Lymphatic vessels in human adipose tissue

Despite being considered present in most vascularised tissues, lymphatic vessels have not been properly shown in human adipose tissue (AT). Our goal in this study is to investigate an unanswered question in AT biology, regarding lymphatic network presence in tissue parenchyma. Using human subcutaneous (S-) and visceral (V-) AT samples with whole mount staining for lymphatic specific markers and three-dimensional imaging, we showed lymphatic capillaries and larger lymphatic vessels in the human VAT. Conversely, in the human SAT, microcirculatory lymphatic vascular structures were rarely detected and no initial lymphatics were found

The Effects of Dasatinib in Experimental Acute Respiratory Distress Syndrome Depend on Dose and Etiology

Background/Aims: Evidence suggests that tyrosine-kinase inhibitors may attenuate lung inflammation and fibrosis in experimental acute respiratory distress syndrome (ARDS). We hypothesized that dasatinib, a tyrosine-kinase inhibitor, might act differently depending on the ARDS etiology and the dose. Methods: C57/BL6 mice were divided to be pre-treated with dasatinib (1mg/kg or 10mg/kg) or vehicle (1% dimethyl-sulfoxide) by oral gavage. Thirty-minutes after pre-treatment, mice were subdivided into control (C) or ARDS groups. ARDS animals received Escherichia coli lipopolysaccharide intratracheally (ARDSp) or intraperitoneally (ARDSexp). A new dose of dasatinib or vehicle was administered at 6 and 24h. Results: Forty-eight hours after ARDS induction, dasatinib 1mg/kg yielded: improved lung morphofunction and reduced cells expressing toll-like receptor (TLR)-4 in lung, independent of ARDS etiology; reduced neutrophil and levels of interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-β in ARDSp. The higher dose of dasatinib caused no changes in lung mechanics, diffuse alveolar damage, neutrophil, or cells expressing TLR4, but increased IL-6, vascular endothelial growth factor (VEGF), and cells expressing Fas receptor in lung in ARDSp. In ARDSexp, it improved lung morphofunction, increased VEGF, and reduced cells expressing TLR4. Conclusion: Dasatinib may have therapeutic potential in ARDS independent of etiology, but careful dose monitoring is required. © 2015 S. Karger AG, Basel

Oleanolic Acid Initiates Apoptosis in Non-Small Cell Lung Cancer Cell Lines and Reduces Metastasis of a B16F10 Melanoma Model In Vivo

Drug resistance, a process mediated by multiple mechanisms, is a critical determinant for treating lung cancer. The aim of this study is to determine if oleanolic acid (OA), a pentacyclic triterpene present in several plants, is able to circumvent the mechanisms of drug resistance present in non-small cell lung cancer (NSCLC) cell lines and to induce their death.OA decreased the cell viability of the NSCLC cell lines A459 and H460 despite the presence of active, multidrug-resistant (MDR) MRP1/ABCC1 proteins and the anti-apoptotic proteins Bcl-2 and survivin. These effects are due to apoptosis, as evidenced by the capacity of OA to induce fragmentation of DNA and activate caspase 3. Induction of NSCLC cell death by OA cannot be explained by inhibition of the MDR proteins, since treatment with triterpene had little or no effect on the activity or expression of MRP1. Moreover, treatment with OA had no effect on the expression of the anti-apoptotic protein Bcl-2, but increased the expression of the pro-apoptotic protein Bax, altering the Bcl-2/Bax balance towards a pro-apoptotic profile. OA also decreased the expression of the anti-apoptotic protein survivin. Furthermore, OA decreased the expression of the angiogenic vascular endothelial growth factor (VEGF) and decreased the development of melanoma-induced lung metastasis.Our data provide a significant insight into the antitumoral and antimetastatic activity of OA in NSCLC and suggest that including OA in the NSCLC regimens may help to decrease the number of relapses and reduce the development of metastases

Low somatostatin receptor subtype 2, but not dopamine receptor subtype 2, expression predicts the lack of biochemical response of somatotropinomas to treatment with somatostatin analogs.

Objectives: to evaluate somatostatin receptor 2A (SSTR2A) and dopamine receptor 2 (DR2) protein expression in somatotropinomas and to relate it to response to somatostatin analogues (SA). Design and patients: SSTR2A and DR2 expression was analyzed by immunohistochemistry in 88 somatotropinomas from patients submitted to either presurgical or adjuvant SA treatment. Tumors were scored according to percent of immunostained cells: 0 (50%). Relation between protein expression and response to SA was performed in 66 patients. Response to SA was assessed by percent IGF-I reduction, being considered as an IGF-I percent reduction higher than 50%. It was also assessed disease control (GH<1.0 ng/mL and normal IGF-I). Results: SSTR2A and DR2 were expressed in 100% and 98% of tumors, respectively. Biochemical response and disease control rates were 48% and 32%, respectively. Median IGF-I percent reduction after 3 months of SA treatment was lower in the SSTR2A score 0 than in the scores 1 and 2 (p<0.001, both), and after 6 months in the score 0 than in the score 1 (p=0.001) and 2 (p<0.001). Biochemical response and disease control were associated with SSTR2 expression (p<0.001 and p=0.004, respectively). A negative predictive value for biochemical response of 100% was found when a SSTR2A expression <25% of immunostained cells cut-off point was considered. No relation was found between DR2 expression and biochemical response and disease control. Conclusion: SSTR2A and DR2 are highly expressed in somatotropinomas. Low SSTR2A, but not DR2, expression is a negative predictive factor to response to SA

