Vascular endothelial growth factor A (VEGFA) modulates bovine placenta steroidogenesis in vitro

Our objectives were to investigate the possible role of VEGFA in bovine placenta steroid synthesis and to determine whether cloned derived placental cells present similar responses as non-cloned ones. Placental cells from cloned (term) and non-cloned (days 90, 150, 210 and term) pregnancies were isolated and treated with VEGFA (50 ng/ml) for 24, 48 or 96 h. Progesterone (P-4) and estrone sulfate (E1S) were assessed by RIA, while aromatase P450-positive cells were quantified using the point counting test. The percentages of steroidogenic and non-steroidogenic populations were determined by flow cytometry. VEGFA augmented or decreased P-4 and E1S concentrations as well as aromatase P450-positive cell density, depending on gestational age and time in culture. The percentage of steroidogenic cells was lower than that of non-steroidogenic ones for each culture time (P < 0.05). VEGFA treatment did not change the proportion of steroidogenic and non-steroidogenic cells. Placental cells derived from cloned pregnancies presented higher concentrations of E1S and P4 than the non-cloned group. However, aromatase P450-positive cells were similar between groups (P > 0.05). VEGFA treatment altered P-4 and E1S levels in placental cells depending on type of gestation. These results suggest that VEGFA acts locally in the bovine placenta to modulate steroidogenesis during gestation, but in a different pattern between cloned and non-cloned derived placental cells at term. Therefore, this factor can be considered an important regulator of placental development and function. (C) 2012 Elsevier Ltd. All rights reserved.

The relationship between lymphatic vascular density and vascular endothelial growth factor A (VEGF-A) expression with clinical-pathological features and survival in pancreatic adenocarcinomas

Abstract: Background Pancreatic cancer is a rare tumor with an extremely low survival rate. Its known risk factors include the chronic use of tobacco and excessive alcohol consumption and the presence of chronic inflammatory diseases, such as pancreatitis and type 2 diabetes. Angiogenesis and lymphangiogenesis, which have been the focus of recent research, are considered prognostic factors for cancer development. Knowing the angiogenic and lymphangiogenic profiles of a tumor may provide new insights for designing treatments according to the different properties of the tumor. The aim of this study was to evaluate the density of blood and lymphatic vessels, and the expression of VEGF-A, in pancreatic adenocarcinomas, as well as the relationship between blood and lymphatic vascular density and the prognostically important clinical-pathological features of pancreatic tumors. Methods Paraffin blocks containing tumor samples from 100 patients who were diagnosed with pancreatic cancer between 1990 and 2010 were used to construct a tissue microarray. VEGF expression was assessed in these samples by immunohistochemistry. To assess the lymphatic and vascular properties of the tumors, 63 cases that contained sufficient material were sectioned routinely. The sections were then stained with the D2-40 antibody to identify the lymphatic vessels and with a CD34 antibody to identify the blood vessels. The vessels were counted individually with the Leica Application Suite v4 program. All statistical analyses were performed using SPSS 18.0 (Chicago, IL, USA) software, and p values ≤ 0.05 were considered significant. Results In the Cox regression analysis, advanced age (p=0.03) and a history of type 2 diabetes (p=0.014) or chronic pancreatitis (p=0.02) were shown to be prognostic factors for pancreatic cancer. Blood vessel density (BVD) had no relationship with clinical-pathological features or death. Lymphatic vessel density (LVD) was inversely correlated with death (p=0.002), and by Kaplan-Meyer survival analysis, we found a significant association between low LVD (p=0.021), VEGF expression (p=0.023) and low patient survival. Conclusions Pancreatic carcinogenesis is related to a history of chronic inflammatory processes, such as type 2 diabetes and chronic pancreatitis. In pancreatic cancer development, lymphangiogenesis can be considered an early event that enables the dissemination of metastases. VEGF expression and low LVD can be considered as poor prognostic factors as tumors with this profile are fast growing and highly aggressive. Virtual slides. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5113892881028514

Suppression of Hypoxia-Inducible Factor-1 alpha Contributes to the Antiangiogenic Activity of Red Propolis Polyphenols in Human Endothelial Cells

