Divergence in mating signals correlates with genetic distance and behavioural responses to playback.

Animals use acoustic signals to defend resources against rivals and attract breeding partners. As with many biological traits, acoustic signals may reflect ancestry; closely related species often produce more similar signals than do distantly related species. Whether this similarity in acoustic signals is biologically relevant to animals is poorly understood. We conducted a playback experiment to measure the physical and vocal responses of male songbirds to the songs of both conspecific and allopatric-congeneric animals that varied in their acoustic and genetic similarity. Our subjects were territorial males of four species of neotropical Troglodytes wrens: Brown-throated Wrens (Troglodytes brunneicollis), Cozumel Wrens (T. beani), Clarion Wrens (T. tanneri) and Socorro Wrens (T. sissonii). Our results indicate that birds respond to playback of both conspecific and allopatric-congeneric animals; that acoustic differences increase with genetic distance; and that genetic divergence predicts the strength of behavioural responses to playback, after removing the effects of acoustic similarity between subjects' songs and playback stimuli. Collectively, these results demonstrate that the most distantly related species have the most divergent songs; that male wrens perceive divergence in fine structural characteristics of songs; and that perceptual differences between species reflect evolutionary history. This study offers novel insight into the importance of acoustic divergence of learned signals and receiver responses in species recognition.

Targeting the MHC class II pathway of antigen presentation enhances immunogenicity and safety of allergen immunotherapy.

BACKGROUND: Current s.c. allergen-specific immunotherapy (SIT) leads to amelioration of IgE-mediated allergy, but it requires numerous allergen injections over several years and is frequently associated with severe side-effects. The aim of this study was to test whether modified recombinant allergens can improve therapeutic efficacy in SIT while reducing allergic side-effects. METHODS: The major cat allergen Fel d 1 was fused to a TAT-derived protein translocation domain and to a truncated invariant chain for targeting the MHC class II pathway (MAT-Fel d 1). The immunogenicity was evaluated in mice, while potential safety issues were assessed by cellular antigen stimulation test (CAST) using basophils from cat-dander-allergic patients. RESULTS: MAT-Fel d 1 enhanced induction of Fel d 1-specific IgG2a antibody responses as well as the secretion of IFN-gamma and IL-2 from T cells. Subcutaneous allergen-specific immunotherapy of mice using the modified Fel d 1 provided stronger protection against anaphylaxis than SIT with unmodified Fel d 1, and MAT-Fel d 1 caused less degranulation of human basophils than native Fel d 1. CONCLUSION: MAT-Fel d 1 allergen enhanced protective antibody and Th1 responses in mice, while reducing human basophil degranulation. Immunotherapy using MAT-Fel d 1 allergen therefore has the potential to enhance SIT efficacy and safety, thus, shortening SIT. This should increase patient compliance and lower treatment costs.

Medication with antihistamines impairs allergen-specific immunotherapy in mice.

BACKGROUND: Histamine released from activated mast cells and basophils is an important mediator in allergy. Therefore, antihistamines are efficiently and widely used to suppress allergic symptoms. OBJECTIVE: This study evaluated the role of antihistamines in sensitization against allergens and in the efficiency of allergen-specific immunotherapy. METHODS: CBA mice were sensitized and de-sensitized with bee venom allergen extracts and the major allergen phospholipase A2. Clemastine was used to test the effect of a histamine-1 receptor antagonist on the immune responses to phospholipase A2. RESULTS: The results demonstrated that sensitization against bee venom was strongly enhanced during treatment with antihistamines. Clemastine increased IgE production while decreasing IgG2a production against bee venom. This T-helper type 2 shift of the humoral response appeared to be caused by reduced IFN-gamma and enhanced IL-4 secretion from allergen-specific T cells. We also found reduced TNF-alpha, IL-6 and major histocompatibility complex class-II expression by macrophages. In sensitized mice, the efficiency of allergen-specific immunotherapy was reduced by clemastine treatment. CONCLUSION: Antihistamines may enhance allergic sensitization and reduce the efficiency of allergen-specific immunotherapy. Future studies will need to demonstrate to what extent pre-medication with antihistamine also affects allergen-specific immunotherapy in humans.

