Brain natriuretic peptide is able to stimulate cardiac progenitor cell proliferation and differentiation in murine hearts after birth.

Brain natriuretic peptide (BNP) contributes to heart formation during embryogenesis. After birth, despite a high number of studies aimed at understanding by which mechanism(s) BNP reduces myocardial ischemic injury in animal models, the actual role of this peptide in the heart remains elusive. In this study, we asked whether BNP treatment could modulate the proliferation of endogenous cardiac progenitor cells (CPCs) and/or their differentiation into cardiomyocytes. CPCs expressed the NPR-A and NPR-B receptors in neonatal and adult hearts, suggesting their ability to respond to BNP stimulation. BNP injection into neonatal and adult unmanipulated mice increased the number of newly formed cardiomyocytes (neonatal: +23 %, p = 0.009 and adult: +68 %, p = 0.0005) and the number of proliferating CPCs (neonatal: +142 %, p = 0.002 and adult: +134 %, p = 0.04). In vitro, BNP stimulated CPC proliferation via NPR-A and CPC differentiation into cardiomyocytes via NPR-B. Finally, as BNP might be used as a therapeutic agent, we injected BNP into mice undergoing myocardial infarction. In pathological conditions, BNP treatment was cardioprotective by increasing heart contractility and reducing cardiac remodelling. At the cellular level, BNP stimulates CPC proliferation in the non-infarcted area of the infarcted hearts. In the infarcted area, BNP modulates the fate of the endogenous CPCs but also of the infiltrating CD45(+) cells. These results support for the first time a key role for BNP in controlling the progenitor cell proliferation and differentiation after birth. The administration of BNP might, therefore, be a useful component of therapeutic approaches aimed at inducing heart regeneration.

Hypothermia Prevention During Surgery: Comparison Between Thermal Mattress And Thermal Blanket


This study aimed to compare the efficiency of the thermal blanket and thermal mattress in the prevention of hypothermia during surgery. Thirty-eight randomized patients were divided into two groups (G1 – thermal blanket and G2 - thermal mattress). The variables studied were: length of surgery, length of stay in the post-anesthetic care unit, period without using the device after thermal induction, transport time from the operating room to post-anesthetic care unit, intraoperative fluid infusion, surgery size, anesthetic technique, age, body mass index, esophageal, axillary and operating room temperature. In G2, length of surgery and starch infusion longer was higher (both p=0.03), but no hypothermia occurred. During the surgical anesthetic procedure, the axillary temperature was higher at 120 minutes (p=0.04), and esophageal temperature was higher at 120 (p=0.002) and 180 minutes (p=0.03) and at the end of the procedure (p=0.002). The thermal mattress was more effective in preventing hypothermia during surgery.

Dietary vitamin D and cancers of the oral cavity and esophagus.

BACKGROUND: Data on the association between vitamin D and upper digestive tract neoplasms are limited. METHODS: In two case-control studies in Italy, we examined the relation between dietary vitamin D intake and squamous cell carcinoma of the esophagus (SCCE; 304 cases) and oral/pharyngeal cancer (804 cases). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by multiple logistic regression. RESULTS: Adjusted ORs for SCCE and oral/pharyngeal cancer were 0.58 (95% CI 0.39-0.86) and 0.76 (95% CI 0.60-0.94), respectively, for the highest tertile of vitamin D intake. Using a reference group of those in the highest tertile of vitamin D who were never/former smokers, ORs were 8.7 (95% CI 4.1-18.7) for SCCE and 10.4 (95% CI 6.9-15.5) for oral/pharyngeal cancer among heavy smokers in the lowest vitamin D tertile; similarly, compared with those in the highest tertile of vitamin D who drank <3 alcoholic drinks/day, corresponding ORs were 41.9 (95% CI 13.7-128.6) for SCCE and 8.5 (95% CI 5.7-12.5) for oral/pharyngeal cancer, among heavy alcohol drinkers in the lowest vitamin D tertile. CONCLUSION: We observed inverse associations between dietary vitamin D intake and risk of SCCE and, perhaps, oral/pharyngeal cancer, which were most pronounced among heavy current smokers and heavy consumers of alcohol.

Dietary folates and cancer risk in a network of case-control studies.

