Age-related changes in the brain of obese Zucker rat: Morphological and immunochemical analysis.

Metabolic syndrome (MetS) is defined as a combination of glucose intolerance, arterial hypertension, dyslipidemia and obesity with insulin resistance as the main cause of these imbalances. In general, obesity increases the risk of vascular diseases. Both cardiovascular and cerebrovascular disorders are often linked to impaired cognitive functions. A relationship between metabolic disease and mild cognitive impairment, and/or vascular dementia was hypothesized. The obese Zucker rat (OZR), represents a model of obesity and type 2 diabetes exhibiting a moderate degree of arterial hypertension. OZRs are characterized by the simultaneous occurrence of hyperglycaemia, hyperinsulinaemia and hyperlipidaemia. This study has investigated brain microanatomy of OZRs compared with their nonobese cohort lean Zucker rats (LZRs) to assess possible relationships between MetS and brain damage. Male OZRs and LZRs of 12, 16 and 20 weeks of age were used. Body weight, blood pressure and blood chemistry parameters were checked every two weeks and before killing. The brain was dissected out and processed for immunochemical and immunohistochemical analysis of nerve cells identified by neuronal specific nuclear protein (NeuN) and axons identified by neurofilament (NF) immunohistochemistry. Glial-fibrillary acid protein (GFAP) immunoreactive astrocytes were also investigated. OZRs of different ages, were characterized by a high body weight, an increase of systolic pressure, glycemia, triglycerides and cholesterol levels in comparison with LZRs. An age-dependent increase of these parameters was observed in OZRs. A decrease of brain/body weight ratio was found in OZRs. In frontal cortex and hippocampus, morphological and immunochemical analysis revealed a decrease of NeuN immunoreactive neurons not related to apoptosis in older OZRs group compared to age matched LZRs. In OZRs a decrease of NF immunoreaction and an increase of GFAP immunoreactive astrocytes was observed compared to LZRs These findings suggest that OZRs, used for investigating mechanisms and pathophysiology of obesity and type 2 diabetes, may also represent a model for assessing the influence of MetS on brain

Survey on HIV risk perception and sexual behaviours among seafarers

Because the nature of their work seafarers spend long periods of time away from their families and therefore represent a group at risk for sexually transmitted diseases, including HIV infection. This paper reports the results of a survey to evaluate awareness and knowledge of the risk of HIV infection among seafarers. Risky behaviours for HIV transmission were also assessed. The survey was conducted using anonymous questionnaires on 197 workers of 9 vessels and 26 office employees of an Italian shipping company (FINAVAL S.p.A., Rome). The respondents considered HIV/AIDS as one of the diseases with a high risk of transmission. Most respondents had a good general knowledge of HIV/AIDS and on the ways of its transmission. However, there is still lack of knowledge on the basics of this disease. On the other hand, in spite of knowledge and awareness about the risks of the disease, only 56.35% of the interviewed crewmembers used protection in sexual intercourse with occasional partners. Compared to data available in literature, the percentage of self-protecting people is increasing, but the number of seafarers exposing themselves to risky behaviours is still high. As expected, condoms are used with regular partners with lower frequency compared to occasional intercourse. The results of this survey indicate that adequate prevention campaigns and major attention paid to seafarers health is useful for stimulating responsible conduct for the prevention of infectious diseases, including HIV infection. Nevertheless, it is still necessary to increase information about the risk of sexually transmitted diseases and how to reduce it. (Int Marit Health 2011; 62, 2: 131–137

new route for tizanidine administration: a pharmacokinetics and light microscope autoradiography study

