Unsupervised clustering to differentiate rheumatoid arthritis patients based on proteomic signatures.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have different presentations and prognoses. Cluster analysis based on proteomic signatures creates independent phenogroups of patients with different pathophysiological backgrounds. We aimed to identify distinct pathophysiological clusters of RA patients based on circulating proteomic biomarkers. METHOD: This was a cohort study including 399 RA patients. Clustering was performed on 94 circulating proteins (92 CVDII Olink®, high-sensitivity troponin T, and C-reactive protein). Unsupervised clustering was performed using a partitioning cluster algorithm. RESULTS: The clustering algorithm identified two distinct clusters: cluster 1 (n = 223) and cluster 2 (n = 176). Compared with cluster 1, cluster 2 included older patients with a higher burden of comorbidities (cardiovascular and RA related), more erosive and longer RA duration, more dyspnoea and fatigue, walking a shorter distance in the Six-Minute Walk Test, with more severe diastolic dysfunction, and a 4.5-fold higher risk of death or hospitalization for cardiovascular reasons. Tumour necrosis factor (TNF) receptor superfamily-related pathways were mainly responsible for the model's discriminative ability. CONCLUSION: Using unsupervised cluster analysis based on proteomic phenotypes, we identified two clusters of RA patients with distinct biomarkers profiles, clinical characteristics, and different outcomes that could reflect different pathophysiological backgrounds. TNF receptor superfamily-related proteins may be used to distinguish subgroups.

Desenvolvimento reprodutivo de tourinhos Gir selecionados para produção de leite / Reproductive development of Gyr young bulls selected for milk production

O estudo visou identificar tourinhos Gir precoces e não precoces quanto à puberdade e avaliar diferenças durante seu desenvolvimento reprodutivo. Peso vivo e perímetro escrotal foram mensurados mensalmente junto com a coleta e a avaliação física e morfológica do sêmen de 16 animais, dos 13 aos 23 meses de idade. Animais precoces foram mais leves na pré-puberdade e apresentaram menores idades à puberdade e à maturidade sexual - 17,0 e 18,7 meses -, respectivamente, - em relação aos não precoces - 19,2 e 20,5 meses, respectivamente. A motilidade aumentou na pré-puberdade dois meses mais cedo nos animais precoces - 1,75 por cento a 18,4 por cento dos 14 aos 17 meses - em relação aos não precoces - 2,5 por cento a 12,4 por cento dos 15 aos 18 meses de idade. Registrou-se aumento mais cedo da concentração espermática em animais precoces, a qual foi maior - 660 milhões/mL - aos 23 meses em relação aos animais não precoces -66.7 milhões/mL. As diferenças observadas no desenvolvimento dos dois grupos foram favoráveis aos animais precoces e indicam que a seleção para a maturidade sexual precoce é indicada para a antecipação da fase reprodutiva de touros Gir.

This study aimed to identify precocious and non-precocious Gyr young bulls according to puberty and evaluate differences during their reproductive development. Live weight and scrotal circumference were measured monthly with collection and evaluation of semen samples from 16 animals, from 13 to 23 months of age. Precocious animals were lighter at the pre-puberty period and younger at puberty and sexual maturity, 17.0 and 18.7 months, respectively, regarding non-precocious, 19.2 and 20.5 months, respectively. Sperm motility increased during pre-puberty two months earlier for precocious animals, 1.75 percent to 18.4 percent from 14 to 17 months, regarding non-precocious, 2.5 percent to 12.4 percent from 16 to 18 months. Sperm concentration increase occurred earlier in precocious animals, and was higher, 669 million/mL, at 23 months of age in relation to non-precocious animals, 66.7 million/mL. The differences in reproductive development of both groups were favorable for precocious animals and indicate that the selection for precocious sexual maturity is advised to anticipate the reproductive phase of Gyr bulls.

Secondary intracardiac Burkitt-like lymphoma in the absence of HIV infection.

Malignant lymphoma can involve the cardiac cavity or myocardium as a mass. Since clinical symptoms of its cardiac involvement are usually absent or non-specific, they may be undetected during life. Burkitt-like lymphoma (BLL) is a highly aggressive B-cell lymphoma with a high proliferative rate. Histopathological characteristics are considered borderline between those of classic Burkitt lymphoma and diffuse large B-cell lymphoma. Extensive cardiac involvement of BLL is rare and poorly documented in the literature. We report the case of a child with BLL, presenting with extensive infiltration of the heart in the absence of HIV infection, and with right-sided heart failure and positional dyspnoea as the major clinical problems. We highlight the challenges for diagnosis and adequate treatment in poor settings like ours.

