Doppler-Derived Renal Functional Reserve in the Prediction of Postoperative Acute Kidney Injury in Patients Undergoing Robotic Surgery.

BACKGROUND: Postoperative acute kidney injury (PO-AKI) is a frequent complication after surgery. Various tools have been proposed to identify patients at high risk for AKI, including preoperative serum creatinine or estimated glomerular filtration rate (eGFR), urinary cell cycle arrest, and tubular damage biomarkers; however, none of these can appropriately assess AKI risk before surgery. Renal functional reserve (RFR) screened by the Doppler-derived intraparenchymal renal resistive index variation (IRRIV) test has been proposed to identify patients at risk for AKI before a kidney insult. IRRIV test has been developed in healthy individuals and previously investigated in cardiac surgery patients. This study aims to evaluate the value of the IRRIV test in identifying PO-AKI among patients undergoing robotic abdominal surgery in the Trendelenburg position for pelvic oncological disease. METHODS: We performed a prospective, double-blinded, observational study. Preoperative baseline renal function and RFR were assessed in 53 patients with baseline eGFR >60 mL/min/1.73 m2, undergoing robotic surgery in the Trendelenburg position for pelvic oncological disease. The capability of Doppler-derived RFR in predicting PO-AKI was investigated with the area under the receiver operating characteristic curve (ROC-AUC). RESULTS: Approximately 15.1% of patients developed AKI within the first 3 postoperative days. Thirty-one (58.5%) patients had a physiologic delta-RRI (ie, ≥0.05), while 22 (41.5%) patients did not. The ROC-AUC for PO-AKI was 0.85 (95% confidence interval [CI], 0.74-0.97; P = .007) for serum creatinine, 0.84 (95% CI, 0.71-0.96; P = .006) for eGFR, and 0.84 (95% CI, 0.78-0.91; P = .017) for delta-RRI. When combined with eGFR, the ROC-AUC for delta-RRI was 0.95 (95% CI, 0.9-1). CONCLUSIONS: Our findings show that the preoperative assessment of Doppler-derived RFR combined with baseline renal function improves the capability of identifying patients at high risk for PO-AKI with eGFR >60 mL/min/1.73 m2 after robotic abdominal surgery in Trendelenburg position for pelvic oncological disease.

Sampling from Extracorporeal Circuit: A Step Forward for Dose Monitoring in Continuous Renal Replacement Therapy.

INTRODUCTION: Continuous renal replacement therapies (CRRTs) require constant monitoring and periodic treatment readjustments, being applied to highly complex patients, with rapidly changing clinical needs. To promote precision medicine in the field of renal replacement therapy and encourage dynamic prescription, the Acute Dialysis Quality Initiative (ADQI) recommends periodically measuring the solutes extracorporeal clearance with the aim of assessing the current treatment delivery and the gap from the therapeutic prescription (often intended as effluent dose). To perform this procedure, it is therefore necessary to obtain blood and effluent samples from the extracorporeal circuit to measure the concentrations of a target solute (usually represented by urea) in prefilter, postfilter, and effluent lines. However, samples must be collected simultaneously from the extracorporeal circuit ports, with the same suction flow at an unknown rate. METHODS: The proposed study takes the first step toward identifying the technical factors that should be considered in determining the optimal suction rate to collect samples from the extracorporeal circuit to measure the extracorporeal clearance for a specific solute. RESULTS: The results obtained identify the low suction rate (i.e., 1 mL/min) as an ideal parameter for an adequate sampling method. Low velocities do not perturb the external circulation system and ensure stability prevailing pressures in the circuit. Higher velocities can be performed only with blood flows above 120 mL/min preferably in conditions of appropriate filtration fraction. DISCUSSION/CONCLUSIONS: The specific value of aspiration flow rate must be proportioned to the prescription of CRRT treatments set by the clinician.

The Impact of Fast Microbiology in Intensive Care Units in the Era of Antibiotic Resistance: An Observational Retrospective Study.