Simultaneous assessment of the effects of L-type current modulators on sensory and motor pathways of the mouse spinal cord in vitro.

The effects of modulators of L-type currents in the processing of nociceptive stimuli across sensory and motor circuits were studied using an in vitro preparation of the young mouse spinal cord. Responses to repetitive C-fibre intensity stimuli delivered to a lumbar dorsal root were simultaneously recorded from motor axons in the corresponding ventral root and from putative sensory axons in the anterolateral pathway. L-current antagonists verapamil, diltiazem and nimodipine as well as the agonist Bay K8644 were superfused at a range of concentrations and their effects on responses to afferent stimulation were assessed. All antagonists produced a concentration-dependent depression of transmission across sensory and motor pathways by inhibiting sustained firing and wind-up. All antagonists showed concentration-dependent depression of evoked firing in anterolateral fibres with LogIC50 of -4.2 for verapamil, -4.1 for diltiazem and -4.9 for nimodipine. Applied at high concentrations (>or=100 microM) verapamil and diltiazem produced almost complete blockade of the ascending signals whereas nimodipine produced only partial depression. The effects of the antagonists on motor pathways were significantly greater and the LogIC50 decreased to -5 for verapamil, to -4.9 for diltiazem and to -5.3 for nimodipine. Bay K8644 applied at 2 microM produced only a slight potentiation of responses in anterolateral axons and a very large and long-lasting potentiation of responses from motor neurons. We conclude that mice motor pathways are more sensitive to L-type current modulators than the anterolateral pathway and that analgesic effects reported for some L-type antagonists may be due to a mixture of selective and non-selective effects of these agents on sensory neurones.

Efficacy and safety of allergen-specific immunotherapy in rhinitis, rhinoconjunctivitis, and bee/wasp venom allergies.

The prevalence of allergic diseases, such as rhinoconjunctivitis, is increasing worldwide, particularly in Westernized countries, where more than 30% of the population is affected. Insect venom allergy is also very common, affecting up to 5% of the population. Allergen-specific immunotherapy is the only immunomodulatory treatment that may alter the natural course of allergic disease, for example by preventing the development of asthma in rhinitic patients. Nonetheless, the risk-benefit ratio for subcutaneous immunotherapy has changed little from when it was first developed a century ago. However, the rapid evolution of new developments, including new methods of administration and new forms of antigen to stimulate the immune system, now offers improvements in both the safety and the efficacy of specific immunotherapy. These developments include the sublingual administration of the relevant antigens, which has a superior safety profile than the original subcutaneous route. This may enable higher dosages to be used over shorter treatment periods, with a lower risk of anaphylactic reactions. Improvements in the purity, specificity, and immunogenicity of the antigens, often as a result of advances in biotechnology, coupled with the development of new adjuvants, may further increase the efficacy of this form of treatment. This review describes and discusses these new developments in the context of the many recent advances in our understanding of the mechanisms by which immunotherapy appears to act.

Electrophysiological and pharmacological characterisation of ascending anterolateral axons in the in vitro mouse spinal cord.

Here we describe a procedure to obtain electrophysiological recordings from cut ends of ascending axons of the spinal cord white matter. This procedure involves the use of an in vitro preparation of the neonate mouse spinal cord and suction microelectrodes of about 10 microm tip diameter. Using this procedure, we have recorded from axons of the anterolateral quadrant at the thoracic level which responded to electrical stimulation of a lumbar dorsal root. Using adequate stimulation parameters, we have identified axons responding exclusively to activation of C-fibres and axons responding to activation of A- and C-fibres. These axons are likely to originate at dorsal horn second order sensory neurons of different functional types. Simultaneous recordings from a lumbar ventral root and from ascending axons were used to assess the effects of noradrenaline and sevoflurane on motor and sensory pathways. The results obtained show that noradrenaline can potentiate responses of motor neurons to dorsal root stimulation while depressing responses of ascending axons to the same stimulus. In contrast both motor and sensory pathways were inhibited by sevoflurane. We believe that the procedures developed here may be of great interest to assess spinal nociceptive and antinociceptive mechanisms in vitro.

