Tumor redifferentiation in papillary thyroid carcinoma alter retinoic acid administration

Male patient, 73 year old, with papillary thyroid carcinoma treated by surgery, 131I and L-Tyroxine, with bone metastasis, detected by bone scintigraphy and CT scan, which negative radioiodine uptake. In order to induce tumoral redifferentiation, retinoic acid (70 mg/day) was administered for three months before 131I treatment. A radioiodine scan performed after treatment showed uptake in some of the bone metastasis. Nine months later, and due to disease progression, a second induction with retinoic acid was performed before 131I treatment. The radioiodine scan performed after treatment showed greater uptake and higher number of bone lesions than the previous scan.     

IL-1beta induces VEGF, independently of PGE2 induction, mainly through the PI3-K/mTOR pathway in renal mesangial cells

Vascular endothelial growth factor (VEGF) could play a relevant role in angiogenesis associated with chronic allograft nephropathy. Interleukin-1beta (IL-1beta) has a key role in inflammatory response. It induces prostaglandin (PG) E2, which is involved in VEGF release by some normal and tumor cells. In the present work, we studied the effect of IL-1beta on VEGF release by rat mesangial cells, the transduction signal, and whether or not PGE2 is involved in this effect. IL-1beta induced a time-dependent formation of VEGF (analyzed by enzyme-linked immunosorbent assay) and PGE2 (analyzed by enzyme immunoassay). The latter correlated with microsomal-PGE-synthase (mPGES)-1 expression rather than with cyclooxygenase (COX)-2 in terms of protein, determined by Western blotting. No effect of IL-1beta on COX-1, cytosolic PGES, or mPGES-2 expression was observed. Indomethacin exerted a nonsignificant effect on IL-1beta-induced VEGF, and exogenously added PGE2 exhibited a nonsignificant stimulatory effect on VEGF formation. SB 203580, a p38 mitogen-activated protein kinase inhibitor, weakly inhibited the induction of VEGF by IL-1beta in a concentration-dependent manner, whereas LY 294002, a phosphoinoside 3-kinase (PI3-K) inhibitor, and rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, strongly inhibited both IL-1beta- and tumor necrosis factor-alpha-induced VEGF formation in a concentration-dependent manner. Rapamycin also decreased glomerular VEGF levels in the anti-Thy1.1 model of experimental glomerulonephritis. In conclusion, the PI3-K-mTOR pathway seems to be essential in cytokine-induced release of VEGF in mesangial cells.     

Relationship between ischemia/reperfusion injury and the stimulus of fibrogenesis in an experimental model: comparison among different preservation solutions

Background and Aims

Orthotopic liver transplantation (OLT) has been the standard treatment for end-stage acute and chronic liver disease. Ischemia-reperfusion (I/R) injury is one of the major causes of poor graft function early after OLT, and adversely influencing graft and patient survivals. It is unknown whether I/R injury influences liver fibrogenesis.

Materials and Methods

Livers from 25 adult male Wistar rats were randomly assigned into 5 experimental groups according to the preservation solution: saline solution (SS); University of Wisconsin (UW) solution; Fructose 1, 6-biphosphate (FBP); S-Nitroso-N-Acetylcysteine (SNAC): or UW + SNAC (SNAC+UW). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH) were determined in preservation solution samples at 2, 4, and 6 hours. After 6 hours of cold ischemia, ex situ reperfusion was applied to the liver for 15 minutes. Serum AST, ALT, LDH, and renin levels were determined. Fresh liver slices were processed for histological studies, determination of thiobarbituric acid reactive substances, catalase, and glutathione, and expression of TGF-β1 and angiotensin II AT1 receptor.

Results

AST was significantly lower during cold storage with UW than with the older media (P = .001); ALT was lower in the FBP group (P = .023) and LDH was lower in the FBP and SNAC groups (P = .007). After reperfusion, serum AST, ALT, LDH, and TBARS showed no significant differences among the groups. Catalase was significantly lower in the SS and FBP groups (P = .008 and P = .006, respectively). Compared with UW, glutathione concentrations were significantly higher in SS, FBP, and SNAC 200 (P = .004). Renin levels were significantly lower in the FBP group (P = .022). No histological signs of preservation injury were observed in the hepatic sample. No expressions were detected of TGF-β1 or AT1 receptor.