The increasing prevalence of multi-drug-resistant bacteria responsible for bloodstream infections (BSIs) makes therapeutic choices progressively more complex. Fast microbiology quickly detects the presence of pathogens and clinically relevant determinants of antibiotic resistance, offering the potential for early administration of antibiotics. In this retrospective observational study, we comparatively evaluated the performances of FilmArray and the current standard method using blood samples collected from intensive care unit (ICU) patients with suspected BSI. A full agreement with the standard was observed in 97/102 samples (95.1 ± 4.2%), a mismatch in 3/102 samples (2.9 ± 3.2%) and detection failure in 2/102 cases (1.96 ± 2.7%). Statistical analysis demonstrated a near-perfect/perfect level of agreement between the two methods, with an overall degree of agreement of 95%. The high performance demonstrated by the FilmArray could allow a "watch and wait" approach helping clinicians in decision-making processes related to choice and initiation of the antimicrobial therapy, thus avoiding ineffective and excessive use of drugs.

Closing the serological gap in the diagnostic testing for COVID-19: The value of anti-SARS-CoV-2 IgA antibodies.

During coronavirus disease 2019 (COVID-19) pandemic, the early diagnosis of patients is a priority. Serological assays, in particular immunoglobulin (Ig)M and IgG anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have today several applications but the interpretation of their results remains an open challenge. Given the emerging role of the IgA isotype in the COVID-19 diagnostics, we aimed to identify the SARS-CoV-2 IgA antibodies in a COVID-19 population seronegative for IgM. A total of 30 patients hospitalized in San Giovanni di Dio Hospital (Florence, Italy) for COVID-19, seronegative for IgM antibodies, have been studied for anti-SARS-CoV-2 antibodies. They all had a positive oro/nasopharyngeal swab reverse transcription-polymerase chain reaction result. Assays used were a chemiluminescent assay measuring SARS-CoV-2 specific IgM and IgG (S + N) and an ELISA, measuring specific IgG (S1) and IgA antibodies against SARS-CoV-2. Among the 30 patients, eight were positive for IgA, seven were positive for IgG (N + S), and two for IgG (S1), at the first point (5-7 days from the onset of symptoms). The IgA antibodies mean values at the second (9-13 days) and third (21-25 days) time points were even more than twice as high as IgG assays. The agreement between the two IgG assays was moderate (Cohen's K = 0.59; SE = 0.13). The inclusion of the IgA antibodies determination among serological tests of the COVID-19 diagnostic is recommended. IgA antibodies may help to close the serological gap of the COVID-19. Variations among anti-SARS-CoV-2 IgG assays should be considered in the interpretation of results.

Methods for dose quantification in continuous renal replacement therapy: Toward a more precise approach.

Periodic dose assessment is quintessential for dynamic dose adjustment and quality control of continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury (AKI). The flows-based methods to estimate dose are easy and reproducible methods to quantify (estimate) CRRT dose at the bedside. In particular, quantification of effluent flow and, mainly, the current dose (adjusted for dialysate, replacement, blood flows, and net ultrafiltration) is routinely used in clinical practice. Unfortunately, these methods are critically influenced by several external unpredictable factors; the estimated dose often overestimates the real biological delivered dose quantified through the measurement of urea clearance (the current effective delivered dose). Although the current effective delivered dose is undoubtedly more precise than the flows-based dose estimation in quantifying CRRT efficacy, some limitations are reported for the urea-based measurement of dose. This article aims to describe the standard of practice for dose quantification in critically ill patients with AKI undergoing CRRT in the intensive care unit. Pitfalls of current methods will be underlined, along with solutions potentially applicable to obtain more precise results in terms of (a) adequate marker solutes that should be used in accordance with the clinical scenario, (b) correct sampling procedures depending on the chosen indicator of transmembrane removal, (c) formulas for calculations, and (d) quality controls and benchmark indicators.

Diagnostic accuracy of an automated chemiluminescent immunoassay for anti-SARS-CoV-2 IgM and IgG antibodies: an Italian experience.

A pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading throughout the world. Though molecular diagnostic tests are the gold standard for COVID-19, serological testing is emerging as a potential surveillance tool, in addition to its complementary role in COVID-19 diagnostics. Indubitably quantitative serological testing provides greater advantages than qualitative tests but today there is still little known about serological diagnostics and what the most appropriate role quantitative tests might play. Sixty-one COVID-19 patients and 64 patients from a control group were tested by iFlash1800 CLIA analyzer for anti-SARS CoV-2 antibodies IgM and IgG. All COVID-19 patients were hospitalized in San Giovanni di Dio Hospital (Florence, Italy) and had a positive oro/nasopharyngeal swab reverse-transcription polymerase chain reaction result. The highest sensitivity with a very good specificity performance was reached at a cutoff value of 10.0 AU/mL for IgM and of 7.1 for IgG antibodies, hence near to the manufacturer's cutoff values of 10 AU/mL for both isotypes. The receiver operating characteristic curves showed area under the curve values of 0.918 and 0.980 for anti-SARS CoV-2 antibodies IgM and IgG, respectively. iFlash1800 CLIA analyzer has shown highly accurate results for the anti-SARS-CoV-2 antibodies profile and can be considered an excellent tool for COVID-19 diagnostics.

Osteogenic differentiation of adipose tissue-derived mesenchymal stem cells on nanostructured Ti6Al4V and Ti13Nb13Zr.

Bone tissue engineering and nanotechnology enable the design of suitable substitutes to restore and maintain the function of human bone tissues in complex fractures and other large skeletal defects. Long-term stability and functionality of prostheses depend on integration between bone cells and biocompatible implants. Human adipose tissue-derived mesenchymal stem cells (hAMSCs) have been shown to possess the same ability to differentiate into osteoblasts and to produce bone matrix of classical bone marrow derived stem cells (BMMSCs). Ti6A14V and Ti13Nb13Zr are two different biocompatible titanium alloys suitable for medical bone transplantation. Preliminary results from our Research Group demonstrated that smooth Ti6Al4V surfaces exhibit an osteoconductive action on hAMSCs, granting their differentiation into functional osteoblasts and sustaining bone matrix synthesis and calcification. The purpose of this study is to assay the ability of nanostructured Ti6Al4V and Ti13Nb13Zr alloys to preserve the growth and adhesion of hAMSCs and, mostly, to sustain and maintain their osteogenic differentiation and osteoblast activity. The overall results showed that both nanostructured titanium alloys are capable of sustaining cell adhesion and proliferation, to promote their differentiation into osteoblast lineage, and to support the activity of mature osteoblasts in terms of calcium deposition and bone extracellular matrix protein production.

In vitro effects of extracts of extra virgin olive oil on human colon cancer cells.

The Mediterranean diet is associated with a lower incidence of atherosclerosis, cardiovascular diseases, and some types of cancer. Recent interest has been focused on the biological activity of phenolic compounds present in extra virgin olive oils (EVOOs). Both in vivo and in vitro studies have shown that EVOO components have positive effects on metabolic parameters, such as plasma lipoproteins, oxidative damage, inflammatory markers, platelet function, and antimicrobial activity. We have investigated the possible interactions between 2 extracts of extra virgin olive oil and estrogen receptor ß (ERß) in an in vitro model of colon cancer. The qualification and quantification of the components of the 2 samples tested showed that phenolic compounds-hydroxytyrosol, secoiridoids, and lignans-are the major represented compounds. EVOO extracts were tested on a colon cancer cell line engineered to overexpress ERß (HCT8-ß8). By using custom made Oligo microarray, gene expression profiles of colon cancer cells challenged with EVOO-T extracts when compared with those of cells exposed to 17ß-estradiol (17ß-E2). This study demonstrated that the EVOO extracts tested showed an antiproliferative effect on colon cancer cells through the interaction with estrogen-dependent signals involved in tumor cell growth. Specifically, the ability of EVOO extracts to inhibit cell proliferation was superimposable to the activation of the ERß receptor, similar to what was observed after 17ß-E2 challenge.

