Analysis of susceptibility of mature human T lymphocytes to dexamethasone-induced apoptosis

We present evidence that dexamethasone (Dex), a synthetic glucocorticosteroid, causes apoptosis in mature human T cells, similarly to what has been reported for murine T lymphocytes. Human T cell clones and short-term activated T lymphocytes treated with Dex show the characteristic pattern of apoptotic cells, such as hypodiploid nuclei, chromatin condensation and DNA fragmentation into oligonucleosomal fragments. However, Dex susceptibility of T cells to apoptosis is cell cycle-dependent. The progression in the proliferative cell cycle (G1 versus S) rescues Dex-treated T cells from apoptosis. Moreover, occupancy of the T cell receptor reverses Dex-induced apoptotic phenomena. These observations suggest that glucocorticoids contribute to the regulation of the proliferative or the suicidal response of antigen-activated human T cells.     

Ranitidine, cimetidine and antacids in the prevention of recurrence after healed duodenal ulcer: one-year experience

A total of 110 subjects with duodenal ulcer healed with cimetidine (C) (50 patients), ranitidine (R) (40 patients) or pirenzepine (20 patients) was randomly divided in 3 groups. The first group (40 patients) was treated with R (150 mg nightly); the second group (40 patients) with C (400 mg nightly) and the third group with antacids as needed for symptomatic relief. The presence of the ulcer and its healing were established by endoscopy, which was repeated after 6 and 12 months of treatment, or previously if symptoms suggested recurrence. At the end of the year's follow-up, no recurrence of ulcers was observed in 75% of the R group, in 77.5% of the C group and in 40% of the antacids group. Some erosive duodenitis developed in the first and second groups (17.5% and 20% respectively), but none in the antacids group. Most of the ulcers that recurred did so in the first 6 months of treatment. No relevant side-effects were observed with the treatments described. Although no significant difference was detected between C and R treatments, both appeared to be clearly more effective than antacids. The usefulness of adequate prophylactic treatment against the tendency of duodenal ulcer to recur is stressed.     

Bronchoscopic treatment of complex persistent air leaks with endobronchial one-way valves

We reported a case series including 5 patients with persistent air-leaks refractory to standard treatment. All patients were unfit for surgery for the presence of co-morbidities and/or severe respiratory failure due to underlying lung diseases. They were successfully treated with bronchoscopic placement of endobronchial one-way valves. Air-leaks stopped in the first 24 h after the procedure in three patients and 3 and 5 days later, respectively, in the remaining two. No complications were observed and follow-up was uneventful in all patients but one died 25 days after the procedure for systemic sepsis due to peritonis. Patients with important, refractory air leaks having clinical repercussions and unfit for surgery should be early reviewed for bronchoscopic valves treatment.     

High fecal calprotectin levels are associated with SARS-CoV-2 intestinal shedding in COVID-19 patients: A proof-of-concept study

BACKGROUNDOne third of coronavirus disease 2019 (COVID-19) patients have gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA has been detected in stool samples of approximately 50% of COVID-19 individuals. Fecal calprotectin is a marker of gastrointestinal inflammation in the general population.AIMTo investigate if fecal calprotectin correlates with SARS-CoV-2 intestinal shedding in COVID-19 patients with pneumonia.METHODSPatients with SARS-CoV-2 pneumonia admitted to the Infectious Disease Unit (University Hospital of Trieste, Italy) from September to November 2020 were consecutively enrolled in the study. Fecal samples were collected and analyzed for quantification of fecal calprotectin (normal value < 50 mg/kg) and SARS-CoV-2 RNA presence by polymerase chain reaction (PCR). Inter-group differences were determined between patients with and without diarrhea and patients with and without detection of fecal SARS-CoV-2.RESULTSWe enrolled 51 adults (40 males) with SARS-CoV-2 pneumonia. Ten patients (20%) presented with diarrhea. Real-time-PCR of SARS-CoV-2 in stools was positive in 39 patients (76%), in all patients with diarrhea (100%) and in more than two thirds (29/41, 71%) of patients without diarrhea. Obesity was one of the most common comorbidities (13 patients, 25%); all obese patients (100%) (P = 0.021) tested positive for fecal SARS-CoV-2. Median fecal calprotectin levels were 60 mg/kg [interquartile range (IQR) 21; 108]; higher fecal calprotectin levels were found in the group with SARS-CoV-2 in stools (74 mg/kg, IQR 29; 132.5) compared to the group without SARS-CoV-2 (39 mg/kg, IQR 14; 71) (P < 0.001).CONCLUSIONHigh fecal calprotectin levels among COVID-19 patients correlate with SARS-CoV-2 detection in stools supporting the hypothesis that this virus can lead to bowel inflammation and potentially to the ‘leaky gut’ syndrome.     

Treatment of patients with acute ulcerative colitis: Conventional corticosteroid therapy (MP) versus granulocytapheresis (GMA): A pilot study

AIM: The aim of our pilot study is to report the efficacy of granulocytapheresis in patients with acute ulcerative colitis with respect to the use of conventional corticosteroids such as methylprednisolone. METHODS: The activity of disease was evaluated by clinical activity index and endoscopic index. Forty patients with acute ulcerative colitis were randomly divided in two groups of 20 subjects each: one group was treated with five sessions of granulocytapheresis, the other one with methylprednisolone for 5 weeks. Complete response was defined as clinical activity index lower than 6 and endoscopic index lower than 4 after 6 weeks of follow-up. Partial response was defined as clinical activity index lower than 6 but endoscopic index more than 4 after 6 weeks of follow-up. All the conditions not included are classified as nonresponders. RESULTS: All the patients completed the trial. Complete clinical response was observed in 70% of patients treated with granulocytapheresis versus 60% of patients treated with methylprednisolone. A partial response was observed in 20% of patients treated with granulocytapheresis versus 15% of patients treated with methylprednisolone. During the sessions of granulocytapheresis only a transient mild headache was recorded in 10% of patients, while side effects were more common (50%) in the patients treated with methylprednisolone. CONCLUSION: Granulocytapheresis represents a new and promising approach to active ulcerative colitis. In fact, even if more expensive than conventional corticosteroids, it seems slightly more effective and, above all, with side effects much less frequent and serious. Thus, granulocytapheresis cycles could be prolonged or repeated, if necessary, in more severe diseases without significant risks for the patients.     