Efeitos do diluidor na viabilidade espermática pós-criopreservação em tourinhos da raça Gir Leiteiro aos 25 meses de idade, pré-selecionados pela classificação andrológica por pontos / Effects of the extender in the semen post - thaw viability in young dairy Gyr bulls (Bos taurus indicus), pre - selected by breeding soundness evaluation

Procedeu-se à criopreservação do sêmen de oito tourinhos Gir Leiteiro, com idade média de 25 meses, pré-selecionados para elevada pontuação (média 84,4±5,6) na classificação andrológica por pontos (CAP), em dois diferentes diluidores: um à base de lactose-gema-glicerol e outro à base de lecitina de soja. As curvas de resfriamento e congelação foram padronizadas com o auxílio da máquina CRYOGEN®. Os parâmetros pós-congelação avaliados no sêmen submetido aos dois diluidores - motilidade, vigor, defeitos maiores, menores e totais, defeitos de acrossoma, cauda dobrada, reação ao teste hiposmótico (Thos) e células normais - foram comparados aos do sêmen fresco, exceto para Thos e entre eles. O sêmen de todos os animais foi congelado com êxito no diluidor lactose-gema-glicerol. Houve diferença (P<0,05) em todas as variáveis analisadas no sêmen fresco e pós-congelado, exceto para defeitos maiores. Entre diluidores, houve diferença (P<0,05) para motilidade, vigor, cauda dobrada e Thos. Estes resultados indicam que a seleção pelo CAP médio >80 é um bom índice para selecionar touros com maior taxa de espermatozoides viáveis pós-congelação.

Semen cryopreservation from eight young dairy Gyr bulls was performed using two different semen extenders. Bulls aging 25 months old and pre-selected for a high average score (84.4±5.6 in a 0-100 scale) in Zebu breeding soundness evaluation (BSE) composed the experimental group. Extenders were based on lactosis-egg yolk-glycerol and soya lecithin. Chilling and freezing curves were standardized by CRYOGEN® machine. Post-thaw features evaluated in semen frost in both extenders - motility, vigor, major, minor and total deffects, morphological alteration in acrossome, bent tail, reative cells to hyposmotic sweeling test (Thos), and normal cells - were compared to the ones in the fresh ejaculate (except Thos) and among them. It was possible to freeze semen from all animals in the lactosis-egg yolk-glycerol extender. There were difference (P<0.05) in all analyzed features between fresh and cryopreserved semen, except for major deffects. Between extenders, there were differences (P<0.05) in motility, vigor, bent tail, and Thos. All bulls had successfull semen freezability. These results sustain that pre-selection for high BSE values (average >80 points) is a good index to identify bulls with good post semen - thaw features. However, the choice of the extender is critical for obtaining acceptable results.

Echocardiography accurately assesses the pathological abnormalities of chronic endomyocardial fibrosis.

Endomyocardial fibrosis (EMF) is a cardiomyopathy with high prevalence in Sub-Saharan Africa with unclear etiology, pathogenesis and natural history. Most pathological abnormalities can potentially be diagnosed by echocardiography allowing surgery in some cases. With increasing availability of echocardiography in endemic areas for EMF we designed a study aiming at assessing its accuracy in defining EMF structural abnormalities pre-operatively, and describe pathological findings through detailed intraoperative examination and evaluation of histopathological changes in tissue obtained from excisional biopsies. Transthoracic echocardiography was performed pre-operatively to 29 patients with chronic severe EMF. All patients were submitted to excisional endomyocardial biopsies during surgery and careful standardized intra-operative evaluation was also done. Surgical and histopathological findings were compared to those obtained by echocardiography. Of the 29 patients studied, 16 had moderate lesions while 13 had severe disease. Their mean age was 12 (±4.6) years and 17 were males. All but one patient were in NYHA functional class III or IV at time of surgery. All patients had severe atrioventricular valve regurgitation with valves considered suitable for repair. We evaluated tissue from 25 left ventricles and 12 right ventricles. Endocardial thickening was the most prominent abnormality due to deposition of hyaline and cellular collagen underneath a layer of apparently normal endocardial endothelial cells. The mean endocardial thickness was 2,541 ± 1,707 µm. There was high agreement between echocardiographic and intraoperative findings, with the findings coinciding completely in 24 patients. Severe EMF assessed by echocardiography was associated with intense endocardial fibrosis on histology. In contrast, the presence of inflammation in peripheral blood was not associated with tissue inflammation. Structural abnormalities of chronic severe EMF are accurately diagnosed by transthoracic echocardiography, allowing this non-invasive technique to be used as the gold standard for diagnosis and surgical management of chronic EMF in endemic areas.

