Lack of effect of dietary nucleotide supplementation on erythrocyte 2,3-diphosphoglycerate concentration. A study on preterm neonates.

BACKGROUND: Recently we demonstrated an increased 2,3-diphosphoglycerate (2,3-DPG) erythrocyte concentration in rat pups subjected to nucleotide-enriched artificial feeding. DESIGN: The present study was carried out to test the hypothesis that a possible increase in 2,3-DPG concentration can also be obtained in human neonates who are fed nucleotide-enriched formula. Preterm neonates born or referred to the neonatal intensive care unit of the G. Gaslini Hospital, Genoa University, with a gestational age >30 weeks and <37 weeks were enrolled in our randomized trial. Recruitment took place within 48-72 hours from birth. Only newborns of mothers deciding not to breast-feed were eligible to be randomized for the supplemented group (FN) or non-supplemented group (RF). Breast-fed newborns were considered the control group (C). The study window (for supplementation and blood samples) was restricted to the first two weeks following birth (from the 2nd (t1) to the 16th (t2) day of life). At the end of our study, only 21 neonates were eligible for statistical analysis. RESULTS: The stimulating action of dietary nucleotides on 2,3-DPG concentration failed to be demonstrated; increases in 2,3-DPG concentration that were observed in newborns fed with nucleotide supplemented formula (FN) were comparable to those observed in newborns fed with regular formula (RF) and breast-fed newborns. CONCLUSIONS: The EC recommendation for the amount of nucleotides allowed in formula milk does not seem to be high enough to have positive effects on 2,3-DPG synthesis. Whether this possible 'pharmacological' effect can be achieved by a higher intake of ingested nucleotides and/or a change in the proportions of single nucleotides contained in milk formulas remain interesting end points to be elucidated.     

Effect of nolomirole on monocrotaline-induced heart failure.

Neurohormonal activation has been shown to be a major factor in congestive heart failure progression and mortality. The beneficial effects obtained in clinical trials with angiotensin converting enzyme (ACE) inhibitors, beta-blockers and aldosterone antagonists have confirmed this hypothesis. 5,6-Diisobutirroyloxy-2-methyl-aminotetraline hydrochloride (nolomirole) is a selective agonist of prejunctional D(2)-dopaminergic and alpha(2)-adrenergic receptors. The stimulation of these receptors inhibits catecholamine release from sympathetic nerve endings. To confirm that this mechanism can be useful in congestive heart failure, we studied the effects of nolomirole on monocrotaline-induced congestive heart failure. The ACE inhibitor trandolapril was used as reference compound. Rats were given single intraperitoneal injection of either saline (control group; n=20) or monocrotaline (50 mg kg(-1)). Three days later, the monocrotaline-treated animals were randomly allocated (n=50 per group) to oral treatment with distilled water (vehicle group), nolomirole (0.25 mg kg(-1)) twice a day, or trandolapril (0.3 mg kg(-1)) once a day up to sacrifice. On the fourth week after monocrotaline injection, animals with signs of congestive heart failure were sacrificed for evaluation of heart hypertrophy and neuroendocrine alterations. Atrial natriuretic peptide (ANP) and alderosterone were determined by radioimmunoassay in plasma. Tissue norepinephrine concentration was quantified by high-pressure liquid chromatography. Nolomirole and trandolapril significantly reduced (a) hypertrophy of right atria and ventricles, (b) plasma levels of ANP and presence of pleural/peritoneal effusions and (c) norepinephrine depletion of right ventricle. These findings confirmed that nolomirole, like trandolapril, is able to attenuate the heart failure signs in the monocrotaline-induced congestive heart failure model.     

Spinal fractures in patients with ankylosing spondylitis

The ankylosed spine is prone to fracture even after minor trauma due to its changed biomechanical properties. The two central features of ankylosing spondylitis (AS) that promote the pathological remodeling of the spine are inflammation and new bone formation. AS is also associated with osteoporosis that is attributed to an uncoupling of the bone formation and bone resorption processes. Therefore, bone resorption occurs and promotes weakening of the spine as well as increased risk of vertebral fractures which can be hugely different in terms of clinical relevance. Even in the presence of symptomatic clinical vertebral fractures, the diagnosis can be overruled by attributing the pain to disease activity. Furthermore, given the highly abnormal structure of the spine, vertebral fracture diagnosis can be difficult on the basis of radiography alone. CT can show the fractures in detail. Magnetic resonance imaging is considered the method of choice for the imaging of spinal cord injuries, and a reasonable option for exclusion of occult fractures undetected by CT. Since it is equally important for radiologists and clinicians to have a common knowledge base rather than a compartmentalized view, the aim of this review article was to provide the required clinical knowledge that radiologists need to know and the relevant radiological semiotics that clinicians require in diagnosing clinically significant injury to the ankylosed spine.     

Fractional CO₂ vaginal laser for the genitourinary syndrome of menopause in breast cancer survivors

Adjuvant chemotherapy and endocrine therapy can induce early iatrogenic menopause or worsen pre-existing menopausal symptoms in breast cancer survivors (BCS). The second most frequent menopausal symptom after hot flushes is the genitourinary syndrome (GSM). Since hormone replacement therapy is contraindicated in BCS, vaginal laser might represent a new nonhormonal option for GSM. This study aims at evaluating the effectiveness of the fractional CO₂ vaginal laser for GSM in BCS compared with healthy women. This is a retrospective study on 135 postmenopausal women (45 BCS and 90 healthy women) who underwent fractional CO₂ laser for GSM. Objective (VHI and VVHI) and subjective outcomes (VAS for dyspareunia and vaginal dryness and a pain questionnaire) were evaluated at baseline visit and at every follow-up visit. Subjective and objective parameters improved significantly in both groups after laser therapy. The improvement was progressive and long-lasting up to 12 months after the end of the treatment. No severe adverse events were observed during the treatment. Fractional CO₂ vaginal laser induces a significant and long-lasting improvement on GSM symptoms in BCS. However, this improvement is slower than in healthy women undergoing the same treatment. Laser therapy turns out to be safe and well-tolerated.     

Emergence and Spread of SARS-CoV-2 Lineages B.1.1.7 and P.1 in Italy

Italy’s second wave of SARS-CoV-2 has hit hard, with more than three million cases and over 100,000 deaths, representing an almost ten-fold increase in the numbers reported by August 2020. Herein, we present an analysis of 6515 SARS-CoV-2 sequences sampled in Italy between 29 January 2020 and 1 March 2021 and show how different lineages emerged multiple times independently despite lockdown restrictions. Virus lineage B.1.177 became the dominant variant in November 2020, when cases peaked at 40,000 a day, but since January 2021 this is being replaced by the B.1.1.7 ‘variant of concern’. In addition, we report a sudden increase in another documented variant of concern—lineage P.1—from December 2020 onwards, most likely caused by a single introduction into Italy. We again highlight how international importations drive the emergence of new lineages and that genome sequencing should remain a top priority for ongoing surveillance in Italy.     

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

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