Polyphenol-enriched fractions from natural sources have been proposed to interfere with angiogenesis in pathological conditions. We recently reported that red propolis polyphenols (RPP) exert antiangiogenic activity. However, molecular mechanisms of this activity remain unclear. Here, we aimed at characterizing molecular mechanisms to explain the impact of RPP on endothelial cells' (EC) physiology. We used in vitro and ex and in vivo models to test the hypothesis that RPP inhibit angiogenesis by affecting hypoxia-inducible factor-1 alpha (HIF1 alpha) stabilization in EC. RPP (10 mg/L) affected angiogenesis by reducing migration and sprouting of EC, attenuated the formation of new blood vessels, and decreased the differentiation of embryonic stem cells into CD31-positive cells. Moreover, RPP (10 mg/L) inhibited hypoxia- or dimethyloxallylglycine-induced mRNA and protein expression of the crucial angiogenesis promoter vascular endothelial growth factor (VEGF) in a time-dependent mariner. Under hypoxic conditions, RPP at 10 mg/L, supplied for 1-4 h, decreased HIF1 alpha protein accumulation, which in turn attenuated VEGF gene expression. In addition, RPP reduced the HIF1 alpha protein half-life from similar to 58 min to 38 min under hypoxic conditions. The reduced HIF1 alpha protein half-life was associated with an increase in the von Hippel-Lindau (pVHL)-dependent proteasomal degradation of HIF1 alpha. RPP (10 mg/L, 4 h) downregulated Cdc42 protein expression. This caused a corresponding increase in pVHL protein levels and a subsequent degradation of HIF1 alpha. In summary, we have elucidated the underlying mechanism for the antiangiogenic action of RPP, which attenuates HIF1 alpha protein accumulation and signaling. J. Nutr. 142: 441-447, 2012.

Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy

Abstract Background Phagocytosis of apoptotic cells by macrophages induces a suppressor phenotype. Previous data from our group suggested that this occurs via Platelet-activating factor receptor (PAF-R)-mediated pathways. In the present study, we investigated the impact of apoptotic cell inoculation or induction by a chemotherapeutic agent (dacarbazine, DTIC) on tumour growth, microenvironmental parameters and survival, and the effect of treatment with a PAF-R antagonist (WEB2170). These studies were performed in murine tumours: Ehrlich Ascitis Tumour (EAT) and B16F10 melanoma. Methods Tumour growth was assessed by direct counting of EAT cells in the ascitis or by measuring the volume of the solid tumour. Parameters of the tumour microenvironment, such as the frequency of cells expressing cyclo-oxygenase-2 (COX-2), caspase-3 and galectin-3, and microvascular density, were determined by immunohistochemistry. Levels of vascular endothelium growth factor (VEGF) and prostaglandin E2 (PGE2) were determined by ELISA, and levels of nitric oxide (NO) by Griess reaction. PAF-R expression was analysed by immunohistochemistry and flow cytometry. Results Inoculation of apoptotic cells before EAT implantation stimulated tumour growth. This effect was reversed by in vivo pre-treatment with WEB2170. This treatment also reduced tumour growth and modified the microenvironment by reducing PGE2, VEGF and NO production. In B16F10 melanoma, WEB2170 alone or in association with DTIC significantly reduced tumour volume. Survival of the tumour-bearing mice was not affected by WEB2170 treatment but was significantly improved by the combination of DTIC with WEB2170. Tumour microenvironment elements were among the targets of the combination therapy since the relative frequency of COX-2 and galectin-3 positive cells and the microvascular density within the tumour mass were significantly reduced by treatment with WEB2170 or DTIC alone or in combination. Antibodies to PAF-R stained the cells from inside the tumour, but not the tumour cells grown in vitro. At the tissue level, a few cells (probably macrophages) stained positively with antibodies to PAF-R. Conclusions We suggest that PAF-R-dependent pathways are activated during experimental tumour growth, modifying the microenvironment and the phenotype of the tumour macrophages in such a way as to favour tumour growth. Combination therapy with a PAF-R antagonist and a chemotherapeutic drug may represent a new and promising strategy for the treatment of some tumours.

