Mortality Risks after Two Years in Frail and Pre-Frail Older Adults Admitted to Hospital.

BACKGROUND: Frailty is characterized by a progressive decline in the physiological functions of multiple body systems that lead to a more vulnerable condition, which is prone to the development of various adverse events, such as falls, hospitalization, and mortality. This study aims to determine whether frailty increases mortality compared to pre-frailty and to identify variables associated with a higher risk of mortality. MATERIALS: Two cohorts, frail and pre-frail subjects, are evaluated according to the Fried phenotype. A complete examination of frailty, cognitive status, comorbidities and pharmacology was carried out at hospital admission and was extracted through electronic health record (EHR). Mortality was evaluated from the EHR. METHODS: Kaplan-Meier estimates of survival probability functions were calculated at two years censoring time for frail and pre-frail cohorts. The log-rank test assessed significant differences between survival probability functions. Significant variables for frailty (p < 0-05) were extracted by independent sample t-test. Further selection was based on variable significance found in multivariate logistic regression discrimination between frail and pre-frail subjects. Cox regression over univariate t-test-selected variables was calculated to identify variables associated with higher proportional hazard risks (HR) at two years. RESULTS: Frailty is associated with greater mortality at two years censoring time than pre-frailty (log-rank test, p < 0.0001). Variables with significant (p < 0.05) association with mortality identified in both cohorts (HR 95% (CI in the frail cohort) are male sex (0.44 (0.29-0.66)), age (1.05 (1.01-1.09)), weight (0.98 (0.96-1.00)), and use of proton-pump inhibitors (PPIs) (0.60 (0.41-0.87)). Specific high-risk factors in the frail cohort are readmission at 30 days (0.50 (0.33-0.74)), SPPB sit and stand (0.62 (0.45-0.85)), heart failure (0.67 (0.46-0.98)), use of antiplatelets (1.80 (1.19-2.71)), and quetiapine (0.31 (0.12-0.81)). Specific high-risk factors in the pre-frail cohort are Barthel's score (120 (7.7-1700)), Pfeiffer test (8.4; (2.3-31)), Mini Nutritional Assessment (MNA) (1200 (18-88,000)), constipation (0.025 (0.0027-0.24)), falls (18,000 (150-2,200,000)), deep venous thrombosis (8400 (19-3,700,000)), cerebrovascular disease (0.01 (0.00064-0.16)), diabetes (360 (3.4-39,000)), thyroid disease (0.00099 (0.000012-0.085)), and the use of PPIs (0.062 (0.0072-0.54)), Zolpidem (0.000014 (0.0000000021-0.092)), antidiabetics (0.00015 (0.00000042-0.051)), diuretics (0.0003 (0.000004-0.022)), and opiates (0.000069 (0.00000035-0.013)). CONCLUSIONS: Frailty is associated with higher mortality at two years than pre-frailty. Frailty is recognized as a systemic syndrome with many links to older-age comorbidities, which are also found in our study. Polypharmacy is strongly associated with frailty, and several commonly prescribed drugs are strongly associated with increased mortality. It must be considered that frail patients need coordinated attention where the diverse specialist taking care of them jointly examines the interactions between the diversity of treatments prescribed.

Survival of Frail Elderly with Delirium.

