Lymphocyte subsets and Langerhans cells in the skin of kidney transplant recipients under three different immunosuppressive regimens.

BACKGROUND: Renal transplant recipients (RTRs) are at increased risk of developing skin cancer; however, the role of immunosuppression is not yet fully understood. In this study, we evaluated the immunohistochemical changes in the skin of RTRs under three different immunosuppression regimens: mTOR inhibitors (mTORi), sirolimus or everolimus, mycophenolic acid (MPA) precursors such as mycophenolate sodium or mofetil, or azathioprine (AZA). METHODS: We evaluated biopsies of sun-exposed and sun-protected skin for immunohistochemical quantification of B lymphocytes (CD20+ ), T lymphocytes (CD3+ , CD4+ , and CD8+ ), and Langerhans cells (LCs) (CD1a+ ) in 30 RTRs and 10 healthy controls. The RTRs were divided into three groups: mTORi (n = 10), MPA (n = 10), and AZA (n = 10). RESULTS: No differences were observed in the number of B lymphocytes. However, a significant decrease in the number of T lymphocytes and LCs was observed in both sun-protected and sun-exposed skin in the AZA and MPA groups, although to a lesser degree in the latter group. The skin of the mTORi group did not differ from that of the control group in terms of the number of B and T lymphocytes and LCs. CONCLUSIONS: Patients treated with mTORi exhibit preserved cellular elements related to cutaneous immune surveillance. The use of AZA induced a greater degree of skin immunosuppression than in the control group, as demonstrated by the decrease in T lymphocytes and LCs.

Paracoccidioidomycosis: characterization of subpopulations of macrophages and cytokines in human mucosal lesions.

Mucosal lesions of paracoccidioidomycosis (PCM) are frequently described and clinically important. Macrophages are classified as M1 or M2. M1 are proinflammatory and M2 are related to chronicity. Dectin-1 recognizes ß-glucan and plays an important role against fungal cells. The objective was to verify the presence of M1, M2, and dectin-1 and a possible correlation with Th1/Th2 cytokines in mucosal PCM lesions. In sum, 33 biopsies of oral PCM were submitted to histological and immunohistochemistry analysis, and positive cells were quantified. Eleven biopsies were characterized by compact granulomas (G1), 12 with loose granulomas (G2), and 10 with both kind of granulomas (G3). pSTAT-1 was equally increased in the three groups. G1 was characterized by an increased number of CD163+ macrophages. G2 presented similar number of arginase 1, iNOS, and CD163 expressing cells. G3 presented an increased number of cells expressing arginase 1 and CD163 over iNOS. G1 and G3 presented high number of cells expressing interferon (IFN)-γ; interleukin (IL) 5 was increased in G2 and G3; the expression of IL10 was similar among the three groups, and the expression of tumor necrosis factor (TNF)-α was higher in G3. G1 correlates to Th1 cytokines and pSTAT-1 and G2 correlates to Th2 cytokines. G3 presents both kinds of cytokines. We could not associate the expression of arginase-1, CD163, iNOS, and dectin-1 with the pattern of cytokines or kind of granuloma.

Digestible methionine+cysteine in the diet of commercial layers and its influence on the performance, quality, and amino acid profile of eggs and economic evaluation.

This work aimed at evaluating the effects of 4 digestible Met+Cys levels on the diet of commercial layers and their influence on the productive performance, quality, and amino acid profile of eggs and economic viability of the activity. A total of 576 white Lohmann LSL-Lite layers was distributed into 6 replicates of 24 birds for each diet. The experimental design was completely randomized, with 4 treatments defined by levels evaluated in the feed (0.465, 0.540, 0.581, and 0.647%). The productive performance was measured for 30 weeks. The quality (34 and 50 wk old) and the amino acid profile of eggs (43 wk old) also were evaluated. A linear positive response was observed at higher Met+Cys levels for feed intake, number of eggs per housed bird, and digestible Met+Cys intake. Egg production, egg weight, egg mass, feed efficiency, and weight gain had their optimal values determined by the quadratic regression model at 0.638, 0.654, 0.647, 0.644, and 0.613% digestible Met+Cys, respectively. In the 34th wk, eggshell thickness decreased linearly at higher Met+Cys levels. In the 50th week, the optimal levels detected for eggshell thickness and percentage were 0.571 and 0.570% digestible Met+Cys, respectively. The percentages of proteins, branched-chain amino acids (leucine, isoleucine, and valine), histidine, and proline in eggs (albumen+yolk) showed a linear negative response in function of higher Met+Cys levels. Higher digestible Met+Cys levels (>0.630%) led to a good performance of layers, while lower Met+Cys levels improved the eggshell quality of layers in peak production. Optimal Met+Cys levels may change according to the price of the synthetic amino acid.

