CORonavirus-19 mild to moderate pneumonia Management with blood Ozonization in patients with Respiratory failure (CORMOR) multicentric prospective randomized clinical trial.

Background: Following positive experience on the use of blood ozonation in SARS-CoV-2, the CORMOR randomized trial was designed to evaluate the adjuvant role of oxygen/ozone therapy in mild to moderate SARS-CoV-2 pneumonia.

Methods: The trial (ClinicalTrial.gov NCT04388514) was conducted in four different Italian centers (April-October 2020).

PI3K class II α controls spatially restricted endosomal PtdIns3P and Rab11 activation to promote primary cilium function.

Multiple phosphatidylinositol (PtdIns) 3-kinases (PI3Ks) can produce PtdIns3P to control endocytic trafficking, but whether enzyme specialization occurs in defined subcellular locations is unclear. Here, we report that PI3K-C2α is enriched in the pericentriolar recycling endocytic compartment (PRE) at the base of the primary cilium, where it regulates production of a specific pool of PtdIns3P. Loss of PI3K-C2α-derived PtdIns3P leads to mislocalization of PRE markers such as TfR and Rab11, reduces Rab11 activation, and blocks accumulation of Rab8 at the primary cilium.

The trigger-maintenance model of persistent mild to moderate hyperoxaluria induces oxalate accumulation in non-renal tissues.

Persistent mild to moderate hyperoxaluria (PMMH) is a common side effect of bariatric surgery. However, PMMH's role in the progression to calcium oxalate (CaOx) urolithiasis and its potential effects on non-renal tissues are unknown. To address these points, a trigger + maintenance (T + Mt) model of PMMH was developed in rats (Experiment 1).

Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception.

The ability to perceive noxious stimuli is critical for an animal's survival in the face of environmental danger, and thus pain perception is likely to be under stringent evolutionary pressure. Using a neuronal-specific RNAi knock-down strategy in adult Drosophila, we recently completed a genome-wide functional annotation of heat nociception that allowed us to identify α2δ3 as a novel pain gene. Here we report construction of an evolutionary-conserved, system-level, global molecular pain network map.

Real-world management of atrial fibrillation in Internal Medicine units: the FADOI 'FALP' observational study.

Background: Atrial fibrillation is the most frequent arrhythmia, but few data are available on patients' characteristics and management in the context of Internal Medicine wards.

Methods: Data were collected at the beginning of 2010 in 18 Internal Medicine units of the regions Liguria and Piemonte (Italy). Each centre reviewed the hospital charts of the last 50 patients discharged during the year 2009 in whom a diagnosis of atrial fibrillation had been made (patient's history or during the hospitalization).

The RacGAP ArhGAP15 is a master negative regulator of neutrophil functions.

In phagocytes, GTPases of the Rac family control crucial antimicrobial functions. The RacGAP ArhGAP15 negatively modulates Rac activity in leukocytes, but its in vivo role in innate immunity remains largely unknown. Here we show that neutrophils and macrophages derived from mice lacking ArhGAP15 presented higher Rac activity but distinct phenotypes.

The absence of functional PI3Kgamma prevents leukocyte recruitment and ameliorates DSS-induced colitis in mice.

Phosphatidylinositol-3-kinase gamma (PI3Kgamma) is the major PI3K that is activated in response to chemoattractants. It is responsible for the migration of leukocytes from the bloodstream to sites of injury or infection. Constant migration of new leukocytes to the intestinal mucosa may be an important factor in maintenance of inflammation and tissue damage in inflammatory bowel disease (IBD).

Partitioning of 14C-oxalate excretion in rats during a persistent oxalate challenge.

This study was done to resolve published discrepancies in oxalate excretion between humans and rats and to characterize oxalate partitioning in rats during persistent severe hyperoxaluria, such as that seen in many bariatric patients. Osmotic minipumps dispensing 360 micromole/day KOx + 3.9 +/- 0.

Phosphoinositide 3-kinase p110beta activity: key role in metabolism and mammary gland cancer but not development.