This study aims to determine when frailty increases the risks of delirium mortality. Hospital patients falling into the elderly frail or pre-frail category were recruited, some without delirium, some with delirium at admission, and some who developed delirium during admission. We screened for frailty, cognitive status, and co-morbidities whenever possible and extracted drug information and mortality data from electronic health records. Kaplan-Meier estimates of survival probability functions were computed at four times, comparing delirium versus non delirium patients. Differences in survival were assessed by a log-rank test. Independent Cox's regression was carried out to identify significant hazard risks (HR) at 1 month, 6 months, 1 year, and 2 years. Delirium predicted mortality (log-rank test, p < 0.0001) at all four censoring points. Variables with significant HRs were frailty indicators, comorbidities, polypharmacy, and the use of specific drugs. For the delirium cohort, variables with the most significant 2-year hazard risks (HR(95%CI)) were: male gender (0.43 20 (0.26,0.69)), weight loss (0.45 (0.26,0.74)), sit and stand up test (0.67 (0.49,0.92)), readmission within 30 days of discharge (0.50 (0.30,0.80)), cerebrovascular disease (0.45 (0.27,0.76)), head trauma (0.54 22 (0.29,0.98)), number of prescribed drugs (1.10 (1.03,1.18)), and the use of diuretics (0.57 (0.34,0.96)). These results suggest that polypharmacy and the use of diuretics increase mortality in frail elderly patients with delirium.

The Nutritional Status of Long-Term Institutionalized Older Adults Is Associated with Functional Status, Physical Performance and Activity, and Frailty.

Among older adults living in long-term nursing homes (LTNHs), maintaining an adequate functional status and independence is a challenge. Whilst a poor nutritional status is a potential risk factor for a decreased function in this population, its role is not fully understood. Here, using a transversal multicenter study of 105 older adults living in 13 LTNHs, we analyzed the associations between nutritional status, as measured by the Mini Nutritional Assessment (MNA), and the parameters of functional status, physical performance, physical activity, and frailty as well as comorbidity and body composition. The MNA scores were positively correlated with the Barthel Index, handgrip strength, Short Physical Performance Battery (SPPB) scores, absolute muscle power, and Assessment of Physical Activity in Frail Older People (APAFOP) scores and were negatively correlated with dynamic balance and frailty. In a multiple linear regression model controlling for gender and age, the APAFOP score (ß = 0.386), BMI (ß = 0.301), and Barthel Index (ß = 0.220) explained 31% of the variance in the MNA score. Given the observed close relationship between the MNA score and functional status, physical performance and activity, and frailty, interventions should jointly target improvements in both the nutritional status and functional status of LTNH residents. Strategies designed and implemented by interdisciplinary professional teams may be the most successful in improving these parameters to lead to better health and quality of life.

Protein intake, weight loss, dietary intervention, and worsening of quality of life in older patients during chemotherapy for cancer.

Decreased health-related quality of life (HRQoL) is common in patients with cancer. We investigated the effects of dietary intervention and baseline nutritional status on worsening of HRQoL in older patients during chemotherapy. In this randomized control trial assessing the effect on mortality of dietary advice to increase dietary intake during chemotherapy, this post hoc analysis included 155 patients with cancer at risk of malnutrition. The effects of dietary intervention, baseline Mini Nutritional Assessment item scores, weight loss, and protein and energy intake before treatment on the worsening of HRQoL (physical functioning, fatigue) and secondary outcomes (Timed Up and Go test, one-leg stance time, depressive symptoms, basic (ADL), or instrumental (IADL) activities of daily living) were analyzed by multinomial regressions. Dietary intervention increased total energy and protein intake but had no effect on any examined outcomes. Worsening of fatigue and ADL was predicted by very low protein intake (< 0.8 g kg-1 day-1) before chemotherapy (OR 3.02, 95% CI 1.22-7.46, p = 0.018 and OR 5.21, 95% CI 1.18-22.73, p = 0.029 respectively). Increase in depressive symptomatology was predicted by 5.0-9.9% weight loss before chemotherapy (OR 2.68, 95% CI 1.10-6.80, p = 0.038). Nutritional intervention to prevent HRQoL decline during chemotherapy should focus on patients with very low protein intake along with those with weight loss.

Role of Angiotensin-(1-7) via MAS receptor in human sperm motility and acrosome reaction.