Monoclonal antibodies anti-TGF beta 1 and anti-VEGF inhibit the experimental pleurodesis induced by silver nitrate

Background. The mechanisms underlying pleural inflammation and pleurodesis are poorly understood. We hypothesized that the cytokines transforming growth factor beta (TGF beta 1) and vascular endothelial growth factor (VEGF) play a major role in pleurodesis after intrapleural silver nitrate (SN) injection. Method. Forty rabbits received intrapleurally 0.5% SN alone or 0.5% SN + anti-TGF beta 1, anti-IL-8, or anti-VEGF. After 28 days, the animals were euthanized and macroscopic pleural adhesions, microscopic pleural fibrosis, and collagen deposition were analyzed for characterization of the degree of pleurodesis (scores 0-4). Results. Scores of pleural adhesions, pleural fibrosis, total collagen, and thin collagen fibers deposition after 28 days were significantly lower for 0.5% SN + anti-TGF beta 1 and 0.5% SN + anti-VEGF. Significant correlations were found between macroscopic adhesion and microscopic pleural fibrosis with total collagen and thin collagen fibers. Conclusions. We conclude that both TGF beta 1 and VEGF, but not IL-8, mediate the pleural inflammatory response and pleurodesis induced by SN.

Proinflammatory and Antiinflammatory Cytokine Levels in Complicated and Noncomplicated Parapneumonic Pleural Effusions

Objectives: This study aimed to evaluate a panel of proinflammatory and antiinflammatory cytokines in noncomplicated and complicated parapneumonic pleural effusions and to correlate their levels with pleural fluid biochemical parameters. Methods: Serum and pleural effusion were collected from 60 patients with noncomplicated (n = 26) or complicated (n = 34) parapneumonic effusions and assayed for cytologic, biochemical, and proinflammatory and antiinflammatory cytokines. Student t test was used to compare serum and pleural fluid values, Spearman correlation to analyze the relationship between pleural fluid cytokines and biochemical parameters, and accuracy of pleural fluid cytokine levels to determine the optimal cutoff value for identification of complicated effusions. Corrections for multiple comparisons were applied and a P value < .05 was accepted as significant. Results: Serum and pleural fluid cytokine levels of IL-8, vascular endothelial growth factor (VEGF), IL-10, and tumor necrosis factor (TNF) soluble receptor (sR) II were similar between groups. In contrast, complicated effusions had higher levels of pleural fluid IL-1 beta, IL-1 receptor antagonist (ra), and TNF sRI. Negative correlations were found between pleural fluid glucose with IL-1 beta and TNF sRI and positive correlations between lactic dehydrogenate (LDH) with IL-1 beta, IL-8, and VEGF. Pleural fluid levels of IL-1 beta, IL-1ra, and TNF sRI were more accurate than IL-8, VEGF, IL-10, and TNF sRII in discriminating complicated effusions. Conclusions: Both proinflammatory and antiinflammatory cytokine levels in pleural fluid are elevated in complicated in comparison with noncomplicated parapneumonic pleural effusions, and they correlate with both pleural fluid glucose and LDH levels. IL-1 beta, IL-1ra, and TNF sRI had higher sensitivity and specificity than IL-8, VEGF, IL-10, and TNF sRII in discriminating complicated effusions. CHEST 2012; 141( 1):183-189

Transforming growth factor alpha immunoreactivity. A study in hepatocellular carcinoma and in non-neoplastic liver tissue

