Greater Body Weight Loss Research Articles

Plasmacytoid Dendritic Cells Mediate the Regulation of Inflammatory Type T Cell Response for Optimal Immunity against Respiratory Chlamydia Pneumoniae Infection

Chlamydia pneumoniae (Cpn) infection is a leading cause for a variety of respiratory diseases and has been implicated in the pathogenesis of chronic inflammatory diseases. The regulatory mechanisms in host defense against Cpn infection are less understood. In this study, we investigated the role of plasmacytoid dendritic cells (pDCs) in immune regulation in Cpn respiratory tract infection. We found that in vivo depletion of pDCs increased the severity of infection and lung pathology. Mice depleted of pDC had greater body weight loss, higher lung bacterial burden and excessive tissue inflammation compared to the control mice. Analysis of specific T cell cytokine production pattern in the lung following Cpn infection revealed that pDC depleted mice produced significantly higher amounts of inflammatory cytokines, especially TNF-α, but lower IL-10 compared to the controls. In particular, pDC depleted mice showed pathogenic T cell responses characterized by inflammatory type-1 (CD8 and CD4) and inflammatory Th2 cell responses. Moreover, pDC depletion dramatically reduced CD4 regulatory T cells (Tregs) in the lungs and draining lymph nodes. Furthermore, pDC-T cell co-culture experiments showed that pDCs isolated from Cpn infected mice were potent in inducing IL-10 producing CD4 Tregs. Together, these findings provide in vivo evidence for a critical role of pDCs in homeostatic regulation of immunity during Cpn infection. Our findings highlight the importance of a ‘balanced’ immune response for host protective immunity and preventing detrimental immunopathology during microbial infections.

Post-grazing sward height imposed during the first 10 weeks of lactation: Influence on early and total lactation dairy cow production, and spring and annual sward characteristics

Increasing the proportion of grazed grass in the diet of the dairy cow is the main target of grass-based milk production systems. Imposing a severe post-grazing sward height (PGSH) in early lactation is one strategy to increase grass utilisation. A grazing experiment was undertaken to investigate the direct and carryover effects of PGSH imposed in early lactation on sward and dairy cow lactation performance. Ninety Holstein–Friesian dairy cows (mean calving date: February 13) were randomly assigned to one of three target PGSH treatments: 2.7cm (severe; S), 3.5cm (low; L) and 4.2cm (moderate; M) from February 14 to April 24, 2011 (period 1; P1). This was followed by a carryover period (period 2; P2) during which cows were randomly re-assigned within their P1 treatment across two PGSH treatments: 3.5 or 4.5cm until November 13. Sward utilisation (>2.7cm) during P1 was significantly improved by decreasing PGSH from M (0.74) to L (0.82) and further to S (0.94). At the end of the entire grazing season, the M treatment swards had produced +1.4t dry matter (DM)/ha than the S and L treatment swards which had similar total DM yields (14.1t DM/ha). Treatment had no immediate or carryover effect on the proportions of leaf, stem and senescent material in the sward or the quality of herbage selected by the animals. During P1 the cows in S had greater bodyweight loss (−18kg), reduced milk (−2.1kg/day) and milk solids yields (−0.21kg/day) as well as lower grass DM intake (−1.7kg DM/day) compared with the cows in L and M, which performed similarly (−5kg, 24.1kg/day, 1.94kg/day, and 13.0kg DM/day, respectively). There was no carryover effect of early lactation PGSH on milk and milk solids yields, fat and protein concentrations during P2. This indicates that cows restricted in P1 were able to adjust production in accordance with the higher PGSH imposed during the remainder of the lactation. The S treatment had numerically lower, though not significantly lower, total lactation milk and milk solids yields, reflecting their significantly reduced yields in early lactation. It was concluded that grazing to 2.7cm in early lactation is too restrictive for dairy cows. Cows in L and M had very similar total cumulative production performance. As a result, grazing to 3.5cm during the first 10 weeks of lactation contributes to achieving both high milk output from pasture and high grass utilisation.