Efeitos da granulometria e da forma física da ração sobre o desempenho de frangos de corte / Effects of particle size and physical form of diets on broiler performance

Foram utilizados 936 pintos de corte machos e 1008 fêmeas da linhagem Cobb(r) criados no período de um a 45 dias. Os tratamentos foram compostos por duas formas físicas da ração (farelada e peletizada) e duas granulometrias do milho (3,8mm e 7,0mm). O delineamento experimental foi inteiramente ao acaso, em arranjo fatorial 2 x 2 (duas granulometrias x duas formas físicas), com seis repetições de 39 aves cada para os machos e seis repetições de 42 aves cada para as fêmeas. A ração peletizada produzida com moagem 3,8mm apresentou melhor PDI (P≤0,05). Aves fêmeas alimentadas com ração peletizada apresentaram maior consumo de ração, ganho de peso e melhor conversão alimentar que aquelas que receberam ração farelada. Não foi observada diferença significativa (P>0,05) entre os tratamentos para as variáveis ganho de peso, conversão alimentar e consumo de ração dos machos. Não houve influência da forma física e da granulometria sobre a viabilidade das aves em nenhuma fase de criação (P>0,05).

A total of 936 male chickens and 1008 female Cobb(r) were used from 1 to 45 days old. Treatments consisted of two physical forms (mash and pelleted diets) and two particle sizes ( corn ground through 3.8mm and 7.0mm sieves). The experimental design was completely randomized in a 2 x 2 factorial design (two particle sizes x two physical forms), with six replicates of 39 birds each for males and six replicates of 42 birds each for females. PDI from the pelleted physical form that was produced with 3.8mm grinding showed better results (P≤0.05). Female birds fed pelleted diets had greater feed intake, weight gain and better feed conversion than those fed mash diet. No significant difference (P>0.05) was observed between the treatments for male feed intake, weight gain and feed conversion from 1 to 45 days of age. There was no influence of the physical form and particle size on the feasibility of birds in any phase (P>0.05).

Efficiency of microbial phytase supplementation in diets formulated with different calcium:phosphorus ratios, supplied to broilers from 22 to 33 days old.

An experiment was conducted with broilers from 22 to 33 days of age to evaluate the efficiency of six microbial phytases supplemented in diets (1500 FTU/kg) that were formulated with three different calcium:available phosphorus (Ca:P(avail)) ratios (4.5:1.0, 6.0:1.0 and 7.5:1.0). A positive control diet without phytase was formulated with a Ca:P(avail) ratio of 7.5:3.4 to meet the nutritional requirements of the broilers. The P and ash contents of the tibia, magnesium in the plasma, performance, balance and retention of phytate phosphorus (P(phyt)), intake of total P and nitrogen (N), nitrogen-corrected apparent metabolizable energy and apparent digestibility of dry matter of the diets were not influenced (p > 0.05) by the type of phytase or the dietary Ca:P(avail) ratio. However, there was an interaction (p < 0.05) between the phytase type and the Ca:P(avail) ratio for the retention coefficients of total P, Ca and N. Phytase B resulted in the highest Ca deposition in the tibia (p < 0.01). Phytases D, E and F reduced the Ca concentrations in the tibia (p < 0.01) and plasma (p < 0.05). Phytase D increased the P level in the plasma and decreased the total P excretion (p < 0.01). Phytases E and F increased Ca excretion, while phytase A reduced it (p < 0.01). Regardless of the phytase type, increasing the dietary Ca:P(avail) ratio reduced (p < 0.05) the plasma P concentration and the excretion of total P and N and, conversely, increased (p < 0.05) the plasma concentration, intake and excretion of Ca. For the rearing period evaluated, it is possible to reduce the P(avail) of the diet to 1.0 g/kg when Ca is maintained at 7.5 g/kg, and the diet is supplemented with 1500 FTU of phytase A, C, D or E/kg. This diet allows the maintenance of performance and adequate bone mineralization, and it improves the Ca, total P and P(phyt) utilization in addition to reducing the excretion of N and P into the environment.

Content of plasmatic glycerol and activity of hepatic glycerol kinase in broiler chickens fed diets containing different sources and concentrations of glycerine.

