Assunzione di glucosio in vitro da parte di frammenti di arterie umane e bovine in diverse condizioni

Riassunto E' stata studiata l'assunzione di glucosioin vitro da parte di frammenti d'arteria provenienti da animali o da uomo, affetto e non affetto, da diabete mellito. Le arterie provenienti da uomo non diabetico assumono in genere meno glucosio rispetto alla arteria proveniente da bovini. Tali differenze si riducono se le arterie umane vengono private dell'avventizia. Le arterie umane non diabetiche assumono più glucosio nei confronti delle arterie provenienti da soggetti affetti da diabete mellito. Mentre l'incubazione con plasma umano normale aumenta nettamente l'assunzione di glucosio in tutte le arterie di uomo diabetico e non, essa non determina significativi miglioramenti della'assunzione di glucosio da parte dei frammenti di arterie bovine. L'aggiunta di insulina cristallizzata di bue al liquido di incubazione delle arterie umane non induce significativi incrementi dell'assunzione di glucosio se non a concentrazioni di 2 mU/ml nell'incubazione di arterie umane private dell'avventizia.

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Summary The AA. have studied thein vitro glucose uptake by fragments derived from animals and from humans, both diabetic and non-diabetic. The arteries derived from non-diabetic humans generally assume less glucose than those derived from oxen. Such differences decrease if the human arteries are deprived of theadventitia. The human non-diabetic arteries assume more glucose than those derived from subjects suffering from diabetes mellitus. While incubation with normal human plasma clearly increases the glucose uptake in all the arteries of man, both diabetic and not, it does not cause significant improvements in the glucose uptake by the fragments of bovine arteries. The addition of crystallized ox insulin to the incubation liquid of the human arteries does not cause significant improvements in the glucose uptake except at 2 mU/ml, when human arteries deprived of theadventitia are used.

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Zusammenfassung Es wurde die Aufnahme von Glukosein vitro durch Arterien-Fragmente von Tieren oder Menschen mit oder ohne Diabetes mellitus untersucht. Die Arterien von nicht diabetischen Menschen nehmen im allgemeinen weniger Glukose auf, als die Arterien von Rindern. Diese Unterschiede werden geringer, wenn man den Humanarterien dieadventitia entzieht. Die Arterien von nicht diabetischen Menschen nehmen mehr Glukose auf, als die Arterien von Menschen mit Diabetes mellitus. Während die Inkubation mit normalem Humanplasma die Glukoseaufnahme in allen Arterien von Menschen mit oder ohne Diabetes klar steigert, bewirkt sie keine signifikante Verbesserung der Glukose-Aufnahme durch Arterien-Fragmente von Rindern. Der Zusatz von kristallisiertem Rinderinsulin zur Inkubations-Flüssigkeit der Human-Arterien induziert keine signifikanten Zunahmen der Glukoseaufnahme, es sei denn mit einer Konzentration von 2 mE/ml bei der Inkubation von Humanarterien ohneadventitia.

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Resumen Se estudió la captación de glucosain vitro de parte de fragmentos de arteria procedentes de animales o de hombres afectos y no de diabetes mellitus. En general, las arterias del hombre no diabético captan menos glucosa que las de los bovinos. Estas diferencias se reducen si se privan a las arterias humanas de la adventicia. Las arterias humanas no diabéticas captan más glucosa que las arterias de sujetos afectos de diabetes mellitus. Mientras la incubación con plasma humano normal aumenta netamente la captación de glucosa en todas las arterias del hombre diabético y no, la misma no determina mejorías significativas de la captación de glucosa de parte de los fragmentos de arterias bovinas. La adición de insulina cristalizada de buey al líquido de incubación de las arterias humanas no produce aumentos significativos en la captación de glucosa sino a concentraciones de 2 mU/ml en la incubación de arterias humanas sin adventicia.

