Combined anti CXC receptors 1 and 2 therapy is a promising anti-inflammatory treatment for respiratory diseases by reducing neutrophil migration and activation.

Neutrophil infiltration and activation in the lung are important pathophysiological features in COPD, severe asthma and bronchiectasis mostly mediated by CXCL8 and CXCL1 via CXCR1 and CXCR2. No thorough study to date has been performed to compare the anti-inflammatory effect profile of dual CXCR1/2 vs. selective CXCR2 antagonists in relevant human neutrophil assays and pulmonary inflammation models. Dual CXCR1/2 (SCH527123, diaminocyclobutandione-1) and selective CXCR2 (SB265610, thiopyrimidine-1) antagonist activity and receptor residence time were determined by [(35)S]GTPγS binding in human (h)- and guinea pig (gp)-CXCR1 and CXCR2 overexpressing membranes. h-neutrophil chemotaxis, degranulation and ROS production were established using CXCL8 or CXCL1 to evaluate dual CXCR1/2- or selective CXCR2-dependent activities. LPS-induced lung inflammation in gp was selected to assess in vivo potency. Dual CXCR1/2 antagonists blocked both CXCL8 and CXCL1-induced h-neutrophil functions and [(35)S]GTPγS binding. In contrary, selective CXCR2 antagonists displayed significantly reduced potency in CXCL8 -mediated h-neutrophil responses despite being active in CXCR2 assays. Upon LPS challenge in gp, administration of SCH527123 inhibited the increase of neutrophils in BALF, modestly reduced blood neutrophils and induced minor neutrophil accumulation in bone marrow. Differentiation of CXCR1/2 vs. CXCR2 antagonists could not be extended to in vivo due to differences in CXCR1 receptor homology between h and gp. Dual CXCR1/2 therapy may represent a promising anti-inflammatory treatment for respiratory diseases reducing more effectively neutrophil migration and activation in the lung than a CXCR2 selective treatment. However, the in vivo confirmation of this claim is still missing due to species differences in CXCR1.

House dust mite induces direct airway inflammation in vivo: implications for future disease therapy?

House dust mite (HDM) is the major source of allergen in house dust and is strongly associated with the development of asthma. HDM can evoke a direct, nonallergic inflammatory reaction in vitro. We aimed to determine whether this apparent nonallergic, inflammatory response can be observed in a more complex in vivo setting. Vehicle, Alum or HDM (Dermatophagoides pteronyssinus 5 microg, i.p. with Alum) sensitised Brown-Norway rats were challenged intratracheally with vehicle (saline), HDM (Der p 10 microg) or heat-inactivated HDM on day 21. Lung function changes and the associated inflammatory response were evaluated. Tissue and bronchoalveolar lavage from Alum sensitised Der p challenged animals exhibited strong eosinophilia and neutrophilia associated with an early release of pro-inflammatory cytokines (interleukin-13 and 1beta, eotaxin and thymus and activation-regulated chemokine). This response was not attenuated by removal of HDM-associated protease activity. Interestingly, the vehicle sensitised group (no Alum) lacked this inflammatory response. HDM allergen evokes nonallergic airways inflammation with an inflammatory profile similar to that of the asthmatic airway. This response, independent of the protease activity of the HDM extract, appeared to be linked to prior administration of the adjuvant Alum and the subsequent increase in total immunoglobulin E. This finding could have important implications in the development of future asthma therapies.

Inferring genetic parameters of lactation in Tropical Milking Criollo cattle with random regression test-day models.

This study inferred genetic and permanent environmental variation of milk yield in Tropical Milking Criollo cattle and compared 5 random regression test-day models using Wilmink's function and Legendre polynomials. Data consisted of 15,377 test-day records from 467 Tropical Milking Criollo cows that calved between 1974 and 2006 in the tropical lowlands of the Gulf Coast of Mexico and in southern Nicaragua. Estimated heritabilities of test-day milk yields ranged from 0.18 to 0.45, and repeatabilities ranged from 0.35 to 0.68 for the period spanning from 6 to 400 d in milk. Genetic correlation between days in milk 10 and 400 was around 0.50 but greater than 0.90 for most pairs of test days. The model that used first-order Legendre polynomials for additive genetic effects and second-order Legendre polynomials for permanent environmental effects gave the smallest residual variance and was also favored by the Akaike information criterion and likelihood ratio tests.

Mechanisms of the neuroprotective effect of aspirin after oxygen and glucose deprivation in rat forebrain slices.