Background. Transforming growth factor alpha (TGF alpha) is an important mitogen that binds to epidermal growth factor receptor and is associated with the development of several tumors. Aims. Assessment of the immunoexpression of TGF alpha in hepatocellular carcinoma (HCC) and in non-neoplastic liver tissue and its relationship to morphological patterns of HCC. Material and methods. The immunohistochemical expression of TGF alpha was studied in 47 cases of HCC (27 multinodular, 20 nodular lesions). Five lesions measured up to 5 cm and 15 lesions above 5 cm. Thirty-two cases were graded as I or II and 15 as III or IV. The non-neoplastic tissue was examined in 40 cases, of which 22 had cirrhosis. HBsAg and anti-HCV were positive in 5/38 and 15/37 patients, respectively. The statistical analysis for possible association of immunostaining of TGF alpha and pathological features was performed through chi-square test. Results. TGF alpha was detected in 31.9% of the HCC and in 42.5% of the non-neoplastic. There was a statistically significant association between the expression of TGF alpha and cirrhosis (OR = 8.75, 95% CI = [1.93, 39.75]). The TGF alpha was detected more frequently in patients anti-HCV(+) than in those HBsAg(+). The immunoexpression of TGF alpha was not found related to tumor size or differentiation. In conclusion the TGF alpha is present in hepatocarcinogenesis in HBV negative patients. Further analysis is needed to examine the involvement of TGF alpha in the carcinogenesis associated with HCV and other possible agents. In addition, TGF alpha has an higher expression in hepatocyte regeneration and proliferation in cirrhotic livers than in HCC.

Exercise training restores the endothelial progenitor cells number and function in hypertension: implications for angiogenesis

Objectives: Aerobic exercise training has been established as an important nonpharmacological treatment for hypertension. We investigated whether the number and function of endothelial progenitor cells (EPCs) are restored after exercise training, potentially contributing to neovascularization in hypertension. Methods: Twelve-week-old male spontaneously hypertensive rats (SHRs, n = 14) and Wistar Kyoto (WKY, n = 14) rats were assigned to four groups: SHR; trained SHR (SHR-T); WKY; and trained WKY. Exercise training consisted of 10 weeks of swimming. EPC number and function, as well as the vascular endothelial growth factor (VEGF), nitrotyrosine and nitrite concentration in peripheral blood were quantified by fluorescence-activated cell sorter analysis (CD34+/Flk1+ cells), colony-forming unit assay, ELISA and nitric oxide (NO) analyzer, respectively. Soleus capillary/fiber ratio and protein expression of VEGF and endothelial NO synthase (eNOS) by western blot were assessed. Results: Exercise training was effective in reducing blood pressure in SHR-T accompanied by resting bradycardia, an increase in exercise tolerance, peak oxygen uptake (VO2) and citrate synthase activity. In response to hypertension, the amount of peripheral blood-EPC and number of colonies were decreased in comparison with control levels. In contrast, exercise training normalized the EPC levels and function in SHR-T accompanied by an increase in VEGF and NO levels. In addition, oxidative stress levels were normalized in SHR-T. Similar results were found in the number and function of bone marrow EPC. Exercise training repaired the peripheral capillary rarefaction in hypertension by a signaling pathway VEGF/eNOS-dependent in SHR-T. Moreover, improvement in EPC was significantly related to angiogenesis. Conclusion: Our data show that exercise training repairs the impairment of EPC in hypertension, which could be associated with peripheral revascularization, suggesting a mechanism for its potential therapeutic: application in vascular diseases.

Cediranib Plus FOLFOX/CAPOX Versus Placebo Plus FOLFOX/CAPOX in Patients With Previously Untreated Metastatic Colorectal Cancer: A Randomized, Double-Blind, Phase III Study (HORIZON II)