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Resume Les AA. ont étudié l'assimilation de glucosein vitro par des fragments d'artère provenantes de animaux ou de sujets atteints ou non de diabète sucré. Les artères des sujets non diabétiques assument en général moins glucose que les artères d'origine bovine. Cettes différences sont réduites si les artères humaines sont privées de l'adventice. Les artères humaines non diabétiques assument plus glucose que les artères provenantes de sujets atteints de diabète sucré. Tandis que l'incubation avec du sérum humain normal augmente nettement l'assimilation du glucose dans toutes les artères du sujet diabétique et non diabétique, elle ne porte pas des améliorations significatives dans l'assimilation du glucose par les fragments des artères bovines. L'addition d'insuline cristallisée du boeuf au liquide d'incubation des artères humaines ne porte pas des augmentations significatives de l'assimilation du glucose, si non avec des concentrations de 2 mU/ml dans l'incubation des artères humaines privées de l'adventice.

     

Impaired saccadic eye movement in diabetic patients: the relationship with visual pathways function

The aim of this study was to evaluate whether a correlation existed between saccadic eye movements and visual pathways function in diabetic patients. Saccadic or fast Eye Movement System (EMS) and Visual Evoked Potentials (VEPs) were assessed in 20 insulin-dependent diabetic mellitus (IDDM) patients without long-term complications and in stable metabolic control and in 21 age-matched control subjects. In IDDM patients we observed significantly (p<0.01) longer EMS latency, while EMS velocity and accuracy were similar to those of controls; VEPs showed a significant delay in N75, P100, N145 latencies and significant reduction of N75-P100 and P100-N145 amplitudes. In IDDM patients no relationships between EMS and VEP parameters were found. In conclusion, EMS latency delay suggests an impairment of the saccadic eye movement system, while impaired VEPs may be ascribed to a dysfunction of the visual pathways. The lack of correlation between VEPs impairment and EMS latency delay suggests that in our IDDM patients the delay of saccadic latency cannot be exclusively related to a visual pathways dysfuction and could be ascribed to a diffuse neuronal involvement. This revised version was published online in July 2006 with corrections to the Cover Date.     

In vivo characterization of the inflammatory infiltrate and apoptotic status in imiquimod-treated basal cell carcinoma

Background Imiquimod use in the treatment of basal cell carcinoma (BCC) has proven to be successful in a large percentage of cases, inducing tumor regression; however, the exact cellular mechanism has not been fully clarified. Aim To measure the morphological changes in the tumor microenvironment and the markers of apoptosis in skin biopsies from patients with BCC before and after imiquimod treatment. Methods In this open label study, skin biopsies obtained from 11 patients with BCC were evaluated before and after imiquimod treatment for: (i) morphological changes in the tumor microenvironment, with specific emphasis on the immunophenotype of inflammatory cells around the tumor; and (ii) markers of apoptosis, including expression of death receptors. Results Imiquimod treatment induced a significant increase in the mononuclear inflammatory response. In the majority of cases, the cellular infiltrate was predominantly composed of CD3⁺/CD4⁺ T cells, suggesting that the effector response is mediated by CD3⁺/CD4⁺ lymphocytes, with a minor cytotoxic and natural killer (NK) component. An increase in the cytotoxic CD3⁺/CD8⁺ T‐cell population was also observed. Imiquimod treatment was associated with a marked increased in CD20⁺ B cells, and a less pronounced enhancement in cells of monocyte–macrophage origin (CD68⁺) surrounding, or within, the tumor. This finding indicates either that macrophages play a minor role in the imiquimod‐induced response, or the recruitment of these cells is related to time and dose. Imiquimod treatment decreased CD1A⁺ Langerhans cells in the epidermis and increased the number of CD1A⁺ dendritic cells within the tumor aggregates. Imiquimod reduced Bcl‐2 expression, but no difference was found in Bax, Fas/FasL, and p53 expression in BCC cells. Conclusions Our results support the hypothesis that imiquimod activity in the treatment of BCC is partly a result of a pro‐inflammatory action mediated by CD3⁺/CD4⁺ lymphoid cells and of a pro‐apoptotic activity associated with decreased Bcl‐2 expression.     