Familial osteopetrosis in Agouti paca: report of nine cases / Osteopetrose familiar em Agouti paca: relato de nove casos

Nine cases of familial osteopetrosis were studied in Agouti paca rodents maintained in captivity. Animals were distributed in three groups depending on the severity of their skeletal lesions. Based upon clinical, radiological, and microscopic findings, it was concluded that one animal had level I lesions, three animals had level II lesions, and five animals had level III osteopetrosis and osteonecrosis. Throughout the entire axial and appendicular skeleton, there was an increased amount of both trabecular and cortical bone tissue. All analyzed bones showed thickened cortex and reduced medullary canals. Bone trabeculae were thick and confluent. Cortex showed a narrowing of Haversian canals. Numerous cementing lines resulted in typical mosaic patterns. Osteocytes were pycnotic. Osteonecrosis was characterized by the disappearance of osteocytes and bone matrix decomposition.

Descreveram-se nove casos de osteopetrose familiar em Agouti paca mantidas em cativeiro. Os animais foram distribuídos em três grupos de acordo com a gravidade das lesões do esqueleto. Com base nos exames clínico, radiológico e microscópico, foi concluído que um animal apresentou lesões de nível I, três animais tiveram lesões de nível II e cinco animais tiveram osteopetrose de nível III. Por todo o esqueleto axial e apendicular, a quantidade de osso trabecular e osteônico estava aumentada. Todos os ossos analisados mostraram córtex espesso e canais medulares reduzidos. As trabéculas ósseas eram espessas e confluentes. No córtex, verificou-se um estreitamento de canais de Havers. Numerosas linhas de cimentação resultaram em um padrão de mosaico típico. Osteócitos estavam picnóticos e a osteonecrose foi caracterizada pela morte dos osteócitos, com desintegração da matriz óssea.

Preoperative predictors of moderate to intense acute postoperative pain in patients undergoing abdominal surgery.

BACKGROUND: Pain is a sensory and emotional experience that is influenced by physiologic, sensory, affective, cognitive, socio-cultural, and behavioral factors. Consistent with the perspective to improve the postoperative pain control, the present study has the purpose of assessing the effect of presurgical clinical factors, psychological and demographic characteristics as predictors for reporting moderate to intense acute postoperative pain. METHODS: A prospective cohort study was performed with 346 inpatients undergoing abdominal elective surgery (ASA physical status I-III, age range 18-60 years). The measuring instruments were Pain Visual Analog Scale, the State-Trait Anxiety Inventory, and the Montgomery-Asberg Depression Rating Scale. Multivariate conditional regression modeling was used to determine independent predictors for moderate to intense acute postoperative pain. RESULTS: Moderate to intense acute postoperative pain was associated with status ASA III (odds ratio (OR) = 1.99), age (OR = 4.72), preoperative moderate to intense pain (OR = 2.96), chronic pain (OR = 1.75), high trait-anxiety and depressive mood moderate to intense (OR = 1.74 and OR = 2.00, respectively). Patients undergoing surgery to treat cancer presented lower risk for reporting moderate to intense pain OR = 0.39, as well as those that received the epidural analgesia and multimodal analgesia with systemic opioid (OR = 0.09 and OR = 0.16, respectively). CONCLUSIONS: The identification of predictive factors for intense acute postoperative pain may be useful for designing specific preventive interventions to relieve patient suffering. Especially because few of these variables are accessible for medical intervention, which would improve the clinical outcomes and quality of life of patients at risk of moderate to intense acute postoperative pain.

Effect of pre-operative anxiolysis on postoperative pain response in patients undergoing total abdominal hysterectomy.

