Antioxidant, anti-inflammatory and neuroprotective actions of resveratrol after experimental nervous system insults. Special focus on the molecular mechanisms involved.

After different types of acute central nervous system insults, including stroke, subarachnoid haemorrhage and traumatic brain and spinal cord injuries, secondary damage plays a central role in the induction of cell death, neurodegeneration and functional deficits. Interestingly, secondary cell death presents an attractive target for clinical intervention because the temporal lag between injury and cell loss provides a potential window for effective treatment. While primary injuries are the direct result of the precipitating insult, secondary damage involves the activation of pathological cascades through which endogenous factors can exacerbate initial tissue damage. Secondary processes, usually interactive and overlapping, include oxidative stress, neuroinflammation and dysregulation of autophagy, ultimately leading to cell death. Resveratrol, a natural stilbene present at relatively high concentrations in grape skin and red wine, exerts a wide range of beneficial health effects. Within the central nervous system, in addition to its inherent free radical scavenging role, resveratrol increases endogenous cellular antioxidant defences thus modulating multiple synergistic pathways responsible for its antioxidant, anti-inflammatory and anti-apoptotic properties. During the last years, a growing body of in vitro and in vivo evidence has been built, indicating that resveratrol can induce a neuroprotective state and attenuate functional deficits when administered acutely after an experimental injury to the central nervous system. In this review, we summarize the most recent findings on the molecular pathways involved in the neuroprotective effects of this multi target polyphenol, and discuss its neuroprotective potential after brain or spinal cord injuries.

Resveratrol exerts anti-oxidant and anti-inflammatory actions and prevents oxaliplatin-induced mechanical and thermal allodynia.

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a frequent and devastating side effect of cancer therapy. No preventive strategies are currently available. We investigated the use of resveratrol (RESV) in the prevention of CIPNP and evaluated key components of the antioxidant defense system and neuroinflammatory factors as possible mediators contributing to RESV actions. Male rats were injected with oxaliplatin (OXA) and received daily oral RESV. Paw mechanical and thermal allodynia, oxidative stress, antioxidant, pro-inflammatory and neuronal injury/activation markers were evaluated in the sciatic nerve (SN), lumbar dorsal root ganglia (DRG) and spinal cord (SC). OXA-injected animals developed mechanical and thermal allodynia, while those receiving OXA + RESV showed patterns of response similar to control animals. Higher TBARS levels and lower GSH/GSSG ratios were observed in the SN of animals receiving OXA. The mRNA levels of the transcription factor NFκB and the pro-inflammatory cytokine TNFα were found to be upregulated both in lumbar DRG and SC. In addition, the antioxidant enzymes NQO-1 and HO-1 and the neuronal injury marker ATF3 showed increased levels of expression in lumbar DRG. In the dorsal SC the neuronal activation marker c-fos and the transcription factor Nrf2, main regulator of antioxidant defenses, were found to be upregulated. RESV early and sustained administration prevented NFκB, TNFα, ATF3 and c-fos upregulation, while increasing the expression of Nrf2, NQO-1, HO-1 and the redox-sensitive deacetylase SIRT1. RESV treatment was also able to restore TBARS levels and GSH/GSSG ratio. Thus, RESV administration resulted in the upregulation of antioxidant mediators, suppression of pro-inflammatory parameters and prevention of OXA-induced mechanical and thermal allodynia.

A new method based on fuzzy logic to evaluate the contract service provider performance.

This paper puts forward a fuzzy inference system for evaluating the service quality performance of service contract providers. An application service provider (ASP) model for computerized maintenance management was used in establishing common performance indicators of the quality of service. This model was implemented in 10 separate hospitals. As a result, inference produced a service cost/acquisition cost (SC/AC) ratio reduction from 16.14% to 6.09%, an increase of 20.9% in availability, with a maintained repair quality (NRR) in the period of December 2001 to January 2003.

Local knowledge and treatment of malaria in Agusan del Sur, The Philippines.

