High-density neutrophils in MGUS and multiple myeloma are dysfunctional and immune-suppressive due to increased STAT3 downstream signaling.

To understand neutrophil impairment in the progression from MGUS through active MM, we investigated the function of mature, high-density neutrophils (HDNs), isolated from peripheral blood. In 7 MM, 3 MGUS and 3 healthy subjects by gene expression profile, we identified a total of 551 upregulated and 343 downregulated genes in MM-HDN, involved in chemokine signaling pathway and FC-gamma receptor mediated phagocytosis conveying in the activation of STAT proteins. In a series of 60 newly diagnosed MM and 30 MGUS patients, by flow-cytometry we found that HDN from MM, and to a lesser extend MGUS, had an up-regulation of the inducible FcγRI (also known as CD64) and a down-regulation of the constitutive FcγRIIIa (also known as CD16) together with a reduced phagocytic activity and oxidative burst, associated to increased immune-suppression that could be reverted by arginase inhibitors in co-culture with lymphocytes. In 43 consecutive newly-diagnosed MM patients, who received first-line treatment based on bortezomib, thalidomide and dexamethasone, high CD64 could identify at diagnosis patients with inferior median overall survival (39.5 versus 86.7 months, p = 0.04). Thus, HDNs are significantly different among healthy, MGUS and MM subjects. In both MGUS and MM neutrophils may play a role in supporting both the increased susceptibility to infection and the immunological dysfunction that leads to tumor progression.

Current aspects of gynecological pathology in postmenopause.

Between 1982 and 1984 330 women in postmenopause for at least one year were admitted to the First Clinic of Obstetrics and Gynecology, Catania University Medical School, Catania, Italy, with a frequency of 10.04% of gynecological admissions. The most frequent pathologies were metrorrhagia (32.72%; 108 cases) from an atrophic endometrium or glandular hyperplasia of the endometrium, vaginoperineal lacerations with cystorectocoele with or without urinary incontinence (10.90%; 36 cases), cancer (11.21%; 37 cases) and ovarian cystoma (11.21%; 37 cases), uterine prolapse (9.30%; 31 cases), and endometrial polyps (9.09%; 30 cases). Uterine fibromyoma (3.93%; 13 cases) and carcinoma of the portio (3.93%; 13 cases) were among the rare pathologies. Uterine pathologies were the most prevalent (68.78%; 227 cases), followed by ovarian (15.15%; 50 cases), pathology of involving the pelvic and perineal containment (10.90%; 36 cases), vulvar pathology (2.72%; 6 cases), and vaginal pathology (1.51%; 5 cases). Malignant neoplastic pathology was reported in 25.45% of cases (84 cases) consisting only of uterine cancer (47.61%; 40 cases) and ovarian cancer (45.23%; 38 cases). In comparison with the study performed by Cetroni in 1952 one notes a net reduction in the frequency of uterine prolapse (by about three times), and a smaller reduction in cancer of the uterine cervix with a slight increase in cervical polyps, endometrial cancer, and above all in metrorrhagia from atrophic endometrium or glandular hyperplasia of the endometrium.

[Rapid effect of glucuronyl glucosamine glycan sulfate on the blood levels of HDL-cholesterol in vascular diseases]. / Effetto rapido del glucuronilglucosamin-glicano solfato sui livelli ematici di HDL-colesterolo in vasculopatici.

The Authors investigated on the main lipidemic parameters in vascular diseases after acute administration of glucuronyl-glucosamine-glycan sulfate (3GS). The study was carried out in 48 subjects, aged 33 to 78, of whom 38 males and 10 females so divided: 6 metabolically healthy controls (N), 10 with vascular cerebral disease (VCD), 15 with coronary heart disease, 17 with peripheral vascular disease (PVD). Each subject, fasting and without drug treatment at least since 14 hours, after venous blood withdrawal, was given endovenous rapid bolus of 570 lipasemic units of glucuronyl-glucosamine-glycan sulfate (3GS); after 10', 20' and 30' other blood samples were taken; plasma NEFA (colorimetric method) triglycerides (TG), total cholesterol (TC) and HDL-cholesterol (C-HDL) (enzyme method) were assayed; C-HDL/TC ratio was calculated and LDL-cholesterol value (C-LDL) according to the Friedwald-Fredrickson's formula was obtained. In controls NEFA increase after 20' (+ 57%) and triglycerides drop (-49%) were detected; TC significant fall (-13%, P less than 0,05) after 20' was found, preceded by both C-HDL marked increase and C-HDL/TC ratio, and followed (30') by C-LDL slight rise. In the 3 groups of vascular patients a striking NEFA increase (respectively + 50%, + 43%, + 26%) was found; in subjects with PVD/TG blunted drop was observed, whereas in VCD and in CHD TG percentage fall -41 and -44%) did not differ from that one of controls. Evident remarked in control, drop of total cholesterolemia, lacked in the 3 groups of vascular diseases; in patients with VCD and PVD C-HDL and C-HDL/TC ratio increasing profile was like normal, while in CHD both progressive reduction of C-HDL (-19% after 30') and C-HDL/TC ratio with C-LDL increase were appreciated. On the basis of their results the Authors believed that in PVD a striking deficit of total plasma lipoprotein lipase (LPL), already in vitro documented, may occur, whereas LPL resulted normal in VCD and in CHD; on the contrary, in CHD an abnormally cholesterol-apo-VLDL affinity, like metabolic atherogenic derangement, was found; in the 3 groups of vascular diseases slow peripheral cholesterol removal was detectable.

[Effect of metformin on plasma lipoprotein lipase]. / Effetto della metformina sulla lipoproteinlipasi plasmatica.

The action of metformin with respect to in vitro turbidimetric clarification of a glyceridic system (lipostrate) has been studied in a group of metabolically healthy subjects. It is observed that biguanide associated with 3GS, heparinoid with known structure and costant liposemec activity, significantly accentuates clarifying activity whereas biguanide alone leads to only a slight increase in the clarification index, at least 5 times less than that induced by 3GS. Results are discussed. These agree with some recent experiments on the catabolic and antiatherogenic effect in vivo of biguanide on the VLDL and LDL, fostering their conversion into high density lipoproteins.