Purpose Cediranib is a highly potent inhibitor of vascular endothelial growth factor (VEGF) signaling with activity against all three VEGF receptors. HORIZON II [Cediranib (AZD2171, RECENTIN) in Addition to Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Untreated Metastatic Colorectal Cancer] assessed infusional fluorouracil, leucovorin, and oxaliplatin/capecitabine and oxaliplatin (FOLFOX/CAPOX) with or without cediranib in patients with previously untreated metastatic colorectal cancer (mCRC). Patients and Methods Eligible patients were initially randomly assigned 1:1:1 to receive cediranib (20 or 30 mg per day) or placebo plus FOLFOX/CAPOX. In an early analysis of this and two other cediranib studies (HORIZON I [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Previously Treated Metastatic Colorectal Cancer] and HORIZON III [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Untreated Metastatic Colorectal Cancer]), the 20-mg dose met the predefined criteria for continuation. Subsequent patients were randomly assigned 2: 1 to the cediranib 20 mg or placebo arms. Progression-free survival (PFS) and overall survival (OS) were coprimary end points. Results In all, 860 patients received cediranib 20 mg (n = 502) or placebo (n = 358). The addition of cediranib to FOLFOX/CAPOX resulted in PFS prolongation (hazard ratio [HR], 0.84; 95% CI, 0.73 to 0.98; P = .0121; median PFS, 8.6 months for cediranib v 8.3 months for placebo) but had no impact on OS (HR, 0.94; 95% CI, 0.79 to 1.12; P = .5707; median OS, 19.7 months for cediranib v 18.9 months for placebo). There were no significant differences in the secondary end points of objective response rate, duration of response, or liver resection rate. Median chemotherapy dose-intensity was decreased by approximately 10% in patients treated with cediranib. Adverse events (AEs) associated with cediranib were manageable. Conclusion Addition of cediranib 20 mg to FOLFOX/CAPOX resulted in a modest PFS prolongation, but no significant difference in OS. The cediranib AE profile was consistent with those from previous studies. Because of the lack of improvement in OS, cediranib plus an oxaliplatin-based regimen cannot be recommended as a treatment for patients with mCRC. J Clin Oncol 30:3596-3603. (C) 2012 by American Society of Clinical Oncology

Prenatal retinoic acid improves lung vascularization and VEGF expression in CDH rat

OBJECTIVE: We sought to investigate the effects of antenatal retinoic acid on the pulmonary vasculature and vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) expression in a nitrofen-induced congenital diaphragmatic hernia (CDH) model. STUDY DESIGN: Rat fetuses were exposed to nitrofen at gestational day 9.5 and/or all-trans retinoic acid (ATRA) at gestational days 18.5-20.5. We assessed lung growth, airway, and vascular morphometry. VEGF, VEGFR1, and VEGFR2 expression was analyzed by Western blotting and immunohistochemistry. Continuous data were analyzed by analysis of variance and Kruskal-Wallis test. RESULTS: CDH decreased lung to body weight ratio, increased mean linear intercept and mean transection length/airspace, and decreased mean airspace cord length. ATRA did not affect lung growth or morphometry. CDH increased proportional medial wall thickness of arterioles while ATRA reduced it. ATRA recovered expression of VEGF and receptors, which were reduced in CDH. CONCLUSION: Retinoic acid and VEGF may provide pathways for preventing pulmonary hypertension in CDH.

VEGF-C expression in oral cancer by neurotransmitter-induced activation of beta-adrenergic receptors

The aim of this study was to investigate the expression of vascular endothelial growth factor type C (VEGF-C) in oral squamous cell carcinoma (OSCC) cell lines through norepinephrine-induced activation of beta-adrenergic receptors. Human OSCC cell lines (SCC-9 and SCC-25) expressing beta-adrenergic receptors were stimulated with different concentrations of norepinephrine (0.1, 1, and 10 μM) and 1 μMof propranolol, and analyzed after 1, 6, and 24 h. VEGF-C gene expression and VEGF-C production in the cell supernatant were evaluated by real-time PCR and by ELISA, respectively. The results showed that beta-adrenergic receptor stimulation by different concentrations of norepinephrine or blocking by propranolol did not markedly alter VEGF-C expression by SCC-9 and SCC-25 cells. VEGF-C protein levels produced by oral malignant cell lines after stimulation with different norepinephrine concentrations or blocking with propranolol was statistically similar (p>0.05) to those of the control group (nonstimulated OSCC cell lines). Our findings suggest that stimulation of beta-adrenergic receptors by means of norepinephrine does not seem to modulate the VEGF-C expression in OSCC cell lines. These findings reinforce the need for further studies in order to understand the responsiveness of oral cancer to beta-adrenergic receptor stimulation or blockage, especially with regard to VEGF-C production.