In a double blind, placebo-controlled trial, we have assessed the effects of pre-operative anxiolysis on postoperative pain scores in 112 ASA I-II women, aged 18-65 years, scheduled to undergo total abdominal hysterectomy. Subjects were randomly allocated to receive either oral diazepam 10 mg (n=56) or placebo (n=56) pre-operatively. Postoperative anxiety, pain scores, analgesic consumption, and sedation were evaluated at several time points during the first 24 h following surgery. Postoperative pain scores were found to be significantly higher in the diazepam group. Trait and state anxiety showed a significant effect on pain scores, independent of the treatment group. No difference was found between the groups in morphine consumption, but there was a significant reduction in morphine consumption with time.

Efficacy of ropivacaine compared with ropivacaine plus sufentanil for postoperative analgesia after major knee surgery.

This study compared the analgesic efficacy of an epidural infusion of ropivacaine and ropivacaine with sufentanil following major knee surgery. In a double-blind clinical trial, 115 adult patients received either epidural ropivacaine (R group, 2 mg.ml(-1)), or ropivacaine (2 mg.ml(-1)) with sufentanil (RS group, 1 microg.ml(-1)), using a patient-controlled epidural analgesia technique. Pain scores (visual analogue scale, VAS, and the simple descriptive scale, SDS), side-effects, motor block and treatment quality were recorded at 6, 12 and 24 h after the insertion of the epidural catheter. In the RS group, analgesic efficacy was significantly greater than in the R group between 12 and 24 h following insertion of the epidural catheter (VAS: 92.9% vs. 72.9%, p = 0.009). There was no significant difference during the other periods. Pruritus, nausea and vomiting were significantly more frequent in the RS group. Good postoperative analgesia was obtained with an epidural infusion of ropivacaine (2 mg.ml(-1)). When this local anaesthetic was administered with sufentanil, there was an improvement in the analgesic effect but a significant increase in the number of patients who reported adverse effects. The differences were more pronounced 12 h after the beginning of the analgesic schedule. This study failed to demonstrate any worthwhile clinical benefit from the addition of sufentanil.

Risk factors for postoperative anxiety in adults.

We identified risk factors for postoperative anxiety and quantified their effect on 712 adults between 18 and 60 years of age (ASA I-III physical status) undergoing elective surgery under general anaesthesia, neural blockade or both. The measuring instruments were a structured questionnaire, a pain visual analogue scale, the McGill Pain Questionnaire, the State-Trait Anxiety Inventory, the Montgomery-Asberg Depression Rating Scale, a Self-Reporting Questionnaire-20, and a Self-Perception of Future Questionnaire. Multivariate conditional regression modelling taking into account the hierarchical relationship between risk factors revealed that postoperative anxiety was associated with ASA status III (OR = 1.48), history of smoking (1.62), moderate to intense postoperative pain (OR = 2.62) and high pain rating index (OR = 2.35), minor psychiatric disorders (OR = 1.87), pre-operative state-anxiety (OR = 2.65), and negative future perception (OR = 2.20). Neural block anaesthesia (OR = 0.72), systemic multimodal analgesia (OR = 0.62) and neuroaxial opioids with or without local anaesthesia (OR = 0.63) were found to be protective factors against postoperative anxiety.

Risk factors for preoperative anxiety in adults.

BACKGROUND: Patients who undergo surgery experience acute psychological distress in the preoperative period. The objective of this study was to identify and quantify the effect of risk factors for preoperative anxiety in adults. METHODS: A cross-sectional study was performed with 592 inpatients scheduled for elective surgery. Age ranged from 18 to 60 years (ASA physical status I-III). Demographic information was collected using a structured questionnaire. The measuring instruments were a visual analog scale, the State-Trait Anxiety Inventory; the Montgomery-Asberg Depression Rating Scale, the WHO Self-Reporting Questionnaire-20, and the future self-perception questionnaire. Multivariate conditional regression modeling was used to control confounding factors and to determine independent predictors of preoperative anxiety, taking into account the hierarchical relationship between risk factors. RESULTS: High preoperative anxiety was associated with history of cancer (odds ratio (OR)=2.26) and smoking (OR=7.47), psychiatric disorders (OR=5.93), negative future perception (OR= 2.30), moderate to intense depressive symptoms (3.22), high trait-anxiety (3.83), moderate to intense pain (2.12), medium surgery (OR=1.52), female gender (OR=2.0), ASA category III (OR=3.41), up to 12 years of education (OR=1.36), and more than 12 years of education (OR=1.68). Previous surgery (OR= 0.61) was associated with lower risk for preoperative state-anxiety. CONCLUSIONS: History of cancer and smoking, psychiatric disorders, negative future perception, moderate to intense depressive symptoms, high trait-anxiety, moderate to intense pain, medium surgery, female gender, ASA category III, up to 12 years of education and more than 12 years of education constituted independent risk factors for preoperative state-anxiety. Previous surgery reduced the risk for preoperative anxiety.