Assessment of advanced age candidates for liver transplantation warrants more caution

For patients with fulminant liver failure and end-stage liver disease, liver transplantation remains the only effective treatment. Over the years, as a result of the ageing population, the average age of liver transplant donors and recipients has increased and currently about one quarter of patients receiving transplantation in the United States are above the age of 65. Recently, a study reported that patients aged 65 years or older had lower one-year survival compared to a younger cohort. Herein, we express our opinion about this interesting publication.     

Omentopexy with Glubran®2 for reducing complications after laparoscopic sleeve gastrectomy: results of a randomized controlled study

Background

Gastric fistulas, bleeding, and strictures are commonly reported after laparoscopic sleeve gastrectomy (LSG), that increase morbidity and hospital stay and may put the patient’s life at risk. We report our prospective evaluation of application of synthetic sealant, a modified cyanoacrylate (Glubran®2), on suture rime, associated with omentopexy, to identify results on LSG-related complications.

Methods

Patients were enrolled for LSG by two Bariatric Centers, with high-level activity volume. Intraoperative recorded parameters were: operative time, estimated intraoperative bleeding, conversion rate. We prospectively evaluated the presence of early complications after LSG during the follow up period. Overall complications were analyzed. Perioperative data and weight loss were also evaluated. A control group was identified for the study.

Results

Group A (treated with omentopexy with Glubran®2) included 96 cases. Control group included 90 consecutive patients. There were no differences among group in terms of age, sex and Body Mass Index (BMI). No patient was lost to follow-up for both groups. Overall complication rate was significantly reduced in Group A. Mean operative time and estimated bleeding did not differ from control group. We observed three postoperative leaks in Group B, while no case in Group A (not statistical significancy). We did not observe any mortality, neither reoperation. Weight loss of the cohort was similar among groups. In our series, no leaks occurred applying omentopexy with Glubran®2.

Conclusion

Our experience of omentopexy with a modified cyanoacrylate sealant may lead to a standardized and reproducible approach that can be safeguard for long LSG-suture rime.

Trial registration

Retrospective registration on clinicaltrials.gov PRS, with TRN NCT03833232 (14/02/2019).

     

Relationship between plasma insulin and left ventricular mass in normotensive participants of the Gubbio Study

BACKGROUND: There is substantial but not conclusive evidence that insulin resistance is related to left ventricular mass (LVM) in hypertensive individuals. To what extent this association is mediated by the relationship between plasma insulin and body size and build is still debated, and is poorly explored in nonhypertensive people. OBJECTIVE: To explore the relationship between insulin or insulin resistance and LVM in a population-based sample of nonhypertensive participants of the Gubbio Study. METHOD: Echocardiographic LVM was determined in 91 nondiabetic, nonhypertensive individuals aged 45-54 years, participating in a population-based screening. LVM normalized for height2.7 was used in the analyses; LV hypertrophy was defined as a value of > or = 50 g/m2.7 in men or > or = 47 g/m2.7 in women. Fasting plasma insulin and glucose were measured and the Homeostasis Model Assessment (HOMA) index was used as a measure of insulin resistance. RESULTS: LVM was positively and significantly correlated with body mass index (BMI) (P < 0.01), waist circumference (P < 0.01) and HOMA index (P < 0.05), whereas correlations with plasma glucose and triglycerides did not reach statistical significance (P = 0.07 for both); all correlations were offset after adjusting for BMI. Fasting plasma insulin and HOMA index were not significantly different in subjects with or without LV hypertrophy (70.8 +/- 27.8 vs. 77.7 +/- 29.6 pmol/l and 2.2 +/- 1.0 vs. 2.6 +/- 1.4, respectively). Bivariate analysis performed stratifying participants above or below the 75th percentile of the sex-specific distribution for BMI (29.1 and 29.4 kg/m2 for males and females, respectively) and plasma insulin (84 pmol/l for either gender), did not result in appreciable differences in LVM due to insulin levels. Similar results were obtained replacing the HOMA index for insulin in the analysis. CONCLUSION: In nonhypertensive individuals left ventricular mass is not associated with plasma insulin independently of body mass index.     