M-current modulators alter rat spinal nociceptive transmission: an electrophysiological study in vitro.

M-currents constitute a unique effector system to control neuronal excitability due to their voltage and ligand sensitivities. Here we have used retigabine, an M-current agonist, and XE-991, an M-current antagonist, to study the possible involvement of these currents in the processing of spinal sensory and motor processing of nociceptive information in normal, untreated rats. Experiments were performed in a hemisected spinal cord preparation from rat pups using extracellular recordings. Responses to activation of nociceptive and non-nociceptive afferent fibres were recorded. M-current modulators were bath applied to the entire cord or applied locally by pressure ejection. Retigabine and XE-991 produced long-lasting and concentration-dependent effects on nociceptive reflexes showing only minor effects on non-nociceptive reflexes. Retigabine depressed responses to repetitive stimulation of the dorsal root recorded from motor neurones and dorsal horn neurones, whereas XE-991 showed the opposite potentiatory effect and reversed effects of retigabine. Local application of the modulators close by motor nuclei produced changes in reflex responses similar to those caused by bath application. These results constitute a clear indication of the existence of functional M-currents in dorsal and ventral horn elements of the mammalian spinal cord where they may serve to regulate early sensory and motor processing of nociceptive information. The weak effect of modulators on non-nociceptive reflexes suggest that M-currents constitute a promising novel target for analgesics.

[Prevalence of mental retardation in teenagers with dissocial conduct disorder]. / Prevalencia del retarso mental en adolescentes con trastorno disocial de la conducta.

INTRODUCTION: Prevalence of adolescents with conduct disorder (CD) has been calculated between 4 y 10%. OBJECTIVE: To estimate the prevalence of mental retardation in Colombian adolescent offenders, using the Wechsler Intelligence Scales for Children Revised (WISC R). PATIENTS AND METHODS: 106 male adolescent offenders with CD, aged 12 to 16 years, and attending to institutions of re education in Medell n Colombia were selected in a randomized approach. WISC R Hispanic version was administered to the sample, using 4 verbal (information, vocabulary, similarities and arithmetic) and 4 performance (Picture completion, block design, picture arrangement, and digit symbol) subtests for calculating verbal, performance and full scale IQs (VIQ, PIQ, and FSIQ), according to the manual instructions. RESULTS: 43 participants (40.6%) obtained a FSIQ < 70, then they were categorized as mild mental retardation. 34 offenders (32.1%) had a FSIQ between 70 and 84, then they were classified as people with borderline intellectual functioning, only 29 participants (27.4%) obtained a FSIQ over 85. CONCLUSION: 72.7% of the institutionalized adolescents offenders had low intellectual functioning, which may be interfere with the re education programs.

Toll-like receptor ligands as adjuvants in allergen-specific immunotherapy.