Interaction between repeated restraint stress and concomitant midazolam administration on sweet food ingestion in rats

Emotional changes can influence feeding behavior. Previous studies have shown that chronically stressed animals present increased ingestion of sweet food, an effect reversed by a single dose of diazepam administered before testing the animals. The aim of the present study was to evaluate the response of animals chronically treated with midazolam and/or submitted to repeated restraint stress upon the ingestion of sweet food. Male adult Wistar rats were divided into two groups: controls and exposed to restraint 1 h/day, 5 days/week for 40 days. Both groups were subdivided into two other groups treated or not with midazolam (0.06 mg/ml in their drinking water during the 40-day treatment). The animals were placed in a lighted area in the presence of 10 pellets of sweet food (Froot loops(r)). The number of ingested pellets was measured during a period of 3 min, in the presence or absence of fasting. The group chronically treated with midazolam alone presented increased ingestion when compared to control animals (control group: 2.0 +/- 0.44 pellets and midazolam group: 3.60 +/- 0.57 pellets). The group submitted to restraint stress presented an increased ingestion compared to controls (control group: 2.0 +/- 0.44 pellets and stressed group: 4.18 +/- 0.58 pellets). Chronically administered midazolam reduced the ingestion in stressed animals (stressed/water group: 4.18 +/- 0.58 pellets; stressed/midazolam group: 3.2 +/- 0.49 pellets). Thus, repeated stress increases appetite for sweet food independently of hunger and chronic administration of midazolam can decrease this behavioral effect

Risk factors for postoperative anxiety in children.

BACKGROUND: Anxiety is defined as a set of behavioural manifestations that can be divided into state- and trait-anxiety. State-anxiety is a transitory emotional condition that varies in intensity and fluctuates over time. Trait-anxiety is a personality trait which remains relatively stable over time. The objective of this study was to identify and quantify perioperative risk factors for immediate postoperative anxiety in children. METHODS: A prospective cohort study was performed with 90 schoolchildren, ages ranging from 7 to 13 years old, ASA physical status I-II, submitted to elective surgery. The measuring instruments were verbal scale of pain, visual analogue scale (VAS), Trait-State Anxiety Inventory for Children (STAIC), Trait-State Anxiety Inventory (STAI) for parents, and structured questionnaire. RESULTS: Patients not submitted to analgesic block and patients with moderate and intense pain presented an estimated risk 5- and 13-fold greater for high levels of postoperative state-anxiety, respectively. High levels of preoperative state-anxiety and administration of doses of midazolam less than 0.056 mg x kg(-1) constituted an estimated risk for postoperative state-anxiety of 3- and 4-fold, respectively. A positive history of previous surgery was associated with lower risk for postoperative anxiety. CONCLUSIONS: High levels of preoperative state-anxiety, administration of less than 0.056 mg x kg(-1) of midazolam, absence of analgesic block and presence of moderate and intense postoperative pain constituted risk factors for immediate postoperative state-anxiety in children. Previous surgery reduced the risk for postoperative anxiety.

Prescribing practice for antibiotic prophylaxis for 3 commonly performed surgeries in a teaching hospital in Brazil.

BACKGROUND: The contribution of antibiotic prophylaxis to reduce surgical wound infection for some procedures is well known. In spite of extensive knowledge about the effectiveness of antibiotic prophylaxis, its administrative regimens are often inappropriate. METHODS: Antibiotic prophylaxis was evaluated in a university-affiliated community teaching hospital. Data were collected from medical records of patients undergoing cholecystectomy, hysterectomy, and herniorrhaphy during a 9-month observation period. A total of 598 procedures were observed. Data were collected about the patient, the surgery, and the antibiotic prophylaxis. RESULTS: Based on the existing guidelines, the choice to use the prophylactic antibiotic was correct in 75% of the cases. Of these cases, only 3% of the patients received the recommended regimen according to the proposed procedure. It was verified that antibiotic prophylaxis was performed more frequently in patients undergoing open cholecystectomy than laparoscopic cholecystectomy (P =.004). In 46% of the cholecystectomies, more than 4 doses were administered. In hysterectomy, a single dose was used in 54% of the patients, and the antibiotic was administered preoperatively in 80% of the cases. Prophylactic antibiotics were used in 47% of herniorrhaphies. CONCLUSION: The surgeons infrequently met the hospital guideline for antibiotic prophylaxis, and compliance varied by type of procedure.