Spallation and particles infusion into the extracorporeal circuit during CRRT: a preventable phenomenon.

Patients in intensive care are exposed to the risk of microparticle infusion via extracorporeal lines and the resulting complications. A possible source of microparticle release could be the extracorporeal circuit used in blood purification techniques, such as continuous renal replacement therapy (CRRT). Disposable components of CRRT circuits, such as replacement bags and circuit tubing, might release microparticles such as salt crystals produced by precipitation in replacement bags and plastic microparticles produced by spallation. In-line filtration has proven effective in retaining microparticles both in in-vitro and in-vivo studies. In our study, we performed an in-vitro model of CRRT-treatment with the aim of detecting the microparticles produced and released into the circuit by means of a qualitative and quantitative analysis, after sampling the replacement and patient lines straddling a series of in-line filters. Working pressures and flows were monitored during the experiment. This study showed that microparticles are indeed produced and released into the CRRT circuit. The inclusion of in-line filters in the replacement lines allows to reduce the burden of microparticles infused into the bloodstream during extracorporeal treatments, reducing the concentration of microparticles from 14 mg/mL pre in-line filter to 11 mg/mL post in-line filter. Particle infusion and related damage must be counted among the pathophysiological mechanisms supporting iatrogenic damage due to artificial cross-talk between organs during CRRT applied to critically ill patients. This damage can be reduced by using in-line filters in the extracorporeal circuit.

COL1A1 Sp1 variation and bone phenotypes in an Italian population.

BACKGROUND: Osteoporosis is the most common metabolic bone disorder of the elderly, affecting the normal bone turnover with an increased bone resorption and subsequent higher risk of fragility fractures. Collagen type 1 is the most represented protein in bone matrix. A genetic variation (Sp1) in intron 1 of COL1A1 gene has been associated to modulation of expression of the alpha 1 chain of collagen type 1 and it is considered a candidate polymorphism for predisposition to osteoporosis status and fragility fractures. Association studies, in ethnically different populations, are needed to strongly confirm the role of this polymorphism in bone metabolism. MATERIALS AND METHODS: We enrolled over 2,000 Italian individuals and studied their bone mineral density (BMD) and fractures in relation to age, sex and body mass index (BMI). Moreover, we analyzed the distribution of Sp1 polymorphism in these individuals and associated it to normal bone status, osteopenic condition or osteoporosis diagnosis, BMD and the presence of low-trauma fractures. RESULTS: The most rare ss genotype showed a trend for osteoporosis diagnosis with respect to both normal and osteopenic status. The same genotype resulted to be associated to lower values of BMD both at spine and femur sites. No association was found with fractures. DISCUSSION: In conclusion the presence of the homozygote ss genotype seemed to predispose to osteoporosis diagnosis and to be more frequent in subjects with lower spine and femur BMD values.

Palliative Care for Patients with Kidney Disease.

Interest in palliative care has increased in recent times, particularly in its multidisciplinary approach developed to meet the needs of patients with a life-threatening disease and their families. Although the modern concept of palliative simultaneous care postulates the adoption of these qualitative treatments early on during the life-threatening disease (and potentially just after the diagnosis), palliative care is still reserved for patients at the end of their life in most of the clinical realities, and thus is consequently mistaken for hospice care. Patients with acute or chronic kidney disease (CKD) usually experience poor quality of life and decreased survival expectancy and thus may benefit from palliative care. Palliative care requires close collaboration among multiple health care providers, patients, and their families to share the diagnosis, prognosis, realistic treatment goals, and treatment decisions. Several approaches, such as conservative management, extracorporeal, and peritoneal palliative dialysis, can be attempted to globally meet the needs of patients with kidney disease (e.g., physical, social, psychological, or spiritual needs). Particularly for frail patients, pharmacologic management or peritoneal dialysis may be more appropriate than extracorporeal treatment. Extracorporeal dialysis treatment may be disproportionate in these patients and associated with a high burden of symptoms correlated with this invasive procedure. For those patients undergoing extracorporeal dialysis, individualized goal setting and a broader concept of adequacy should be considered as the foundations of extracorporeal palliative dialysis. Interestingly, little evidence is available on palliative and end of life care for acute kidney injury (AKI) patients. In this review, the main variables influencing medical decision-making about palliative care in patients with kidney disease are described, as well as the different approaches that can fulfill the needs of patients with CKD and AKI.

