Antrodia cinnamomea reduces obesity and modulates the gut microbiota in high-fat diet-fed mice.

BACKGROUND: Obesity is associated with gut microbiota dysbiosis, disrupted intestinal barrier and chronic inflammation. Given the high and increasing prevalence of obesity worldwide, anti-obesity treatments that are safe, effective and widely available would be beneficial. We examined whether the medicinal mushroom Antrodia cinnamomea may reduce obesity in mice fed with a high-fat diet (HFD). METHODS: Male C57BL/6J mice were fed a HFD for 8 weeks to induce obesity and chronic inflammation. The mice were treated with a water extract of A. cinnamomea (WEAC), and body weight, fat accumulation, inflammation markers, insulin sensitivity and the gut microbiota were monitored. RESULTS: After 8 weeks, the mean body weight of HFD-fed mice was 39.8±1.2 g compared with 35.8±1.3 g for the HFD+1% WEAC group, corresponding to a reduction of 4 g or 10% of body weight (P<0.0001). WEAC supplementation reduced fat accumulation and serum triglycerides in a statistically significant manner in HFD-fed mice. WEAC also reversed the effects of HFD on inflammation markers (interleukin-1ß, interleukin-6, tumor necrosis factor-α), insulin resistance and adipokine production (leptin and adiponectin). Notably, WEAC increased the expression of intestinal tight junctions (zonula occludens-1 and occludin) and antimicrobial proteins (Reg3g and lysozyme C) in the small intestine, leading to reduced blood endotoxemia. Finally, WEAC modulated the composition of the gut microbiota, reducing the Firmicutes/Bacteroidetes ratio and increasing the level of Akkermansia muciniphila and other bacterial species associated with anti-inflammatory properties. CONCLUSIONS: Supplementation with A. cinnamomea produces anti-obesogenic, anti-inflammatory and antidiabetic effects in HFD-fed mice by maintaining intestinal integrity and modulating the gut microbiota.

Dietary zinc supplementation inhibits NFkappaB activation and protects against chemically induced diabetes in CD1 mice.

Zinc status in patients with Type I diabetes is significantly lower than healthy controls. Whether zinc supplementation can prevent the onset of Type I diabetes is unknown. Recent studies have suggested that the generation of reactive oxygen species (ROS) is a cause of beta cell death leading to Type I diabetes. In addition, we found that activation of NFkappaB (a ROS-sensitive transcription factor that regulates immune responses) may be the key cellular process that bridges oxidative stress and the death of beta cells. Zinc is a known antioxidant in the immune system. Therefore, this study is designed to test whether an increase in dietary zinc can prevent the onset of Type I diabetes by blocking NFkappaB activation in the pancreas. The results show that high zinc intake significantly reduced the severity of Type I diabetes (based on hyperglycemia, insulin level, and islet morphology) in alloxan and streptozotocin-induced diabetic models. Zinc supplementation also inhibited NFkappaB activation and decreased the expression of inducible NO synthase, a downstream target gene of NFkappaB. It is concluded that zinc supplementation can significantly inhibit the development of Type I diabetes. The ability of zinc to modulate NFkappaB activation in the diabetogenic pathway may be the key mechanism for zinc's protective effect. Inhibition of the NFkappaB pathway may prove to be an important criterion for choosing nutritional strategies for Type I diabetes prevention.

Cytotoxicity and immunogenicity of SACCHACHITIN and its mechanism of action on skin wound healing.