The objective of this study was to evaluate the effect of three sources of glycerine (crude glycerine from soya bean oil - CGSO, mixed crude glycerine from frying oil and lard--MCG, and a semipurified glycerine from soya bean oil--SPGSO) in four concentrations in the diet (17.5, 35.0, 52.5 and 70.0 g of each type of glycerine per kg of feed) on the levels of plasmatic glycerol and the activity of the hepatic enzyme glycerol kinase in broilers of 22-35 days old (experiment I) and 33-42 days old (experiment II). The highest (p < 0.05) plasmatic glycerol level was detected in broilers fed diet containing CGSO. Independent of the source, increasing the concentration of glycerine led to a linear increase (p < 0.05) in the plasmatic glycerol concentration. In experiment I, all the diets containing glycerine resulted in increased concentrations of plasmatic glycerol, in relation to the control diet without glycerine. However, in experiment II, only the diet containing 17.5 g of CGSO per kg of feed and the diets formulated with any of the three types of glycerine in the inclusion concentrations of 35, 52.5 and 70 g/kg of feed resulted in higher plasmatic glycerol levels than those observed in the control broilers. The source of glycerine influenced the glycerol kinase activity only in experiment II, where the use of CGSO in the diet increased the enzyme activity. For both experiments, the glycerol kinase activity increased with the inclusion of glycerine in the diet. In conclusion, based on the absence of saturation of the glycerol kinase activity for the three glycerine sources and for both rearing periods evaluated, the broilers can metabolize the glycerol (at the level of the phosphorylation of the glycerol to glycerol-3-phosphate in the liver) present in the glycerine when the diet is supplemented with up to 70 g of glycerine per kg of feed.

Nicotinamide N-methyltransferase expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling.

Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide (MeN). We have previously shown that NNMT expression protected against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis. This was mediated via protection of the NDUFS3 subunit of CxI from degradation by increased MeN production. In the present study, we have investigated the effects of NNMT expression on neurone morphology and differentiation. Expression of NNMT in SH-SY5Y human neuroblastoma and N27 rat mesencephalic dopaminergic neurones increased neurite branching, synaptophysin expression and dopamine accumulation and release. siRNA gene silencing of ephrin B2 (EFNB2), and inhibition of Akt phosphorylation using LY294002, demonstrated that their sequential activation was responsible for the increases observed. Incubation of SH-SY5Y with increasing concentrations of MeN also increased neurite branching, suggesting that the effects of NNMT may be mediated by MeN. NNMT had no significant effect on the expression of phenotypic and post-mitotic markers, suggesting that NNMT is not involved in determining phenotypic fate or differentiation status. These results demonstrate that NNMT expression regulates neurone morphology in vitro via the sequential activation of the EFNB2 and Akt cellular signalling pathways.

Interleukin-10 and interferon-gamma patterns during tuberculosis treatment: possible association with recurrence.

Interleukin (IL) 10 and interferon-gamma (IFN-) levels in induced sputum supernatants of 21 tuberculosis (TB) patients at diagnosis and during chemotherapy were correlated to recurrence rates. IL-10 decreased until day 60 of treatment (T60), and between T60 and T180 it increased again in 7 cases (Pattern 1) and further decreased in 14 cases (Pattern 2). Follow-up of 69 months was performed in 20/21 cases; 6 had recurrence of TB, of which 5/7 (71%) had Pattern 1 and 1/13 (7.7%) Pattern 2 (OR 30.0, 95%CI 2.19411.3, P 0.0072). This was not observed for IFN-. High IL-10 levels at the end of treatment may function as a risk factor for TB recurrence.

Long-term visual and retinopathy outcomes in a predominately type 2 diabetic patient population undergoing early vitrectomy and endolaser for severe vitreous haemorrhage.