Information about local knowledge of malaria, its transmission, treatment and prevention were gathered at the outset of a Malaria Control Program in order to incorporate this information into community interventions. Data were collected using focus groups and indepth interviews with caretakers of children who had had a recent episode of malaria. These were supplemented as baseline data through a survey and the ongoing participation of researchers in the intervention. Local knowledge of malaria was influenced by clinical diagnosis and was based on the coexistence of signs of illness. People conventionally self-medicated or used herbs for symptomatic relief prior to seeking clinical diagnosis and treatment, with treatment delay influenced by the logistic difficulties within the region, direct and indirect costs associated with treatment seeking, and delays in the return of results once a blood film for diagnosis was made. People were familiar with mosquito control activities conducted by the Malaria Control Service and, as a result, most respondents associated malaria with mosquitos. However, the role of the mosquito as the sole vector, and the means by which malaria was transmitted, were not well appreciated.

Patterns of treatment for malaria in Tayabas, The Philippines: implications for control.

This paper describes local understandings of illness and documents treatment-seeking behaviour in Tayabas, Quezon, The Philippines. Data were collected using focus group discussions and narrative interviews with adults and with mothers of children, who had had confirmed malaria during a two-month surveillance period. Signs and symptoms of malaria are important in directing individual diagnosis, treatment-seeking and therapy. Household therapy with antimalarials, and more commonly antipyretics and herbs, as used before seeking care from either the formal or informal sector. Care outside the home was sought where symptoms continued and/or worsened, with an average period of time from onset of symptoms to presentation to a clinic of six days. Accessibility to clinics is not a problem in the study area and hence the primary reason for delay was propensity to self-treat first and to discontinue medication when feeling better. These factors affect the control of malaria and the potential to reduce transmission. Better advice to the community regarding the importance of diagnosis and compliance with antimalarial therapy is indicated.

Patterns of acute respiratory tract infection in children: a longitudinal study in a depressed community in Metro Manila.

The incidences of acute respiratory tract infection (ARI) and acute lower respiratory infection (ALRI) were 6.1 and 0.5 per child-year, respectively, in children less than 5 years old in a depressed urban community in Manila. The peak age-specific incidence occurred in those children 6-23 months old for ARI and 6-11 months old for ALRI. Age less than 2 years, malnutrition, household crowding, and parental smoking were associated with a statistically significant, though modest, increase in ARI morbidity. The crude mortality rate was 14.3 per 1,000 children 0-4 years old, with a corresponding ARI-specific mortality rate of 8.9 per 1,000. The prevalence of viral infection was 32.8 and that of bacteremic ALRI was 6.7 per 1,000 children with moderate ALRI. Respiratory syncytial virus was the predominant viral pathogen, while Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus were the most frequently isolated bacterial pathogens. Transmission of respiratory pathogens in depressed communities, facilitated by inadequate housing, inaccessible health services, and prevalent malnutrition, will continue unless meaningful socioeconomic improvement is realized.

Child care practices of mothers: implications for intervention in acute respiratory infections.

An epidemiological study of acute respiratory infection (ARI) in an urban community showed poor utilization of available health services. This prompted us to undertake this study to identify determinants of child care practices of mothers through a focus group discussion and survey of the knowledge, attitudes and practices of mothers. The results will form the basis of appropriate health education strategy geared towards control of ARI. They showed that, generally, the mothers were unable to recognize a severe infection. Poor diagnostic ability compounded by a limited knowledge of the appropriate management of varying types or degrees of ARI resulted in inappropriate action. Consequently, there was a high rate of self-medication and a low rate of health service utilization. In addition, there was low compliance with childhood immunizations. With these limitations in the mother's knowledge and practices, an education programme utilizing an informative print material was devised to upgrade the mother's ability to recognize signs of ARI and to improve her management of the condition.

Determinants of morbidity and mortality due to acute respiratory infections: implications for intervention.

Acute respiratory infections (ARI) were monitored every two weeks in an urban community in Metro Manila, Philippines, to determine the incidence and risk factors for ARI morbidity. Hospitalized children with acute lower-respiratory-tract infection (ALRI) were studied to determine case-fatality rates (CFR) and predictors for mortality. Incidence rates were highest in infants, 3.2-4.0 per person, followed by children one to four years of age, with corresponding rates of 3.0-3.4 per person. The risk factors for ARI morbidity were low socioeconomic status and age less than one year. A CFR of 5% in children with ALRI was observed. Malnutrition and a positive culture of blood were significant risk factors for mortality. These identified risk factors underscore the value of primary health care interventions, such as the standard ARI case management, immunization, health education, promotion of breast-feeding, and vitamin A supplementation, as strategies for reducing ARI mortality in developing countries.