Increased training prevents the impairing effect of intra-amygdala infusion of the non-NMDA receptor antagonist CNQX on inhibitory avoidance expression

Intra-amygdala infusion of the non-N-methyl-D-aspartate (NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) prior to testing impairs inhibitory avoidance retention test performance. Increased training attenuates the impairing effects of amygdala lesions and intra-amygdala infusions of CNQX. The objective of the present study was to determine the effects of additional training on the impairing effects of intra-amygdala CNQX on expression of the inhibitory avoidance task. Adult female Wistar rats bilaterally implanted with cannulae into the border between the central and the basolateral nuclei of the amygdala were submitted to a single session or to three training sessions (0.2 mA, 24-h interval between sessions) in a step-down inhibitory avoidance task. A retention test session was held 48 h after the last training. Ten minutes prior to the retention test session, the animals received a 0.5-µl infusion of CNQX (0.5 µg) or its vehicle (25 percent dimethylsulfoxide in saline). The CNQX infusion impaired, but did not block, retention test performance in animals submitted to a single training session. Additional training prevented the impairing effect of CNQX. The results suggest that amygdaloid non-NMDA receptors may not be critical for memory expression in animals given increased training

Prognostic significance of intraperitoneal free cancer cells obtained by laparoscopic peritoneal lavage in patients with gastric cancer.

Laparoscopy is a safe and useful method for examining the local extent and regional spread of disease in patients with gastric cancer. Peritoneal dissemination remains a frequent type of recurrence after surgical treatment. The aim of this study was to determine the prognostic value of intraperitoneal free cancer cells (IFCCs) detected by laparoscopic peritoneal lavage. Forty-nine patients with advanced gastric cancer underwent laparoscopy with cytologic examination for staging. Peritoneal lavage was performed when ascites was not present. Aspirated fluid from the peritoneal cavity was centrifuged and subjected to cytologic examination using Giemsa and Papanicolaou staining methods. Patients were surgically treated and followed for a minimum of 5 years. IFCCs were detected in 41% of the patients. In eight cases (16.3%) laparoscopy revealed carcinomatosis and/or multiple liver metastases, so laparotomy was not performed. Patterns of recurrence after curative resection included the following: peritoneal (n = 3), local (n = 4), liver (n = 1), and other (n = 1). All patients who tested positive for IFCCs had peritoneal recurrence. The absence of IFCCs was associated with improved overall survival (21 months for a 95% confidence interval of 7.4 to 34.6 vs. 4 months for a 95% confidence interval of 2.4 to 5.6). Overall survival adjusted for type of resection also demonstrated a favorable outcome for patients who were negative for IFCCs. The following conclusions were drawn: (1) laparoscopic peritoneal lavage cytology may be useful in identifying patients at high risk for peritoneal relapses and may alter treatment, and (2) lFCCs provide additional prognostic information in patients with gastric cancer.

Involvement of hippocampal NMDA receptors in retention of shuttle avoidance conditioning in rats

The purpose of this research was to evaluate the role of hippocampal N-methyl-D-aspartate (NMDA) receptors in acquisition and consolidation of memory during shuttle avoidance conditioning in rats. Adult male Wistar rats were surgically implanted with cannulae aimed at the CA1 area of the dorsal hippocampus. After recovery from surgery, animals were trained and tested in a shuttle avoidance apparatus (30 trials, 0.5-mA footshock, 24-h training-test interval). Immediately before or immediately after training, animals received a bilateral intrahippocampal 0.5-µl infusion containing 5.0 µg of the NMDA competitive receptor antagonist aminophosphonopentanoic acid (AP5) or vehicle (phosphate-buffered saline, pH 7.4). Infusion duration was 2 min per side. Pre-training infusion of AP5 impaired retention test performance (mean Ý SEM number of conditioned responses (CRs) during retention test session was 16.47 Ý 1.78 in the vehicle group and 9.93 Ý 1.59 in the AP5 group; P<0.05). Post-training infusion of AP5 did not affect retention (mean Ý SEM number of conditioned responses during retention test session was 18.46 Ý 1.94 in the vehicle group and 20.42 Ý 2.38 in the AP5 group; P>0.10). This impairment could not be attributed to an effect on acquisition, motor activity or footshock sensitivity since AP5 affected neither training session performance measured by the number of CRs nor the number of intertrial crossings during the training session. These data suggest that NMDA receptors in the hippocampus are critical for retention of shuttle avoidance conditioning, in agreement with previous evidence showing a role of NMDA receptors in fear memory

