295 research outputs found
Prolonging nephrogenesis in preterm infants: a new approach for prevention of kidney disease in adulthood?
Chronic kidney disease represents a dramatic worldwide resourceconsuming problem. This problem is of increasing importance even in preterm infants, since nephrogenesis may go on only for a few weeks (4 to 6 weeks) after birth. Recent literature focusing on traditional regenerative medicine does not take into account the presence of a high number of active endogenous stem cells in the preterm kidney, which represents a unique opportunity for starting regenerative medicine in the perinatal period. Pluripotent cells of the blue strip have the capacity to generate new nephrons, improving kidney function in neonates and potentially protecting them from developing chronic kidney disease and end-stage renal disease in adulthood. There is a marked interindividual neonatal variability of nephron numbers. Moreover, the renal stem/progenitor cells appear as densely-packed small cells with scant cytoplasm, giving rise to a blue-appearing strip in hematoxylin-eosin–stained kidney sections (“the blue strip”). There are questions concerning renal regenerative medicine: among preliminary data, the simultaneous expression of Wilms tumor 1 and thymosin β4 in stem/progenitor cells of the neonatal kidney may bring new prospects for renal regeneration applied to renal stem cells that reside in the kidney itself. A potential approach could be to prolong the 6 weeks of postnatal renal growth of nephrons or to accelerate the growth of nephrons during the 6 weeks or both. Considering what we know today about perinatal programming, this could be an important step for the future to reduce the incidence and global health impact of chronic kidney disease
Editorial: Looking for a culprit: The role of environmental co-factors in complex neuropsychiatric disorders
S100B protein expression in the heart of deceased individuals by overdose: a new forensic marker?
OBJECTIVE: The evaluation of S100B protein expression in the human heart and its correlation with drug-related death. METHOD: Left ventricular samples were collected from 74 serial forensic autopsies (15 overdose-related deaths; 59 non-overdose-related deaths) from 2007 to 2010. Tissue sections from each sample were immunostained for S100B protein by a commercial antibody. RESULTS: The S100B protein was detected in the heart samples of all 15 cases of drug-related deaths; S100B immunoreactivity was mainly observed in the cytoplasm of cardiomyocytes and as globular deposits in the interstitial spaces. No reactivity or weak reactivity was found in the cardiomyocytes of the 59 subjects who died of other causes. CONCLUSION: Our preliminary data show that the S100B protein accumulates in injured cardiomyocytes during drug-related sudden death. Given the near absence of S100B protein in the heart of subjects who died from causes other than drug overdose, S100B immunopositivity may be used as a new ancillary screening tool for the postmortem diagnosis of overdose-related cardiac death
Hypoxia/reoxygenation-induced myocardial lesions in newborn piglets are related to interindividual variability and not to oxygen concentration
OBJECTIVE: Evaluation of myocardial histological changes in an experimental animal model of neonatal hypoxiareoxygenation. METHODS: Normocapnic hypoxia was induced in 40 male Landrace/Large White piglets. Reoxygenation was initiated when the animals developed bradycardia (HR <60 beats/min) or severe hypotension (MAP <15 mmHg). The animals were divided into four groups based on the oxygen (O2) concentration used for reoxygenation; groups 1, 2, 3, and 4 received 18%, 21%, 40%, and 100% O2, respectively. The animals were further classified into five groups based on the time required for reoxygenation: A: fast recovery (<15 min); B: medium recovery (15-45 min); C: slow recovery (45-90 min); D: very slow recovery (>90 min), and E: nine deceased piglets. RESULTS: Histology revealed changes in all heart specimens. Interstitial edema, a wavy arrangement, hypereosinophilia and coagulative necrosis of cardiomyocytes were observed frequently. No differences in the incidence of changes were observed among groups 1-4, whereas marked differences regarding the frequency and the degree of changes were found among groups A-E. Coagulative necrosis was correlated with increased recovery time: this condition was detected post-asphyxia in 14%, 57%, and 100% of piglets with fast, medium, and slow or very slow recovery rates, respectively. CONCLUSIONS: The significant myocardial histological changes observed suggest that this experimental model might be a reliable model for investigating human neonatal cardiac hypoxia-related injury. No correlation was observed between the severity of histological changes and the fiO2 used during reoxygenation. Severe myocardial changes correlated strictly with recovery time, suggesting an unreported individual susceptibility of myocardiocytes to hypoxia, possibly leading to death after the typical time-sequence of events
Heparins and 2019-nCoV infection: a narrative review
Abstract. – OBJECTIVE: Patients with
2019-nCoV infection have a high risk to develop venous thrombotic events. Several guidelines recommend the use of either unfractionated heparin or low molecular weight heparins in
preventing thrombotic events in these patients.