A faster running speed is associated with a greater body weight loss in 100-km ultra-marathoners

In 219 recreational male runners, we investigated changes in body mass, total body water, haematocrit, plasma sodium concentration ([Na+]), and urine specific gravity as well as fluid intake during a 100-km ultra-marathon. The athletes lost 1.9 kg (s = 1.4) of body mass, equal to 2.5% (s = 1.8) of body mass (P < 0.001), 0.7 kg (s = 1.0) of predicted skeletal muscle mass (P < 0.001), 0.2 kg (s = 1.3) of predicted fat mass (P < 0.05), and 0.9 L (s = 1.6) of predicted total body water (P < 0.001). Haematocrit decreased (P < 0.001), urine specific gravity (P < 0.001), plasma volume (P < 0.05), and plasma [Na+] (P < 0.05) all increased. Change in body mass was related to running speed (r = −0.16, P < 0.05), change in plasma volume was associated with change in plasma [Na+] (r = −0.28, P < 0.0001), and change in body mass was related to both change in plasma [Na+] (r = −0.36) and change in plasma volume (r = 0.31) (P < 0.0001). The athletes consumed 0.65 L (s = 0.27) fluid per hour. Fluid intake was related to both running speed (r = 0.42, P < 0.0001) and change in body mass (r = 0.23, P = 0.0006), but not post-race plasma [Na+] or change in plasma [Na+] (P > 0.05). In conclusion, faster runners lost more body mass, runners lost more body mass when they drank less fluid, and faster runners drank more fluid than slower runners.

Abstract 1689: Impact of pre-treatment body mass index on patients with head and neck cancer treated with radiation

Abstract Purpose: Radiation therapy (RT) may lead to difficulty in swallowing and subsequently weight loss in patients with head and neck cancer. We investigated the association of pre-treatment body mass index (preT BMI) with outcomes of head and neck cancer in patients treated with radiation. Methods: All 1562 patients diagnosed with head and neck cancer and treated with curative-intent RT to a dose of 60Gy or higher between 1994 and 2004 were retrospectively studied. Body weight was measured both at entry and at the end of RT. cancer-specific survival (CSS), overall survival (OS), locoregional control (LRC) and distant metastasis (DM) were analyzed by preT BMI (&amp;lt; 25 Kg/m2 vs ≤ 25Kg/m2). The median follow-up was 8.6 years. Results: Patients with higher preT BMI appeared to have earlier T and N stage. Patients with lower preT BMI were statistically significantly associated with poor CSS (p = 0.023) and OS (p &amp;lt; 0.0001) than those with higher preT BMI. There is no significant difference between high and low preT BMI in LRC and DM. Body weight loss (BWL) during radiation did not influence survival outcomes. However, in the group of higher preT BMI, CSS, OS and DM-free survival of patients with less BWL during radiation was statistically longer when compared with greater BWL (p = 0.002, &amp;lt; 0.0001, and 0.033). Conclusion: This study demonstrates preT BMI greater than or equal to 25 Kg/m2 positively influenced survival outcomes for patients with head and neck cancer. Patients with higher preT BMI who were able to maintain their weight during radiation had significantly better survival and distant outcomes than patients experiencing greater BWL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1689. doi:1538-7445.AM2012-1689

Anti-obesity effects of the combined administration of CB1 receptor antagonist rimonabant and melanin-concentrating hormone antagonist SNAP-94847 in diet-induced obese mice