PURPOSE: To evaluate the long-term visual outcome of type 2 diabetic patients receiving early vitrectomy and endolaser for severe vitreous haemorrhage (VH). MATERIALS AND METHODS: Retrospective case note review of 88 eyes (69 type 2 diabetics and 19 type 1 diabetics) of 80 patients who underwent vitrectomy and endolaser within 6 months of VH. Post-operative and most recent VA, in addition to long-term retinopathy grading, were analysed. A subset of patients fulfilling the criteria for the Diabetic Retinopathy Vitrectomy Study was compared with this study. RESULTS: Mean pre-operative visual acuity (VA) in the type 2 group was 0.64 logMAR, with 1 eye showing perception light (PL), 10 eyes detecting hand movements (HMs), and 7 eyes counting fingers (CFs). At the 2-week post-operative visit, the mean VA had improved to 0.46 logMAR, with two eyes showing PL, two eyes detecting HM, and one eye CF (P=0.0002); at the last review, mean VA score was 0.36 logMAR, with three eyes showing PL and four eyes detecting HM (P=0.0008). Mean pre-operative VA in the type 1 group was 0.47 logMAR, with one eye showing PL, one eye detecting HM, and two eyes CF. At the 2-week post-operative visit, the mean VA had improved to 0.37 logMAR, with one eye showing PL (P=0.002), and at the latest review, the mean VA was 0.20 logMAR (P=0.027). CONCLUSION: Our study shows that type 2 DM patients can observe improvement in VA and stabilisation of their proliferative retinopathy after early vitrectomy and endolaser for vitreous haemorrahage, which is maintained after long-term follow-up.

[Anticoagulation in elderly patients with atrial fibrillation: from the guidelines to the daily medical practice]. / Terapêutica anti trombótica no idoso com fibrilhação auricular: das guidelines à prática clínica.

BACKGROUND: Atrial fibrillation (AF) is a common medical problem with increasing prevalence among the elderly. Warfarin is effective in the prevention of AF-related-stroke but is often underutilized, especially in high-risk populations, like the elderly. OBJECTIVES: To determine, in a group of elderly patients with AF, if those treated in-line with the clinical recommendations differ from patients who were not, regarding morbidity and mortality and also to determine independent predictors of mortality. A second objective was to verify if the CHADS2 score is a good predictor of thromboembolic risk in the elderly. POPULATION AND METHODS: A total of 161 consecutive elderly patients with AF admitted in a single centre were evaluated. Clinical follow-up was available for 88.4%, with a mean duration of 9 months. RESULTS: Mean age was 80.9 ± 6.6 years; 96.3% of the patients had permanent AF, with controlled ventricular rate in 56.4%. Previous stroke was verified in 30.4%. Only 37.3% had oral anticoagulation at hospital discharge, despite 87.6% had guideline recommendation. Cumulative mortality rate in follow-up was 48.4% and the thromboembolism rate was 8.1%. We verified that CHADS2 score was a good predictor of thromboembolic risk in this population (c-statistic=0.742). Clinical follow-up showed that patients treated according with the clinical recommendations were more likely to survive (33.33% vs 53.93%; p=0.048). Multivariate analysis showed that age >80 years, renal disease, neoplasm and neuropsychic disease as independent predictors of mortality (c-statistic=0.83). CONCLUSION: A gap of 50% existed between the guideline recommendations and actual practice. The use of risk stratification scores can help guide the decision to use anticoagulation in older patients with AF. Elderly patients treated according with the clinical recommendations had a better prognosis.

Comparação da qualidade de vida nos diferentes tipos de incontinência urinária feminina / Comparison of quality of life for different types of female urinary incontinence

OBJETIVOS: Comparar o impacto do tipo de incontinência urinária sobre a qualidade de vida em mulheres. MÉTODOS: Foram avaliados retrospectivamente 77 prontuários de mulheres incontinentes que realizaram tratamento fisioterapêutico entre fevereiro de 2005 a outubro de 2006. De acordo com os dados do exame urodinâmico, as mulheres foram classificadas em três grupos: incontinência urinária de esforço (IUE), hiperatividade vesical (HV) e incontinência urinária mista (IUM). As voluntárias responderam a uma anamnese com dados demográficos e ao King's Health Questionnaire, questionário específico para avaliação da qualidade de vida em indivíduos com incontinência urinária. RESULTADOS: A maioria das pacientes (44%) apresentou IUM. A idade das pacientes acometidas por HV foi significativamente maior se comparada à idade das pacientes dos demais grupos. As mulheres acometidas por IUM apresentaram um impacto negativo significativamente maior sobre a qualidade de vida (domínio percepção geral da saúde) e sobre a percepção de que a incontinência afeta de modo negativo a própria vida em comparação com as pacientes dos demais grupos. CONCLUSÃO: Este estudo indicou que pacientes com IUM apresentaram um maior impacto negativo sobre a qualidade de vida.

