Burden and risk factors for Pseudomonas aeruginosa community-acquired pneumonia:a Multinational Point Prevalence Study of Hospitalised Patients

Pseudornonas aeruginosa is a challenging bacterium to treat due to its intrinsic resistance to the antibiotics used most frequently in patients with community-acquired pneumonia (CAP). Data about the global burden and risk factors associated with P. aeruginosa-CAP are limited. We assessed the multinational burden and specific risk factors associated with P. aeruginosa-CAP. We enrolled 3193 patients in 54 countries with confirmed diagnosis of CAP who underwent microbiological testing at admission. Prevalence was calculated according to the identification of P. aeruginosa. Logistic regression analysis was used to identify risk factors for antibiotic-susceptible and antibiotic-resistant P. aeruginosa-CAP. The prevalence of P. aeruginosa and antibiotic-resistant P. aeruginosa-CAP was 4.2% and 2.0%, respectively. The rate of P. aeruginosa CAP in patients with prior infection/colonisation due to P. aeruginosa and at least one of the three independently associated chronic lung diseases (i.e. tracheostomy, bronchiectasis and/or very severe chronic obstructive pulmonary disease) was 67%. In contrast, the rate of P. aeruginosa-CAP was 2% in patients without prior P. aeruginosa infection/colonisation and none of the selected chronic lung diseases. The multinational prevalence of P. aeruginosa-CAP is low. The risk factors identified in this study may guide healthcare professionals in deciding empirical antibiotic coverage for CAP patients

ACTIVITY OF CHOLINE ALPHOSCERATE ON CEREBROVASCULAR MORPHOLOGY AND INFLAMMATORY MARKERS IN SPONTANEOUSLY HYPERTENSIVE RATS

The effect of cholinergic precursors on choline availability and acetylcholine synthesis/release is established. It is thought that this increase contributes to counter cognitive impairment occurring in adult-onset dementia disorders. Choline alphoscerate (alpha-gliceryl-phosphoryl-choline, GPC) is among cholinergic precursors so far available the most effective in enhancing acetylcholine biosynthesis and release in animal models. Chronic brain vascular injury is a severe risk factor of cerebral dysfunction. White matter lesions represent relevant and early consequences of cerebrovascular injury. Cerebral hypoperfusion can induce small vessel disease (SVD) and is linked to the development of white matter lesions. Brain hypoperfusion and white matter lesions correlate with the development of cognitive impairment in Alzheimer’s disease (AD) or vascular dementia (VaD). The present study has assessed if long term treatment with GPC has a cerebroprotective effect on brain injury of vascular origin in the rat. Analysis was made on spontaneously hypertensive rats (SHR used as an animal model of brain vascular injury. Male SHR aged 32 weeks and age-matched normotensive Wistar–Kyoto (WKY) rats were treated for 4 weeks with GPC (150 mg/kg/day) or vehicle. On pial and intracerebral arteries of different brain areas, vascular astrocytes, blood brain barrier (BBB) and endothelial markers were assessed by neuromorphological and immunohistochemical techniques associated with quantitative analysis. No significant changes in the size of perivascular astrocytes were found in SHR compared to WKY rats, whereas the expression of the BBB marker aquaporin-4 decreased in SHR. This phenomenon was countered by GPC treatment. Endothelial markers and vascular adhesion molecules (ICAM, VCAM, PECAM, and P-selectine) expression were not homogeneously affected by hypertension in both pial and intracerebral vessels. The observation that treatment with GPC reversed cerebral microanatomical changes occurring in SHR is consistent with data of clinical trials reporting an improvement of cognitive function in subjects suffering from cerebrovascular disorders. These preclinical results suggest a re-evaluation of GPC activity in cerebrovascular patients with cognitive dysfunction

BRAIN MORPHOLOGICAL ANALYSIS OF OBESE ZUCKER RAT: MODEL OF METABOLIC SYNDROME.

Metabolic syndrome (MetS) is a disorder characterized by the development of insulin resistance, with subsequent hyperinsulinemia, that increases the risk of cerebrovascular and cardiovascular diseases. Obesity is probably a risk factor for Alzheimer’s disease and vascular dementia and is associated with impaired cognitive function. The obese Zucker rat (OZR) represents a model of type 2 diabetes exhibiting a moderate degree of arterial hypertension and hyperlipidemia. To clarify the possible relationships between MetS and brain damage, the present study has investigated brain microanatomy of OZRs compared with their littermate controls lean Zucker rats (LZRs). Male OZRs and LZRs of 12 weeks of age were used. Their brain was processed for analysis of nerve cell number by neuronal specific nuclear protein (NeuN) immunohistochemistry and phosphorylated neurofilament (NFP) immunoreactive axons analysis. The possible occurrence of astrogliosis was investigated by processing brains for immunohistochemical analysis of glial fibrillary acidic protein (GFAP). In frontal cortex and hippocampus of OZRs reduced number of neurons was related to a decrease of Neu-N expression compared to LZRs. A significant increase in the size and number of GFAP immunoreactive astrocytes was also observed. These findings suggest that OZRs developed as an animal model of type 2 diabetes, may also represent a model for assessing the influence of MetS on brain. This could clarify the pathophysiology of neurological injury reported in obese individuals and/or affected by MetS

ACTIVITY OF THIOCTIC ACID ENANTIOMERS ON SPINAL CORD CHANGES CONSEQUENT TO PERIPHERAL NERVE INJURY

Peripheral neuropathies are disorders characterized by hyperalgesia and allodynia with impaired muscular sensitivity and functions. Oxidative stress, which is an imbalance between the production of free radicals and the antioxidant defence mechanisms is increased in peripheral neuropathies. Antioxidants and in particular thioctic acid, have been proposed as potential therapeutic agents for treating and/or preventing several pathologies related to increased oxidative stress. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (-)-thioctic acid and in the racemic form (+/-)-thioctic acid. The present study has assessed if chronic constriction injury (CCI) induced by loose ligation of the sciatic nerve, is accompanied by spinal cord changes and if thioctic acid enantiomers treatment has any therapeutic activity. Loose ligation of the right sciatic nerve was performed in spontaneously hypertensive rats (SHR), used as a model of increased oxidative stress, and in normotensive Wistar-Kyoto rats (WKY) taken as a control group. Animals with sciatic nerve ligation were left untreated or were treated intraperitoneally for 14 days with (+/-)-(250 mmol/kg/day and 125 mmol/kg/day), (+)-(125 mmol/kg/day) or (-)-(125 mmol/kg/day) thioctic acid. Effects elicited by thioctic acid were compared with those of pregabalin (300 mmol/kg/day), an anticonvulsant used for treating neuropathic pain. Analysis was focused on injury phenomena at level of dorsal root ganglia and spinal cord and was made using immunochemical and immunohistochemical techniques. An increase of oxidative stress markers was observed after CCI of the sciatic nerve. An obvious astrogliosis and neuronal damage independent by activation of apoptotic processes occurred primarily in the spinal cord posterior horn. Treatment with thioctic acid reduced oxidative stress and astrogliosis in spinal cord. (+)-Thioctic acid and the higher dose of (+/-)-thioctic acid were the most active. (-)-Thioctic acid and pregabalin were without effect. The above results demonstrated a spinal cord damage after peripheral nerve injury and a neuroprotective effect induced by thioctic acid. These findings suggest a neuroprotective activity of thioctic acid on central nervous system lesions consequent to CCI and that the compound may represent an option for entrapment neuropathies treatment