Cytokines and asthma.

Some of the main cytokines involved in the pathophysiology of bronchial asthma, their pathogenic role, and evidence concerning the importance of their action in asthma exacerbations and in perpetuating airway inflammation are reviewed. Therapeutic approaches using cytokines which counteract the inflammatory process of asthma are also examined.

Involvement of hippocampal NMDA receptors in retention of shuttle avoidance conditioning in rats.

The purpose of this research was to evaluate the role of hippocampal N-methyl-D-aspartate (NMDA) receptors in acquisition and consolidation of memory during shuttle avoidance conditioning in rats. Adult male Wistar rats were surgically implanted with cannulae aimed at the CA1 area of the dorsal hippocampus. After recovery from surgery, animals were trained and tested in a shuttle avoidance apparatus (30 trials, 0.5-mA footshock, 24-h training-test interval). Immediately before or immediately after training, animals received a bilateral intrahippocampal 0.5-microliter infusion containing 5.0 microgram of the NMDA competitive receptor antagonist aminophosphonopentanoic acid (AP5) or vehicle (phosphate-buffered saline, pH 7.4). Infusion duration was 2 min per side. Pre-training infusion of AP5 impaired retention test performance (mean +/- SEM number of conditioned responses (CRs) during retention test session was 16.47 +/- 1.78 in the vehicle group and 9.93 +/- 1.59 in the AP5 group; P < 0.05). Post-training infusion of AP5 did not affect retention (mean +/- SEM number of conditioned responses during retention test session was 18.46 +/- 1.94 in the vehicle group and 20.42 +/- 2.38 in the AP5 group; P > 0.10). This impairment could not be attributed to an effect on acquisition, motor activity or footshock sensitivity since AP5 affected neither training session performance measured by the number of CRs nor the number of intertrial crossings during the training session. These data suggest that NMDA receptors in the hippocampus are critical for retention of shuttle avoidance conditioning, in agreement with previous evidence showing a role of NMDA receptors in fear memory.

Memory enhancement by intrahippocampal, intraamygdala, or intraentorhinal infusion of platelet-activating factor measured in an inhibitory avoidance task.

Platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), which is thought to be a retrograde messenger in long-term potentiation (LTP), enhances glutamate release and LTP through an action on presynaptic nerve endings. The PAF antagonist BN 52021 blocks CA1 LTP in hippocampal slices, and, when infused into rat dorsal hippocampus pre- or posttraining, blocks retention of inhibitory avoidance. Here we report that memory is affected by pre- or posttraining infusion of the PAF analog 1-O-hexadecyl-2-N-methylcarbamoyl-sn-glycerol-3-phosphocholine (mc-PAF) into either rat dorsal hippocampus, amygdala, or entorhinal cortex. Male Wistar rats were implanted bilaterally with cannulae in these brain regions. After recovery from surgery, the animals were trained in step-down inhibitory avoidance or in a spatial habituation task and tested for retention 24 h later. mc-PAF (1.0 microgram per side) enhanced retention test performance of the two tasks when infused into the hippocampus before training without altering training session performance. In addition, mc-PAF enhanced retention test performance of the avoidance task when infused into (i) the hippocampus 0 but not 60 min after training; (ii) the amygdala immediately after training; and (iii) the entorhinal cortex 100 but not 0 or 300 min after training. In confirmation of previous findings, BN 52021 (0.5 microgram per side) was found to be amnestic for the avoidance task when infused into the hippocampus or the amygdala immediately but not 30 or more minutes after training or into the entorhinal cortex 100 but not 0 or 300 min after training. These findings support the hypothesis that memory involves PAF-regulated events, possibly LTP, generated at the time of training in hippocampus and amygdala and 100 min later in the entorhinal cortex.