SACCHACHITIN membrane, a weavable skin substitute made from the residual fruiting body of Ganoderma tsugae, has been demonstrated to promote skin wound healing. Prior to its clinical application, it is critical to learn more about any possible cytotoxicity, immunogenicity, or allergy response, and at least some of its mechanism(s) of action(s). In the present studies, it has been found that SACCHACHITIN suspension at less than 0.05% shows no cytotoxicity to the primary culture of rat fibroblasts. However, at higher concentrations (> or = 0.1%), it does reduce the growth of fibroblasts, based on MTT assays. This might be caused by positive charges on chitin molecules that are too strong, and may be harmful to the cell membrane. SACCHACHITIN showed no immunogenicity after it was inoculated into rats three times; however, the unmodified, purified rabbit type I and type II collagens did. Subcutaneous injection of SACCHACHITIN suspension into rats showed no gross allergic responses on skin. Nevertheless, it did cause local acute inflammation, as observed by histological investigation. This is similar to what occurred in the wound site covered with SACCHACHITIN membrane. The chemotactic effect of SACCHACHITIN was exhibited in both intact and wounded skin tissues. This may be one of the initial beneficial effects of SACCHACHITIN membrane to wound healing. The rapid acute inflammatory process was followed by the appearance of angiogenesis and granulation tissue formation, which occurred earlier than it normally would. Coverage of the wound area with SACCHACHITIN membrane also induced an earlier formation of scar tissue to replace the granulation tissue. A 1.5 x 1.5 cm(2) wound area covered by SACCHACHITIN completely healed by 21 days, while that covered with cotton gauze did not. Therefore, SACCHACHITIN is a safe biomaterial for use as a wound dressing for skin healing. Its promoting action for wound healing might be due to its chemotactic effect for inflammatory cells. This, in turn, may facilitate subsequent angiogenesis, granulation tissue formation, and faster new tissue formation, leading to faster wound healing.

Mechanisms mediating lipoprotein responses to diets with medium-chain triglyceride and lauric acid.

Medium-chain triglycerides (MCT) are often used in specialized formula diets or designer fats because of their special properties. Yet their influence on lipid metabolism is not completely understood. In this two-period cross-over study, the effects of MCT (8:0 + 10:0) in contrast to a similar saturated fatty acid (12:0) were compared. Eighteen healthy women ate a baseline diet [polyunsaturated (PUFA)/saturated fat = 0.9] for 1 wk. Then, they consumed test diets (PUFA/saturated fat = 0.2) for 4 wk. Monounsaturated fat and cholesterol were constant in baseline and treatment diets. MCT and 12:0, substituted for part of the PUFA, provided 14 energy (en)% of the test diets. In comparison to the PUFA baseline diet, a 16% increase in mean serum low density lipoprotein (LDL)-cholesterol (C) on the 12:0 diet was accompanied by a 21% decrease in mean receptor-mediated degradation of LDL by freshly isolated mononuclear cells (MNC) in vitro. The MNC assay theoretically gives an indication of receptor-mediated degradation of LDL. In contrast, the MCT diet raised mean receptor-mediated degradation of LDL by 42%, a finding out of line with the mean 11% increase in serum LDL-C. Perhaps MCT, by increasing the rate of LDL-C production, overcame the rate of LDL-C clearance. The 12:0 diet enhanced some factors involved in reverse cholesterol transport (e.g., high density lipoprotein fractions) while MCT had a different or less pronounced effect. The overall effects of MCT on cholesterol metabolism may or may not be desirable, whereas those of 12:0 appear largely undesirable as previously reported.

Efficacy of cefepime in a Staphylococcus aureus endocarditis rat model.

The efficacy of cefepime, a new broad-spectrum cephalosporin, was compared with those of cefpirome, ceftazidime, vancomycin, imipenem-cilastatin and penicillin G in a rat model of endocarditis caused by a methicillin-susceptible strain of Staphylococcus aureus. Rats were infected intravenously with approximately 10(5) cfu of a penicillin-resistant strain of S. aureus 24 h after placement of a catheter into the left ventricle of the heart via the carotid artery. Efficacy was evaluated by comparing bacterial counts in the cardiac vegetations of treated rats with those of untreated controls. Rats treated with cefepime, cefpirome, ceftazidime, imipenem-cilastatin and vancomycin showed a reduction in the number of bacteria recovered from cardiac vegetations compared with infected control animals; penicillin G was ineffective in this respect. Serum concentrations of the study antimicrobials were determined at selected times following the administration of a single subcutaneous dose. The pharmacokinetic parameters of the cephalosporins were similar in these animals. This study shows that cefepime may be of value in the treatment of staphylococcal endocarditis.

