A morphometric study of human submandibular gland in type 2 diabetic status

Diabetes Mellitus Type 2 represents one of the principal diseases that afflict the world population. It is well documented that diabetes affects both morphology and function of several organs. In diabetic rats significant structural changes have been demonstrated in salivary glands, such as accumulation of secretory material and lipid droplets within secretory cells, parenchymal degeneration and its replacement with fibrous connective tissue (1). With regard to human salivary glands, the data are scanty and conflicting. Our work, carried out by light and electron microscopy, is based on the evaluation of the morphological changes which occur in human submandibular glands of diabetic with respect to non diabetic patients. Surgical fragments of glandular tissue were fixed, dehydrated, and processed for light and electron microscopy. Randomly chosen images were analyzed with Image Pro Plus software to record the dimension of acini, serous cells, secretory granules and other variables. Data were analyzed by Student’s t-test and Mann Whitney test. In diabetic glands statistically significant morphological changes were observed, such as enlargement of serous acini and increase of secretory granules area. These results suggest that the secretory activity of human submandibular gland is severely affected by the diabetic status. Obviously these data need to be confirmed with further measurements in order to explain better how diabetes affects human salivary glands

Ultrastructural evidence of a secretory role for melatonin in the human parotid gland

In vivo animal studies show that pentagastrin, cholecystokinin and melatonin cause the secretion and synthesis of salivary proteins. Melatonin occurs in large amounts in the gut and is released into the blood on food intake. In vitro experiments suggest that pentagastrin exerts secretory activity in human salivary glands, as judged by ultrastructural changes, reflecting secretion, and an actual protein output. Currently, it is hypothesised that melatonin induces secretory exocytotic events in the human parotid gland. Human parotid tissues were exposed to a high single concentration of melatonin in vitro, processed for high resolution scanning electron microscopy and then assessed morphometrically with the emphasis on the membrane of the intercellular canaliculi, a site of protein secretion. Compared with controls and in terms of density, the melatonin-exposed parotid tissues displayed increases in protrusions (signalling anchored granules) and microbuds (signalling membrane recycling and/or vesicle secretion) and decreases in microvilli (signalling cytoskeletal re-arrangement related to exocytosis), phenomena abolished or very largely reduced by the melatonin receptor blocker, luzindole. In conclusion, acinar serous cells of parotid tissue displayed in vitro exocytotic activity to melatonin, signalling protein secretion. Whether, under physiological conditions, melatonin influences the secretion of human parotid glands remains to be explored, however

Intake of palmitic acid and its association with metabolic flexibility in middle-aged individuals: a preliminary study

Objective: This study aimed to assess the relationship between dietary palmitic acid (PA) intake and its association with body fat deposition and metabolic flexibility (MF) in middle-aged healthy individuals. Methods: Fifteen healthy participants (n = 15; 6 males, 9 females) with a mean age of 54 were enlisted. They were subjected to graded exercise tests using a cycle ergometer coupled with a calorimeter. Respiratory gas exchange was evaluated to determine two MF parameters. First, the MF index was derived by multiplying peak fatty acid oxidation (PFO) per kg of fat-free mass (FFM) with the percentage of VO2max at PFO. The second parameter, peak energy substrates’ oxidation (aka PESO), was computed by aggregating the kilocalories from PFO and peak carbohydrate oxidation, normalized per kg FFM. Dietary intake was gauged using a 7-day dietary record. Spearman’s regression was employed to analyze the association between dietary intake of specific fat classes, PA, MF parameters, and body fat percentage. Results: Preliminary results demonstrate that dietary saturated fatty acids (SFA) within physiological limits correlate with enhanced substrate oxidation capacity. This suggests augmented MF in middle-aged subjects. Among dietary SFA, PA was identified as the primary factor in this favorable correlation. Conclusions: Our initial observations, even though preliminary, strongly suggest a beneficial association between PA intake, MF, and body fat percentage. This underscores the potential nutritional importance of PA in promoting MF

