The long pentraxin PTX3 at the crossroads between innate immunity and tissue remodelling.

Innate immunity represents the first line of defence against pathogens and plays key roles in the activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules that recognize pathogen-associated molecular patterns and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. Pentraxins are essential constituents of the humoral arm of innate immunity and represent a superfamily of highly conserved acute phase proteins, traditionally classified into short and long pentraxins. Pentraxin 3 (PTX3) is the prototypic member of the long pentraxins subfamily. As opposed to C-reactive protein, whose sequence and regulation have not been conserved during evolution from mouse to man, the evolutionary conservation of sequence, gene organization and regulation of PTX3 has allowed addressing its pathophysiological roles in genetically modified mice, in diverse conditions, ranging from infections to sterile inflammation, angiogenesis and female fertility. Despite this conservation, a number of predominantly non-coding polymorphisms have been identified in the PTX3 gene which, when associated in particular haplotypes, have been shown to be relevant in clinical conditions including infection and fertility. Here we review the studies on PTX3, with emphasis on pathogen recognition, tissue remodelling and crosstalk with other components of the innate immune system.

Posatirelin for the treatment of degenerative and vascular dementia: results of explanatory and pragmatic efficacy analyses.

In order to confirm the efficacy and safety of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide), a synthetic peptide having cholinergic, catecholaminergic and neurotrophic activities, a multicentre, double-blind, controlled study versus placebo was planned in elderly patients suffering from Alzheimer's disease and vascular dementia, according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria, respectively. The trial consisted of a 2-week run-in phase with placebo administered once a day orally, followed by a double-blind period of 3 months, with posatirelin or placebo administered once a day intramuscularly. Efficacy was assessed using the Gottfries-Bråne-Steen (GBS) Rating Scale (primary variable) and the Rey Memory Test (secondary variable). Laboratory tests, vital signs and adverse events were monitored. A total of 360 patients were randomized, the intent-to-treat sample (ITT) being made up of 357 patients and the per protocol sample (PP) of 260 patients. Both pragmatic and explanatory analyses showed significant differences between treatment groups in the GBS Rating Scale and the Rey Memory Test, with no difference in the two types of dementia. No difference between treatments was observed in safety variables, the incidence of adverse events in the posatirelin group being 7.3%. The study confirms previous results showing that treatment with posatirelin can improve cognitive and functional abilities of patients suffering from degenerative or vascular dementia.

Oxiracetam in the treatment of primary degenerative and multi-infarct dementia: a double-blind, placebo-controlled study.

A multicentre, double-blind, between-patient study was carried out to evaluate the efficacy and tolerability of oxiracetam (800-mg tablets), in comparison with placebo, each given twice daily for 12 weeks to patients suffering from primary degenerative, multi-infarct or mixed forms of dementia. Efficacy was assessed by the Inventory of Psychic and Somatic Complaints in the Elderly (IPSC-E), administered at entry and after 4, 8 and 12 weeks of treatment, and by the Blessed Dementia Scale and the Newcastle Memory, Information and Concentration Scale (NMICS), administered at the beginning and at the end of the study. Three hundred and seven patients were enrolled, 18 of whom were excluded from the analysis because of violation of the protocol. Two hundred and eighty-nine patients were analyzed (145 m, 144 f, mean age 73 years) and 272 completed the study; 3 patients in each treatment group were withdrawn because of poor tolerability, 10 because of poor compliance and 1 patient because of the occurrence of a cerebral stroke. A significantly (p less than 0.01) different effect, in favor of oxiracetam, was observed in the three main efficacy criteria (i.e. IPSC-E, Blessed Dementia Scale and NMIC total scores), and confirmed by descriptive analyses carried out on some subitems of the scales used. Thirty-one patients on oxiracetam and 27 on placebo complained of a total of 35 and 32 minor unwanted effects, respectively. No clinically or statistically significant changes were observed on routine laboratory examinations.

Study of the efficacy and tolerability of L-acetylcarnitine therapy in the senile brain.

The aim of this study was to evaluate the efficacy and tolerability of L-acetylcarnitine therapy in the senile brain. The trial was conducted on a double-blind basis, with a total of 40 patients divided into two groups of 20, treated for 40 days with L-acetylcarnitine and placebo, respectively--the therapeutic regimen being two 500 mg tablets t.i.d. Mental parameters of the senile brain were assessed at 0, 20 and 40 days of treatment, while basal and final values were recorded for a number of laboratory tests. Statistical analysis of results confirmed that short-term, intensive L-acetylcarnitine treatment can determine a significant improvement of the main mental parameters of the senile brain, without incidence of significant side effects.

Combined cefuroxime plus acetylcysteine in the treatment of bacterial infections of the respiratory tract.

Fifty adult patients (29 males, 21 females) suffering from respiratory tract infections with substantial production of mucus were treated with cefuroxime 1 g and acetylcysteine 300 mg administered simultaneously by i.m. injection twice daily for 10 days. Bacteriological tests were performed before and after treatment. Clinical variables (fever, cough, quantity and type of sputum, difficulty in expectorating) were evaluated, and assigned scores ranging from 0 to 3 according to an arbitrary semiquantitative scoring system. The therapeutic results obtained were positive. No side-effects were observed.

Combined labetalol plus flunarizine treatment for arterial hypertension.

Forty-one patients (21 males and 20 females) suffering from arterial hypertension associated with peripheral and cerebral vascular distress were treated for a period of 60 days with an extempore combination of labetalol (an antihypertensive drug with an alpha- and beta-blocking action) and flunarizine (a calcium-antagonist). Changes in supine and standing arterial blood pressure and in supine heart rate were evaluated periodically. Haematological and urinary controls of a number of biomedical indices were performed in basal conditions and after 60 days. The combination was found to show a rapid efficacy in the entire patient group: both supine and standing systolic and diastolic blood were significantly reduced as early as the tenth day of treatment. No significant changes in heart rate were observed. The combination revealed neither orthostatic hypotensive effects nor side-effects of such a degree of severity as to require reduction of the dose or discontinuation of the treatment.