Current anti-obesity monotherapies have proven only marginally effective and are often accompanied by adverse side effects. The cannabinoid 1 (CB1) receptor antagonist rimonabant, while effective at producing weight loss, has been discontinued from clinical use owing to increased incidence of depression. This study investigates the interaction between the cannabinoid and melanin-concentrating hormone (MCH) systems in food intake, body weight control, and mood. Lean male C57BL/6 mice were injected i.p. with rimonabant (0.0, 0.03, 0.3 and 3.0 mg kg(-1)) or the MCH1-R antagonist SNAP-94847 (0.0, 1.0, 5.0 and 10.0 mg kg(-1)) to establish dose response parameters for each drug. Diet-induced obese (DIO) mice were given either vehicle, sub-threshold dose of rimonabant and SNAP-94847 alone or in combination. Impact on behavioral outcomes, food intake, body weight, plasma metabolites and expression of key metabolic proteins in the brown adipose tissue (BAT) and white adipose tissue (WAT) were measured. The high doses of rimonabant and SNAP-94847 produced a reduction in food intake after 2 and 24 h. Combining sub-threshold doses of rimonabant and SNAP-94847 produced a significantly greater loss of body weight in DIO mice compared with vehicle and monotherapies. In addition, combining sub effective doses of these drugs led to a shift in markers of thermogenesis in BAT and lipid metabolism in WAT consistent with increased energy expenditure and lipolysis. Furthermore, co-administration of rimonabant and SNAP-94847 produced a transient reduction in food intake, and significantly reduced fat mass and adipocyte size. Importantly, SNAP-94847 significantly attenuated the ability of rimonabant to reduced immobility time in the forced swim test. These results provide proof of principle that combination of rimonabant and a MCH1 receptor antagonist is highly effective in reducing body weight below that achieved by rimonabant and SNAP-94847 monotherapies. In addition, the combination therapy normalizes the rimonabant-induced behavioral changes seen in the forced swim test.

Impact of Pretreatment Body Mass Index on Patients With Head-and-Neck Cancer Treated With Radiation

To investigate the association of pretreatment body mass index (preT BMI) with outcomes of head-and-neck cancer in patients treated with radiotherapy (RT). All 1,562 patients diagnosed with head-and-neck cancer and treated with curative-intent RT to a dose of 60 Gy or higher were retrospectively studied. Body weight was measured both at entry and at the end of RT. Cancer-specific survival (CSS), overall survival (OS), locoregional control (LRC), and distant metastasis (DM) were analyzed by preT BMI (<25 kg/m(2) vs. ≥25 kg/m(2)). The median follow-up was 8.6 years. Patients with lower preT BMI were statistically significantly associated with poorer CSS and OS than those with higher preT BMI. There was no significant difference between preT BMI groups in terms of LRC and DM. Body weight loss (BWL) during radiation did not influence survival outcomes. However, in the group with higher preT BMI, CSS, OS, and DM-free survival of patients with less BWL during radiation were statistically longer when compared with greater BWL. This study demonstrates that higher preT BMI positively influenced survival outcomes for patients with head-and-neck cancer. Patients with higher preT BMI who were able to maintain their weight during radiation had significantly better survival than patients with greater BWL.

A Weight‐Loss Diet Including Coffee‐Derived Mannooligosaccharides Enhances Adipose Tissue Loss in Overweight Men but Not Women

Mannooligosaccharides (MOS), extracted from coffee, have been shown to promote a decrease in body fat when consumed as part of free-living, weight-maintaining diets. Our objective was to determine if MOS consumption (4 g/day), in conjunction with a weight-loss diet, would lead to greater reductions in adipose tissue compartments than placebo. We conducted a double-blind, placebo-controlled weight-loss study in which 60 overweight men and women consumed study beverages and received weekly group counseling for 12 weeks. Weight and blood pressure were measured weekly, and adipose tissue distribution was assessed at baseline and at end point using magnetic resonance imaging. A total of 54 subjects completed the study. Men consuming the MOS beverage had greater loss of body weight than men consuming the Placebo beverage (-6.0 ± 0.6% vs. -2.3 ± 0.5%, respectively, P < 0.05). Men consuming the MOS beverage also had reductions in total body volume (P < 0.0001), total (P < 0.0001), subcutaneous (P < 0.0001), and visceral (P < 0.05) adipose tissue that were greater than changes observed in those consuming the Placebo beverage. In women, changes in body weight and adipose tissue compartments were not different between groups. Adding coffee-derived MOS to a weight-loss diet enhanced both weight and adipose tissue losses in men, suggesting a potential functional use of MOS for weight management and improvement in adipose tissue distribution. More studies are needed to investigate the apparent gender difference in response to MOS consumption.