BACKGROUND: Allergen-specific immunotherapy (SIT) leads to long-term amelioration of T-helper type 2 (Th2)-mediated allergic symptoms and is therefore recommended as a first line therapy for allergies. The major disadvantage of SIT is its low efficiency, requiring treatment over years. OBJECTIVE: In this study, we evaluated the potential of Toll-like receptor (TLR) ligands to facilitate Th1-type immune responses. METHODS: The immunogenicity and therapeutic potential of the major bee venom allergen phospholipase A2 (PLA2) combined with various TLR ligands were tested in mice and compared with immune responses induced by conventional aluminium-based preparations. RESULTS: Regarding total IgG against PLA2, TLR2/4-binding lipopolysaccharide and TLR3-binding polyriboinosinic polyribocytidylic (PolyI:C) were the superior adjuvants for prophylactic vaccination. However, TLR9-binding phosphorothioate-modified cytosine-guanosine-rich oligonucleotide (CpG), TLR-3-binding PolyI:C, and TLR2/6-binding peptidoglycan skewed the immune responses more towards IgG2a isotype and Th1 cytokines. Furthermore, in a therapeutic approach, CpG, PolyI:C and TLR7/8-binding 3M003 had immune modulating properties as they suppressed established IgE titres. CONCLUSION: The potential of TLR ligands to adjuvate the immunogenicity of bee venom PLA2 and to skew the Th1-Th2 balance proved very heterogeneous. With respect to SIT, CpG, PolyI:C, and 3M003 were very promising. Hence, TLR ligands should be considered as adjuvants or immune modulators in SIT in human as to improve its efficiency regarding the Th1-Th2 balance of the immune response with a likely effect on therapy duration.

[Alpha-1 antitrypsin deficiency in infancy and childhood]. / Déficit de alfa 1 antitripsina en la infancia.

We present our experience with 5 pediatric patients, 3 males and 2 females, with alpha 1 antitrypsin deficiency. These patients were between the ages of 15 months and 8 years and 4 were of the PI ZZ phenotype and 1 of the PI SZ phenotype. All cases presented with liver disease (neonatal cholestasis, cirrhosis, hepatitis). We comment on the different clinical forms of this entity during childhood, most of which are liver diseases, whereas in the adult it is generally manifest as lung disease.

[Suprarenal hemorrhage as the first manifestation of a small cell pulmonary carcinoma. Presentation of a case]. / Hemorragia suprarrenal como primera manifestación de un carcinoma pulmonar de células pequeñas. Presentación de un caso.

OBJECTIVE: To report on a case of small cell lung carcinoma presenting as adrenal hemorrhage. METHODS: A case of small cell lung carcinoma presenting as adrenal hemorrhage in a 60-year-old male is presented. The most important features of this tumor type and the adrenal metastasis are described. RESULTS: Treatment with carboplatin and VP-16 was unsuccessful. A brain CT scan showed several space occupying parenchymal lesions. Palliative radiotherapy was administered. The patient's condition has progressively become worse. He is currently receiving only palliative treatment. CONCLUSIONS: The adrenal gland is a common site of metastasis. One of the tumor types that frequently metastasize to the adrenals is small cell lung carcinoma, which is characterized by early local and systemic dissemination, associated paraneoplastic syndromes and its sensitivity to cytostatic agents. Adrenal metastasis from lung carcinoma should be suspected in patients with a large, heterogeneous, bilateral lesion.

[Dermatitis herpetiformis vs. celiac disease]. / Dermatitis herpetiforme versus enfermedad celíaca.

Twenty-nine patients affected with dermatitis herpetiformis (HD), all of whom were on a diet including gluten, were investigated for symptoms of enteropathy. Of these patients, 71% presented severe intestinal lesions, indistinguishable from those found in coeliac disease (CD). However, there were little other clinical manifestations of this finding since only three children in this group had weight and height < or = P3. Of the remaining children, 18% had moderate intestinal atrophy and 10% had normal mucosa or mucosa with negligible changes. When changed to a gluten free diet, the intestinal lesions subsided, dermic lesions disappeared in 17 patients, improved in 8 others and remained the same in the other three patients that were still on variable diets. A study of human leukocyte antigens (HLA) class II showed a total association with Dqw2 and 85% association to DR3, which was identical to the coeliac disease control group. These findings lead one to conclude that HD and CD are different clinical expressions of the same sensitivity to gluten which is associated to an immunological disorder with a common genetic base linked to certain HLA molecules.