Rennin-angiotensin system (RAS) has been involved in sperm function, even so, little is known about the implication of one of the RAS axis formed by Ang-(1-7) (angiotensin-(1-7)) and MAS receptor. Hence, in the present work, we focused on elucidating the function of the MAS receptor in human spermatozoa. We analyzed the expression and localization of MAS receptor in human spermatozoa and we observed if its activation is able to modulate the sperm motility of normal motility and/or asthenozoospermic patients, as well as, the acrosome reaction of the spermatozoa. MAS receptor is present in human mature spermatozoa, not only at the mRNA level but also at protein level. MAS is localized at the acrosome region, as well as, in the tail of spermatozoa. The sperm incubation with MAS agonist Ang-(1-7) activates at dose-dependent manner the PI3K/AKT pathway (P < 0.01 vs control) and improves the motility of asthenozoospermic patients (P < 0.01 vs control), which is blocked by the specific antagonist (A779) (P < 0.01), but it do not modulate the acrosome reaction. These findings suggest that the ACE2/Ang-(1-7)/Mas axis may be a useful biochemical tool for the treatment of male infertility related to sperm mobility.

Physical Activity, Physical Fitness, Body Composition, and Nutrition Are Associated with Bone Status in University Students.

Understanding the modifiable factors that improve and maximize peak bone mass at an early age is necessary to design more effective intervention programs to prevent osteoporosis. To identify these modifiable factors, we analyzed the relationship of physical activity (PA), physical fitness, body composition, and dietary intake with bone stiffness index (SI), measured by quantitative ultrasonometry in young university students (18-21 years). Moderate-to-vigorous PA (MVPA) was the strongest predictor of SI (ß = 0.184; p = 0.035). SI was most closely related with very vigorous PA in males (ß = 0.288; p = 0.040) and with the number of steps/day in females (ß = 0.319; p = 0.002). An association between thigh muscle and SI was consistent in both sexes (ß = 0.328; p < 0.001). Additionally, extension maximal force was a bone SI predictor factor in females (ß = 0.263; p = 0.016) independent of thigh muscle perimeter. Calcium intake was the only nutrition parameter that had a positive relationship with SI (R = 0.217; p = 0.022). However, it was not included as a predictor for SI in our regression models. This study identifies predictors of bone status in each sex and indicates that muscle and bone interrelate with PA and fitness in young adults.

Fibroblast activation protein predicts prognosis in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma is a complex disease with only partial response to therapy and scarce reliable clinical parameters indicative of progression and survival. Fibroblast activation protein expression has been correlated with prognosis in several malignancies but never in renal cancer. We aim to analyze the immunohistochemical expression of fibroblast activation protein in 208 clear cell renal cell carcinomas and to evaluate its impact on the prognosis and survival. A positive cytoplasmic immunostaining of this protein in the stromal fibroblasts associated to cancer cells is associated with large tumor diameter (≥4cm), high-grade (G3/4) tumors, and high-stage (≥pT3) tumors. Fibroblast activation protein-positive cases had significantly shorter survivals after 5 (P=.00015), 10 (P=.0000042), and 15 (P=.000043) years of follow-up, with a hazard ratio of 0.31. Multivariate analysis showed that fibroblast activation protein (P=.00117) was stronger than grade and stage in predicting clinical aggressiveness in clear cell renal cell carcinoma. This study confirms the usefulness of fibroblast activation protein detection in the stromal fibroblast associated to cancer in clear cell renal cell carcinoma and adds a new immunohistochemical marker to predict clinical behavior in these patients.

Aminopeptidase N activity predicts 5-year survival in colorectal cancer patients.

