Wearable piezoelectric mass sensor based on pH sensitive hydrogels for sweat pH monitoring.

Colorimetric and electrochemical (bio)sensors are commonly employed in wearable platforms for sweat monitoring; nevertheless, they suffer from low stability of the sensitive element. In contrast, mass-(bio)sensors are commonly used for analyte detection at laboratory level only, due to their rigidity. To overcome these limitations, a flexible mass-(bio)sensor for sweat pH sensing is proposed. The device exploits the flexibility of piezoelectric AlN membranes fabricated on a polyimide substrate combined to the sensitive properties of a pH responsive hydrogel based on PEG-DA/CEA molecules. A resonant frequency shift is recorded due to the hydrogel swelling/shrinking at several pH. Our device shows a responsivity of about 12 kHz/pH unit when measured in artificial sweat formulation in the pH range 3-8. To the best of our knowledge, this is the first time that hydrogel mass variations are sensed by a flexible resonator, fostering the development of a new class of compliant and wearable devices.

Natural and synthetic avenanthramides activate caspases 2, 8, 3 and downregulate hTERT, MDR1 and COX-2 genes in CaCo-2 and Hep3B cancer cells.

Avenanthramides (AVNs) are natural polyphenols obtained from oat sprouts and can also be chemically synthetized. The aim of the present study was to assess the anticancer, anti-inflammatory and antioxidant effects of individual synthetized AVNs (s-2c, s-2p, s-2f) and a natural AVN mixture (n-MIX) on CaCo-2 and Hep3B cancer cells. In CaCo-2, the AVN s-2c was found to be the most cytotoxic followed by the n-MIX. In Hep3B cells, a marked cytotoxic effect was found but no significant difference was observed between the synthesized AVNs and the n-MIX. In both CaCo-2 and Hep3B cells, natural and synthetic AVNs activated caspases 8 and 3, and the n-MIX and the AVN s-2c were also able to activate caspase 2. Both synthetic and natural AVNs downregulated pro-survival genes hTERT, COX-2 and MDR1, inhibited the activity of pro-inflammatory COX-2 enzyme and reduced prostaglandin E2 levels, showing the potent chemopreventive effects of these oat-derived phytochemicals. Synthetic AVN s-2c was found to have the highest chemical antioxidant capacity, as indicated by ORAC, DPPH and ABTS values, whereas all AVNs and n-MIX were shown to have similar intracellular antioxidant activity, evaluated by means of the DCFH-DA assay. As AVNs have high bioavailability in humans, results of this study suggest that oat-based foods, fortified with AVNs, could be an alternative to produce functional foods with anticancer, anti-inflammatory and antioxidant effects for health benefits.

Betalains increase vitexin-2-O-xyloside cytotoxicity in CaCo-2 cancer cells.

Vitexin-2-O-xyloside (XVX) from Beta vulgaris var. cicla L. (BVc) seeds, betaxanthin (R1) and betacyanin (R2) fractions from Beta vulgaris var. rubra L. (BVr) roots were combined and tested for cytotoxicity in CaCo-2 colon cancer cells. XVX was the most cytotoxic molecule, but the combination of XVX with R1 and R2 significantly prolonged its cytotoxicity. Cytotoxicity was mediated by the intrinsic apoptotic pathway, as shown by an increase in Bcl2-like protein 4, cleaved Poly ADP-Ribosyl Polymerase 1 and cleaved Caspase 3 levels with a parallel decrease in anti-apoptotic protein B-cell leukemia/lymphoma 2 levels. R1 and R2, used alone or in combination, reduced oxidative stress triggered by H2O2 in CaCo-2 cells. Betalains dampened cyclooxygenase-2 and interleukin-8 mRNA expression after lipopolysaccharide induction in CaCo-2, showing an anti-inflammatory action. Our results support the use of a cocktail of R1, R2 and XVX as a chemopreventive tool against colon cancer.

Betacyanins enhance vitexin-2-O-xyloside mediated inhibition of proliferation of T24 bladder cancer cells.