NUTRITION AND PATIENTS WITH HIV/AIDS

Immune status of an individual depends on the organism’s nutritional status as well as on the choice of nutrients that enter the body. Malnutrition and HIV progression are closely linked and require an active cooperation between infectious disease physicians and nutritionist. It has been noticed that patients with HIV that receive antiretroviral therapy have a significantly greater loss of body weight, and therefore need an adequate diet modification. Oxidative stress represents an important etiological factor in diseases of immune deficiency, so that antioxidant agents (Vitamin A, Vitamin E, Vitamin B12 and certain minerals, such as zinc and selenium) are crucial factors in HIV dietotherapy. Polyphenols from cocoa beans as well as from green and black tea (catechins and teaflavins) have an important role in disease progress modification as well as disease transmission prevention. The patients also need their probiotic intestinal flora to be encouraged to grow properly in order to prevent opportunistic infections. All of these nutrition elements are already in use in prevention, therapy and alleviation of HIV symptoms, and further science development will make a personal diet modification for each patient possible. Acta Medica Medianae 2011; 50(3):63-68.

The Short-Term Effect of Diacylglycerol Oil Consumption on Total and Dietary Fat Utilization in Overweight Women

Diacylglycerol (DAG) is a natural component of edible oils with metabolic characteristics distinct from those of triacylglycerol (TAG). Consumption of DAG oil (containing > 80% DAG) induces greater fat oxidation than consumption of TAG oil. We compared the effects of 4 days of DAG oil consumption with those of TAG oil consumption on total and dietary fat oxidation over 24 h in overweight women using a whole-room respiratory chamber. Overweight (BMI (kg/m²) ≥ 25) females participated in this double-blind, crossover-controlled trial. The subjects consumed test diets containing either TAG or DAG oil as 15% of their total caloric intake (mean test oil intake was 33.0 ± 3.1 g/day) during each 4-day treatment. Fat oxidation and energy expenditure were measured in a respiratory chamber on the 4th day of each treatment. Compared with TAG oil, DAG oil consumption significantly increased total fat oxidation and dietary fat oxidation in overweight subjects. Total energy expenditure (TEE) and carbohydrate (CHO) oxidation did not significantly differ between DAG oil and TAG oil consumption in overweight subjects. Compared with TAG oil, DAG oil consumption enhanced total fat oxidation and dietary fat oxidation in overweight subjects. The enhanced fat metabolism in overweight subjects that consumed DAG oil partly explains the greater loss of body weight and body fat related to DAG oil consumption in weight-loss studies.

Teores de proteína bruta no concentrado e níveis de suplementação para vacas leiteiras em pastagens de capim-braquiária cv. marandu no período da seca

Avaliou-se a resposta de 40 vacas meio-sangue Holandês/Zebu em pastagem de Brachiaria brizantha à suplementação com concentrados contendo diferentes teores de proteína bruta. Além da pastagem, foram fornecidos diariamente 5,0 kg de cana-de-açúcar por animal. Utilizou-se como testemunha o fornecimento exclusivo de 200 g de suplemento mineral contendo 10% de fósforo. Foram comparados três concentrados contendo 50,0; 28,6 e 20% de proteína bruta na matéria natural, fornecidos nas quantidades de 2,0; 3,5 e 5,0 kg/vaca/dia. O delineamento experimental utilizado foi em blocos casualizados com dez repetições. Os suplementos foram fornecidos em duas porções diárias, após as ordenhas, em baias individuais. Após a ordenha e suplementação matinal, as 40 vacas foram mantidas no pasto até a ordenha da tarde. A cada 21 dias pós-parto, até os 84 dias, foram feitas avaliações da produção de leite, do peso vivo e do escore corporal. A maior produção de leite ocorreu aos 63 dias pós-parto, quando foram fornecidos 3,5 kg de concentrado. Como resposta produtiva, foram obtidos valores de 1,04; 1,20; e 0,63 kg de leite por kg de concentrado, respectivamente, para o fornecimento de 2,0; 3,5 e 5,0 kg, em relação ao controle. Os animais do grupo controle tiveram maior perda de peso vivo e de escore corporal, enquanto entre os demais não houve diferença.