Acetylsalicylic acid (ASA, Aspirin) is an anti-inflammatory drug with a wide spectrum of pharmacological activities and multiple sites of action. Apart from its preventive actions against stroke due to its antithrombotic properties, recent data in the literature suggest that high concentrations of ASA also exert direct neuroprotective effects. We have used an in vitro model of brain ischaemia using rat forebrain slices deprived of oxygen and glucose to test ASA neuroprotective properties. We have found that ASA inhibits neuronal damage at concentrations lower than those previously reported (0.1-0.5 mM), and that these effects correlate with the inhibition of excitatory amino acid release, of NF-kappaB translocation to the nucleus and iNOS expression caused by ASA. All of these three mechanisms may mediate the neuroprotective effects of this drug. Our results also show that the effects of ASA are independent of COX inhibition. Taken together, our present findings show that ASA is neuroprotective in an in vitro model of brain ischaemia at doses close to those recommended for its antithrombotic effects.

Changes induced by sodium cromoglycate in brain catecholamine turnover in morphine dependent and abstinent mice.

The effects of sodium cromoglycate (CRO) were studied in relation to the metabolism of brain catecholamines: dopamine (DA) and noradrenaline (NA), and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG). CRO was injected SC in control mice, morphine-tolerant mice (tolerance was induced by SC implantation of a 75 mg morphine pellet; CRO was administered on day 4 of addiction) and 30 min before abstinence (withdrawal was induced by SC injection of naloxone (1 mg/kg) on day 4 of addiction). Brain catecholamines and their metabolites were measured using high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD), for DA, NA, DOPAC and HVA, and coupled with fluorescence detection for MHPG. The ratios of DOPAC + HVA/DA and MHPG/NA were kept as an index of DA and NA turnovers, respectively. CRO administered 30 min before naloxone-precipitated withdrawal diminished significantly NA levels in frontal cortex. CRO increased DA turnover in striatum and frontal cortex in naive animals and significantly diminished DA levels in frontal cortex and DOPAC levels in frontal cortex and midbrain in morphine-dependent mice. These findings are discussed in relation to the protective effects of CRO on opiate withdrawal and the effects of CRO on locomotor activity.

Granulomatous amebic encephalitis due to Balamuthia mandrillaris (Leptomyxiidae): report of four cases from Mexico.

In this report, we describe four cases of granulomatous amebic encephalitis caused by Balamuthia (Leptomyxid ameba) in four previously healthy Mexican patients. All four cases were characterized by focal neurologic signs, increased intracranial pressure, and cerebral hyperdense lesions in computed tomography scans of the head. These patients underwent craniotomies for evaluation of mass lesions for possible brain tumors. Granulomatous chronic inflammatory reaction and amebic trophozoites were found in brain biopsies. At autopsy, areas of hemorrhagic encephalomalacia were located in both basal frontal lobes, right parieto-occipital lobes, and, less often, in the brainstem and cerebellum. Angiitis, necrotizing granulomatous encephalitis, and large numbers of amebic trophozoites in perivascular spaces were present. Amebic trophozoites were seen in the left adrenal gland in one of the cases. The amebas in all four cases were identified as Balamuthia mandrillaris (Leptomyxiidae) based on their reactivity with the anti-Balamuthia (Leptomyxiidae) serum in an immunofluorescence test.

Protective effect of N-(3-(aminomethyl)benzyl) acetamidine, an inducible nitric oxide synthase inhibitor, in brain slices exposed to oxygen-glucose deprivation.

It has been suggested that large amounts of nitric oxide (NO) produced by inducible NO synthase are involved in the mechanisms of neurotoxicity after cerebral ischaemia. We have recently demonstrated that inducible NO synthase was expressed within hours after rat forebrain slices were exposed to oxygen-glucose deprivation. Therefore, we sought to determine whether NO produced by inducible NO synthase contributes to tissue damage in this model, by using a new, highly selective, inhibitor of inducible NO synthase, N-(3-(aminomethyl)benzyl)acetamidine (1400W). We found that incubation with 1400W from the start of the oxygen-glucose deprivation period until the end of the experiment decreases tissue damage determined as lactate dehydrogenase (LDH) efflux 4 h after the oxygen-glucose deprivation period, the time at which inducible NO synthase expression is maximal in this model. This effect may be a result of direct inhibition of inducible NO synthase activity, raising the possibility of a clinical use of selective inhibitors of this NO synthase isoform in the management of cerebral ischaemia.

Inducible nitric oxide synthase is involved in the mechanisms of cocaine enhanced neuronal apoptosis induced by HIV-1 gp120 in the neocortex of rat.