The phosphoinositide 3-kinase (PI3K) pathway crucially controls metabolism and cell growth. Although different PI3K catalytic subunits are known to play distinct roles, the specific in vivo function of p110beta (the product of the PIK3CB gene) is not clear. Here, we show that mouse mutants expressing a catalytically inactive PIK3CB(K805R) mutant survived to adulthood but showed growth retardation and developed mild insulin resistance with age.

Oxalate in renal stone disease: the terminal metabolite that just won't go away.

The incidence of calcium oxalate nephrolithiasis in the US has been increasing throughout the past three decades. Biopsy studies show that both calcium oxalate nephrolithiasis and nephrocalcinosis probably occur by different mechanisms in different subsets of patients. Before more-effective medical therapies can be developed for these conditions, we must understand the mechanisms governing the transport and excretion of oxalate and the interactions of the ion in general and renal physiology.

Maturing the sperm: unique mechanisms for modifying integral proteins in the sperm plasma membrane.

The epididymis has been understudied, in part due to its cancer resistance and the development of effective technologies for sperm injection and in vitro fertilization. However, it is worthy of study because--absent advanced reproductive technology--its proper function is essential for conceiving children: sperm leaving the testis are immature and nonfertile. Epididymal functions can be divided into several general categories (1) concentration of sperm; (2) functional maturation; (3) storage in a quiescent state until ejaculation; (4) removal of degenerating sperm; (5) provision of appropriate conditions for survival; (6) transport by the myoid cells; (7) protection; (8) maintenance of the blood epididymal barrier.

Intraprostatic lymphocyte profiles in aged wistar rats with estradiol induced prostate inflammation.

Purpose: We report LS phenotypes in aged Wistar rats (Charles Rivers, Wilmington, Massachusetts) with EPI.

Materials And Methods: EPI was induced in 36 to 40-week-old male rats by castration with subcutaneous injections of 17beta-estradiol (0.25 mg/kg daily) plus dihydrotestosterone propionate (2.

Gene expression in the LNCaP human prostate cancer progression model: progression associated expression in vitro corresponds to expression changes associated with prostate cancer progression in vivo.

Identification of the genes involved in prostate cancer (PCa) progression to a virulent and androgen-independent (AI) form is a major focus in the field. cDNA microarray was used to compare the gene expression profile of the indolent, androgen sensitive (AS) LNCaP PCa cell line to the aggressively metastatic, AI C4-2. Thirty-eight unique sequences from a 6388 cDNA array were found differentially expressed (> or =2-fold, 95% CI).

Continuous infusion of oxalate by minipumps induces calcium oxalate nephrocalcinosis.

It is hypothesized that oxalate plays an active role in calcium oxalate (CaOx) nephrocalcinosis and oxalate driven nephrolithiasis by interacting with the kidney. We developed an adjustable, nonprecursor, continuous infusion model of hyperoxaluria and CaOx nephrocalcinosis to investigate this hypothesis. Minipumps containing PBS or KOx (60-360 micromol/day; n = 5-7/dose) were implanted subcutaneously in male Sprague-Dawley rats on D0 and D6.

A simple procedure for isolating microgram quantities of biologically active bikunin from human urine.

Objective: To report a simple, relatively rapid protocol to isolate biologically active bikunin from human urine using ion-exchange-trypsin affinity chromatography. Bikunin is a protease inhibitor which has been shown to play a role in various processes, including inhibition of calcium oxalate crystallization, the regulation of proliferation and modulation of carcinogenesis. The unavailability of the purified protein has hampered studies on bikunin's expanding role in these processes.

Constitutive activation of P I3 K-Akt and NF-kappaB during prostate cancer progression in autochthonous transgenic mouse model.

Background: Cancer progression is usually facilitated by independent growth signals that may lead to increased cell survival and evasion of apoptosis. Phosphatidylinositol 3'-OH kinase (P I3 K)-Akt and transcription factor NF-kappaB are important signaling molecules and key survival factors involved in the control of cell proliferation, apoptosis, and oncogenesis. Although P I3 K-Akt and NF-kappaB have been implicated in the development and progression of prostate cancer, expression of these molecules during progression of autochthonous disease has not been elucidated.