IFN-γup-regulates Th17/IL-17 response against Chlamydia trachomatis lung infection

Objective To investigate the regulation of IFN-γ to Th17 response in Chlamydia muridarum （Cm） lung infection in mice. Methods A murine model of pneumonia induced by intranasal inoculation of Cm was used for this study. Anti-mouse IFN-γ McAbs were used to neutralize endogenous IFN-γfollowing Cm lung infection. Control group received the same dose of isotype antibody （IgG2a）. Mice were sacrificed at day 7 postinfection. Chlamydial growth in the lung was assessed by immunoenzyme technique.IL-17 and IL-23 mRNA expression in the lung was assayed by RT-PCR and the proliferation of IL-17 ＋ CD4 ＋T cells in the spleen was assayed by intracellular cytokine staining. Results IFN-γ-neutralized mice exhibited serious disease course, include greater body weight loss, higher organism growth and much more severe pathological changes in the lung compared with control mice. The mRNA expression of IL-17 and IL-23 in the lung and the proliferation of IL-17 ＋ CD4 ＋ T cells in the spleen significantly decreased in the IL-17- neutralized mice. Conclusion IFN-γ was protective in Cm lung infection through up-regulating the antigen specific Th17 responses. Key words: Chlamydia muridarum IFN-γ Th17

Blood pressure responses to consumption of two different carbohydrate‐restricted diets versus a lower fat diet

During weight loss, carbohydrate‐restricted diets produce favorable metabolic effects; however, few studies have evaluated the potential role of the type of food consumed in these fat‐rich diets. Eighteen subjects (BMI=30–38) consumed three diets in a randomized, balanced cross‐over design for 4 weeks separated by 4‐week washout periods. Diets were designed to provide 1600 kcals for women (n=14) and 2200 kcals for men (n=4) to promote weight loss. Diets included approximately 61% of energy from carbohydrate (CHO), 18% protein (PRO), and 21% fat for the low fat (LF) diet and 10% CHO, 30% PRO, and 60% fat for the very low carbohydrate (VLC) diets. One of the VLC diets was primarily plant and mushroom (170 g/d) based (VLCPM) and the other provided more fat and protein from animal foods. Significant main effects for decreased (p&lt;0.05) systolic and diastolic blood pressures (BPs) for the trials were detected. Post‐hoc examination with paired t‐tests revealed that only within the VLCPM trial were the decreases in both BPs statistically significant (p&lt;0.05). The change in systolic BP during the LF diet bordered on significance (p=0.065). It is unclear whether the more robust decreases in BP after consuming the VLCPM diet is due to slightly greater loss of body weight or a diet component. Further investigation into the potential influence of plants and mushrooms on BP is warranted.Supported by the Mushroom Council.

Increased intestinal permeability results in B/T cell mediated responses that protect from development of colitis

Junctional Adhesion Molecule A (JAM‐A) is a tight junction protein known to regulate intestinal epithelial permeability and leukocyte migration. We have previously shown that JAM‐A−/− mice have increased colonic permeability and B cell lymphoid hyperplasia but do not develop spontaneous colitis. We also observed that JAM‐A−/− mice have increased levels of serum and fecal IgA. To study the role of lymphocytic responses to increased colonic permeability, we generated B/T cell deficient (JAM‐A−/− × RAG1−/−) double knockout mice. JAM‐A−/− × RAG1−/− were more susceptible to dextran sulfate sodium (DSS) induced colitis, manifested by premature mortality and greater body weight loss than JAM‐A+/+ mice. In addition, JAM‐A−/− and JAM‐A−/− × RAG1−/− mice showed increased bacterial translocation to secondary lymphoid organs and colonic submucosa. Broad‐spectrum antibiotic treatment of JAM‐A−/− × RAG1−/− mice significantly reduced disease progression. These data suggest that colonic B cell hyperplasia and increased IgA production serve as protective responses to enhanced translocation of microbial products under conditions of increased mucosal permeability. Furthermore, these findings show that dysfunctional adaptive immunity predisposes to pathologic gut inflammation particularly under conditions of increased colonic permeability. This work is supported by NIH grants DK061379, DK59888 and AA017870.