A morphometric study of human submandibular gland in type 2 diabetic status

Diabetes Mellitus Type 2 represents one of the principal diseases that afflict the world population. It is well documented that diabetes affects both morphology and function of several organs. In diabetic rats significant structural changes have been demonstrated in salivary glands, such as accumulation of secretory material and lipid droplets within secretory cells, parenchymal degeneration and its replacement with fibrous connective tissue (1). With regard to human salivary glands, the data are scanty and conflicting. Our work, carried out by light and electron microscopy, is based on the evaluation of the morphological changes which occur in human submandibular glands of diabetic with respect to non diabetic patients. Surgical fragments of glandular tissue were fixed, dehydrated, and processed for light and electron microscopy. Randomly chosen images were analyzed with Image Pro Plus software to record the dimension of acini, serous cells, secretory granules and other variables. Data were analyzed by Student’s t-test and Mann Whitney test. In diabetic glands statistically significant morphological changes were observed, such as enlargement of serous acini and increase of secretory granules area. These results suggest that the secretory activity of human submandibular gland is severely affected by the diabetic status. Obviously these data need to be confirmed with further measurements in order to explain better how diabetes affects human salivary glands. Maria Alberta Lilliu gratefully acknowledges Sardinia Regional Government for the financial support of her PhD scholarship (P.O.R. Sardegna F.S.E. Operational Programme of the Autonomous Region of Sardinia, European Social Fund 2007-2013 - Axis IV Human Resources, Objective l.3, Line of Activity l.3.1.). Michela Isola gratefully acknowledges Sardinia Regional Government for the financial support (P.O.R. Sardegna F.S.E. Operational Programme of the Autonomous Region of Sardinia, European Social Fund 2007-2013 - Axis IV Human Resources, Objective l.3, Line of Activity l.3.1 “Avviso di chiamata per il finanziamento di Assegni di Ricerca”)

Minimally Invasive Aortic Valve Replacement with Sutureless Valves:Results From an International Prospective Registry

Objective: To report the early and mid-term results of patients who underwent minimally invasive aortic valve replacement (MI-AVR) with a sutureless prosthesis from an international prospective registry. Methods: Between March 2011 and September 2018, among 957 patients included in the prospective observational SURE-AVR (Sorin Universal REgistry on Aortic Valve Replacement) registry, 480 patients underwent MI-AVR with self-expandable Perceval aortic bioprosthesis (LivaNova PLC, London, UK) in 29 international institutions through either minithoracotomy (n = 266) or ministernotomy (n = 214). Postoperative, follow-up, and echocardiographic outcomes were analyzed for all patients. Results: Patient age was 76.1 ± 7.1 years; 64.4% were female. Median EuroSCORE I was 7.9% (interquartile range [IQR], 4.8 to 10.9). Median cardiopulmonary bypass and cross-clamp times were 81 minutes (IQR 64 to 100) and 51 minutes (IQR 40 to 63). First successful implantation was achieved in 97.9% of cases. Two in-hospital deaths occurred, 1 for noncardiovascular causes and 1 following a disabling stroke. In the early (≤30 days) period, stroke rate was 1.4%. Three early explants were reported: 2 due to nonstructural valve dysfunction (NSVD) and 1 for malpositioning. One mild and 1 moderate paravalvular leak were reported. In 16 patients (3.3%) pacemaker implantation was needed. Mean follow-up was 2.4 years (maximum = 7 years). During follow-up 5 explants were reported, 3 due to endocarditis and 2 due to NSVD. Follow-up stroke rate was 2.5%. Three structural valve deteriorations not requiring reintervention were reported. Five-year survival was 91.45%. Conclusions: In this large prospective international registry, MI-AVR with Perceval valve confirmed to be safe, reproducible, and effective in an intermediate-risk population, providing excellent clinical recovery both in early and mid-term follow-up

Malattie neurodegenerative e metalli: cosa lega la sindrome di Parkinson al manganese

E' noto come l'accumulo dei metalli nel cervello possa portare, o quantomeno contribuire, allo sviluppo di malattie neurodegenerative, attraverso meccanismi che solo ora cominciano a essere lentamente chiariti. La malattia di Parkinson, cosiddetta “idiopatica” in quanto non presenta alcuna causa apparente, è stata messa di recente in correlazione con l'esposizione o l'avvelenamento da manganese. Studi epidemiologici condotti da diverse università degli Stati Uniti hanno evidenziato come gli abitanti in zone urbane con alte concentrazioni di questo metallo avessero una probabilità di sviluppare il Parkinson quasi due volte più alta rispetto agli abitanti in zone meno inquinate, o inquinate da altri metalli (quali ad esempio il rame). Altri studi apparsi di recente in letteratura correlano l'esposizione al manganese con alcune modificazioni di un gene legato alla sinucleina, proteina presente con diverse funzioni in tutte le malattie neurodegenerative. Lo studio è stato effettuato su una proteina di un lievito la YPK9, al 58% simile e al 38% uguale all'analoga umana PARK9, la cui mutazione causa appunto lo sviluppo di una forma ereditaria di Parkinson. Silenziando il gene YPK9 nei lieviti si è notato che in assenza della relativa proteina questi mostravano disturbi nella crescita se sottoposti all'azione di diversi metalli, mentre in presenza del manganese la crescita era particolarmente ridotta. Veniva quindi dimostrata l'azione protettiva della YPK9 nei confronti dei cationi bivalenti, specialmente del manganese. Pare dunque possibile che una modifica sull'analogo umano, il PARK9, sia in grado di inficiare i normali meccanismi con cui il nostro organismo si protegge da ioni metallici dannosi, quali il manganese, e dando il via a una serie di processi che portano allo sviluppo della malattia neurodegenerativa. Abbiamo pertanto voluto verificare l'effettiva propensione di tale proteina a interagire con ioni Mn(II), selezionando sulla sequenza della YPK9 dei frammenti promettenti per il legame con il metallo e investigando la possibilità di una interazione efficace di questi frammenti con diversi cationi bivalenti, tra cui appunto il manganese, ma anche il calcio e lo zinco. I risultati preliminari, ottenuti attraverso alcune tecniche spettroscopiche quali l'NMR mono- e bidimensionale e l'EPR, verranno esposti in questa comunicazione