Periodontal treatment downregulates protease-activated receptor 2 in human gingival crevicular fluid cells

Protease-activated receptor 2 (PAR2) is implicated in the pathogenesis of chronic inflammatory diseases, including periodontitis; it can be activated by gingipain and produced by Porphyromonas gingivalis and by neutrophil protease 3 (P3). PAR2 activation plays a relevant role in inflammatory processes by inducing the release of important inflammatory mediators associated with periodontal breakdown. The effects of periodontal treatment on PAR2 expression and its association with levels of proinflammatory mediators and activating proteases were investigated in chronic periodontitis patients. Positive staining for PAR2 was observed in gingival crevicular fluid cells and was reflective of tissue destruction. Overexpression of PAR2 was positively associated with inflammatory clinical parameters and with the levels of interleukin-6 (IL-6), IL-8, tumor necrosis factor alpha, matrix metalloprotease 2 (MMP-2), MMP-8, hepatocyte growth factor, and vascular endothelial growth factor. Elevated levels of gingipain and P3 and decreased levels of dentilisin and the protease inhibitors secretory leukocyte protease inhibitor and elafin were also associated with PAR2 overexpression. Healthy periodontal sites from individuals with chronic periodontitis showed diminished expression of PAR2 mRNA and the PAR2 protein (P < 0.05). Furthermore, periodontal treatment resulted in decreased PAR2 expression and correlated with decreased expression of inflammatory mediators and activating proteases. We concluded that periodontal treatment resulted in decreased levels of proteases and that proinflammatory mediators are associated with decreased PAR2 expression, suggesting that PAR2 expression is influenced by the presence of periodontal infection and is not a constitutive characteristic favoring periodontal inflammation.

Manipulation of the periovulatory sex steroidal milieu affects endometrial but not luteal gene expression in early diestrus Nelore cows

In beef cattle, the ability to conceive has been associated positively with size of the preovulatory follicle (POF). Proestrus estradiol and subsequent progesterone concentrations can regulate the endometrium to affect receptivity and fertility. The aim of the present study was to verify the effect of the size of the POF on luteal and endometrial gene expression during subsequent early diestrus in beef cattle. Eighty-three multiparous, nonlactating, presynchronized Nelore cows received a progesterone-releasing device and estradiol benzoate on Day–10 (D 10). Animals received cloprostenol (large follicle-large CL group; LF-LCL; N ¼ 42) or not (small follicle-small CL group; SF-SCL; N ¼ 41) on D 10. Progesterone devices were withdrawn and cloprostenol administered 42 to 60 hours (LF-LCL) or 30 to 36 hours (SF-SCL) before GnRH treatment (D0). Tissues were collected at slaughter on D7. The LF-LCL group had larger (P < 0.0001) POF (13.24 0.33 mm vs. 10.76 0.29 mm), greater (P < 0.0007) estradiol concentrations on D0 (2.94 0.28 pg/mL vs. 1.27 0.20 pg/mL), and greater (P < 0.01) progesterone concentrations on D7 (3.71 0.25 ng/mL vs. 2.62 0.26 ng/mL) compared with the SF-SCL group. Luteal gene expression of vascular endothelial growth factor A, kinase insert domain receptor, fms-related tyrosine kinase 1, steroidogenic acute regulatory protein, cytochrome P450, family 11, subfamily A, polypeptide 1, and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid deltaisomerase 7 was similar between groups. Endometrial gene expression of oxytocin receptor and peptidase inhibitor 3, skin-derived was reduced, and estrogen receptor alpha 2, aldo-keto reductase family 1, member C4, and lipoprotein lipase expression was increased in LF-LCL versus SF-SCL. Results support the hypothesis that the size of the POF alters the periovulatory endocrine milieu (i.e., proestrus estradiol and diestrus progesterone concentrations) and acts on the uterus to alter endometrial gene expression. It is proposed that the uterine environment and receptivity might also be modulated. Additionally, it is suggested that increased progesterone secretion of cows ovulating larger follicles is likely due to increased CL size rather than increased luteal expression of steroidogenic genes.

Pleural tuberculosis: is radiological evidence of pulmonary-associated disease related to the exacerbation of the inflammatory response?