BACKGROUND: Aminopeptidase N (APN; EC 3.4.11.2) is a membrane dimeric metallopeptidase involved in differentiation, development, and proliferative processes of several tissues. Recent studies have demonstrated the increased expression and activity of this enzyme in several cancers. However, there are no available data about the impact of this peptidase in the biological aggressiveness and the survival of colorectal cancer (CRC) patients. METHODS: The activity and mRNA expression of APN in tumor tissue (n = 81) and plasma (n = 40) of patients with CRC of low and high grades and stages were prospectively analyzed by fluorimetric and quantitative reverse transcriptase-polymerase chain reaction methods. Data obtained in adenoma and CRC were compared with those from the surrounding normal mucosa. Classic clinical and pathological parameters were stratified following APN data and analyzed for 5-year survival. RESULTS: mRNA levels of APN (ANPEP) were lower in colorectal adenomas and adenocarcinomas than in the surrounding uninvolved mucosa (Kruskal-Wallis, P < 0.001). Aminopeptidase N activity in CRC tissue was higher in patients with better overall survival (log-rank P < 0.05, Cox analysis P < 0.05). By contrast, higher plasmatic APN activity correlated with worse overall survival (log-rank P < 0.01, Cox analysis P < 0.05). CONCLUSIONS: Aminopeptidase N activity in tissue and plasma from CRC patients is an independent prognostic factor of 5-year survival. The determination of APN activity levels in the plasma may be a safe, minimally invasive, and inexpensive way to define the aggressiveness of CRC in daily practice.

Plasma peptidases as prognostic biomarkers in patients with first-episode psychosis.

The plasma activity of nine aminopeptidases was monitored over a year in first-episode psychotic patients. We observed significant differences in aminopeptidase B (APB), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPPIV), but not in puromycin-sensitive aminopeptidase (PSA), prolyl endopeptidase (PEP), cysteine aminopeptidase (Cys-AP), aspartate aminopeptidase (Asp-AP), glutamate aminopeptidase (Glu) or piroglutamate aminopeptidase (PGI) in these patients compared to controls, and also a progressive increase in plasma activity, correlated to changes in scores on clinical scales, Global Assessment of Functioning scale (GAF) and Hamilton Depression Rating Scale (HDRS), at 1 month of follow-up. At 1 month after diagnosis, the median score obtained by patients on the GAF was negatively associated with the plasma activity of APB and PEP measured at the beginning of the psychotic episode, indicating a role as a negative prognostic factor that can predict psychiatric symptomatology. In the case of HDRS, scores at 1 month after diagnosis were found to be positively associated with the initial plasma activity of DPPIV, APN and PSA, indicating that their initial elevation is a negative prognostic factor that can predict subsequent depressive symptomatology. Taken together, these results suggest a pathophysiological involvement of plasma peptidases and indicate that aminopeptidase activity can predict the course of first-episode psychosis patients, acting as a prognostic indicator.

Prolyl endopeptidase activity is correlated with colorectal cancer prognosis.

BACKGROUND AND OBJECTIVE: Prolyl endopeptidase (PEP) (EC 3.4.21.26) is a serine peptidase involved in differentiation, development and proliferation processes of several tissues. Recent studies have demonstrated the increased expression and activity of this cytosolic enzyme in colorectal cancer (CRC). However, there are no available data about the impact of this peptidase in the biological aggressiveness of this tumor in patient survival. METHODS: The activity of PEP in tissue (n=80) and plasma (n=40) of patients with CRC was prospectively analyzed by fluorimetric methods. Results were correlated with the most important classic pathological data related to aggressiveness, with 5-year survival rates and other clinical variables. RESULTS: 1) PEP is more active in early phases of CRC; 2) Lower levels of the enzyme in tumors were located in the rectum and this decrease could be related with preoperative chemo-radiotherapy; 3) PEP activity in tissue was higher in patients with better overall and disease-free survival (log-rank p<0.01, Cox analysis p<0.01); 4) Plasmatic PEP activity was significantly higher in CRC patients than in healthy individuals and this was associated with distant metastases and with worse overall and disease-free survivals (log-rank p<0.05, Cox analysis p<0.05). CONCLUSIONS: PEP activity in tissue and plasma from CRC patients is an independent prognostic factor in survival. The determination of PEP activity in the plasma may be a safe, minimally invasive and inexpensive way to define the aggressiveness of CRC in daily practice.