Multiple transportable carbohydrates enhance gastric emptying and fluid delivery

This study compared the effects of ingesting water (WATER), an 8.6% glucose solution (GLU) and an 8.6% glucose+fructose solution (2:1 ratio, GLU+FRU) on gastric emptying (GE), fluid delivery, and markers of hydration status during moderate intensity exercise. Eight male subjects (age=24+/-2 years, weight=74.5+/-1.2 kg, VO2max=62.6+/-2.5 mL/kg/min) performed three 120 min cycling bouts at 61% VO2max. Subjects ingested GLU, GLU+FRU (both delivering 1.5 g/min carbohydrate), or WATER throughout exercise, ingesting 2.1 L. Serial dye dilution measurements of GE were made throughout exercise and subjects ingested 5.00 g of D2O and 150 mg of 13C-acetate at 60 min to obtain measures of fluid uptake and GE, respectively. GLU+FRU resulted in faster rates of deuterium accumulation, an earlier time to peak in the 13C enrichment of expired air and a faster rate of GE compared with GLU. GLU+FRU also attenuated the rise in heart rate that occurred in GLU and WATER and resulted in lower ratings of perceived exertion. There was a greater loss in body weight with GLU corrected for fluid intake. These data suggest that ingestion of a combined GLU+FRU solution increases GE and "fluid delivery" compared with a glucose only solution.

Radiosensitizing Effect of Electrochemotherapy in a Fractionated Radiation Regimen in Radiosensitive Murine Sarcoma and Radioresistant Adenocarcinoma Tumor Model

Electrochemotherapy can potentiate the radiosensitizing effect of bleomycin, as shown in our previous studies. To bring this treatment closer to use in clinical practice, we evaluated the interaction between electrochemotherapy with bleomycin and single-dose or fractionated radiation in two murine tumor models with different histology and radiosensitivity. Radiosensitive sarcoma SA-1 and radioresistant adenocarcinoma CaNT subcutaneous tumors grown in A/J and CBA mice, respectively, were used. The anti-tumor effect and skin damage around the treated tumors were evaluated after electrochemotherapy with bleomycin alone or combined with single-dose radiation or a fractionated radiation regimen. The anti-tumor effectiveness of electrochemotherapy was more pronounced in SA-1 than CaNT tumors. In both tumor models, the tumor response to radiation was not significantly influenced by bleomycin alone or by electroporation alone. However, electrochemotherapy before the first tumor irradiation potentiated the response to a single-dose or fractionated radiation regimen in both tumors. For the fractionated radiation regimen, normal skin around the treated tumors was damaged fourfold less than for the single-dose regimen. Electrochemotherapy prior to single-dose irradiation induced more damage to the skin around the treated tumors and greater loss of body weight compared to other irradiated groups, whereas electrochemotherapy combined with the fractionated radiation regimen did not. Electrochemotherapy with low doses of bleomycin can also be used safely for radiosensitization of different types of tumors in a fractionated radiation regimen, resulting in a good anti-tumor effect and no major potentiating effect on radiation-induced skin damage.

Ablation of gly96/immediate early gene-X1 (gly96/iex-1) aggravates DSS-induced colitis in mice: Role for gly96/iex-1 in the regulation of NF-κB

