Search

Cancer-associated mesothelial cells (CAMCs) in the tumor microenvironment are thought to promote growth and immune evasion. We find that, in mouse and human ovarian tumors, cancer cells express anti-Müllerian hormone (AMH) while CAMCs express its receptor AMHR2, suggesting a paracrine axis. Factors secreted by cancer cells induce AMHR2 expression during their reprogramming into CAMCs in mouse and human in vitro models. Overexpression of AMHR2 in the Met5a mesothelial cell line is sufficient to induce expression of immunosuppressive cytokines and growth factors that stimulate ovarian cancer cell growth in an AMH-dependent way. Finally, syngeneic cancer cells implanted in transgenic mice with Amhr2 −/− CAMCs grow significantly slower than in wild-type hosts. The cytokine profile of Amhr2 −/− tumor-bearing mice is altered and their tumors express less immune checkpoint markers programmed-cell-death 1 (PD1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4). Taken together, these data suggest that the AMH/AMHR2 axis plays a critical role in regulating the pro-tumoral function of CAMCs in ovarian cancer. [Display omitted] • Cancer-cell-secreted factors reprogram normal omental mesothelial cells to induce AMHR2 • AMH secreted by cancer cells modulates cancer-associated mesothelial cell cytokines • The paracrine AMH/AMHR2 axis regulates the pro-tumoral and immune functions of CAMCs • Deletion of Amhr2 in mesothelium reduces ovarian tumor growth and immune exhaustion Cancer cells reprogram normal omental mesothelium into cancer-associated mesothelial cells (CAMCs) by inducing expression of AMHR2. In turn, cancer cells secrete AMH to regulate expression of immunosuppressive cytokines and growth factors by CAMCs. Ovarian tumors implanted in transgenic mice deficient in AMHR2 have a slower growth and reduced immune exhaustion. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Osteopenia and osteoporosis after renal transplantation have been associated with factors related to the cause of end-stage renal disease, as well as to clinical events and therapeutic factors in the posttransplant period. We studied the prevalence of low bone density (LBD) according to WHO criteria. Methods: A cross-sectional study was performed in a cohort of 106 patients (54 men and 52 women) with functioning renal allografts, who underwent bone densitometry (DEXA) of the lumbar spine and femoral neck. Patients were grouped according to DEXA into those with normal bone density (NBD) or LBD. We studied clinical, analytical, and therapeutic variables. Results: Thirtysix patients (34%) had NBD and 70 patients (66%) LBD. Weight was the only parameter showing a significant difference (P = .034), namely, among NBD it was 80.44±15.13 versus LBD 73.94 ± 14.54 kg, respectively. Creatinine clearance (CCr) tended to be lower among patients with LBD 59.62 ± 22.73 versus 69.59 ± 28.15 mL/min in patients with NBD (P = .052). PTHi levels were higher in patients with LBD (149.39 ± 110.75) than those with NBD (110.94 ± 82.61) (P = .069). In the multivariate analysis the important determinants were weight Exp(ß) = 0.967 [CI = 0.939 to 0.996] (P = .036); CCr Exp(ß) = 0.982 [CI = 0.965 to 1.000] (P = .055); and PTHi levels Exp(ß) = 1.003 [CI = 0.932 to 0.994] (P = .059). Conclusions: Osteopenia and osteoporosis are frequent among kidney transplant patients (66%), with a similar distribution between the lumbar spine and femoral neck. Excess weight and possibly better renal function may be protective factors. The cumulative steroid dose showed a significant effect on bone density. As expected, secondary hyperparathyroidism in patients with renal impairment seemed to be a risk factor for LBD. [Copyright &y& Elsevier]