Cocaine, often abused by human immunodeficiency virus (HIV) infected patients, has been suggested to worsen the HIV associated dementia via unknown mechanisms. Here we report that subchronic treatment with a dose of cocaine (30 mg/kg i.p.), unable per se to cause neuronal death, increases the number of apoptotic cells typically observed in the neocortex of rats treated with HIV-1 gp120 (100 ng given i.c.v.). A pre-treatment with MK801 (0.3 mg/kg i.p.), a NMDA receptor antagonist, L-NAME (10 mg/kg i.p.) and 7-nitroindazole (50 mg/kg i.p.), two specific inhibitors of NOS, or with 1400 W (1 mg/kg s.c.), a selective inhibitor of inducible NOS (iNOS), minimized neurotoxicity by combined administration of cocaine and gp120 thus implicating iNOS. This conclusion is supported by the evidence that cocaine increases brain neocortical citrulline, the co-product of NO synthesis.

Event-related brain potentials during a continuous performance test (CPT) task in normal children.

BACKGROUND: Continuous Performance Test (CPT) is a commonly used paradigm to assess attention disorders that could involve working memory processes. METHODS: Event-related potentials (ERPs) during a CPT (X-AX) test were obtained in 16 healthy male students, with ages ranging from 9 to 11 years (X = 10.3). In grouped averaged ERPs, an endogenous slow positive potential was recorded in the first task (infrequent letter detection); maximum was at 460 msec with a slight lateralization tendency toward left parietal area. In the second task (target detection with an A as warning signal), an early (maximum at 330 msec) and more acute peak was detected without evidence of any lateralization. RESULTS: Reaction times were significantly shorter for the second task. Electrophysiologic differences between both target conditions showed an early, remarkable, and statistically significant component located at the parietal area at 340 msec. CONCLUSIONS: These ERPs findings could be interpreted as correlates with working memory processes in children.

Event related brain potentials to semantically incongruent words in children of different ages.

In this study, developmental changes of N400 elicited by a simple paradigm to semantic incongruity were examined. Subjects were divided in three different age groups and educational levels: Group I (first grade) = 7-8 years, n = 10; Group II (third grade) = 9-10 years, n = 10; and Group III (sixth grade) = 11-12 years, n = 10. EEG activity was recorded from 8 monopolar sites referred to linked earlobes. Data showed that the amplitude of the N400 like component did not change significantly from first to sixth grade, although the onset latency appeared to be shorter in older children. No significant latency and amplitude changes were found among groups.

Lead based remedies for empacho: patterns and consequences.

This paper discusses research designed to investigate the patterns and consequences of the use of lead based folk remedies in the treatment of some gastrointestinal problems in Mexico. Use of lead is seen in 35% of the population sampled in Guadalajara who treated the folk illness empacho, and 5% of a similar population in Oaxaca. Lead use seems to be associated with mestizo ethnic background, and with lower levels of parental education and income.

Mexican use of lead in the treatment of empacho: community, clinic, and longitudinal patterns.

This paper discusses research designed to investigate community, clinic, and longitudinal patterns in use of lead as a treatment for empacho, a folk illness manifest by gastrointestinal symptoms. The same questionnaire used in a clinic-based study seven years previously in Guadalajara, Mexico, was used to interview a randomly selected community sample: in addition, the study was repeated at the same clinic sites that had been studied previously. The goals were to investigate: (1) What are community wide prevalences of empacho and use of lead based remedies? (2) To what extent are current patterns of use of lead for treatment of empacho in clinic-based samples similar to those seven years ago. The attributable risk to the population as a whole from use of lead based remedies was found to be 11% of the households of Guadalajara. Essentially this same estimate was seen for the 1987 and 1994 clinic populations. Interestingly, while percentages of lead users have declined since 1987, twice as great a percentage of informants reported treating empacho. Other patterns originally identified in 1987 persisted in 1994; lead use continues to be associated with lower levels of parental education and income.

Transitory cognitive impairment in epileptic children during a CPT task.

EEGs and behavioral responses were studied in two sex matched groups of 58 epileptic and 20 healthy children between 8 and 12 years of age, during the execution of a go-no go CPT (X; A-X) task to determine transitory cognitive impairment (TCI) incidence. Paroxysmal discharges were found on 87.9% and 5% of the EEGs in the epileptic and control groups respectively, with no differences related to sex. The predominant EEG findings with respect to paroxysmal discharges were the association of two or more types of paroxysms with frequency higher than 5/minute, an average duration less than 0.5 second and topographical distribution over temporal-parietal-occipital areas without significant interhemispheric differences. TCI was detected in 36.2% of epileptic children. The epileptic group showed significantly higher numbers of behavioral errors and longer reaction times (RTs) in relation to the control group. Analyzing RTs on the two blocks of the task, linear discriminant analysis showed an acceptable classification of TCI incidence between groups.