However, results from clinical studies, so far
published, reached controversial conclusions
on heparin efficacy in this kind of patients since
the incidence of venous thromboembolism remains high despite prophylaxis. This narrative
review aims to provide an overview of the antiviral and anti-inflammatory properties of heparins and their efficacy and safety in SARSCoV-2 medical ward-patients. Moreover, anatomical findings and ongoing trials are also reported. Finally, this narrative review tries to explain why heparins fail to prevent venous thrombosis.
MATERIALS AND METHODS: We searched
for the most relevant published studies on heparins and 2019-nCoV infected patients using the
MEDLINE electronic database in the period between January and December 2020. Articles
were preliminarily defined as eligible if they:
a) were in English language, b) enrolled 250 or
more medical ward-patients and 100 or more
ICU-patients, c) reported results on patients
treated with heparins in a percentage of at least
70% and d) performed an objectively confirmed
diagnosis of VTE.
RESULTS: Data from medium to large scientific studies show that the incidence of venous
thrombotic events in medical ward-patients with
SARS-CoV-2 vary between 0% and 8.3%, while
this rate is higher, from 6.2% to 49%, in Intensive Care Unit-patients. However, heparins reduce the mortality rate in these patients of about
50%. Histological findings show that thrombosis could affect capillaries, main and small-midsized vessels, and it is associated with diffuse
alveolar damage.
CONCLUSIONS: Heparins have anti-inflammatory and anti-viral properties, which may be
of help in reducing mortality in SARS-CoV-2 patients. Failure of heparins at prophylactic dosages in preventing VTE, especially in ICU-patients,
could be due to the severity of the disease. Data
on the use of heparins in an early phase of the
2019-nCoV infection are still lacking
Antenatal Thymosin β4: a New Tool for Accelerating Fetal Development in Preterms? Thymosin Beta-4: a Breakthrough in the "Physiological" Regenerative Medicine in Preterm Newborns
To prevent the health risks related to prematurity, multiple drugs have been introduced in
clinical practice in recent years. This paper focuses on a new "physiological" regenerative approach to
be started in the perinatal period, particularly on very low birth weight preterm infants. This new
preventive approach underlined the necessity to start regenerative medicine very early after birth, a
period in which kidney, brain, pancreas, and lung stem cells maintain their proliferative and
differentiating abilities. Among the multiple factors proposed in the literature as potential growth
promoters for preterm neonates, thymosin beta-4 (Tβ4) has been indicated as one of the most important
candidates for regenerative medicine
Breast milk stem cells: four questions looking for an answer
The finding of stem/progenitor cells in the maternal milk and the discovery of their multilineage potential, associated with some evidence regarding the ability of maternal cells to cross the gastrointestinal barrier and integrate into the organs of the breastfed neonate, has opened an intriguing debate, regarding the strict relationship between mother and son in the postnatal period. In particular, thanks to the discovery of the presence in high quantities of mammary stem cells, a new vision of maternal milk is emerging, in which breastfeeding appears as an unique occasion for reinforcing the physiological development of the newborn, putting all the formulas at a different level of relevance for the neonate. In this contribution the authors try to give an answer to the following 4 questions: 1. is there heterogeneity and a hierarchy among breast milk stem cells? 2. can stem cells present in breast milk enter into the newborn organism? 3. can breast milk stem cells integrate in the neonatal organs and differentiate toward different tissues, including neurons and neuroglia? 4. could metabolomics be useful for the study of stem cells in the human milk
Metabolomic analysis of plasma from breast tumour patients. A pilot study
Background: Patients at risk of breast cancer are submitted to mammography, resulting in a classification of the lesions following the Breast Imaging Reporting and Data System (BI-RADS®). Due to BI-RADS 3 classification problems and the great uncertainty of the possible evolution of this kind of tumours, the integration of mammographic imaging with other techniques and markers of pathology, as metabolic information, may be advisable.Design and Methods: Our study aims to evaluate the possibility to quantify by gas chromatography-mass spectrometry (GC-MS) specific metabolites in the plasma of patients with mammograms classified from BI-RADS 3 to BI-RADS 5, to find similarities or differences in their metabolome. Samples from BI-RADS 3 to 5 patients were compared with samples from a healthy control group. This pilot project aimed at establishing the sensitivity of the metabolomic classification of blood samples of patients undergoing breast radiological analysis and to support a better classification of mammographic cases.Results: Metabolomic analysis revealed a panel of metabolites more abundant in healthy controls, as 3-aminoisobutyric acid, cholesterol, cysteine, stearic, linoleic and palmitic fatty acids. The comparison between samples from BI-RADS 3 and BI-RADS 5 patients, revealed the importance of 4-hydroxyproline, found in higher amount in BI-RADS 3 subjects.Conclusion: Although the low sample number did not allow the attainment of high validated statistical models, some interesting data were obtained, revealing the potential of metabolomics for an improvement in the classification of different mammographic lesions
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