Background Folate deficiency leads to DNA damage and inadequate repair, caused by a decreased synthesis of thymidylate and purines. We analyzed the relationship between dietary folate intake and the risk of several cancers. Patients and methods The study is based on a network of case-control studies conducted in Italy and Switzerland in 1991-2009. The odds ratios (ORs) for dietary folate intake were estimated by multiple logistic regression models, adjusted for major identified confounding factors. Results For a few cancer sites, we found a significant inverse relation, with ORs for an increment of 100 μg/day of dietary folate of 0.65 for oropharyngeal (1467 cases), 0.58 for esophageal (505 cases), 0.83 for colorectal (2390 cases), 0.72 for pancreatic (326 cases), 0.67 for laryngeal (851 cases) and 0.87 for breast (3034 cases) cancers. The risk estimates were below unity, although not significantly, for cancers of the endometrium (OR = 0.87, 454 cases), ovary (OR = 0.86, 1031 cases), prostate (OR = 0.91, 1468 cases) and kidney (OR = 0.88, 767 cases), and was 1.00 for stomach cancer (230 cases). No material heterogeneity was found in strata of sex, age, smoking and alcohol drinking. Conclusions Our data support a real inverse association of dietary folate intake with the risk of several common cancers.

Rapid fatal outcome from pulmonary arteries compression in transitional cell carcinoma.

Transitional cell carcinoma of the urinary bladder is a malignancy that metastasizes frequently to lymph nodes including the mediastinal lymph nodes. This occurrence may produce symptoms due to compression of adjacent structures such as the superior vena cava syndrome or dysphagia from esophageal compression. We report the case of a 59-year-old man with metastatic transitional cell carcinoma for whom mediastinal lymphadenopathy led to pulmonary artery compression and a rapidly fatal outcome. This rare occurrence has to be distinguished from pulmonary embolism, a much more frequent event in cancer patients, in order that proper and prompt treatment be initiated.

Diabetes mellitus and cancer risk in a network of case-control studies.

Diabetes has been associated to the risk of a few cancer sites, though quantification of this association in various populations remains open to discussion. We analyzed the relation between diabetes and the risk of various cancers in an integrated series of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1,468 oral and pharyngeal, 505 esophageal, 230 gastric, 2,390 colorectal, 185 liver, 326 pancreatic, 852 laryngeal, 3,034 breast, 607 endometrial, 1,031 ovarian, 1,294 prostate, and 767 renal cell cancer cases and 12,060 hospital controls. The multivariate odds ratios (OR) for subjects with diabetes as compared to those without-adjusted for major identified confounding factors for the cancers considered through logistic regression models-were significantly elevated for cancers of the oral cavity/pharynx (OR = 1.58), esophagus (OR = 2.52), colorectum (OR = 1.23), liver (OR = 3.52), pancreas (OR = 3.32), postmenopausal breast (OR = 1.76), and endometrium (OR = 1.70). For cancers of the oral cavity, esophagus, colorectum, liver, and postmenopausal breast, the excess risk persisted over 10 yr since diagnosis of diabetes. Our data confirm and further quantify the association of diabetes with colorectal, liver, pancreatic, postmenopausal breast, and endometrial cancer and suggest forthe first time that diabetes may also increase the risk of oral/pharyngeal and esophageal cancer. [Table: see text] [Table: see text].

Identification of a new cancer/testis gene family, CT47, among expressed multicopy genes on the human X chromosome.

Cancer/testis (CT) genes are normally expressed in germ cells only, yet are reactivated and expressed in some tumors. Of the approximately 40 CT genes or gene families identified to date, 20 are on the X chromosome and are present as multigene families, many with highly conserved members. This indicates that novel CT gene families may be identified by detecting duplicated expressed genes on chromosome X. By searching for transcript clusters that map to multiple locations on the chromosome, followed by in silico analysis of their gene expression profiles, we identified five novel gene families with testis-specific expression and >98% sequence identity among family members. The expression of these genes in normal tissues and various tumor cell lines and specimens was evaluated by qualitative and quantitative RT-PCR, and a novel CT gene family with at least 13 copies was identified on Xq24, designated as CT47. mRNA expression of CT47 was found mainly in the testes, with weak expression in the placenta. Brain tissue was the only positive somatic tissue tested, with an estimated CT47 transcript level 0.09% of that found in testis. Among the tumor specimens tested, CT47 expression was found in approximately 15% of lung cancer and esophageal cancer specimens, but not in colorectal cancer or breast cancer. The putative CT47 protein consists of 288 amino acid residues, with a C-terminus rich in alanine and glutamic acid. The only species other than human in which a gene homologous to CT47 has been detected is the chimpanzee, with the predicted protein showing approximately 80% identity in its carboxy terminal region.

Actions of β2-adrenoceptor agonist drug on human soleus muscle contraction.