Tempo para exaustão no acúmulo de lactato sanguíneo em corredores com diferentes habilidades atléticas / Time to exhaustion at the onset of blood lactate accumulation in runners with different athletic ability

OBJETIVO: Caracterizar as respostas fisiológicas de corredores com diferentes habilidades de velocidade durante o lactato sanguíneo (OBLA) e determinar se 4 mmol•L-1 representam a mesma intensidade de exercício relativa para cada corredor. MÉTODOS: Onze corredores treinados e doze bem treinados completaram dois testes de corrida em esteira: primeiramente, um teste máximo de lactato com incremento para calcular o OBLA (Teste 1) e a seguir um outro no OBLA correspondente até exaustão (Teste 2). As trocas de gases e frequência cardíaca (FC) foram continuamente medidas e plotadas em porcentagem de tempo referente à exaustão no Teste 2 (TET 2). A velocidade de limite de lactato individual (VLL) e concentração de lactato ([La-1]LL) foram calculadas de acordo com o método de D-max. RESULTADOS: OBLA e VLL foram maiores em corredores bem treinados (P<0.001).[La-1]LL foi<4 mmol•L-1 nos corredores bem treinados (P<0.001), mas não nos treinados. Os corredores bem treinados foram mais rápidos em OBLA do que em VLL (P<0.001). Os corredores bem treinados correram um TET2 mais curto do que os corredores treinados (P<0.05). Além disso, os corredores bem treinados apresentaram taxa respiratória mais alta em 50, 80 e 90% de TET2 e VO2 em 20-100% de TET2 (P<0.05). TET2 se relacionou inversamente (P<0.01) com OBLA e positivamente com melhor rendimento individual em 10km (P<0.01).OBLA se relacionou positivamente com a %VO2max no Teste 2 (P<0.01). O valor padrão (4 mmol•L-1) para a concentração de lactato sanguíneo parece representar uma intensidade de exercício diferente para corredores com habilidades atléticas diferentes. CONCLUSÃO: OBLA pode não ser preciso para desenvolver sessões de treinamento de corrida ou para a avaliação da capacidade aeróbica.

OBJECTIVE: To characterize the physiological responses of runners with different velocity abilities at the onset of blood lactate accumulation (OBLA) and to determine if 4 mmol•L-1 represent the same relative exercise intensity for each runner. METHODS: Eleven trained and twelve well-trained runners completed two running tests on treadmill: first, a maximal incremental lactate test to calculate OBLA (Test 1), and then another one at the corresponding OBLA until exhaustion (Test 2). Gas exchange and heart rate (HR) were continuously measured and plotted as a percentage of time to exhaustion in Test 2 (TET2). The individual lactate threshold velocity (VLT) and lactate concentration ([La-1]LT) were calculated according to the D-max method. RESULTS: VOBLA and VLT were higher in well-trained runners (P<0.001). [La-1]LT was <4 mmol•L-1 in the well-trained runners (P<0.001), but not in the trained ones. Well-trained runners were faster at VOBLA than at VLT (P<0.001). Well-trained runners ran a shorter TET2 than the trained runners (P<0.05). Moreover, well-trained runners presented a higher respiratory rate at 50, 80 and 90% of TET2 and VO2 at 20-100% of TET2 (P<0.05). TET2 was inversely correlated (P<0.01) with VOBLA and positively with personal best 10-km performance (P<0.01). VOBLA was positively correlated with the %VO2max in Test 2 (P<0.01). The standard value (4 mmol•L-1) for the concentration of blood lactate seems to represent a different exercise intensity for runners of different athletic ability. CONCLUSION: VOBLA may not be accurate for the design of running training sessions or for evaluation of aerobic capacity.

Adaptive response in the antioxidant defence system in the course and outcome in first-episode schizophrenia patients: a 12-months follow-up study.

