Antonio E. Pontiroli

Type 2 diabetes is characterized by insulin resistance and inadequate insulin secretion. In the advanced stages of the disease, beta-cell dysfunction worsens and insulin therapy may be necessary to achieve satisfactory metabolic control. Studies in autopsies found decreased beta-cell mass in pancreas of people with type 2 diabetes. Apoptosis, a constitutive program of cell death modulated by the Bcl family genes, has been implicated in loss of beta-cells in animal models of type 2 diabetes. In this study, we compared the effect of 5 days' culture in high glucose concentration (16.7 mmol/l) versus normal glucose levels (5.5 mmol/l) or hyperosmolar control (mannitol 11 mmol/l plus glucose 5 mmol/l) on the survival of human pancreatic islets. Apoptosis, analyzed by flow cytometry and electron and immunofluorescence microscopy, was increased in islets cultured in high glucose (HG5) as compared with normal glucose (NG5) or hyperosmolar control (NG5+MAN5). We also analyzed by reverse transcriptase-polymerase chain reaction and Western blotting the expression of the Bcl family genes in human islets cultured in normal glucose or high glucose. The antiapoptotic gene Bcl-2 was unaffected by glucose change, whereas Bcl-xl was reduced upon treatment with HG5. On the other hand, proapoptotic genes Bad, Bid, and Bik were overexpressed in the islets maintained in HG5. To define the pancreatic localization of Bcl proteins, we performed confocal immunofluorescence analysis on human pancreas. Bad and Bid were specifically expressed in beta-cells, and Bid was also expressed, although at low levels, in the exocrine pancreas. Bik and Bcl-xl were expressed in other endocrine islet cells as well as in the exocrine pancreas. These data suggest that in human islets, high glucose may modulate the balance of proapoptotic and antiapoptotic Bcl proteins toward apoptosis, thus favoring beta-cell death.

Severe coronavirus disease 2019 (COVID-19) is characterized by overproduction of immune mediators, but the role of interferons (IFNs) of the type I (IFN-I) or type III (IFN-III) families remains debated. We scrutinized the production of IFNs along the respiratory tract of COVID-19 patients and found that high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity. Production of specific IFN-III, but not IFN-I, members denotes patients with a mild pathology and efficiently drives the transcription of genes that protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In contrast, compared to subjects with other infectious or noninfectious lung pathologies, IFNs are overrepresented in the lower airways of patients with severe COVID-19 that exhibit gene pathways associated with increased apoptosis and decreased proliferation. Our data demonstrate a dynamic production of IFNs in SARS-CoV-2-infected patients and show IFNs play opposing roles at distinct anatomical sites.

In our retrospective study we compare the effectiveness and safety of transperitoneal laparoscopic versus open adrenalectomy in 40 patients with benign hyperfunctioning unilateral adrenal tumors. Patients 1 to 20 underwent open adrenalectomy between July 1988 and July 1992, and patients 21 to 40 underwent the laparoscopic procedure between September 1992 and January 1994. Student's t test for unpaired data was used to compare intraoperative and postoperative results, and morbidity observed in the 2 groups. The affected adrenal gland was successfully removed in all cases. Mean operative time was significantly longer for laparoscopy, although it shortened progressively due to the learning curve effect. Blood loss was significantly less with laparoscopy, while only 3 patients undergoing open surgery required blood transfusions. Overall invasiveness and analgesic requirement were significantly lower with laparoscopy. The intervals to oral intake and ambulation, hospital stay and return to preoperative normal activity were shorter with laparoscopy. Major complications were noted only in open surgery patients. At 3 months all patients in both groups were cured of the underlying adrenal disease. We conclude that transperitoneal laparoscopic adrenalectomy is equally effective and less invasive than open surgery, and that it should be considered the first choice therapy for benign hyperfunctioning adrenal tumors.

INTRODUCTION: Sexual dysfunction is reported in diabetic women (female sexual dysfunction [FSD]). AIM: To examine the frequency of FSD in diabetic women, and its clinical or metabolic correlates, through meta-analysis of available studies. METHODS: We searched in MEDLINE, EMBASE, Cochrane Library, and in reference lists of articles and systematic reviews; we considered human clinical studies published as full articles reporting on FSD in diabetic and control women. In total, we considered 26 studies, including 3,168 diabetic and 2,823 control women. MAIN OUTCOME MEASURES: Frequency of FSD and score of Female Sexual Function Index (FSFI) as a function of study size, patient details (age, body mass index [BMI], duration of diabetes, metabolic control [HbA1c], chronic complications, Beck Depression Inventory [BDI] score). RESULTS: Frequency of FSD was higher in type 1 (OR [95%CI] 2.27 [1.23, 4.16]), in type 2 diabetes (2.49 [1.55, 3.99]), and in "any diabetes" (type 1 and 2) women (2.02 [1.49, 2.72]) than in controls for any duration of diabetes. FSFI was lower in type 1 (-0.27 [-0.41, -0.12]), in type 2 diabetes (-0.65 [-0.75, -0.54]), and in "any diabetes" women (-0.80 [-0.88, -0.71]) than in controls. Depression was significantly more frequent in diabetic than in control women. At meta-regression only BMI was significantly associated with effect size (P = 0.005). At weighed regression, the only significant association was found between age and FSFI (P = 0.059). The limitations were as follows: only studies of observational nature were available, and heterogeneity was seen among studies. CONCLUSIONS: FSD is more frequent in diabetic than in control women, but it is still poorly understood; low FSFI is associated with high BMI. Further studies are necessary to better understand risk factors for FSD in diabetic women.