Actin polymerization in neutrophils from donors of peripheral blood stem cells: divergent effects of glycosylated and nonglycosylated recombinant human granulocyte colony-stimulating factor

Neutrophil functions can be modified by Recombinant human G-CSF (rhG-CSF) treatment, with divergent effects on phagocytosis, motility, bactericidal activity, and surface molecule expression. Neutrophil morphology is modified by treatment with filgrastim (the nonglycosylated form of rhG-CSF), while it is not affected by lenograstim (the glycosylated type of rhG-CSF). Little information is available about actin polymerization in neutrophils from subjects treated with the two types of rhG-CSF. In the current paper we evaluated two groups of donors of peripheral blood stem cells (PBSC) for allogeneic transplantation. Ten subjects were treated with filgrastim and 10 with lenograstim to mobilize PBSC; 15 blood donors were evaluated as a control group. Actin polymerization (both spontaneous and fMLP-stimulated) was studied by a flow cytometric assay. A microscopic fluorescent assay was also carried out to evaluate F-actin distribution in neutrophils. We found that filgrastim induced an increased F-actin content in resting neutrophils, along with morphologic evidence for increased actin polymerization distributed principally at the cell membrane and frequently polarized in focal areas; in addition, fMLP was not able to induce further actin polymerization. On the contrary, treatment with lenograstim was associated with F-actin content, distribution, and polymerization kinetics indistinguishable from those displayed by control neutrophils. Such experimental results show that filgrastim and lenograstim display divergent effects also on neutrophil actin polymerization and provide further explanation for previous experimental findings.     

Low nutrient intake is an essential component of frailty in older persons

BACKGROUND: Poor nutrient intake is conceptualized to be a component of frailty, but this hypothesis has been little investigated. We examined the association between low energy and nutrient intake and frailty. METHODS: We used data from 802 persons aged 65 years or older participating to the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) study. Frailty was defined by having at least two of the following criteria: low muscle strength, feeling of exhaustion, low walking speed, and reduced physical activity. The European Prospective Investigation into Cancer and nutrition (EPIC) questionnaire was used to estimate the daily intake of energy and nutrients. Low intake was defined using the value corresponding to the lowest sex-specific intake quintile of energy and specific nutrients. Adjusted logistic regression analyses were used to study the association of frailty and frailty criteria with low intakes of energy and nutrients. RESULTS: Daily energy intake < or =21 kcal/kg was significantly associated with frailty (odds ratio [OR]: 1.24; 95% CI: 1.02-1.5). After adjusting for energy intake, a low intake of protein (OR: 1.98; 95% CI: 1.18-3.31); vitamins D (OR: 2.35; 95% CI: 1.48-3.73), E (OR: 2.06; 95% CI: 1.28-3.33), C (OR: 2.15; 95% CI: 1.34-3.45), and folate (OR: 1.84; 95% CI: 1.14-2.98); and having a low intake of more than three nutrients (OR: 2.12; 95% CI: 1.29-3.50) were significantly and independently related to frailty. CONCLUSIONS: This study provides evidence that low intakes of energy and selected nutrients are independently associated with frailty.     

Low socioeconomic status and disability in old age: evidence from the InChianti study for the mediating role of physiological impairments