The aim of this study was to evaluate phenolic composition, antioxidant potential, and lipolytic events in raw milk obtained from goat fed a dietary supplementation with olive leaves (OL), a by-product of the olive oil production chain. For this purpose, 30 Saanen goats were randomly allocated into 2 groups of 15 goats each: the control group received a standard diet that was prepared by taking into account the nutritional needs of lactating goats, whereas the experimental group (EG) was fed with an OL-supplemented diet (10% on a dry matter basis). At the end of the 30 d of the trial, the individual milk samples were collected and immediately analyzed for total phenolic content and antioxidant activity (AOA). Subsequently, the individual phenolic compounds have been identified and quantified through an ultra-high-performance liquid chromatography system and a characterization of free fatty acids released in milk has been performed. The results showed a positive effect of dietary OL supplementation in improving total phenolic content and AOA; furthermore, 19 phenolic compounds, including phenolic acids, flavonoids, simple phenols, and secoiridoids, have been identified in EG milk. In addition to this, a reduced accumulation of free fatty acids has been found in EG milk, and this finding leads us to hypothesize an inhibitory action of the identified phenolic compounds toward the enzymes responsible for lipolytic events. The use of the molecular docking approach verified the interactions, defining a fairly interesting framework for cinnamic acid, which should be able to noncovalently bind these enzymes, interfering with the recruitment of the substrate and therefore, slowing down their hydrolytic activity. In any case, this information will be subjected to in vitro evaluations for an accurate characterization of the biochemical mechanisms that can be established in milk naturally enriched with bioactive compounds. [ABSTRACT FROM AUTHOR]

In order to prevent morbidity and mortality in peritoneal dialysis (PD), sodium and water balance as well as a minimal level of small-solute clearances are needed. The impact of three nocturnal peritoneal ultrafiltration (UF) profiles on UF and small solute clearance in patients on automated PD (APD) was studied: constant glucose concentration of 1.36% (flat) or modifying the glucose concentration of the heater bag (descendant: 3.86–1.36%; ascendant: 1.36–3.86%). Sixty-two patients were enrolled in the study and received each profile within a four-month period, thus serving as their own controls. UF was lower with the flat profile (367±420ml; P<0.01), but no difference was seen between the two higher glucose concentration profiles. Peritoneal Kt/V (pKt/V) and peritoneal creatinine clearance (CrpC) showed statistically higher values from the descendant vs ascendant vs flat profiles (pKt/V: 1.54±0.30 vs 1.45±0.30 vs 1.38±0.27, and CrpC: 36.9±7.9 vs 33.5±7.48 vs 29.92±7.5 mlmin−1). Multivariate analysis showed statistical significance for the following: in the intrasubject comparisons, the profile for pKt/V (F=9.109, P<0.001) and CrpC (F=11.697, P<0.001), and in the intersubjects comparisons, the effects of both gender (F=14.334, P<0.01) for pKt/V and peritoneal permeability for both parameters (pKt/V: F=4.37, P<0.05; CrpC: F=11.697, P<0.001). In conclusion, the application of ascendant and descendant UF profiles in automated PD is feasible and results in better UF and small solute clearances, thus preventing inadequate dialysis and volume overload.Kidney International (2008) 73, S94–S101; doi:10.1038/sj.ki.5002609 [ABSTRACT FROM AUTHOR]

Highlights • Chagas disease, caused by Trypanosoma cruzi , is a global problem with an increasing impact on public health. • Trypanosoma cruzi reactivation may occur in immunosuppressed patients, so it should be taken into account in the screening and differential diagnosis of patients from endemic areas. • Only benznidazole and nifurtimox have been approved for use in the treatment of patients with Chagas disease, a current worldwide health problem. • There is dearth of available information on benznidazole dosage and the levels achieved in cerebrospinal fluid. Abstract There is little published data on benznidazole dosing, or levels in cerebrospinal fluid. In this report, we describe the clinical course of an immunosuppressed patient with Chagas central nervous system involvement. He was treated successfully with larger benznidazole doses than are recommended, in order to reach therapeutically effective concentrations in the brain. [ABSTRACT FROM AUTHOR]