Betacyanins (BC) were purified from beetroot (Beta vulgaris var. rubra L.) and tested, alone or in combination with vitexin-2-O-xyloside (XVX) from Beta vulgaris var. cicla L., for their ability to reduce the proliferation rate in T24 bladder cancer cells. Combination of BC and XVX exhibited a synergistic effect concerning the inhibition of proliferation in T24 cancer cells at 24 and 48 h but not after 72 h of incubation. The induction of apoptosis was evidenced by means of fluorescence activated cell sorting (FACS) analysis, as well as through the increase in caspase 3 and 8 activities. Using RTqPCR experiments, it was shown that the combination of XVX + BC was able to enhance the expression levels of pro-apoptotic BAX and downregulate anti-apoptotic BIRC5 (survivin), as well as pro-survival CTNNB1 (ß-catenin). The most evident effect of BC was the increase of the activity of caspase 8, leading to induction of extrinsic apoptosis. Moreover, XVX, BC and their combination showed no cytotoxic effect on normal human skin NCTC 2544 keratinocytes. These results demonstrated the efficacy and the mechanisms of the action of BC and XVX, extracted from edible plants, and suggested that a diet or a nutrition supplement, enriched with these bioactive molecules, could be used in the prevention of human bladder cancer.

Bone induction at physiological doses of BMP through localization by clay nanoparticle gels.

Bone Morphogenic Protein 2 (BMP2) can induce ectopic bone. This ability, which first motivated the widespread application of BMP2 in fracture healing and spinal arthrodesis has, more recently, been indicated as one of several serious adverse effects associated with the supra-physiological doses of BMP2 relied upon for clinical efficacy. Key to harnessing BMPs and other agents safely and effectively will be the ability to localize activity at a target site at substantially reduced doses. Clay (Laponite) nanoparticles can self assemble into gels under physiological conditions and bind growth factors for enhanced and localized efficacy. Here we show the ability to localize and enhance the activity of BMP2 to achieve ectopic bone formation at doses within the sub-microgram per ml range of concentrations sufficient to induce differentiation of responsive cell populations in vitro and at approximately 3000 fold lower than those employed in clinical practice.

Laparoscopic peritoneal lavage for perforated colonic diverticulitis: a definitive treatment? Retrospective analysis of 63 cases.

BACKGROUND: The ideal treatment of perforated diverticulitis and the indications for elective colon resection remain controversial. Considering the significant morbidity and mortality rates related to traditional resection, efforts have been made to reduce the invasiveness of surgery in recent decades. Laparoscopic peritoneal lavage has emerged as an effective alternative option. We retrospectively investigated the effectiveness of laparoscopic peritoneal lavage for perforated diverticulitis and the possibility that it could be a definitive treatment. METHODS: We included patients treated with laparoscopic peritoneal lavage for perforated diverticulitis. The inclusion criteria were all emergency patients with generalized peritonitis due to Hinchey III perforated diverticulitis and some cases of Hinchey II and IV. RESULTS: Sixty-three patients were treated with laparoscopic peritoneal lavage. Six patients (9.5 %) had Hinchey II diverticulitis; 54 patients (85.7 %) had Hinchey III; and three patients (4.8 %) had Hinchey IV. The mean operative time was 87.3 min (±25.4 min), and the overall morbidity rate was 14.3 %. One patient died because of pulmonary embolism, and there were six early reinterventions because of treatment failure. Delayed colon resection was performed in four of the remaining 57 patients (7 %) because of recurrent diverticulitis. In the other 53 patients (93 %), we saw no recurrence of diverticulitis and no intervention was performed after a median follow-up period of 54 months (interquartile range 27-98 months). CONCLUSIONS: Laparoscopic peritoneal lavage for perforated diverticulitis can be considered a safe and effective alternative to traditional surgical resection, and using this approach, most elective colon resection might be avoided.

The dilemma of pneumatosis intestinalis with pneumoperitoneum: nonoperative or surgical management-analysis of a case.

Pneumatosis intestinalis (PI) is an uncommon condition and can be associated with a wide spectrum of diseases, ranging from life-threatening to innocuous conditions. We report the case of a 46-year-old women coming to our attention for an acute abdominal pain, nausea, vomiting, constipation, and increased inflammatory marks, with a CT showing pneumoperitoneum and pneumatosis intestinalis. The previous diagnosis was advanced neoplasia of unknown origin. Despite the surgical intervention, which excluded an ischemic colitis, the patient died in the early postoperative period. The postmortem diagnosis was carcinoma of thymus gland, and the presence of pneumatosis was put down to metastasis nodes in the pulmonary parenchima. This case demonstrates the wide spectrum of presentation of pneumatosis intestinalis, the importance of a careful radiologic evaluation beside the clinical history, since the identification of correct pathogenesis and treatment can be very difficult.