Long-term use of deferiprone significantly enhances left-ventricular ejection function in thalassemia major patients

A multicenter randomized open-label long-term sequential deferiprone–deferoxamine (DFP-DFO) versus DFP alone trial (sequential DFP-DFO) performed in patients with thalassemia major (TM) was retrospectively reanalyzed to assess the variation in the left ventricular ejection fraction (LVEF) [1].     

猪精子细胞中胰岛素诱导产生的一氧化氮自由基促进精子获能

近期,胰岛素被证实具有诱导猪精子获能的能力。在不同的哺乳动物中,精子获能被认为与一氧化氮信号通路相关;因此,本研究使用荧光激活细胞分选技术探究经胰岛素处理的猪精子中一氧化氮水平。在同一样本中,用金霉素染色、蛋白质酪氨酸磷酸化模式和顶体状态来评估精子获能。结果显示经胰岛素处理的精子内一氧化氮水平及三种评价精子获能的指标均有显著提高;相反,用一氧化氮合成酶抑制剂（N-硝基-L-精氨酸甲酯）或抗胰岛素受体β抗体预处理的精子中胰岛素相关的作用全被逆转。这些结果表明胰岛素具有增强猪精子细胞内一氧化氮浓聚的能力并且提示胰岛素可能通过一氧化氮促进精子获能。     

Exosomes in human atherosclerosis: An ultrastructural analysis study

Cell-to-cell communication, or signaling, is absolutely essential in orchestrating the activities of cells in multicellular organisms, to grow, develop, detect environmental changes and compensate for them in an internal, coordinated fashion. In the last few years, a considerable amount of new data have demonstrated the occurrence of a sophisticated intercellular signaling pathway based on the release of specialized vesicular structures, called exosomes, whose secretion appears to be regulated by various natural and experimental stimuli, physiological states, and disease processes. In the cardiovascular system, the study of exosomes is still in its infancy. Here, we aim to provide the first ultrastructural evidence for the presence of exosomes in human atherosclerotic plaque. We demonstrate by means of transmission electron microscopy that both lesional smooth muscle cells and endothelial cells are able to generate these membraneous microvesicles within specific compartments of the cell, called multivesicular bodies. Notably, in our series no signs of apoptosis have been detected in vascular cells secreting exosomes and no evidence of calcification has been observed associated with these structures in the extracellular space. Our results suggest the possible existence of a new mechanism of intercellular communication in the plaque milieu.     

Human sperm express a functional androgen receptor: effects on PI3K/AKT pathway

BACKGROUND: Results from mice lacking the androgen receptor (AR) showed that it is critical for the proper development and function of the testes. The aim of this study was to investigate whether a functional AR is present in human sperm. METHODS: The expression of AR and its effects on sperm were evaluated by RT-PCR, Western Blot, Immunocytochemistry, PI3Kinase and DNA laddering assays. RESULTS: We showed in human sperm that AR is located at the head region. Dihydrotestosterone (DHT), in a dose-dependent manner, leads to the rapid phosphorylation of the AR on tyrosine, serine and threonine residues and this effect was reduced by the AR antagonist hydroxyflutamide (OH-Flut). The effects of AR were evaluated on the phosphoinositide-3 kinase/protein kinase B (PI3K/AKT) pathway. Specifically, 0.1 and 1 nM DHT stimulated PI3K activity, whereas 10 nM DHT decreased PI3K activity and levels of p-AKT S473 and p-AKT T308, p-BCL2, and enhanced phosphatase and tensin homologue (PTEN) phosphorylation. In addition, 10 nM DHT was able to induce the cleavage of caspases 8, 9 and 3 and cause DNA laddering, and these effects were reversed either by casodex or OHFlut. By using wortmannin, a specific PI3K inhibitor, the cleavage of caspase 3 was reproduced, confirming that in sperm the PI3K/AKT pathway is involved in caspase activation. CONCLUSIONS: Human sperm express a functional AR that have the ability to modulate the PI3K/AKT pathway, on the basis of androgen concentration.     

Continuous intravenous infusion of TRH-T: clinical, cardiovascular and endocrinological effects

Seven patients, six suffering from amyotrophic lateral sclerosis (ALS) and one from Friedreich ataxia, were treated with a placebo i.v. infusion during the first day and with TRH-T i.v. infusion at a rate of 2 mg/h for 8 h daily (total daily dosage 16 mg) on the 2 consecutive days. Continuous blood pressure (BP) and EKG monitorings were performed during 3 days infusion. Blood samples were collected for endocrinological evaluations. The neurological evaluation after acute TRH-T treatment showed an objective improvement in 3 of the 8. We found significantly higher values of systolic (max. difference of 10.1 mm Hg) and diastolic (max. difference of 8.8 mm Hg) BP than during placebo, beginning from the 5th h of the infusion (p less than 0.05). A trend in progressive increase of the heart rate (HR) reached statistical significance (p less than 0.01) at the 8th h of the second TRH-T infusion. The cardiovascular changes during the i.v. continuous TRH-T infusions were clinically irrelevant and never required the interruption of the treatment.