Crude drug (zingiberaceae) enhancement of percutaneous absorption of indomethacin: in vitro and in vivo permeation.

To improve drug permeation through skin, extracts of crude drugs were evaluated using in vitro and in vivo penetration techniques with rabbit skin as a model membrane. The acetone extract of Amomum cardamomum (ae-AC) and Elettaria cardamomum (ae-EC) had the best effect in enhancing the penetration of Indomethacin (IDM). The flux of IDM for the formulation containing ae-AC from pH 7.4 buffer-alcohol donor solution was 3.6 times higher than that from the 50% alcohol donor solution. In order to confirm enhancer/skin interaction, a microscopic study was carried out in order to determine the presence of physical evidence in the skin caused by enhancers. A pharmacokinetic model of percutaneous absorption of IDM after topical administration was employed on the assumption of a zero-order penetration rate through the stratum corneum followed by absorption into the blood by a first-order process. Good correlation was observed between the experimental data point and simulated plasma concentration. From the results of the study, the in vitro permeability coefficient correlates with the in vivo penetration rate through the stratum corneum.

Multifocal atrial tachycardia as a prognostic indicator in patients with severe chronic obstructive pulmonary disease requiring mechanical ventilation.

The records of 121 patients admitted to the Medical Intensive Care Unit (MICU) of Chang Gung Memorial Hospital with severe chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation were reviewed retrospectively. Eighty-seven percent (20/23) of the patients with multifocal atrial tachycardia (MAT) expired during their ICU admission in contrast to 23.5% (23/98) of those without MAT. The only differences between these two groups were incidence of cor pulmonale, and right axis deviation, right bundle branch block, pulmonale P in electrocardiogram. MAT might be considered as a grave prognostic sign in patients with COPD severe enough to require mechanical ventilation.

Therapeutic studies of cefepime (BMY 28142) in murine meningitis and pharmacokinetics in neonatal rats.

Cefepime (BMY 28142) was compared with ceftazidime, cefotaxime, and moxalactam for efficacy in treating experimental meningitis in mice and neonatal rats. Mice were infected intracranially with Streptococcus pneumoniae, S. agalactiae, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa and treated intramuscularly. Five- to eight-day-old neonatal rats were injected intracisternally with Haemophilus influenzae, S. pneumoniae, and S. agalactiae and treated intraperitoneally. Cefepime was found to be the most active compound against induced meningitis in mice infected with S. agalactiae. Cefepime was as active as cefotaxime against Staphylococcus aureus meningitis, slightly more active than cefotaxime against S. pneumoniae and E. coli, and as active as ceftazidime against K. pneumoniae and P. aeruginosa meningitis. Cefepime was found to be the most active compound against S. pneumoniae and S. agalactiae meningitis in neonatal rats. Against H. influenzae, cefepime was as active as moxalactam and cefotaxime. Ceftazidime was the least active compound. The pharmacokinetics of cefepime in neonatal rats were similar to those of ceftazidime. Both compounds penetrated well into cerebrospinal fluid and brain tissues of uninfected neonatal rats. Relative concentrations were twice as high as those of cefotaxime and moxalactam.

Antibacterial activity of phosphanilic acid, alone and in combination with trimethoprim.

We explored the antibacterial activity of phosphanilic acid (P), an analog of sulfanilic acid, alone and in combination with trimethoprim (T; TP, 1:5) with sulfamethoxazole (S) and co-trimoxazole, the combination of this sulfonamide with trimethoprim (TS, 1:5) as the reference. P resembled S in spectrum but, in addition, had significant activity against Pseudomonas aeruginosa. The overall frequency and degree of synergism with TP were lower than with co-trimoxazole. P, like S, was strongly affected by changes in inoculum size and was not bactericidal. P was well absorbed parenterally but not orally in mice. Despite low (but prolonged) blood levels, P, given orally to mice, was effective in treating infections caused by P. aeruginosa. However, against most experimental infections the therapeutic effectiveness of P, as well as that of TP, administered either intramuscularly or orally was unimpressive. Based on in vivo data, the therapeutic application of P or TP would appear to be limited.