Inflammatory bowel diseases (IBDs) result from environmental and genetic factors and are characterized by an imbalanced immune response in the gut and deregulated activation of the transcription factor NF-kappaB. Addressing the potential role of gly96/iex-1 in the regulation of NF-kappaB in IBD, we used the dextran sodium sulfate (DSS) colitis model in mice in which the gly96/iex-1 gene had been deleted. C57BL/6 mice of gly96/iex-1(-/-) or gly96/iex-1(+/+) genotype were treated continuously with 4% DSS (5 days) and repeatedly with 2% DSS (28 days) for inducing acute and chronic colitis, respectively. In addition to clinical and histological exploration, colon organ culture and bone marrow-derived cells (BMCs) were analyzed for chemo/cytokine expression and NF-kappaB activation. Compared to wildtype littermates, gly96/iex-1(-/-) mice exhibited an aggravated phenotype of both acute and chronic colitis, along with a greater loss of body weight and colon length. Colonic endoscopy revealed a higher degree of hyperemia, edema, and bleeding in gly96/iex-1(-/-) mice, and immunohistochemistry detected massive mucosal infiltration of leukocytes and marked histological changes. The expression of proinflammatory chemo- and cytokines was higher in the colon of DSS-treated gly96/iex-1(-/-) mice, and the NF-kappaB activation was enhanced particularly in the distal colon. In cultured BMCs from gly96/iex-1(-/-) mice, Pam(3)Cys(4) treatment induced expression of proinflammatory mediators to a higher degree than in gly96/iex-1(+/+) BMCs, along with greater NF-kappaB activation. Based on the observation that genetic ablation of gly96/iex-1 triggers intestinal inflammation in mice, we demonstrate for the first time that gly96/iex-1 exerts strong antiinflammatory activity via its NF-kappaB-counterregulatory effect.

Acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin in mice after intraperitoneal administration

Aims The objective of this work was to evaluate the acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP), after their intraperitoneal administration in male and female mice. Main methods After single administration of free CDDP (5,10,and 20 mg/kg) or SpHL-CDDP (7,12,30,45 and 80 mg/kg), the body weight was recorded and the LD 50 was calculated. Blood samples were collected for biochemical and hematological analysis. Kidneys, liver, spleen and bone marrow were removed to histopathological examination. Key findings Mice treated with high doses of free CDDP showed a greater loss of body weight and more delayed recovery time than those treated with SpHL-CDDP. The LD 50 values for SpHL-CDDP treatment for male and female mice groups were 2.7 and 3.2 fold higher, respectively, than that obtained for free CDDP. The red and white blood cells counts and quantification of hemoglobin and hematocrit presented no change upon administration of SpHL-CDDP treatment. Free CDDP treatment, however, did lead to an appearance of mild anemia and a reduction in total white blood cell counts. As regards nephrotoxicity, it was observed that free CDDP treatment caused pronounced alterations in the blood urea and creatinine levels of mice. In contrast, these parameters were slightly altered only after SpHL-CDDP treatment at a dose of 30 mg/kg. Microscopic analysis of kidneys from mice treated with SpHL-CDDP showed no morphological alteration. Concerning hepatotoxicity, no histopathological alteration was observed after both treatments. Significance These findings reveal that SpHL-CDDP can eliminate CDDP-induced toxicity and is thus a promising candidate for intraperitoneal chemotherapy.

Green Tea Catechin Consumption Enhances Exercise-Induced Abdominal Fat Loss in Overweight and Obese Adults

This study evaluated the influence of a green tea catechin beverage on body composition and fat distribution in overweight and obese adults during exercise-induced weight loss. Participants (n = 132 with 107 completers) were randomly assigned to receive a beverage containing approximately 625 mg of catechins with 39 mg caffeine or a control beverage (39 mg caffeine, no catechins) for 12 wk. Participants were asked to maintain constant energy intake and engage in >or=180 min/wk moderate intensity exercise, including >or=3 supervised sessions per week. Body composition (dual X-ray absorptiometry), abdominal fat areas (computed tomography), and clinical laboratory tests were measured at baseline and wk 12. There was a trend (P = 0.079) toward greater loss of body weight in the catechin group compared with the control group; least squares mean (95% CI) changes, adjusted for baseline value, age, and sex, were -2.2 (-3.1, -1.3) and -1.0 (-1.9, -0.1) kg, respectively. Percentage changes in fat mass did not differ between the catechin [5.2 (-7.0, -3.4)] and control groups [-3.5 (-5.4, 1.6)] (P = 0.208). However, percentage changes in total abdominal fat area [-7.7 (-11.7, -3.8) vs. -0.3 (-4.4, 3.9); P = 0.013], subcutaneous abdominal fat area [-6.2 (-10.2, -2.2) vs. 0.8 (-3.3, 4.9); P = 0.019], and fasting serum triglycerides (TG) [-11.2 (-18.8, -3.6) vs. 1.9 (-5.9, 9.7); P = 0.023] were greater in the catechin group. These findings suggest that green tea catechin consumption enhances exercise-induced changes in abdominal fat and serum TG.