PURPOSE: The effects of β(2)-agonists on human skeletal muscle contractile properties, particularly on slow fibers, are unclear. Moreover, it remains to be ascertained whether central motor drive (CMD) during voluntary contractions could counter for eventual contractile alterations induced by β(2)-agonists. This study investigated central and peripheral neuromuscular adjustments induced by β(2)-agonist terbutaline on a predominantly slow human muscle, the soleus. METHODS: Ten recreationally active men ingested either a single dose of 8 mg of terbutaline or placebo in a randomized double-blind order (two experimental sessions). Isometric plantarflexion torque was measured during single and tetanic (10 and 100 Hz) stimulations as well as during submaximal and maximal voluntary contractions (MVC). Twitch peak torque and half-relaxation time were calculated. CMD was estimated via soleus electromyographic recordings obtained during voluntary contractions performed at approximately 50% MVC. RESULTS: MVC and twitch peak torque were not modified by terbutaline. Twitch half-relaxation time was 28% shorter after terbutaline administration compared with placebo (P < 0.001). Tetanic torques at 10 and 100 Hz were significantly lower after terbutaline intake compared with placebo (-40% and -24% respectively, P < 0.001). Despite comparable torque of submaximal voluntary contractions in the two conditions, CMD was 7% higher after terbutaline ingestion compared with placebo (P < 0.01). CONCLUSION: These results provide evidence that terbutaline modulates the contractility of the slow soleus muscle and suggest that the increased CMD during submaximal contractions may be viewed as a compensatory adjustment of the central nervous system to counter the weakening action induced by terbutaline on the contractile function of slow muscle fibers.

Aortobronchial and aortoesophageal fistulae as risk factors in surgery of descending thoracic aortic aneurysms.

OBJECTIVE: Assess outcome of patients with descending thoracic aortic aneurysms complicated by aortobronchial and aortoesophageal fistulae in comparison to patients undergoing repair of aortic aneurysms without fistulae. METHODS: In a consecutive series of 145 patients (age 60 +/- 12 years) with repair of descending thoracic and thoracoabdominal aortic aneurysms, 11 patients (8%; age 63 +/- 9; NS) primarily presented for hematemesis and/or hemoptysis. In 8/11 patients (73%) an aortobronchial fistula was identified, and 3/11 patients (27%) suffered from an aortoesophageal fistula. Five of 11 patients (45%) had undergone previous aortic surgery in the same region. RESULTS: Extent of aortic segments (range 1-8) replaced was 3.1 +/- 1.4 for all versus 2.6 +/- 0.9 for fistulae (NS). Aortic cross clamp time was 38 +/- 22 min for all versus 45 +/- 15 min for fistulae (NS). Mortality at 30 days was 18/145 (12%) for all versus 16/134 (12%) without fistulae versus 2/11 (18%) with fistulae (NS). Paraparesis and or paraplegia was observed in 11/145 (8%) for all versus 10/134 (7%) without fistulae versus 1/11 (9%) for cases with fistulae (NS). Nine additional patients died after hospital discharge, seven without fistulae and two with fistulae (days 80, and 120) bringing the 1-year mortality up to 23/134 (17%) without fistulae versus 4/11 (36%) with fistulae (NS). Further analysis shows that the 1-year mortality accounts for 1/8 patients (13%) with aorto-bronchial fistulae versus to 3/3 patients (100%) with aorto-esophageal fistulae (esophageal versus bronchial fistula: P = 0.018; esophageal versus no fistula: P = 0.006). CONCLUSIONS: Outcome of patients suffering from descending thoracic aortic aneurysms complicated by aorto-bronchial fistulae can be similar to that without fistulae, whereas for cases complicated by aorto-esophageal fistulae the prognosis seems to remain poor even after successful hospital discharge.

Partial cricotracheal resection for severe pediatric subglottic stenosis: update of the Lausanne experience.