Endocrinology of the postpartum period in the Pelibuey ewe.

The postpartum (PP) period in the Pelibuey ewe was studied. Laparotomies were performed on 14 ewes in the first year at d 10, 20 and 30 PP, and at d 10 and 20 PP in the second year on 17 ewes. Progesterone concentrations were determined in serum taken daily, from 4 to 7 d after parturition until estrus. Temporal fluctuation of luteinizing hormone (LH) was determined in samples taken at 30-min intervals for 4 h weekly. The mean interval from lambing to first ovulation was longer (P less than .001) in 1980 (59 +/- 4.9 d) than 1979 (26 +/- 3.1 d), the mean interval from lambing to first estrus was also longer (P less than .001) in 1980 (91 +/- 5.6 d) than 1979 (51 +/- 5.5 d). Follicles were present on the ovaries of the majority of the ewes at d 10. The mean diameter of the largest follicles on each ovary was reduced (P less than .025) in ewes in 1980 (6 mm) compared with 1979 (7.7 mm). Corpora lutea (CL) occurred in 67 and 75% of the ewes by d 20 and 30, respectively in 1979; no CL were found by d 20 in 1980. Progesterone profiles suggested that the PP period was composed of a period of anestrus, and a period of cyclic ovarian activity with one, two or three ovulations without behavioral estrus. In some ewes, the first cycle was of shorter duration, and its CL secreted less progesterone (P less than .05) relative to CL of silent and regular estrous cycles. Luteinizing hormone peaks were recorded as early as 6 d PP. When progesterone concentrations were elevated to luteal phase levels, the frequency, but not magnitude, of LH peaks per 4-h bleeding period was reduced (P less than .05) relative to anestrus. It is concluded that there are periods of anestrus and of silent cycles, which precede the first postpartum estrus in Pelibuey ewes.

[Prosthetic endocarditis and splenic abscess caused by Clostridium clostridiformis]. / Endocarditis protésica y absceso esplénico causados por Clostridium clostridiformis.

We report the first case of Clostridium clostridiformis endocarditis in a 71 year old man with an aortic prosthetic valve. He was febrile with left upper quadrant pain and left lower lobe infiltrate in chest X ray. The diagnosis was made by gram-positive bacilli grown from three blood cultures. Transthoracic and transesophageal echocardiogram showed a paraaortic abscess. A computed tomographic scan of the abdomen revealed a large splenic abscess. He received penicillin G 4 million units every 4 hours intravenously. A successful percutaneous drainage guided computed tomographic scan was performed. The patient remained febrile and a new computed tomographic scan of the abdomen revealed residual splenic abscess. A splenectomy was performed. The patient defervesced on the second day of surgery and remained afebrile during the remainder of his hospitalization. He has returned for medical follow-up and two years later the patient is asymptomatic.

[Aortic prosthetic endocarditis and periprosthetic abscess caused by Staphylococcus aureus]. / Endocarditis protésica aórtica y absceso periprotesico por Staphylococcus aureus.

Prosthetic endocarditis with annular abscess formation is a severe complication of cardiac valve replacement fortunately uncommon, though highly lethal. Increasing surgical experience and the high mortality with medical management have led to a widespread recommendation for early prosthetic replacement. We report a case of a 49 year old man with infective endocarditis due to Staphylococcus aureus in aortic ascendens prosthetic and aortic valve prosthetic complicated with periaortic abscess which was as successful treatment by drain of abscess without prosthetic replacement.

Stress distribution under high-pull extraoral chin cup traction. A photoelastic study.

Birefringent materials were employed in the fabrication of a model of a human skull with distinct simulants for teeth, bone, and periodontal ligaments. The following observations were made subsequent to the application of force to this model with an extraoral high-pull chin cup: 1. Reciprocal stresses were observed in the posterior portion of the glenoid fossa and the contacting posterior part of the head of the condyle. 2. A tension coil spring representing the external pterygoid muscle applied reciprocal stresses at its insertions in the lateral pterygoid plate on the greater wing of the sphenoid and the anterior aspect of the head of the condyle. 3. Stresses were seen to radiate from the roots and apices of both the maxillary and mandibular posterior teeth. 4. A distinct concentration of stress was noted in the retromolar area of the mandible, away from the dentition, indicating a bending stress. 5. The posterior half of the sigmoid notch, below the anterior aspect of the head of the condyle, displayed a heavy band of stresses. 6. Selected sectioning of the mandible substantiated observations made from the intact hemimandible and also showed evidence of bending in the area corresponding to the head and neck of the condyle.