The role of granulocyte macrophage-colony-stimulating factor in acute intestinal inflammation

An imbalance of mucosal pro- and anti-inflammatory cytokines is crucial in the pathogenesis of inflammatory bowel disease (IBD). GM-CSF influences the development of hemopoietic cells. The precise role of GM-CSF in IBD remains to be elucidated. GM-CSF gene knockout (GM-CSF(-/-)) and wild-type (Wt) mice were challenged with 2.5% dextran sulfate sodium (DSS) for 7 days. The ensued clinical and pathological changes, macrophage infiltration, colonic cytokine production, and bacterial counts were examined. DSS-treated GM-CSF(-/-) mice developed more severe acute colitis than DSS-treated Wt mice, reflected by a greater body weight loss, more rectal bleeding, and aggravated histopathological changes. More infiltrating macrophages were observed in GM-CSF(-/-), compared with Wt mice following DSS challenge, correlating with monocyte chemoattractant protein-1 (MCP-1) production. The levels of colonic IL-17 and TNF-alpha were increased significantly in GM-CSF(-/-) mice, but not in Wt mice, following DSS administration. The level of IL-6 was increased by 1.5- and 2-fold in the colon of GM-CSF(-/-) and Wt mice, respectively, following DSS challenge. No significant changes in IL-4 and IFN-gamma were detected in Wt and GM-CSF(-/-) mice following DSS treatment. The bacteria recovery from colon was increased about 15- and 5-fold, respectively, in Wt mice and GM-CSF(-/-) mice following DSS challenge. These results suggest that GM-CSF(-/-) mice are more susceptible to acute DSS-induced colitis, possibly because of an impaired gut innate immune response as a result of diminished GM-CSF.

Greater fat oxidation with diacylglycerol oil consumption for 14 days compared with triacylglycerol oil consumption in overweight men and women

Several studies have reported increased fat oxidation with diacylglycerol (DAG) oil consumption. However, the effects of long-term DAG oil consumption on energy metabolism remain to be investigated. The objective of this study was to compare the effects of 14 days of either DAG or triacylglycerol (TAG) oil consumption on substrate oxidation, energy expenditure (EE) and dietary fat oxidation. Eight males and six females participated in this randomized, double-blind, crossover feeding study. Each patient consumed the 14-day controlled test diet containing either 10 g day(-1) of DAG or TAG oil for acclimatization before a respiratory chamber measurement, followed by a 2-week washout period between diet treatments. Substrate oxidation and EE were measured in the respiratory chamber at the end of each dietary treatment. The patients consumed test oil as 15% of total caloric intake in the respiratory chamber (mean test oil intake was 36.1+/-6.6 g day(-1)). Twenty-four hour fat oxidation was significantly greater with 14 days of DAG oil consumption compared with TAG oil consumption (78.6+/-19.6 and 72.6+/-14.9 g day(-1), respectively, P<0.05). There were no differences in body weight or body composition between diet treatments. Dietary fat oxidation was determined using the recovery rate of (13)CO(2) in breath, and was significantly enhanced with DAG oil consumption compared with TAG oil consumption, measured over 22 h after ingestion of (13)C-labelled triolein. Resting metabolic rate (RMR) was significantly greater with DAG oil consumption compared with TAG oil consumption (1766+/-337 and 1680+/-316 kcal day(-1), respectively, P<0.05). Consumption of DAG oil for 14 days stimulates both fat oxidation and RMR compared with TAG oil consumption, which may explain the greater loss of body weight and body fat with DAG oil consumption that has been observed in weight-loss studies.