Conclusion

In this experimental model of early reperfusion injury, preservation changes related to higher levels of renin, which suggest its role in fibrogenesis. FBP was associated with lower renin levels than other solutions including UW.     

Pentafecta: a new concept for reporting outcomes of robot-assisted laparoscopic radical prostatectomy

Background

Widespread use of prostate-specific antigen screening has resulted in younger and healthier men being diagnosed with prostate cancer. Their demands and expectations of surgical intervention are much higher and cannot be adequately addressed with the classic trifecta outcome measures.

Objective

A new and more comprehensive method for reporting outcomes after radical prostatectomy, the pentafecta, is proposed.

Design, setting, and participants

From January 2008 through September 2009, details of 1111 consecutive patients who underwent robot-assisted radical prostatectomy performed by a single surgeon were retrospectively analyzed. Of 626 potent men, 332 who underwent bilateral nerve sparing and who had 1 yr of follow-up were included in the study group.

Measurements

In addition to the traditional trifecta outcomes, two perioperative variables were included in the pentafecta: no postoperative complications and negative surgical margins. Patients who attained the trifecta and concurrently the two additional outcomes were considered as having achieved the pentafecta. A logistic regression model was created to evaluate independent factors for achieving the pentafecta.

Results and limitations

Continence, potency, biochemical recurrence–free survival, and trifecta rates at 12 mo were 96.4%, 89.8%, 96.4%, and 83.1%, respectively. With regard to the perioperative outcomes, 93.4% had no postoperative complication and 90.7% had negative surgical margins. The pentafecta rate at 12 mo was 70.8%. On multivariable analysis, patient age (p = 0.001) was confirmed as the only factor independently associated with the pentafecta.

Conclusions

A more comprehensive approach for reporting prostate surgery outcomes, the pentafecta, is being proposed. We believe that pentafecta outcomes more accurately represent patients’ expectations after minimally invasive surgery for prostate cancer. This approach may be beneficial and may be used when counseling patients with clinically localized disease.     

Absence of Hepatitis E virus circulation in wild rabbits (Oryctolagus cuniculus) and Iberian hares (Lepus granatensis) in Mediterranean ecosystems in Spain

In recent decades, cases of autochthonous hepatitis E (HE) have sharply increased in European countries where foodborne transmission is considered the main route of HE virus (HEV) transmission. Although rabbits are considered the main reservoir of the zoonotic HEV‐3ra subtype, information on the role of wild lagomorphs in the epidemiology of HEV remains scarce. The aim of this study therefore was to assess the circulation of HEV in European wild rabbits (Oryctolagus cuniculus) and Iberian hares (Lepus granatensis), the most important lagomorph species in Spanish Mediterranean ecosystems. Liver samples from 372 wild rabbits and 78 Iberian hares were analysed using a broad‐spectrum RT‐PCR that detects HEV genotypes 1–8. None of the 450 lagomorphs tested were positive for HEV infection. To the best of our knowledge, this is the first study to assess HEV circulation in wild rabbits in Spain and the first to evaluate HEV infection in Iberian hares. Our results indicate absence of HEV circulation in wild rabbits and Iberian hares in southern Spain during the study period, which suggests that the risk of transmission of HEV from wild lagomorphs to other species, including humans, is low.     

Bridges to Better Health and Wellness: An Adapted Health Care Manager Intervention for Hispanics with Serious Mental Illness

This study examined the feasibility, acceptability, and initial impact of bridges to better health and wellness (B2BHW), a culturally-adapted health care manager intervention for Hispanics with serious mental illness (SMI). Thirty-four Hispanics with SMI and at risk for cardiovascular disease were enrolled. Mixed-linear models were used to examine changes over 12-months on patient activation, self-efficacy, patient-rated quality of care, receipt of preventive primary care services, and quality of life. The majority of participants completed the intervention (85%) with high satisfaction. Significant improvements were found for patient activation, self-efficacy, patients’ ratings of quality of care, and receipt of preventive primary care.     