OBJECTIVE: Pleural tuberculosis is the most frequently occurring form of extra pulmonary disease in adults. In up to 40% of cases, the lung parenchyma is concomitantly involved, which can have an epidemiological impact. This study aims to evaluate the pleural and systemic inflammatory response of patients with pleural or pleuropulmonary tuberculosis. METHODS: A prospective study of 39 patients with confirmed pleural tuberculosis. After thoracentesis, a high resolution chest tomography was performed to evaluate the pulmonary involvement. Of the 39 patients, 20 exhibited only pleural effusion, and high resolution chest tomography revealed active associated-pulmonary disease in 19 patients. The total protein, lactic dehydrogenase, adenosine deaminase, vascular endothelial growth factor, interleukin-8, tumor necrosis factor-alpha, and transforming growth factor-beta(1) levels were quantified in the patient serum and pleural fluid. RESULTS: All of the effusions were exudates with high levels of adenosine deaminase. The levels of vascular endothelial growth factor and transforming growth factor-beta(1) were increased in the blood and pleural fluid of all of the patients with pleural tuberculosis, with no differences between the two forms of tuberculosis. The tumor necrosis factor-alpha levels were significantly higher in the pleural fluid of the patients with the pleuropulmonary form of tuberculosis. The interleukin-8 levels were high in the pleural fluid of all of the patients, without any differences between the forms of tuberculosis. CONCLUSION: Tumor necrosis factor-alpha was the single cytokine that significantly increased in the pleural fluid of the patients with pulmonary involvement. However, an overlap in the results does not permit us to suggest that cytokine is a biological marker of concomitant parenchymal involvement. Although high resolution chest tomography can be useful in identifying these patients, the investigation of fast acid bacilli and cultures for M. tuberculosis in the sputum is recommended for all patients who are diagnosed with pleural tuberculosis.

Electroretinographic findings associated with panretinal photocoagulation (PRP) versus PRP plus intravitreal ranibizumab treatment for high-risk proliferative diabetic retinopathy

To evaluate changes in electroretinographic (ERG) findings after panretinal photocoagulation (PRP) compared to PRP plus intravitreal injection of ranibizumab (IVR) in eyes with high-risk proliferative diabetic retinopathy (PDR). Patients with high-risk PDR and no prior laser treatment were assigned randomly to receive PRP (PRP group; n = 9) or PRP plus IVR (PRPplus group; n = 11). PRP was administered in two sessions (weeks 0 and 2), and IVR was administered at the end of the first laser session (week 0) in the PRPplus group. Standardized ophthalmic evaluations including (ETDRS) best-corrected visual acuity (BCVA), and fluorescein angiography to measure area of fluorescein leakage (FLA), were performed at baseline and at weeks 16 (+/- 2), 32 (+/- 2) and 48 (+/- 2). ERG was measured according to ISCEV standards at baseline and at week 48 (+/- 2). At 48 weeks, 2,400-3,000 laser spots had been placed in eyes in the PRP group, while only 1,400-1,800 spots had been placed in the PRPplus group. Compared to baseline, there was a statistically significant (P < 0.05) FLA reduction observed at all study visits in both groups, with the reduction observed in the PRPplus group significantly larger than that in the PRP group at week 48. ROD b-wave amplitude was significantly reduced to 46 +/- A 5 % (P < 0.05) of baseline in the PRP group and 64 +/- A 6 % (P < 0.05) in the PRPplus group. This reduction was significantly larger in the PRP group than in the PRPplus group (P = 0.024; t Test). Similar results were observed for the dark-adapted Combined Response (CR) b-wave amplitude, with a reduction at 48 weeks compared to baseline of 45 +/- A 4 % in the PRP group and 62 +/- A 5 % in the PRPplus group; the reduction in CR b-wave amplitude was significantly larger in the PRP group than in the PRPplus group (P = 0.0094). CR a-wave, oscillatory potentials, cone single flash, and 30 Hz flicker responses showed statistically significant within-group reductions, but no differences in between-group analyses. These results suggest that treating high-risk PDR with PRP plus IVR is effective for PDR control, and permits the use of less extensive PRP which, in turn, induces less retinal functional loss, in particular for rod-driven post-receptoral responses, than treatment with PRP alone.