Correlation of plasma antioxidant enzyme activity with the course and outcome in first-episode schizophrenia patients (n=49) was analyzed in order to assess the possible utility of peripheral markers of oxidative stress as prognostic factors. These markers were measured shortly after the onset of schizophrenia, and again 1, 6 and 12 months later. A decrease in catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione (GSH) levels and total antioxidant status (TAS), as well as an increase in thiobarbituric acid reactive substances (TBARS), were observed 1 month after (p<0.05). 6-Months later, there was a reduction in TAS, GSH, SOD and GPx, and a increase in TBARS (p<0.05), with a normalization of CAT levels, indicating a persistent alteration of the antioxidant system and the maintenance of oxidative stress. At 12-months, a considerable decrease was observed in TBARS. Additionally, while the level of GPx decreased (p<0.05) further, SOD and GSH levels and TAS were normalizing, indicating a partial regeneration of the antioxidant defence system. These results indicate the possible contribution of oxidative stress to the onset and pathophysiology of schizophrenia, suggesting the involvement of an adaptive response in the antioxidant defence system in the course and outcome in first-episode schizophrenia patients.

Influence of nutrient intake on antioxidant capacity, muscle damage and white blood cell count in female soccer players.

BACKGROUND: Soccer is a form of exercise that induces inflammatory response, as well as an increase in free radicals potentially leading to muscle injury. Balanced nutritional intake provides important antioxidant vitamins, including vitamins A, C and E, which may assist in preventing exercise-related muscle damage. The purpose of the present study was to determine the effect of macro/micronutrient intake on markers of oxidative stress, muscle damage, inflammatory and immune response in female soccer players. METHODS: Twenty-eight female players belonging to two soccer teams of the same professional soccer club participated in this study after being informed about the aims and procedures and after delivering written consent. Each team completed an 8-day dietary record and played one competition match the same week. Participants were divided into two groups: the REC group (who complied with recommended intakes) and the NO-REC group (who were not compliant). Laboratory blood tests were carried out to determine hematological, electrolytic and hormonal variables, as well as to monitor markers of cell damage and oxidative stress. Blood samples were obtained 24 h before, immediately after and 18 h after official soccer matches. Student t-test or Mann-Whitney U-test was used to compare both groups throughout the match. RESULTS: At rest, we observed that the REC group had higher levels of total antioxidant status (TAS), glutathione peroxidase (GPx), and lower levels of creatine kinase (CK) and lactate dehydrogenase (LDH) in comparison to the NO-REC group. Immediately after the match, levels of TAS, GPx, superoxide dismutase (SOD), LDH and % lymphocytes were higher and the % of neutrophils were lower in the REC group compared to the NO-REC group. These differences were also maintained 18 h post-match, only for TAS and GPx. CONCLUSIONS: Our data reveal an association between nutritional intake and muscle damage, oxidative stress, immunity and inflammation markers. The benefit of the intake of specific nutrients may contribute to preventing the undesirable physiological effects provoked by soccer matches.

Reduced antioxidant defense in early onset first-episode psychosis: a case-control study.

BACKGROUND: Our objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group. METHODS: Total antioxidant status (TAS) and lipid peroxidation (LOOH) were determined in plasma. Enzyme activities and total glutathione levels were determined in erythrocytes in 102 children and adolescents with a first psychotic episode and 98 healthy controls. RESULTS: A decrease in antioxidant defense was found in patients, measured as decreased TAS and glutathione levels. Lipid damage (LOOH) and glutathione peroxidase activity was higher in patients than controls. Our study shows a decrease in the antioxidant defense system in early onset first episode psychotic patients. CONCLUSIONS: Glutathione deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in early-onset schizophrenia. Oxidative damage is present in these patients, and may contribute to its pathophysiology.

Control of APN/CD13 and NEP/CD10 on sperm motility.