Melatonin and its brain metabolite N1‐acetyl‐5‐methoxykynuramine prevent mitochondrial nitric oxide synthase induction in parkinsonian mice

Melatonin prevents mitochondrial failure in models of sepsis through its ability to inhibit the expression and activity of both cytosolic (iNOS) and mitochondrial (i‐mtNOS) inducible nitric oxide synthases. Because Parkinson's disease (PD), like sepsis, is associated with iNOS induction, we assessed the existence of changes in iNOS/i‐mtNOS and their relation with mitochondrial dysfunction in the MPTP model of PD, which also displays increased iNOS expression. We also evaluated the role of melatonin (aMT) and its brain metabolite, N¹‐acetyl‐5‐methoxykynuramine (AMK), in preventing i‐mtNOS induction and mitochondrial failure in this model of PD. Mitochondria from substantia nigra (SN) and, to a lesser extent, from striatum (ST) showed a significant increase in i‐mtNOS activity, nitrite levels, oxidative stress, and complex I inhibition after MPTP treatment. MPTP‐induced i‐mtNOS was probably related to mitochondrial failure, because its prevention by aMT and AMK reduced oxidative/nitrosative stress and restored complex I activity. These findings represent the first experimental evidence of a potential role for i‐mtNOS in the mitochondrial failure of PD and support a novel mechanism in the neuroprotective effects of aMT and AMK. © 2009 Wiley‐Liss, Inc.     

Adaptation and validation of the Spanish version of the Mood Disorder Questionnaire for the detection of bipolar disorder

Objective: The Mood Disorder Questionnaire (MDQ) is an instrument for the detection of patients with bipolar disorder (BD). The original English version is validated in both the psychiatric and the general population, but a validated Spanish version is not yet available. Psychometric properties of the Spanish adaptation of the MDQ in psychiatry are described. Methods: The MDQ is a self‐administered questionnaire comprising a list of 13 hypomanic symptoms and two questions about concurrence of symptoms and functional impairment caused by the symptoms. We selected patients from 15 psychiatric outpatient departments, diagnosed with BD type I and II (BDI and BDII) and major depression (MD) according to DSM‐IV‐TR criteria (concurrent validity instrument). A control group of healthy subjects (HS) was selected. The patient‐selection criteria included stability of the disorder and pharmacological treatment. The MDQ was administered to 236 subjects, distributed among the four groups, on two occasions, four weeks apart. We analysed the internal consistency, test–retest reliability, and discriminative capacity of the MDQ for the detection of patients with BD. Results: Concurrent validity based on diagnosis according to DSM‐IV‐TR was 0.83. The internal consistency, evaluated by Cronbach’s α, was 0.90. The mean (SD) number of affirmative responses by group was: 9.8 (2.4) for BDI, 8.5 (2.8) for BDII, 2.7 (2.2) for MD, and 1.02 (1.9) for HS. Statistically significant differences between all the groups were found (Kruskal–Wallis test, p < 0.001). Concurrent validity using the diagnostic variable was 0.83. Test–retest reliability was 0.92. We analysed the scale’s discriminative capacity, revealing a sensitivity value of 0.60 [95% confidence interval (CI) = 0.51–0.69] and a specificity value of 0.98 (95% CI = 0.94–0.99) in the detection of BD. The positive and negative probability ratios were 35.5 and 2.4, respectively. If we consider only seven positive responses as the discriminative criterion, sensitivity increases to 0.81 (95% CI = 0.73–0.88), the specificity value is 0.95 (95% CI = 0.89–0.98) and the positive and negative probability quotients are 16 and 5.3. Conclusions: The psychometric characteristics of the Spanish version are similar to those of the original version. In the Spanish adaptation of the MDQ, seven positive responses to hypomanic symptoms show a good discriminative capacity for BD in patients attending psychiatric outpatient facilities; therefore, this cut‐off score is proposed for the detection of BD in psychiatric outpatients.