Spasticity could represent a complication of several central nervous system (CNS) disorders. Multiple sclerosis and painful paroxysmal syndromes (e.g. trigeminal neuralgia) are pathologies in which anti-spastic drugs are used to a greater extent . Baclofen, tizanidine (TIZ), benzodiazepines, dantrolene, and, more recently, gabapentin are the pharmacological agents more widely used. Baclofen, TIZ, benzodiazepines, gabapentin, clonidine but not dantrolene are active on CNS. The alpha2 adrenoceptor agonist TIZ is one of the most eff ective and largely used anti-spastic drugs. Oral treatment is the only route of anti-spastics administration, although it may cause problems of bioavailability and/or compliance in spastic patients with impaired deglutition. This study was designed to assess the possibility of develop a new route of administration of TIZ and to identify its targets in the spinal cord. New Zealand rabbits were treated with oral (OR , n=6), intramuscular (IM, n=6) or intranasal (IN, n=6) TIZ (3.2 mg/kg/day). Plasma concentration was measured by HPLC on samples collected at 0, 30, 60, 90, 120 and 480 min after treatment. Curves of average concentrations of TIZ vs. time were constructed. In plasma, TIZ reached a peak between 45-65 min after administration. Cmax was in the range of 268.33–1213.64 ng/ml for IM treatment, of 73.95–135.92 ng/ml for IN treatment and of 16.86–857.25 ng/ml for OR treatment. After pharmacokinetic studies, diff erent spinal cord tracts were removed and used for radioligand binding assay and autoradiography. Using [3H]-RX821002 ([3H]-RX) (0.1-14nM), the Kd and Bmax for every spinal cord segment were calculated. The non-specifi c binding was obtained with 100μM of (-)-epinephrine. [3H]-RX sites were accumulated in the superfi cial laminae of dorsal horn. Dense [3H]-RX binding in control was seen over the superfi cial dorsal horn (laminae I-II) and centrally located lamina X. The ventral horn showed moderate levels of binding. [3H]-RX was displaced after TIZ treatment using diff erent administration routes. The heaviest accumulation of silver grains (lowest displacement of TIZ) occurred after OR administration of the compound, the lowest after IM administration. These results suggest that both IM and IN administration of TIZ may represent routes of administration of the drug alternative to the OR one. Considering predictable adverse eff ects of IM treatment, the IN administration could represent the elective route to administrate this kind of drugs

Obesity-related blood brain barrier changes in obese Zucker rats

The blood brain barrier (BBB) is the site of exchange between blood and the nervous tissue. Damage of it may impair physiological balance between blood stream and nervous tissue. Metabolic syndrome (MetS) is defined by several interconnected physiological, biochemical, and metabolic factors directly related to obesity. It increases the risk of atherosclerotic cardiovascular and cerebrovascular disease and of all cause mortality. Obese Zucker rats (OZRs), with a mutation in leptin receptor, represent a model of obesity exhibiting diabetes and moderate arterial hypertension. In OZRs hyperglycaemia, hyperinsulinaemia and hyperlipidaemia occur simultaneously. This work had characterized BBB and endothelial alterations of OZRs compared to their non-obese cohort lean Zucker rats (LZRs) for assessing the occurrence of an eventual cerebrovascular injury. Brains of male OZRs and LZRs of 12, 16 and 20 weeks were processed for the immunochemical and immunohistochemical detection of different BBB markers. The water channel protein Aquaporin-4 (AQP4) and the glucose transporter protein- 1 (GLUT1) involved in the glucose passage across the BBB endothelial cells were investigated. The expression of adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) was also assessed within cerebrovascular endothelium as a marker of inflammation. In intracerebral arteries of older OZRs, a decrease of lumen area with an increase of wall area was found. BBB of older OZRs revealed an augmented expression of AQP4 probably related to an edema formation. A downregulation of GLUT1 was observed in OZRs of 12 weeks of age. This may represent the adaptive reaction to prevent excessive glucose entering in neurons. On the contrary, in older OZRs an obvious increase in the expression of GLUT1 was found. These phenomena are probably related to vascular inflammation as confirmed by the increase of ICAM-1 and VCAM-1 expression in the endothelium of older OZRs. The above evidence shows that OZRs develope specific BBB changes. This could contribute to clarify the pathophysiology of nervous system damage reported in obese individuals. OZRs may represent an useful animal model for assessing the influence of obesity/MetS on the brain and the possible correlation of it with neurodegenerative disorders

Acute effects of a selective cannabinoid-2 receptor agonist on neuroinflammation in a model of traumatic brain injury.