Cerebrospinal fluid and serum neuron-specific enolase in acute benign headache.

We determined the cerebrospinal fluid (CSF) and serum neuron-specific enolase (NSE) concentrations in 19 patients with acute benign headache. All patients had normal neurological examination, CSF and head computed tomography scan. The final diagnoses were: primary thunderclap headache (n = 7), primary exertional headache (n = 3), primary cough headache (n = 1), migraine without aura (n = 4), headache unspecified (n = 2), probable infrequent episodic tension-type headache (n = 1), headache attributed to hypertensive crisis without hypertensive encephalopathy (n = 1). A group of 108 healthy subjects served as controls. CSF NSE concentration was 14.16 ng/ml [95% confidence interval (CI) 11.86, 16.47)] in the headache sample (controls 17.19 ng/ml, 95% CI 16.23, 18.15). Serum NSE concentration was 7.50 ng/ml (95% CI 5.20, 9.80) in the headache sample (controls 8.45 ng/ml, 95% CI 7.67, 9.23). CSF/serum ratio was 2.81 (95% CI 2.21, 3.40) in the headache sample (controls 2.23, 95% CI 2.03, 2.42). Acute benign headache is not associated with neuronal damage as estimated by means of CSF and serum NSE concentration.

Cerebrospinal fluid and serum neuron-specific enolase concentrations in a normal population.

The aim of this study was to determine cerebrospinal fluid (CSF) and serum neuron-specific enolase (NSE) concentrations in a normal population and to analyse their relationship with sex and age. The sample was recruited among patients undergoing spinal anaesthesia, without neurological diseases. NSE was determined by means of immunometric assay. One hundred and eight patients (68 men) were recruited. CSF-NSE concentration was (mean +/- SD) 17.3 +/- 4.6 ng/ml (men 17.4 +/- 4.2, women 17.0 +/- 5.2, P = 0.62); serum concentration was 8.7 +/- 3.9 ng/ml (men 8.9 +/- 3.9, women 8.3 +/- 4.0, P = 0.06). The mean CSF/serum NSE ratio was 2.3 +/- 0.8 (men 2.2 +/- 0.8, women 2.4 +/- 0.9, P = 0.22). In both sexes, simple regression analysis showed not significantly increasing concentrations with advancing age for both CSF and serum NSE. Serum and CSF concentrations did not correlate in both sexes. In our study, CSF-NSE was twice the serum concentration; both were not influenced by sex or age. Serum and CSF-NSE values vary widely among different studies on normal populations because of different determination methods; therefore, each laboratory should obtain its own reference values. Finally, serum NSE should be used with caution as an indicator of CSF concentration as no correlation could be demonstrated between them in our study.

Urodinâmica convencional versus cistometria simplificada para caracterização da incontinência urinária feminina / Conventional urodynamics versus simplified cystometry for characterization of female urinary incontinence