The healthy rat prostate contains high levels of natural killer-like cells and unique subsets of CD4+ helper-inducer T cells: implications for prostatitis.

Purpose: Chronic nonbacterial prostatitis spontaneously develops in aged Lewis and Wistar rats but not in Sprague-Dawley rats. We report the unique profile of lymphocyte subsets present in the healthy Sprague-Dawley rat prostate.

Materials And Methods: We compared enzymatic and mechanical methods of intraprostatic lymphocyte isolation in healthy 8 to 10-week-old Sprague-Dawley rats.

Microarray analysis of changes in renal phenotype in the ethylene glycol rat model of urolithiasis: potential and pitfalls.

Objectives: To investigate, in an initial study, the use of microarray analysis (MA) to develop an information base for urolithiasis. MA enables the screening of thousands of genes simultaneously making it the technique of choice for situations where the results are known, but the underlying mechanisms are not. Little is known about the pathological changes occurring in the kidney during urolithiasis and this has severely hampered efforts to develop effective therapeutics.

PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects.

The G protein-coupled, receptor-activated phosphoinositide 3-kinase gamma (PI3Kgamma) mediates inflammatory responses and negatively controls cardiac contractility by reducing cAMP concentration. Here, we report that mice carrying a targeted mutation in the PI3Kgamma gene causing loss of kinase activity (PI3KgammaKD/KD) display reduced inflammatory reactions but no alterations in cardiac contractility. We show that, in PI3KgammaKD/KD hearts, cAMP levels are normal and that PI3Kgamma-deficient mice but not PI3KgammaKD/KD mice develop dramatic myocardial damage after chronic pressure overload induced by transverse aortic constriction (TAC).

Nuclear factor-kappaB/p65 (Rel A) is constitutively activated in human prostate adenocarcinoma and correlates with disease progression.

Aberrant nuclear factor-kappaB (NF-kappaB) activation has been implicated in the pathogenesis of several human malignancies. In this study, we determined whether NF-kappaB is constitutively activated in human prostate adenocarcinoma, and, if so, whether increased NF-kappaB activation and its binding to DNA influence tumor progression. Using tissue samples obtained during transurethral prostatic resection and paraffin-embedded sections of benign and cancer specimens, we determined the nuclear expression of NF-kappaB/p65 and NF-kappaB/p50, cytoplasmic expression of IkappaBalpha, its phosphorylation, and expression of NF-kappaB-regulated genes, specifically Bcl2, cyclin D1, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor (VEGF).

Minipump induced hyperoxaluria and crystal deposition in rats: a model for calcium oxalate urolithiasis.

Purpose: Unraveling the mechanisms leading to clinically active calcium oxalate (CaOx) stone disease and the development of effective medical therapies to treat it have been hampered by the lack of appropriate animal models. To address this problem we developed a model of hyperoxaluria and calcium oxalate crystal deposition by implanting osmotic minipumps subcutaneously into male rats, that is minipump induced hyperoxaluria and crystal deposition in rats.

Materials And Methods: Male Harlan-Sprague Dawley rats (225 to 290 gm) were implanted subcutaneously with 1-week 2 ml osmotic minipumps containing 1.

Levels of urinary inter-alpha-trypsin inhibitor trimer as a function of age and sex-hormone status in males and females not forming stones.

Objectives: To determine if levels of inter-alpha-trypsin inhibitor (I alpha TI)-trimer differ in normal individuals based on age, gender or hormonal status, as the regulation of calcium oxalate (CaOx) crystallization inhibitors, e.g. by sex steroids, could be a mechanism contributing to the differences in CaOx urolithiasis between the sexes.

Decreased renal expression of the putative calcium oxalate inhibitor Tamm-Horsfall protein in the ethylene glycol rat model of calcium oxalate urolithiasis.

Purpose: Tamm-Horsfall protein is believed to inhibit calcium oxalate crystallization, aggregation or adhesion to the renal epithelium. We determined whether ethylene glycol induced urolithiasis changes the expression of renal and urinary Tamm-Horsfall protein. For comparison the expression of another calcium oxalate inhibitor, osteopontin, was also analyzed.