BACKGROUND: Low socioeconomic status (SES) has been associated with increased risk of disability in later life. The purpose of this study was to determine if SES has an impact on mobility functioning and to explore which physiological impairments are also associated with SES and may explain its relationship with mobility. METHODS: The study sample consisted of 1025 individuals aged 65 years or older residing in the Chianti area (Italy). Number of years of education was used as an indicator of SES. Mobility functioning was assessed using gait speed (400 m) and the Short Physical Performance Battery (SPPB). Mobility-related physiological impairments were assessed with tests of executive functioning, nerve conduction velocity, muscle power, hip-ankle range of motion, Ankle-Brachial Index, and visual acuity. Linear regression models were used to study the association between number of years of education and mobility and to estimate the contribution of each of the selected physiological impairments to this association. RESULTS: Adjusting for age and sex, slower gait speed (1.16 vs 1.26 m/s, p <.0001) and lower SPPB scores (9.55 vs 10.11, p =.006) were seen in persons with < or =5 years of total education compared with those persons with >5 years of total education. Leg power and executive function decreased the strength of the association between educational level and gait speed by more than 15%. Controlling for all selected impairments (full model) decreased the education-gait speed association by 49%. Low education continued to be significantly associated with gait speed (p <.01). Adjusting for all physiological impairments substantially reduced the low education-SPPB score association by 100%, and this association was no longer significant. CONCLUSIONS: Low SES is related to multiple physiological impairments, which explain a large amount of the association between education and gait limitations. Further work must be done to understand the mechanisms whereby low SES translates into the impairments that play an important role in mobility.     

Giant congenital aortic aneurysm with cleft sternum in a neonate: pathological and surgical considerations for optimal management

We report a rare case of a neonate with congenital giant aortic aneurysm associated to cleft sternum, who underwent surgical repair. The patient died on postoperative Day 5 from cardiac arrest. Autopsy revealed a circumferential subendocardial myocardial infarction and misdiagnosed coronary ostial anomalies. A critical analysis of this unfortunate case may help optimal surgical planning in similar patients in the future.     

Sudden cardiac death with normal heart:: molecular autopsy

Several culprits may be identified at postmortem in sudden death (SD) victims, including coronary artery, myocardial, valve, conduction system, and congenital heart diseases. However, particularly in young people, the heart can be found grossly and histologically normal in a not-so-minor amount of cases (the so-called unexplained SD or “mors sine materia”) and inherited ion channel diseases are implicated (long and short QT syndromes, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia). These channelopathies are due to defective genes encoding for proteins of sodium and potassium ion channels at the sarcolemma level or for receptors regulating intracellular calcium release at the sarcoplasmic reticulum level. Postmortem investigation may still represent the first opportunity to make the proper diagnosis also in the setting of a structurally normal heart and the employment of molecular biology techniques is of help to solve the puzzle of such “silent” autopsies. For these reasons, autopsy investigation of cardiac SD should always include sampling for genetic testing to search for the invisible inherited arrhythmogenic disorders, as recommended in the recent guidelines by the Association for European Cardiovascular Pathology.     

Neurological and psychiatric effects of hepatitis C virus infection

Hepatitis C virus (HCV) infection is widespread and affects 71 million people worldwide. Although hepatic manifestations are the most frequent, ranging from chronic hepatitis to cirrhosis and hepatocellular carcinoma, it is also associated with several extrahepatic manifestations. Infected patients may present non-specific neurological symptoms, regardless of the presence of liver cirrhosis. Several pathogenetic mechanisms underlying neurological symptoms have been hypothesized: neuroinvasion, immune-mediated damage, neurotransmitter alterations and cryoglobulinemia. Alterations of the central nervous system include cerebral vasculopathy, acute or subacute encephalopathy and inflammatory disorders. HCV infection may be responsible for neuropathies, of which the most frequent form is symmetrical axonal sensory or sensory-motor polyneuropathy which causes loss of leg sensitivity and weakness. Up to 50% of patients with HCV infection may experience cognitive decline and psychological disorders, such as depression and fatigue. HCV associated neurocognitive disorder is independent of the presence of liver cirrhosis and affects different domains than in patients with hepatic encephalopathy. It can be studied using specific tests that mainly explore executive functions, verbal learning and verbal recall. These disorders significantly reduce the quality of life. The new antiviral therapies improve the extrahepatic symptoms of HCV infection and their success depends on the achievement of sustained virological response. However, the effect of therapy may differ depending on the type of organ involved; neurological symptoms can be irreversible if there is organic liver damage. The aim of this review is to provide a critical overview of physiopathological mechanisms, diagnostic and therapeutic strategies of the neurological and psychiatric effects of HCV infection.