Objetivo: avaliar a concordância dos diferentes parâmetros urodinâmicos comparados à cistometria simplificada, permitindo uma diminuição na relação custo-benefício no diagnóstico da incontinência urinária de esforço (IUE) na mulher. Métodos: foram coletadas e avaliadas retrospectivamente as informações contidas dos prontuários de trinta pacientes acompanhadas, no período de janeiro de 2000 a março de 2001. Todas foram submetidas a exame físico geral e ginecológico. O estudo urodinâmico foi realizado pela técnica convencional, utilizando-se aparelho Dynograph Recorder R-611. A cistometria simplificada foi realizada com auxílio de um equipo em "Y" de PVC (pressão venosa central), conectado a um sonda de Foley 14 F, que permitia tanto a infusão de soro fisiológico como a captação da pressão intra-vesical. Foram analisados os parâmetros: volume residual, capacidade vesical, complacência, presença de contrações involuntárias do detrusor e perdas urinárias aos esforços. Para determinação da proporção de concordância entre os métodos foram utilizados o teste de concordância de Pearson e o teste de Wilcoxon, para amostras relacionadas. Resultados: a média de idade foi de 50 anos, com extremos variando de 28 a 70 anos. O índice de concordância entre os estudos, na demonstração das perdas urinárias aos esforços, foi de 67 por cento. Para a detecção das contrações involuntárias do detrusor, a proporção de concordância foi de 90 por cento. A média do volume residual encontrado na cistometria simplificada foi de 16,8 ml contra 2 ml da urodinâmica convencional, com diferença significativa (p < 0, 01). A média de capacidade vesical máxima no estudo urodinâmico foi de 440,5 ml enquanto que, na cistometria simplificada, foi de 387 ml (p < 0,05). A complacência vesical foi, em média, significativamente maior na cistometria simplificada (43,0 ml/cmH2O) quando comparada ao estudo urodinâmico (31,5 ml/cmH2O), com p < 0,01. Conclusão: avaliações preliminares sugerem que a propedêutica uroginecológica associada à cistometria simplificada é uma opção a ser considerada na avaliação clínica e pré-operatória de pacientes com IVE em substituiçâo à urodinâmica convencional, particularmente onde esta última não se encontra disponível. A cistometria simplificada é um exame acessível que é capaz de detectar contrações involuntárias do detrusor, assim como identificar perdas urinárias com relativa sensibilidade, proporcionando ao examinador noções fidedignas do comportamento vesical.

Slow-release lanreotide treatment in acromegaly: effects on quality of life.

BACKGROUND: It is not known whether medical treatment to lower growth hormone (GH) and insulin-like growth factor (IGF)-1 levels may improve the compromised quality of life of patients with acromegaly. METHODS: We studied the effects on quality of life of the slow-release somatostatin analogue lanreotide, 30 mg i.m., every 14 days for 2 months in 10 patients with active acromegaly (8 females/2 males, mean age 57.3 +/- 11.4). Hormone measurements and psychometric evaluation by means of self-rating scales were carried out in baseline conditions and after 1 and 2 months. The Symptom Questionnaire (SQ), the Cognitive Scale of the Screening List for Psychosocial Problems by Kellner and the Social Situation Questionnaire by Marks were employed. RESULTS: Together with a significant decrease in GH and IGF-1, treatment with lanreotide significantly improved SQ psychological distress, SQ well-being and Social Situation Questionnaire social fears. CONCLUSION: Medical treatment with lanreotide may improve the quality of life of patients with acromegaly. Being an open trial, changes could be due to nonspecific effects. However, they did not fade at 2 months. Improvement involved fears of social situations that have been linked to GH abnormalities.

Age-related changes in glucocorticoid fast feedback inhibition of adrenocorticotropin in man.

A decrease in hypothalamic-pituitary-adrenal axis sensitivity to glucocorticoid feedback suppression seems to occur with aging. To investigate possible abnormalities in the inhibitory effect of glucocorticoids on ACTH secretion in the elderly, we evaluated the endogenous ACTH response to hydrocortisone (25 mg as an i.v. bolus) in 15 healthy aged (65-88 yr) and 15 healthy young (18-26 yr) men. Blood samples for ACTH and cortisol determinations were collected at -15, 0, 2, 5, 10, 15, 30, 45, 60, 90, 120, and 180 min. Hydrocortisone injection produced a rapid increase in plasma cortisol levels within the first 2 min in both groups. In old men, in concomitance with the cortisol increase, ACTH levels showed only a slight and nonsignificant decrease within the first 15 min, followed by a pronounced and significant decline thereafter. In young subjects, in concomitance with the plasma cortisol increase, a marked decrease in ACTH levels was observed within the first 15 min, followed by a less pronounced decline thereafter. The response curve of ACTH inhibition could be arbitrarily divided in two parts. The first part (from 0-60 min) showed a significant difference between old and young men, whereas the remaining part of the curve (from 60-180 min) showed no differences between the two groups. The slower response in glucocorticoid feedback inhibition of ACTH in old men supports the concept of some alteration in the central regulation by steroids in aging. Age-related vascular factors affecting cortisol penetration through the blood-brain barrier more than hippocampus-hypothalamus receptor abnormalities could be involved in the fast component of hypothalamic-pituitary-adrenal axis feedback regulation.