OBJECTIVES: To compare the impact of the type of urinary incontinence on women's quality of life. METHODS: A retrospective evaluation was conducted on the medical records of 77 incontinent women who underwent physical therapy treatment between February 2005 and October 2006. Based on the urodynamic test data, the women were classified into three groups: stress urinary incontinence (SUI), overactive bladder (OB) and mixed urinary incontinence (MUI). The subjects' history was taken, the women provided demographic data and they answered the King's Health Questionnaire, which is a specific questionnaire for assessing the quality of life among individuals with urinary incontinence. RESULTS: Most of the patients (44%) had MUI. The patients affected by OB were significantly older than the patients in the other groups. The negative impact of incontinence on quality of life (General Health Perception domain) and lifestyle was significantly greater among the women affected by MUI than among the patients in the other groups. CONCLUSION: This study indicated that the negative impact of incontinence on quality of life was greater among patients with MUI.

Efficacy of indapamide SR compared with enalapril in elderly hypertensive patients with type 2 diabetes.

BACKGROUND: Blood pressure control is the main influential variable in reducing microalbuminuria in patients with type 2 diabetes. In this subanalysis of the Natrilix SR versus Enalapril Study in hypertensive Type 2 diabetics with micrOalbuminuRia (NESTOR) study, we have compared the effectiveness of indapamide sustained release (SR) and enalapril in reducing blood pressure and microalbuminuria in patients > or =65 years of age. METHODS: Of the 570 hypertensive patients with type 2 diabetes and persistent microalbuminuria in the NESTOR study, 187 (33%) individuals > or =65 years of age were included in this analysis. Of these, 95 patients received indapamide SR 1.5 mg and 92 patients received enalapril 10 mg, taken once daily in both cases. Adjunctive amlodipine and/or atenolol was added if required. RESULTS: The urinary albumin-to-creatinine ratio decreased by 46% in the indapamide SR group and 47% in the enalapril group. Noninferiority of indapamide SR over enalapril was demonstrated (P = .0236; 35% limit of noninferiority) with a ratio of 0.95 (95% CI: 0.68, 1.34). Mean arterial pressure decreased by 18 mm Hg and 15 mm Hg in the indapamide SR and the enalapril groups, respectively (P = .1136). The effects of both treatments seen in these elderly patients were similar to those observed in the main population, although the extent of the reduction in microalbuminuria was slightly higher. Both treatments were well tolerated, and no difference between groups was observed regarding glucose or lipid profiles. CONCLUSION: Indapamide SR is not less effective than enalapril in reducing microalbuminuria and blood pressure in patients aged >65 years of age with type 2 diabetes and hypertension.

Equivalence of indapamide SR and enalapril on microalbuminuria reduction in hypertensive patients with type 2 diabetes: the NESTOR Study.

OBJECTIVES: To test whether microalbuminuria in patients with type 2 diabetes and hypertension is primarily dependent on the severity of hypertension, and to compare the effectiveness of two antihypertensive drugs with opposite effects on the renin-angiotensin system [the diuretic, indapamide sustained release (SR), and an angiotensin-converting enzyme inhibitor, enalapril] in reducing microalbuminuria. DESIGN: A multinational, multicentre, controlled, double-blind, double-dummy, randomized, two-parallel-groups study over 1 year. METHODS: After a 4-week placebo run-in period, 570 patients (ages 60.0 +/- 9.9 years, 64% men) with type 2 diabetes, essential hypertension [systolic blood pressure (SBP) 140-180 mmHg, and diastolic blood pressure (DBP) < 110 mmHg], and persistent microalbuminuria (20-200 microg/min) were allocated randomly to groups to receive indapamide SR 1.5 mg (n = 284) or enalapril 10 mg (n = 286) once a day. Amlodipine, atenolol, or both were added, if necessary, to achieve the target blood pressure of 140/85 mmHg. RESULTS: There was a significant reduction in the urinary albumin : creatinine ratio. Mean reductions were 35% [95% confidence interval (CI) 24 to 43] and 39% (95% CI 30 to 47%) in the indapamide SR and enalapril groups, respectively. Equivalence was demonstrated between the two groups [1.08 (95% CI 0.89 to 1.31%); P = 0.01]. The reductions in mean arterial pressure (MAP) were 16.6 +/- 9.0 mmHg for the indapamide SR group and 15.0 +/- 9.1 mmHg for the enalapril group (NS); the reduction in SBP was significantly greater (P = 0.0245 ) with indapamide SR. More than 50% of patients in each group required additional antihypertensive therapy, with no differences between groups. Both treatments were well tolerated. CONCLUSIONS: Indapamide-SR-based therapy is equivalent to enalapril-based therapy in reducing microalbuminuria with effective blood pressure reduction in patients with hypertension and type 2 diabetes.