The influence of psychological interventions on surgical outcomes: a systematic review.

BACKGROUND: An amplified and/or prolonged surgical stress response might overcome the organs' functional reserve, thus leading to postoperative complications. The aim of this systematic literature review is to underline how specific psychological interventions may contribute to improve surgical outcomes through the positive modulation of the surgical stress response in surgical patients. METHODS: We conducted a comprehensive literature search in the Cochrane Register of Controlled Trials, PubMed, EMBASE, Scopus, PsycINFO, and CINAHL databases. Only studies published in English from Jan 2000 to Apr 2022 and reporting pain and/or anxiety among outcome measures were included in the review. The following psychological interventions were considered: (1) relaxation techniques, (2) cognitive-behavioral therapies, (3) mindfulness, (4) narrative medicine, (5) hypnosis, and (6) coping strategies. RESULTS: Among 3167 records identified in the literature, 5 papers were considered eligible for inclusion in this review because reporting the effects that psychological features have on neurochemical signaling during perioperative metabolic adaptation and those metabolic and clinical effects that the psychological interventions had on the observed population. CONCLUSION: Our findings confirm that psychological interventions may contribute to improve surgical outcomes via the positive influence on patients' metabolic surgical stress response. A multidisciplinary approach integrating physical and non-physical therapies can be considered a good strategy to successfully improve surgical outcomes in the perioperative period.

Different effects of tryptophan 2,3-dioxygenase inhibition on SK-Mel-28 and HCT-8 cancer cell lines.

PURPOSE: Indoleamine 2,3-dioxygenase-1 (IDO1) and more recently, tryptophan 2,3-dioxygenase (TDO), are tryptophan-catabolizing enzymes with immunoregulatory properties in cancer. IDO1 is more expressed than TDO in many tumours including melanomas; however, IDO inhibitors did not give expected results in clinical trials, highlighting the need to consider TDO. We aimed to characterize both TDO expression and function in a melanoma cell line, named SK-Mel-28, with the purpose to compare it with a colon cancer cell line, HCT-8, and with a human endothelial cell line (HUVEC). METHODS: TDO expression was assessed as real time-PCR and western blot, for mRNA and protein expression, respectively. While cell proliferation was assessed as cell duplication, cell apoptosis and cell cycle were analysed by means of flow cytometry. RESULTS: SK-Mel-28 cells showed higher TDO levels compared to HCT-8 and to HUVEC cells. A selective TDO inhibitor, 680C91, significantly impaired cell proliferation in a concentration-dependent manner, by inducing cell arrest during the G2 phase for SK-Mel-28 and HUVEC cells, while an early apoptosis was increasing in HCT-8 cells. No toxic effects were observed. These data demonstrated that TDO is highly expressed in SK-Mel-28 cells and may be involved in the regulation of their proliferation. CONCLUSION: TDO may directly modulate cancer cell function rather than immune suppression and can be considered as a target for melanoma progression together with IDO1.

Study of vitamin D status and vitamin D receptor polymorphisms in a cohort of Italian patients with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic arthritis of children and adolescents. Autoimmune mechanisms are suspected to have a central role in its development. Vitamin D is an immuno-modulator in a variety of conditions, including autoimmune diseases. Low levels of vitamin D have commonly been found in JIA patients, but the influence of this hormone insufficiency in JIA pathogenesis is still unclear. Vitamin D receptor (VDR) mediates a great majority of vitamin D biological activities; specific polymorphisms of the VDR gene have been associated with different biologic responses to vitamin D. In this study, we analysed clinical characteristics of a cohort of 103 Italian JIA patients. The distribution of VDR polymorphisms in affected patients versus healthy controls was evaluated, as well as if and how these polymorphic variants associate with different disease presentations (active disease vs non-active disease), different JIA subtypes, serum levels of 25-hydroxy-vitamin D and parathyroid hormone (PTH), and lumbar spine Z-score values (osteopenia vs normal bone mineral density). A great majority of our JIA patients (84.5%) showed a suboptimal vitamin D status, in many cases (84.1%) not solved by vitamin D supplementation. Vitamin D status resulted to be independent of VDR genotypes. ApaI genotypes showed a highly significant different distribution between JIA patients and unaffected controls, with both the TT genotype and the T allele significantly more frequent in patient group.