Aminopeptidase N (APN/CD13) and neutral endopeptidase (NEP/CD10) are enzymes present in human sperm cells and involved in regulation of sperm motility of noncapacitated spermatozoa. We investigated the involvement of APN/CD13 and NEP/CD10 in motility and in kinematic parameters of human capacitated spermatozoa. Sperm cells isolated by a discontinuous Percoll gradient (40%-80%) followed up by swim-up techniques were incubated with the APN/CD13-specific inhibitor, leuhistin (100 µmol L(-1)), and the NEP/CD10-specific inhibitor, thiorphan (1 µmol L(-1)). The complete inhibition of both APN/CD13 and NEP/CD10 improved sperm motility. Spermatozoa incubated with the APN/CD13-specific inhibitor leuhistin showed asymmetrical trajectories, whereas sperm trajectories were more regular after treatment with the NEP/CD10-specific inhibitor thiorphan. In conclusion, APN/CD13 and NEP/CD10 modulate the motility of capacitated spermatozoa, although each of the enzymes seems to participate in the control of different aspects of sperm motility. Therefore, both inhibitors may be useful for sperm activation at different functional stages of spermatozoa.

Angiotensin-converting enzymes (ACE and ACE2) are downregulated in renal tumors.

The angiotensin-converting enzymes (ACE and ACE2) are highly expressed in renal tubules and play an important role in the regulation of renal function by the intrarenal renin-angiotensin system (iRAS). Dysregulation of these cell-surface peptidases has been associated with renal injury. Most of these studies, however, have focused on non-neoplastic kidney diseases. In the present study, ACE and ACE2 activity and protein and mRNA expression were analysed in a subset of clear-cell (CCRCC) and chromophobe (ChRCC) renal cell carcinomas, and in renal oncocytoma (RO). Enzyme activity was measured by spectrofluorometric (ACE2) and spectrophotometric assays (ACE), and protein and mRNA expression were determined by immunohistochemistry and qRT-PCR assays, respectively. The enzyme activities and immunohistochemistry showed that both enzymes are mainly downregulated in these neoplasms. qRT-PCR studies in CCRCC showed no positive correlation between ACE and ACE2 activity/protein expression and mRNA levels, whereas downregulation of ACE2 mRNA levels was observed in tumors from the distal nephron (ChRCC and RO). These findings suggest a metabolic imbalance in iRAS and a role of this system in renal neoplastic diseases, and point to ACE and ACE2 as potential prognostic/diagnostic markers.

Autocrine regulation of human sperm motility by tachykinins.

BACKGROUND: We examined the presence and function of tachykinins and the tachykinin-degrading enzymes neprilysin (NEP) and neprilysin-2 (NEP2) in human spermatozoa. METHODS: Freshly ejaculated semen was collected from forty-eight normozoospermic human donors. We analyzed the expression of substance P, neurokinin A, neurokinin B, hemokinin-1, NEP and NEP2 in sperm cells by reverse-transcriptase polymerase chain reaction (RT-PCR), western blot and immunocytochemistry assays and evaluated the effects of the neprilysin and neprilysin-2 inhibitor phosphoramidon on sperm motility in the absence and presence of tachykinin receptor-selective antagonists. Sperm motility was measured using WHO procedures or computer-assisted sperm analysis (CASA). RESULTS: The mRNAs of the genes that encode substance P/neurokinin A (TAC1), neurokinin B (TAC3), hemokinin-1 (TAC4), neprilysin (MME) and neprilysin-2 (MMEL1) were expressed in human sperm. Immunocytochemistry studies revealed that tachykinin and neprilysin proteins were present in spermatozoa and show specific and differential distributions. Phosphoramidon increased sperm progressive motility and its effects were reduced in the presence of the tachykinin receptor antagonists SR140333 (NK1 receptor-selective) and SR48968 (NK2 receptor-selective) but unmodified in the presence of SR142801 (NK3 receptor-selective). CONCLUSION: These data show that tachykinins are present in human spermatozoa and participate in the regulation of sperm motility. Tachykinin activity is regulated, at least in part, by neprilysins.

Expression and activity profiles of DPP IV/CD26 and NEP/CD10 glycoproteins in the human renal cancer are tumor-type dependent.