Abstract: von Hippel-Lindau (VHL) disease is a genetic syndrome based on an abnormality of the VHL gene located on the short arm of chromosome 3. Clinically, it presents as multiple tumors at several levels. The VHL gene product (pVHL) acts as a tumor-suppressing protein. In conditions of hypoxia it leads to an increase in several growth factor levels. mTOR inhibitors have proved to have dual properties: immunosuppressive and antitumor effects. Herein we have presented a case in which conversion to sirolimus improved graft function and also caused regression of retinal angioblastomas. [Copyright &y& Elsevier]

Abstract: Eighteen pigs weighing a mean 19 ± 4 kg, were divided into group 1 (n = 2), that underwent resection of the left lateral lobe, group 2 (n = 2), resection of the left median and right median lobes; and group 3 (n = 18), resection of the left lateral, left median, right median, and right lateral lobes. All animals were followed for 5 days. Liver failure (n = 8) leading to animal death within 3 days after surgery was observed in 65% of group 3, whereas no group 1 or 2 animal experienced liver insufficiency. Multivariate analysis revealed that the extent of liver resection expressed as a percentage of total body weight <2.3%, international normalized ratio > 1.6 as postoperative day 2, serum bilirubin > 4.2 on postoperative day 2, and serum lactates > 9 mmol/L after resection were independent predictors of liver failure (P < .05). The number of resected liver lobes was not a good predictor of liver failure in swine, whereas the extent of resection expressed as a percentage of total body weight was an independent predictor of early liver failure. A resected liver-to-body weight ratio >2.3% was associated with a 65% probability of developing liver insufficiency. This parameter may be useful when developing a model of liver failure after extended liver resection in swine. [Copyright &y& Elsevier]

Abstract: Currently, long-term experience with Rapamune (RAPA) after renal transplantation is scarce. We present our experience with RAPA in patients who were included in clinical trials. Between 1996 and 1999, 27 renal transplant patients received RAPA alone or in combination with cyclosporine (CyA). We study 15 of them (9 males, 6 females; mean age 36 years) who are currently functioning with a mean follow-up of 6 years (range, 5.2–8 years). The presence of delayed graft function was 40% and acute rejection 26.6%, all of them controlled with steroids. Notably, no patients experienced an acute rejection episode after the first year. Among 15 patients, 12 received steroids, RAPA and CyA; and 3 received steroids, RAPA, azathioprine (AZA) or mycophenolate mofetil (MMF) for immunosuppression. At the end of follow-up, the situation was the opposite: 12 patients received steroids (2.5–5 mg/d) and RAPA associated with or without AZA/MMF, and 3 were maintained with steroids, RAPA and CyA. Renal function was excellent in the entire group: mean SCr 1.1 mg/dL (range, 0.7–1.8) with mean RAPA blood levels (HPLC) of 11 ng/dL (range 8–16). Hyperlipidemia was universal with all patients (100%) receiving statins maintaining acceptable levels of cholesterol (mean 209 ± 28 mg/dL) and tryglycerides (mean 154 ± 76 mg/dL). Arterial hypertension present in 12 of 15 (80%) patients was controlled with a mean of 1.5 drugs. Notably, no patient presented with proteinuria, neoplasia, posttransplant diabetes, or cardiovascular events. In conclusion, these single-center results suggest that Rapamune may be useful in the long-run after renal transplantation. The presence of normal renal function and the absence of proteinuria and neoplasia in these renal transplant patients may have important clinical implications. [Copyright &y& Elsevier]

Abstract: Renal transplantation restores fertility within an average of 6 months, so women of childbearing age are able to consider pregnancy. Successful pregnancies have been reported in recent years under different immunosuppressive regimens, but the optimal treatment to achieve the maximum safety for both the mother and fetus remains unclear. Tacrolimus has been demonstrated to provide long-term immunosuppression and prevent rejection in most renal transplants. It seems safe, but experience is limited compared with cyclosporine. We report our experience highlighting the high rate of successful pregnancies attained in women treated with tacrolimus as the basic immunosuppressant and advised of recommendations to achieve a healthy newborn. Renal function was preserved during the pregnancy. The puerperal period and the rate of gestation-related difficulties appeared similar to that of the general population. [Copyright &y& Elsevier]