Large periampullary villous tumor of the duodenum

A 67-year-old woman, who had symptoms of epigastric pain and abdominal distension, was found, on endoscopy, to have a large sessile villous adenoma of the periampullary duodenum. Despite the lack of evidence of malignancy, a pancreaticoduodenectomy procedure was performed, mainly because of the tumor size and site, involving the ampulla of Vater. The presence of the carcinoma was diagnosed only in the resected specimen by definitive histology. Because there is no general consensus on the optimal surgical procedure for the treatment of villous tumors of the duodenum, especially for the early stages, the indications for the operative procedure are discussed, based on a review of the literature.     

Novel de novo heterozygous loss-of-function variants in MED13L and further delineation of the MED13L haploinsufficiency syndrome

MED13L haploinsufficiency has recently been described as responsible for syndromic intellectual disability. We planned a search for causative gene variants in seven subjects with intellectual disability and overlapping dysmorphic facial features such as bulbous nasal tip, short mouth and straight eyebrows. We found two de novo frameshift variants in MED13L, consisting in single-nucleotide deletion (c.3765delC) and duplication (c.607dupT). A de novo nonsense variant (c.4420A>T) in MED13L was detected in a further subject in the course of routine whole-exome sequencing. By analyzing the clinical data of our patients along with those recently described in the literature, we confirm that there is a common, recognizable phenotype associated with MED13L haploinsufficiency, which includes intellectual disability and a distinctive facial appearance. Congenital heart diseases are found in some subjects with various degree of severity. Our observation of cleft palate, ataxia, epilepsy and childhood leukemia observed in single cases broadens the known clinical spectrum. Haploinsufficiency for MED13L should be considered in the differential diagnosis of the 1p36 microdeletion syndrome, due to overlapping dysmorphic facial features in some patients. The introduction of massive parallel-sequencing techniques into clinical practice is expected to allow for detection of other causative point variants in MED13L. Analysis of genomic data in connection with deep clinical evaluation of patients could elucidate genetic heterogeneity of the MED13L haploinsufficiency phenotype.     

Prognostic Value of p27, p53, and Vascular Endothelial Growth Factor in Dukes A and B Colon Cancer Patients Undergoing Potentially Curative Surgery

PURPOSE Early-stage colon cancer patients (Dukes A or B; pT1–T3 pNO pMO) are excluded from adjuvant chemotherapy following potentially curative surgery because they are expected to have good long-term survival. However, 20 percent to 30 percent of these patients ultimately succumb from recurrent disease. This indicates that the conventional staging procedures may be unable to precisely predict cancer prognosis.METHODS In 65 early-stage colon cancers, we investigated by immunohistochemistry the role of molecular markers such as p27, p53, and vascular endothelial growth factor in identifying high-risk patients who may benefit from adjuvant treatments.RESULTS No clinicopathologic factor, namely Dukes stage, t parameter, number of resected nodes, and vascular or lymphatic invasion, was found be an independent significant predictor of disease-specific and disease-free survival. In contrast, each molecular marker predicted survival and recurrence rates much better than the conventional Dukes staging system. The best combination of variables for prediction of long-term outcome and recurrence rate included p27, p53, and vascular endothelial growth factor. Interestingly, the greater the number of molecular alterations, the lower the five-year estimated survival function. Nearly all cancer-related deaths were observed among patients whose colon cancers expressed all three molecular alterations. Regardless of Dukes stage, the recurrence rate was found to increase with the increase in the number of molecular alterations. Early-stage colon cancers expressing p27 down-regulation and high p53 and vascular endothelial growth factor immunoreactivity showed a 100 percent actuarial four-year recurrence rate.CONCLUSIONS Assessment of molecular alterations may be useful to identify a higher-risk group of early-stage colon cancer patients who may benefit from adjuvant chemotherapy.