In Vitro Control of Genes Critical for Parathyroid Embryogenesis by Extracellular Calcium.

BACKGROUND: The expression of the parathyroid transcription factors, encoded by the genes GATA3, GCM2, and MAFB, persists after parathyroid morphogenesis. This suggests a role of these genes in the regulatory program that governs parathyroid function in the adult. Indeed, these 3 genes form a transcriptional cascade able to activate PTH gene expression. MATERIALS AND METHODS: Adult adenoma parathyroid tissues were put in primary cell culture to evaluate the messenger ribonucleic acid (mRNA) expression of the PTH gene, of the genes involved in the calcium regulatory signaling pathway (CaSR, GNA11, and AP2S1), and of the 3 genes (GATA3, GCM2, and MAFB) involved in the parathyroid morphogenesis in the presence of different extracellular calcium concentrations from 0.1 mM to 3.0 mM. AIM: The aim of the study was to investigate whether different extracellular calcium conditions could control the expression of transcription factors critical for parathyroid embryogenesis. RESULTS: The results of the experiments showed that the mRNA expression of GATA3, GCM2, and MAFB genes follows the same response as the PTH gene to extracellular calcium concentrations, with the highest expression at low calcium (0.1 mM) and the lowest at high calcium (3.0 mM). Conversely, the genes involved in the calcium signaling in the parathyroid cells showed a variable response to the extracellular calcium concentrations, with the CaSR and GNA11 genes exhibiting a sensitivity to low calcium concentrations. CONCLUSIONS: These findings indicate that transcription factors recognized for their role in parathyroid embryogenesis show a response to extracellular calcium later in adulthood that parallels the behavior of the PTH gene.

Supplementation with phytoestrogens and insoluble fibers reduces intestinal carcinogenesis and restores ER-ß expression in Apc-driven colorectal carcinogenesis.

Supplementation with phytoestrogens and insoluble fibers has been reported to reduce duodenal polyps in colectomized familial adenomatous polyposis patients, with a mechanism involving, at least in part, upregulation of estrogen receptor-ß subtype, whose expression is lowered during intestinal tumorigenesis. These data suggest a protective effect also in the colon, the main target organ for tumorigenesis in familial adenomatous polyposis and a major cancer type in non-familial (sporadic) cancers. Therefore, we tested whether a similar preparation might reduce tumorigenesis in the colon of Pirc rats (F344/NTac-Apc) mutated in the Apc gene and thus, like familial adenomatous polyposis patients, spontaneously developing multiple tumors in the colon. We first demonstrate that estrogen receptor-ß expression in Pirc rat colon is significantly down-regulated compared to age-matched wt rats. Then, Pirc rats aged 1 month were treated for 3 months with Adipol (Adi), a patented preparation containing phytoestrogens and insoluble fibers. Colon tumorigenesis was significantly reduced by Adi treatment (colon tumors/rat were 5.3 ± 0.8 and 2.9 ± 0.3, Mucin Depleted Foci/rat 127 ± 6.6 and 97.1 ± 8.6 in Controls and Adi-treated rats, respectively, means ± SE, P < 0.01). The treatment also normalized colon proliferation pattern along the crypt and significantly increased apoptosis in colon tumors. Estrogen receptor-ß expression was increased by Adi treatment, especially in the tumors. These positive effects suggest that Adipol may be exploited as a chemopreventive agent to reduce cancer risk in familial adenomatous polyposis patients and to postpone prophylactic colectomy. Moreover, given the similarities between familial adenomatous polyposis and sporadic colorectal cancer, it might also be used as chemopreventive agent in colorectal cancer patients at risk.