Effect of indapamide SR on microalbuminuria--the NESTOR study (Natrilix SR versus Enalapril Study in Type 2 diabetic hypertensives with micrOalbuminuRia)--rationale and protocol for the main trial.

In type 2 diabetic hypertensive patients, microalbuminuria can be due to hypertension and/or diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors act preferentially on microalbuminuria due to diabetic nephropathy. The objective is to demonstrate the efficacy of a thiazide-like diuretic, indapamide sustained release (SR), at reducing microalbuminuria in hypertensive type 2 diabetic patients in comparison with an ACE inhibitor, enalapril. The study is an international multicentre, 12-month, randomized, double-blind, controlled, two parallel group study of type 2 diabetic patients with hypertension (140 mmHg < or = systolic blood pressure <180 mmHg and diastolic blood pressure <110 mmHg) and microalbuminuria. Intervention is after a 4-week placebo period, patients with microalbuminuria > or = 20 and < or = 200 microg/min are randomized to indapamide SR 1.5 mg or to enalapril 10 mg once a day for a one-year treatment period. An additional label treatment by amlodipine 5-10 mg (1st step) and atenolol 50-100 mg (2nd step) a day is permitted after 6 weeks of treatment based upon blood pressure response. The main outcome measures are microalbuminuria expressed as urinary albumin to creatinine ratio, albumin fractional clearance, and albumin excretion rate evaluated on overnight urine collections. Secondary criteria are supine and standing systolic, diastolic and mean blood pressure; and biological and clinical safety. This study will complete the knowledge of the efficacy of indapamide SR in hypertension and target organ damage and will provide valuable information on the management of type 2 diabetic hypertensives with microalbuminuria.

Physical excercise and thrombotic risk in the elderly.

UNLABELLED: Aging increases certain thrombotic risk factors, such as fibrinogen, factor VII, PAI-1 and plasma viscosity, contributing to cardiovascular diseases being the principal cause of death in developed countries. Physical exercise can counteract this tendency by influencing such factors. PURPOSE: To assess the effect of regular physical exercise on fibrinogen, factor VII, PAI-1 and plasma viscosity in an elderly group. METHODS: Sixty-three old people of both sexes, aged between 65 and 94, participated in this study, and were randomly distributed between a test group (n = 31) and a control group (n = 32). The test group followed a program of physical exercise for eight months, with an intensity of 60% to 80% of heart rate reserve, composed of three weekly sessions, on alternate days, of 60 minutes each. The control group maintained their normal activity. Before the beginning of the program and eight months afterwards, blood samples were collected to assess fibrinogen, factor VII, PAI-1 and plasma viscosity. RESULTS: In the test group, fibrinogen, factor VII and plasma viscosity decreased significantly while PAI-1 showed no significant change. The control group did not present alterations in any of the parameters assessed. CONCLUSIONS: Regular physical exercise decreases thrombotic risk and may help to reduce cardiovascular events in the elderly.

Pentoxifylline improves learning and memory in glutamate-lesioned rats.

The present work shows the effects of pentoxifylline (ptx), on learning and memory in rats with hippocampal lesions induced by glutamate (glu). Immediately after stereotaxic procedures and in the absence or presence of glu lesions, animals were treated with ptx (50, 100, or 200 mg/kg, IP) for 6 days. Twenty-four hours after the last injection, behavior and memory tests were performed, animals were sacrificed, and hippocampi dissected for cAMP determination or histopathological studies. Results from the T-maze task showed a less learning ability in the glu-lesioned group compared to other ones. Ptx alone or associated with glu significantly improved memory acquisition, but not memory consolidation compared to glu-lesioned rats. Except for the increased locomotor activity observed in the ptx100+glu-treated group compared to saline, no other difference was detected in the open-field test. A significant impairment in avoidance performance was observed in glu-lesioned group as compared to saline or to other groups in the short as well as in the late phase of memory. All groups showed an improved water-maze performance over time with similar performances on the final day of acquisition. The impairment in memory retention observed in glu-lesioned rats was reversed by the pretreatment with ptx200. Glu induced hippocampal lesion and reduced cAMP levels. Both effects were blocked by ptx, suggesting that its action may be the result of increased cAMP levels and/or inhibition of adenosine A1 receptors.