BACKGROUND: Cell-surface glycoproteins play critical roles in cell-to-cell recognition, signal transduction and regulation, thus being crucial in cell proliferation and cancer etiogenesis and development. DPP IV and NEP are ubiquitous glycopeptidases closely linked to tumor pathogenesis and development, and they are used as markers in some cancers. In the present study, the activity and protein and mRNA expression of these glycoproteins were analysed in a subset of clear-cell (CCRCC) and chromophobe (ChRCC) renal cell carcinomas, and in renal oncocytomas (RO). METHODS: Peptidase activities were measured by conventional enzymatic assays with fluorogen-derived substrates. Gene expression was quantitatively determined by qRT-PCR and membrane-bound protein expression and distribution analysis was performed by specific immunostaining. RESULTS: The activity of both glycoproteins was sharply decreased in the three histological types of renal tumors. Protein and mRNA expression was strongly downregulated in tumors from distal nephron (ChRCC and RO). Moreover, soluble DPP IV activity positively correlated with the aggressiveness of CCRCCs (higher activities in high grade tumors). CONCLUSIONS: These results support the pivotal role for DPP IV and NEP in the malignant transformation pathways and point to these peptidases as potential diagnostic markers.

Increased prolyl endopeptidase activity in human neoplasia.

Prolyl endopeptidase (EC 3.4.21.26) (PEP) is a serine peptidase that converts several biologically active peptides. This enzyme has been linked to several neurological, digestive, cardiovascular and infectous disorders. However, little is known about its involvement in neoplastic processes. This study analyzes fluorimetrically cytosolic and membrane-bound PEP activity in a large series (n=122) of normal and neoplastic tissues from the kidney, colon, oral cavity, larynx, thyroid gland and testis. Cytosolic PEP activity significantly increased in clear cell renal cell carcinoma, urothelial carcinoma of the renal pelvis and head and neck squamous cell carcinoma. Both cytosolic and membrane-bound PEP activity were also increased in colorectal adenomatous polyps. These data suggest the involvement of PEP in some mechanisms that underlie neoplastic processes.

Cell damage, antioxidant status, and cortisol levels related to nutrition in ski mountaineering during a two-day race.

The aim of this study was to measure the effect of nutrition on cell damage, antioxidant enzymes, and cortisol during a two-day ski mountaineering competition. Twenty-one male skiers participated in the study. Creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (AP), cortisol and C-reactive protein (CRP), glutathione peroxidase (GPx) and reductase activities (GR) and C-reactive protein (CRP) levels, total antioxidant status, and cortisol levels were measured in serum the day before and immediately after the race. Their diet was also analysed during the competition. Enzymes and cortisol levels significantly increased after the competition. CK and LDH and cortisol levels were negatively correlated to total energy, protein, and fat intake. Intake of vitamin A, B1, B2, B6 and niacin was negatively correlated to LDH and AP. A negative correlation was also found between CK activity and Na, Fe, and Zn intake. Cortisol levels were negatively correlated to the intake of vitamins C, B1 and B2, and niacin. A positive correlation was found between serum GPx and intake of energy, carbohydrates, proteins, A and B vitamins, and folic acid. Skiers with the lowest nutrient intake during the competition were the ones who showed greater cell damage and lower antioxidant enzyme activity and cortisol levels, which may impair performance and also cause injuries and accidents. Particularly, skiers should have high intakes of total energy, macronutrients, vitamins A and B, Na, Zn, and Fe in order to decrease the deleterious effect of strenuous exercise. Key pointsA two-day ski mountaineering race produced muscle cell damage and oxidative stress and an increase in cortisol levels.There was a marked insufficient intake of carbohydrates which has been shown to affect performanceThose skiers with lowest nutrient intake showed greater cell damage, lower antioxidant activity and higher cortisol levels.Nutrition should be carefully monitored and assessed in order to minimize the mentioned blood changes to avoid fatigue, injuries and also accidents in this type of sport; particularly when skiers must carry their own food.