Citrus pulp-based supplement reduces the detrimental effects of high grazing pressure on the performance of beef cattle under a rotational system of Urochloa brizantha

The objectives were to evaluate the performance of bull calves under two grazing strategies and the use of energy supplementation in a rotational system of marandu palisade grass (Urochloa brizantha) and to assess the morphological and chemical composition of the grass. Eighty eightmonth-old bulls of 224 ± 2.4 kg body weight (BW) were used in a completely randomized block design in a 2x2 factorial arrangement of two post-grazing heights (i.e.10 cm or 15 cm)and of a citrus pulp-based supplement (i.e.72% total digestible nutrients) fed daily at 0 or 6 g/kg BW. Initial grazing height was set at 25 cm with variable grazing intervals and stocking rate adjustments used to control the grazing heights. Statistical analyses were performed using the SAS Mixed procedure. Significance was set at 0.05. Forage data from 12 pre-determined paddocks showed no differences in forage mass (FM)and morphological composition at pre-grazing, but greater post-grazing FM and shorter grazing interval in pastures managed at 15 cm. Higher grazing pressure resulted in lowest BW gains for non-supplemented bulls in the 10 cm treatment. The use of an energy supplement and 15 cm postgrazing height resulted in the greatest BW gains; however, combination of10 cm post-grazing height and energy supplementation allowed greater stocking rates. Under high grazing pressure, supplementary feed overcame the normal limitations, and high gains were achieved. © 2019 Universidade Federal da Bahia

Intravenous Glutamine Administration Reduces Lung and Distal Organ Injury in Malnourished Rats With Sepsis.

Malnutrition is a risk factor for infection, compromising immune response. Glutamine (Gln) protects the lungs and distal organs in well-nourished septic and non-septic conditions; however, no study to date has analyzed the effects of glutamine in the presence of sepsis and malnutrition. In the present work, we tested the hypothesis that early therapy with intravenous Gln prevents lung and distal organ damage in septic malnourished rats. Protein-energy malnutrition was induced in male Wistar rats for 4 weeks. At the end of 4 weeks, malnourished animals were assigned to a sepsis-inducing cecal ligation and puncture (CLP) group or a Sham surgery group. One hour after surgery, animals were given saline (Sal) or L-alanyl-L-glutamine (Gln) intravenously. In addition, a control group (C) was set up with rats fed ad libitum, not submitted to surgery or treatment. Forty-eight hours after surgery, in Malnutrition-Sham rats, Gln therapy lessened neutrophil lung infiltration and apoptosis in lung and liver. In Malnutrition-CLP rats, Gln therapy yielded: 1) reduced static lung elastance, alveolar collapse, inflammation (neutrophil infiltration, interleukin-6), and collagen deposition; 2) repair of types I and II epithelial cells; 3) no significant changes in heat shock protein (HSP) 70 expression or heat shock factor (HSF)-1 phosphorylation; 4) a greater number of M1 and M2 macrophages in lung tissue; and 5) less apoptosis in the lung, kidney, small intestine, and liver. In conclusion, early therapy with intravenous Gln reduced inflammation, fibrosis, and apoptosis, minimizing lung and distal organ injury, in septic malnourished rats. These beneficial effects may be associated with macrophage activation in the lung

The Effects of Dasatinib in Experimental Acute Respiratory Distress Syndrome Depend on Dose and Etiology.

BACKGROUND/AIMS: Evidence suggests that tyrosine-kinase inhibitors may attenuate lung inflammation and fibrosis in experimental acute respiratory distress syndrome (ARDS). We hypothesized that dasatinib, a tyrosine-kinase inhibitor, might act differently depending on the ARDS etiology and the dose. METHODS: C57/BL6 mice were divided to be pre-treated with dasatinib (1mg/kg or 10mg/kg) or vehicle (1% dimethyl-sulfoxide) by oral gavage. Thirty-minutes after pre-treatment, mice were subdivided into control (C) or ARDS groups. ARDS animals received Escherichia coli lipopolysaccharide intratracheally (ARDSp) or intraperitoneally (ARDSexp). A new dose of dasatinib or vehicle was administered at 6 and 24h. RESULTS: Forty-eight hours after ARDS induction, dasatinib 1mg/kg yielded: improved lung morphofunction and reduced cells expressing toll-like receptor (TLR)-4 in lung, independent of ARDS etiology; reduced neutrophil and levels of interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-\u3b2 in ARDSp. The higher dose of dasatinib caused no changes in lung mechanics, diffuse alveolar damage, neutrophil, or cells expressing TLR4, but increased IL-6, vascular endothelial growth factor (VEGF), and cells expressing Fas receptor in lung in ARDSp. In ARDSexp, it improved lung morphofunction, increased VEGF, and reduced cells expressing TLR4. CONCLUSION: Dasatinib may have therapeutic potential in ARDS independent of etiology, but careful dose monitoring is required. \ua9 2015 S. Karger AG, Basel