Effect of Beta 3 Adrenoreceptor Modulation on Patency of the Ductus Arteriosus.

ß3-adrenoreceptor (ß3-AR), a G-protein coupled receptor, has peculiar regulatory properties in response to oxygen and widespread localization. ß3-AR is expressed in the most frequent neoplasms, also occurring in pregnant women, and its blockade reduces tumor growth, indicating ß3-AR-blockers as a promising alternative to antineoplastic drugs during pregnancy. However, ß3-AR involvement in prenatal morphogenesis and the consequences of its blockade for the fetus remain unknown. In this study, after the demonstrated expression of ß3-AR in endothelial and smooth muscle cells of ductus arteriosus (DA), C57BL/6 pregnant mice were acutely treated at 18.5 of gestational day (GD) with indomethacin or with the selective ß3-AR antagonist SR59230A, or chronically exposed to SR59230A from 15.5 to 18.5 GD. Six hours after the last treatment, fetuses were collected. Furthermore, newborn mice were treated straight after birth with BRL37344, a ß3-AR agonist, and sacrificed after 7 h. SR59230A, at the doses demonstrated effective in reducing cancer progression (10 and 20 mg/kg) in acute and chronic mode, did not induce fetal DA constriction and did not impair the DA ability to close after birth, whereas at the highest dose (40 mg/kg), it was shown to cause DA constriction and preterm-delivery. BRL37344 administered immediately after birth did not alter the physiological DA closure.

Growing Strong and Healthy with Mister Bone: An Educational Program to Have Strong Bones Later in Life.

Optimal peak bone mass and bone health later in life are favored by a sufficient calcium intake in infancy, childhood and adolescence. The purpose of this study was to test a new educational program created to monitor and to improve calcium and vitamin D intake in children. Nutritional habits in children were evaluated through a food frequency questionnaire (FFQ) to assess the intake of calcium, vitamin D, dairy products, and total caloric energy at baseline and after seven months of exposure to a unique educational program applied between November 2013 and May 2014 in 176 schoolchildren (48% male, 52% female) attending the fourth and fifth grades of two selected primary schools in Florence, Italy. A significant increase of calcium (from 870 ± 190 to 1100 ± 200 mg/day, p < 0.05), and vitamin D (from 3.6 ± 1.53 to 4.1 ± 2 µg/day) intake in children was documented after the educational program. The amount of specific foods important for bone health consumed, such as milk and vegetables, increased significantly, both in male and female children (p < 0.05). The proposed educational program appears to be effective in modifying calcium intake in children, with a significant increase in the consumption of dairy products and vegetables, but without a significant change in the total caloric intake.

PTH-C1: a rat continuous cell line expressing the parathyroid phenotype.

The lack of a continuous cell line of epithelial parathyroid cells able to produce parathyroid hormone (PTH) has hampered the studies on in vitro evaluation of the mechanisms involved in the control of parathyroid cell function and proliferation. The PT-r cell line was first established from rat parathyroid tissue in 1987, but these cells were known to express the parathyroid hormone-related peptide (Pthrp) gene, but not the Pth gene. In an attempt to subclone the PT-r cell line, a rat parathyroid cell strain was isolated and named PTH-C1. During 3 years, in culture, PTH-C1 cells maintained an epithelioid morphology, displaying a diploid chromosome number, a doubling time around 15 h during the exponential phase of growth, and parathyroid functional features. PTH-C1 cell line produces PTH and expresses the calcium sensing receptor (Casr) gene and other genes known to be involved in parathyroid function. Most importantly, the PTH-C1 cells also exhibit an in vitro secretory response to calcium. Altogether these findings indicate the uniqueness of the PTH-C1 cell line as an in vitro model for cellular and molecular studies on parathyroid physiopathology.