Proposed therapeutic strategies for attenuating secondary traumatic brain injury (TBI) include modulation of acute neuroimmune responses. The goal of this study was to examine the acute effects of cannabinoid-2 receptor (CB(2)R) modulation on behavioral deficits, cerebral edema, perivascular substance P, and macrophage/microglial activation in a murine model of TBI. Thirty male C57BL/6 mice underwent sham surgery, or cortical contusion impact injury (CCI). CCI mice received vehicle or the CB(2)R agonist 0-1966 at 1 and 24 h after injury. Performance on the rotarod, forelimb cylinder, and open-field tests were evaluated before and at 48 h after sham or CCI surgery. Cerebral edema was evaluated using the wet-dry weight technique. Immunohistochemical analysis was used to examine changes in substance P and macrophage/microglia-specific Iba1 protein immunoreactivity. Locomotor performance and exploratory behavior were significantly improved in mice receiving 0-1966 (CB(2)R agonist) compared to vehicle-treated mice. Significant reductions were found for cerebral edema, number of perivascular areas of substance P immunoreactivity, and number of activated macrophages/microglial cells in the injured brains of 0-1966-treated mice compared to vehicle-treated mice. The findings show that the effects of the CB(2)R agonist 0-1966 on edema, substance P immunoreactivity, and macrophage/microglial activation, were associated with recovery of acute motor and exploratory deficits. This study provides evidence of acute neuroprotective effects derived from selective CB(2)R activation that may represent an avenue for further development of novel therapeutic agents in the treatment of TBI

Intestinal protozoa in HIV-infected patients: effect of rifaximin in Cryptosporidium parvum and Blastocystis hominis infections

In HIV-1 infected patients severe enteritis and chronic diarrhea are often documented as a consequence of multiple opportunistic infections. We analyzed 48 HIV-1 positive patients for the presence of intestinal pathogenic protozoa. Patients with CD4 > or = 200/mm3 showed a higher prevalence of a single pathogenic protozoa than patients with CD4 or = 200/mm3, who presented enteric and systemic symptoms due to Criptosporidium or Blastocystis associated with enteropathogenic bacteri

Artificial Intelligence Models in the Diagnosis of Adult-Onset Dementia Disorders: A Review

Background: The progressive aging of populations, primarily in the industrialized western world, is accompanied by the increased incidence of several non-transmittable diseases, including neurodegenerative diseases and adult-onset dementia disorders. To stimulate adequate interventions, including treatment and preventive measures, an early, accurate diagnosis is necessary. Conventional magnetic resonance imaging (MRI) represents a technique quite common for the diagnosis of neurological disorders. Increasing evidence indicates that the association of artificial intelligence (AI) approaches with MRI is particularly useful for improving the diagnostic accuracy of different dementia types. Objectives: In this work, we have systematically reviewed the characteristics of AI algorithms in the early detection of adult-onset dementia disorders, and also discussed its performance metrics. Methods: A document search was conducted with three databases, namely PubMed (Medline), Web of Science, and Scopus. The search was limited to the articles published after 2006 and in English only. The screening of the articles was performed using quality criteria based on the Newcastle-Ottawa Scale (NOS) rating. Only papers with an NOS score ≥ 7 were considered for further review. Results: The document search produced a count of 1876 articles and, because of duplication, 1195 papers were not considered. Multiple screenings were performed to assess quality criteria, which yielded 29 studies. All the selected articles were further grouped based on different attributes, including study type, type of AI model used in the identification of dementia, performance metrics, and data type. Conclusions: The most common adult-onset dementia disorders occurring were Alzheimer's disease and vascular dementia. AI techniques associated with MRI resulted in increased diagnostic accuracy ranging from 73.3% to 99%. These findings suggest that AI should be associated with conventional MRI techniques to obtain a precise and early diagnosis of dementia disorders occurring in old age