Until recently, severe pediatric subglottic stenosis (SGS) has been treated almost exclusively by laryngotracheoplasty procedures. Even in the most experienced centers, the results of single-stage operations for Cotton's grade III and IV stenoses have been disappointing. This paper reports our experience on 31 partial cricotracheal resections for severe SGS in infants and children. The stenosis was congenital in 6 cases and acquired after prolonged intubation in 25 cases. Twenty-seven patients were tracheotomy-dependent at the time of surgery. Twenty-two cases were classified as grade III and 9 cases as grade IV stenoses according to Cotton. The decannulation rate was 97% (30 of 31 cases) after an open procedure. There were no fatalities and no lesions to the recurrent laryngeal nerves, but there was 1 complete restenosis. Twenty-seven patients show no exertional dyspnea, 3 have a slight stridor with some dyspnea while exercising, and 1 patient is not decannulated. The voice is normal in 21 cases, a dysphonia is present in 9 cases, and the patient with complete restenosis acquired an esophageal voice. Postoperative follow-up is longer than 10 years in 8 cases and longer than 5 years in an additional 6 cases. All patients who reached adulthood show normal growth of the larynx and trachea. Considering the excellent results obtained in this consecutive series of 31 cases, partial cricoid resection with primary thyrotracheal anastomosis should be considered an important treatment option for severe SGS in infants and children.

Eosinophilic esophagitis: overview of clinical management.

A validated disease-specific symptom-assessment tool for eosinophilic esophagitis (EoE) has yet to be approved by regulatory authorities for use in clinical trials. Relevant end points for daily practice include EoE-related symptoms and esophageal eosinophilic inflammation. Endoscopic features should also be taken into account when establishing a therapy plan. A reasonable clinical goal is to achieve a reduction in EoE-related symptoms and esophageal eosinophilic inflammation. Evidence is increasing to support an anti-inflammatory maintenance therapy, as this can reduce esophageal remodeling. In EoE patients in clinical remission, annual disease monitoring with symptom, endoscopic, and histologic assessments of sustained treatment response is recommended.

Endotoxin impairs cardiac hemodynamics by affecting loading conditions but not by reducing cardiac inotropism.

Acute myocardial dysfunction is a typical manifestation of septic shock. Experimentally, the administration of endotoxin [lipopolysacharride (LPS)] to laboratory animals is frequently used to study such dysfunction. However, a majority of studies used load-dependent indexes of cardiac function [including ejection fraction (EF) and maximal systolic pressure increment (dP/dt(max))], which do not directly explore cardiac inotropism. Therefore, we evaluated the direct effects of LPS on myocardial contractility, using left ventricular (LV) pressure-volume catheters in mice. Male BALB/c mice received an intraperitoneal injection of E. coli LPS (1, 5, 10, or 20 mg/kg). After 2, 6, or 20 h, cardiac function was analyzed in anesthetized, mechanically ventilated mice. All doses of LPS induced a significant drop in LV stroke volume and a trend toward reduced cardiac output after 6 h. Concomitantly, there was a significant decrease of LV preload (LV end-diastolic volume), with no apparent change in LV afterload (evaluated by effective arterial elastance and systemic vascular resistance). Load-dependent indexes of LV function were markedly reduced at 6 h, including EF, stroke work, and dP/dt(max). In contrast, there was no reduction of load-independent indexes of LV contractility, including end-systolic elastance (ejection phase measure of contractility) and the ratio dP/dt(max)/end-diastolic volume (isovolumic phase measure of contractility), the latter showing instead a significant increase after 6 h. All changes were transient, returning to baseline values after 20 h. Therefore, the alterations of cardiac function induced by LPS are entirely due to altered loading conditions, but not to reduced contractility, which may instead be slightly increased.

Molecular and functional characterization of a novel cardiac-specific human tropomyosin isoform.

BACKGROUND: Tropomyosin (TM), an essential actin-binding protein, is central to the control of calcium-regulated striated muscle contraction. Although TPM1alpha (also called alpha-TM) is the predominant TM isoform in human hearts, the precise TM isoform composition remains unclear. METHODS AND RESULTS: In this study, we quantified for the first time the levels of striated muscle TM isoforms in human heart, including a novel isoform called TPM1kappa. By developing a TPM1kappa-specific antibody, we found that the TPM1kappa protein is expressed and incorporated into organized myofibrils in hearts and that its level is increased in human dilated cardiomyopathy and heart failure. To investigate the role of TPM1kappa in sarcomeric function, we generated transgenic mice overexpressing cardiac-specific TPM1kappa. Incorporation of increased levels of TPM1kappa protein in myofilaments leads to dilated cardiomyopathy. Physiological alterations include decreased fractional shortening, systolic and diastolic dysfunction, and decreased myofilament calcium sensitivity with no change in maximum developed tension. Additional biophysical studies demonstrate less structural stability and weaker actin-binding affinity of TPM1kappa compared with TPM1alpha. CONCLUSIONS: This functional analysis of TPM1kappa provides a possible mechanism for the consequences of the TM isoform switch observed in dilated cardiomyopathy and heart failure patients.