Coordination abilities of mono and multi-histidinic and glutamate peptide fragments towards manganese(II) and cobalt(II)

It is known that rich repeat domains in peptides can be of interest as the models for the study of molecular phenomena related to metal ion binding in proteins involved in neurodegenerative disorders. Imbalances in transition metal ions are assumed to contribute to the conversion of the multi-histidinic amyloid β-peptide (Aβ) from its soluble form to an amyloidogenic form, and to Aβ deposition. Of these ions, it has been reported that manganese binding to PrP is detrimental and causes a conformational change in the protein, suggesting that manganese binding could potentially play a role in prion disease progression in vivo. It appears that PrP is less stable on binding manganese and quickly converts to a misfolded form. The binding of manganese to PrP potentially results in the conversion of the protein to an abnormal isoform with properties reminiscent of PrPsc. In particular, although PrP can bind the same number of manganese atoms as of copper atoms, the resulting protein becomes proteinase resistant, forms fibrils and loses function.[1,2] Regarding cobalt, a novel low-affinity binding site for Co(II) was discovered between PrP residues 104 and 114, with residue His111 being the key amino acid for coordinating Co(II).[3] Thus, despite the interest in manganese and cobalt binding to PrP, a thorough analysis of the interaction of both metals with proteins related to brain pathies has not yet been reported. The (T1R2S3R4S5H6T7S8E9G10)3 fragment from Cap43 protein, which is induced by metal ions, is characterized by a decarepeat domain comprising three decapeptide units with one histidine and one glutamate residue in each repeat. Therefore the study of the interaction of the 30-aminoacid peptide from Cap43 protein with metal ions can contribute to the understanding of the crucial role of multi-imidazol and glutamate sites in the protein coordination processes and the possible role of divalent metal ions in the pathogenesis of prion disease and other related protein pathies.[4-8] Here we present our recent results on the Cobalt(II) and Manganese(II) complexes of terminally protected mono- and multi-histidine-glutamate peptides studied by combination of potentiometric measurements and spectroscopic techniques (NMR, UV-Vis and EPR). Metal complexation induces important structural changes with the C-terminal portion of the ligand, constraining it to leave its disordered conformation and promoting side chain orientation. Our results give rise to a molecular model of the induced structure for the peptides complexed with cobalt and manganese

Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil

Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd

Prognostic role of endocarditis in isolated tricuspid valve surgery. A propensity-weighted study

Objectives The role of the underlying etiology in isolated tricuspid valve surgery has not been investigated extensively in current literature. Aim of this study was to analyse outcomes of patients undergoing surgery due to endocarditis compared to other pathologies. Methods The SURTRI study is a multicenter study enrolling adult patients who underwent isolated tricuspid valve surgery (n = 406, 55 ± 16 y.o.; 56% female) at 13 international sites. Propensity weighted analysis was performed to compare groups (IE group n = 107 vs Not-IE group n = 299). Results No difference was found regarding the 30-day mortality (Group IE: 2.8% vs Group Not-IE = 6.8%; OR = 0.45) and major adverse events. Weighted cumulative incidence of cardiac death was significantly higher for patients with endocarditis (p = 0.01). The composite endpoint of cardiac death and reoperation at 6 years was reduced in the Group IE (63.2 ± 6.8% vs 78.9 ± 3.1%; p = 0.022). Repair strategy resulted in an increased late survival even in IE cases. Conclusions Data from SURTRI study report acceptable 30-day results but significantly reduced late survival in the setting of endocarditis of the tricuspid valve. Multi-disciplinary approach, repair strategy and earlier treatment may improve outcomes. © 2022 The Author