energy Formulation

Over 35 million adults suffer from fatigue or lack of energy. In this study, we assessed the safety of a novel niacin-bound chromium-based Energy Formulation, which also contained caffeine, D-ribose, Withania somnifera extract, and selected amino acids. Niacin-bound chromium is a novel source of bioavailable chromium (III), and known to promote healthy lipid profile. Male and female Sprague-Dawley rats were fed 125 ppm Energy Formulation for 90 consecutive days. Body weight, feed, and water intake were monitored over the period of 90 days. No significant changes were observed between the control and treatment groups following subchronic supplementation with this Energy Formulation. Furthermore, no significant changes were observed in selected organ weights individually and as percentages of body and brain weights. The Energy Formulation supplementation did not cause changes in hepatic lipid peroxidation or DNA fragmentation after 30, 60, or 90 days of treatment. Hematology, clinical chemistry, and histopathological evaluations revealed no adverse effects in the treatment group. These findings demonstrate the safety of this Energy Formulation.

In vitro activity of cefdinir and comparison agents against β-lactamase-producing pathogens

Abstract: The in vitro activities of the oral agents, cefdinir, ceftibuten, cefixime, cefprozil, cefuroxime, cefpodoxime, cephalexin, loracarbef, ampicillin, and amoxicillin/clavulanate with ceftriaxone were compared against a panel of 210 bacterial strains chosen to represent a diverse range of types of β-lactamase expression. Ceftriaxone was included in the study as a representative parenteral cephalosporin. Activities were determined by NCCLS microdilution methodology. Cefdinir was the most active agent overall in terms of its activity against Enterobacteriaceae, Haemophilus influenzae, Moraxella catarrhalis, and methicillin-susceptible Staphylococcus aureus, with greatest activity against community-acquired pathogens. Cefdinir was significantly more resistant to hydrolysis by β-lactamases than cefprozil, cephalexin, cephalothin, cephaloridine, and loracarbef, and generally comparable to cefixime, cefpodoxime, cefuroxime, ceftibuten, and ceftriaxone. Therefore, cefdinir has a spectrum of activity and resistance to β-lactamases suiting it for therapy for infections caused by a wide range of gram-positive and gram-negative pathogens, particularly those encountered in outpatient settings.