AIDS and condom-related knowledge, beliefs, and behaviors in Mexican migrant laborers.

PIP: A survey of 87 Mexican migrants (55 males and 32 females) who have lived and worked in the US since 1982 assessed AIDS and condom-related knowledge, beliefs, and sexual practices. Although respondents were highly knowledgeable about major modes of HIV transmission, one-third to one-half believed that HIV could be contracted from mosquito bites, public bathrooms, kissing, and the HIV test. Only 15% knew someone with AIDS. Ever-use of condoms was reported by 70.9% of men and 41.9% of women. Of the 68 subjects who had been sexually active in the year preceding the survey, 20 reported two or more partners. Among sexually active respondents, 16.2% always used condoms with their primary partner, while 43.0% used condoms consistently with occasional partners. 48.9% of men and 57.1% of women never used condoms with their primary partner; with casual partners, these rates were 30.8% and 44.4%, respectively. Worry about contracting AIDS, self-rated on a scale from 1 (very often) to 4 (never), averaged 2.84, with higher worry scores among those 18-31 years of age and with multiple partners. Respondents did not anticipate negative consequences of condom use (e.g., reduced sexual pleasure), but females expressed concern that carrying condoms would cause them to be viewed as promiscuous.^ieng

[Acute pancreatitis in thrombotic thrombocytopenic purpura. Apropos 2 cases]. / Pancreatitis aguda en el seno de la púrpura trombocitopénica trombótica. A propósito de dos casos.

Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by fever, microangiopathic hemolytic anemia, thrombocytopenia, renal disease and neurologic changes. The development of little thrombi in the systemic microcirculation is thought to play an important role, however the etiology is unknown. We present two cases in which pancreatic disease was the first manifestation of TTP.

[Usefulness of cholinesterase determination in ascitic fluid in the differential diagnosis of ascites]. / Utilidad de la determinación de la colinesterasa en líquido ascítico en el diagnóstico diferencial de la ascitis.

BACKGROUND: Cholinesterase is an enzyme mainly synthesized in the liver that might play a role in the differential diagnosis of ascites. We prospectively compared the sensitivity, specificity and diagnostic usefulness of the ascites cholinesterase and the classical parameters, ascites total protein concentration and serum-ascites albumin gradient in the differential diagnosis of ascites. In addition, we evaluated the relationship between those parameters and the degree of liver failure. METHODS: A total of 91 patients with ascites were analyzed. According the final diagnosis, patients were classified in two groups, patients with signs of portal hypertension [n = 78] (60 with chronic liver disease, 5 chronic liver disease and hepatocellular carcinoma, 3 chronic liver disease and spontaneous bacterial peritonitis, 3 chronic liver disease and secondary peritonitis, 7 malignancy with liver involvement) and patients with no signs of portal hypertension [n = 13] (12 patients with peritoneal neoplasia without liver involvement and 1 tuberculous peritonitis). RESULTS: The sensitivity of the test for detecting portal hypertensive ascites was lowest for ascites cholinesterase less than 600 U/L (71.7%); intermediate with ascites total protein concentration less than 25 g/l (87.2%) and highest with serum-ascites albumin gradient at least 11 g/l (93.6%). The specificity for ruling out portal hypertensive ascites was 100 percent for ascites total protein > or = 25 g/l and ascites cholinesterase > or = 600 U/L and, 76.9 percent for serum-ascites albumin gradient < 11 g/l). Diagnostic efficiency (percentage of patients accurately classified) was greater for serum-ascitis albumin gradient (91.2%; IC95: 83-95.8), and lower for ascites total protein content (89%, IC95: 80.3-94.3) and, ascites cholinesterase (75.8%; IC95: 65.5-83.9). Ascites cholinesterase showed a significant relationship (p = 0.007) with the degree of liver failure measured by Pugh's classification. CONCLUSION: Serum-ascites albumin gradient was the test with best performance characteristics to identify patients with ascites related with portal hypertension. Our results suggest that ascites cholinesterase is more associated with the degree of liver failure than with the presence of portal hypertension.