Eotaxin levels and eosinophils in guinea pig broncho-alveolar lavage fluid are increased at the onset of a viral respiratory infection

In previous studies we found that guinea pigs demonstrate an increase in airway reactivity and eosinophil numbers 4 days after a respiratory infection with parainfluenza-3 (PI3) virus. Clinical data support the possible involvement of eosinophils in virus-induced airway hyperresponsiveness. Eotaxin, a newly discovered chemokine, could be involved in eosinophil migration to the airways. In this study, eosinophil numbers were counted in blood and bronchoalveolar lavage (BAL) fluid and related with eotaxin concentrations in BAL fluid 1, 2, 3, and 4 days after intratracheal PI3 virus administration. On day 1, blood eosinophils increased by more than 200% ( P  < 0.01). The number of eosinophils were only slightly enhanced from day 2 to day 4 (40%–70%). BAL fluid eosinophils were not increased on day 1 but were significantly elevated on day 2 (180%) and remained high on days 3–4 (>300%, P  < 0.05). This increase in lung eosinophils correlated well with eotaxin levels measured in BAL fluid. There was no significant increase in eotaxin on day 1 following PI3 infection; however, on days 2–4 eotaxin levels in BAL fluid were significantly elevated (four–sixfold increase) when compared with medium inoculated controls. Eotaxin appears to play an important role in eosinophil accumulation in guinea pig lung following PI3 infection.     

A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects

We analysed a Dutch family with autosomal dominant non-syndromic progressive sensorineural hearing loss and mapped the underlying gene defect by genetic linkage analysis to a 11.0 cM region overlapping the DFNA9 interval on chromosome 14q12-q13. Clinically, the Dutch family differs from the original DFNA9 family by a later age at onset and a more clearly established vestibular impairment. A gene that is highly and specifically expressed in the human fetal cochlea and vestibule, COCH (previously described as Coch5B2 ), was mapped to the DFNA9 critical region. Sequence analysis revealed a 208C-->T mutation in the COCH gene, resulting in a Pro51Ser substitution in the predicted protein in all affected individuals of the family but not in unaffected family members and 200 control individuals. The same mutation was also identified in three apparently unrelated families with a similar phenotype, suggesting the presence of a Dutch founder mutation. The function of COCH is unknown but several characteristics of the protein point to a structural role in the extracellular matrix. The mutant serine at position 51 is situated between cysteines and possibly interferes with proper COCH protein folding or its interaction with extracellular matrix proteins.      

Antigen-stimulated lung CD4+ cells produce IL-5, while lymph node CD4+ cells produce Th2 cytokines concomitant with airway eosinophilia and hyperresponsiveness

OBJECTIVE AND DESIGN: We investigated whether airway inflammation in a mouse model of allergic asthma is related to antigen-specific T cell responses in the effector organ, the lung, and in the lung draining lymph nodes (LN). MATERIALS AND SUBJECTS: In BALB/c mice pathophysiological parameters were measured in vivo, and lung draining LN and lung cells were restimulated in vitro. TREATMENT: Mice were sensitized with ovalbumin and repeatedly challenged with ovalbumin or saline inhalation. METHODS: Airway reactivity, inflammation in the airways, serum levels of IgE were measured, and cytokine levels and proliferative responses were determined in antigen-stimulated lymphocyte cultures. RESULTS AND CONCLUSIONS: Sensitization results in antigen-specific Th0-like LN cells, despite the presence of antigen-specific IgE. Repeated antigen inhalation induced airway hyperresponsiveness and eosinophil infiltration concomitant with a shift towards Th2 cytokine production exclusively by lung draining LN T cells. Furthermore, these airway symptoms are associated with antigen-specific CD4+ effector T cells in the airway tissue producing only IL-5, but not IL-4, which are unable to proliferate.     

Pharmacogenetics in Latin American populations: regulatory aspects, application to herbal medicine, cardiovascular and psychiatric disorders

Meeting report of the "Second Symposium on Pharmacology of Cytochrome P450 and Transporters" organized by the Cuban Society of Pharmacology in collaboration with the European Society of Pharmacogenetics and Theranostics (ESPT) and the Ibero-American Network of Pharmacogenetics and Pharmacogenomics (www.ribef.com). The Symposium covered different topics on pharmacogenetics and its clinical implications, focusing on Latin-American populations. The activities of the ESPT were also presented and discussed. The topics addressed were regulatory aspects, the use of pharmacogenetics in pre-clinical research, herbal medicine, and natural products, ending with a discussion about translation into clinical practice, specifically for cardiovascular disorders and psychiatry. Finally, the implication for population diversity in Latin America was also discussed. The RIBEF initiative represents a promising step towards the inclusion of Latin American populations among those to benefit from the implementation of pharmacogenetics in clinical practice. Among current RIBEF activities, the CEIBA.FP Consortium aims to study the variability of pheno- and genotypes in Hispanics that are relevant to pharmacogenetics. For this purpose, populations from Mexico, Cuba, Nicaragua, Costa Rica, Ecuador, Colombia, Brasil, Perú, Chile, Uruguay, Argentina, Portugal, and Spain are currently being studied. The meeting's main conclusion was that population pharmacogenetic studies as well as academic clinical trials might need to be conducted in the different geographic locations/countries. This is important in order to improve drug safety, dosage recommendations, and pharmacovigilance programs, because environmental and ethnic factors vary across locations.     

Calcifying odontogenic cysts: A 20-year retrospective clinical and radiological review

Objective:Calcifying odontogenic cysts (COCs) exhibit diverse clinical behaviours and may be associated with other benign odontogenic tumours. In this study, the clinical and radiological features of COCs were analysed according to subtypes based on the classification by Praetorius et al. Emphasis was placed on cases exhibiting atypical or aggressive radiological appearances. This information may assist the clinician to better understand the radiological spectrum of COCs.Methods:Histologically confirmed cases of COCs were retrospectively reviewed in a 20-year period from three tertiary institutions. The following clinical information was reviewed: patient demographics, main complaint, clinical duration, anatomical site and detailed radiological features.Results:Twenty-seven cases of COCs were included in the study. Asymptomatic swelling was the main clinical presentation with infrequent reports of associated pain. COCs had an anterior mandibular predilection. Well-demarcated borders were seen in all cases with isolated cases showing focal areas with loss of demarcation. Unilocular lesions were more common than multilocular variants. Internal calcifications were frequent and six cases presented with associated odontomas. Maxillary COCs resulted in the displacement of the maxillary sinus and/or nasal cavity walls. Radiological signs of aggression, including cortical destruction, were noted in a few cases.Conclusion:Given the fact that COCs can present with a spectrum of clinical behaviours and radiological presentations, the academic debate regarding the cystic versus neoplastic nature of the entity is justifiable. The cases in the current sample presented with diverse presentations, ranging from indolent to lesions with significant growth and aggression.     

Stress and Hypothermia in Mice in A Nose-Only Cigarette Smoke Exposure System

In nose-only exposure systems, animals need to be restrained inside a tube, which leads to stress. Stress is known to cause hyperthermia in rodents. Chronically repeated episodes of hyperthermia could be detrimental to animal health and influence results of nose-only exposure studies. Therefore we investigated whether hyperthermia occurred in male C57BL/6J mice that were restrained for increasing lengths of time, using nosepieces held at room temperature, preheated at 37°C, or thermostat controlled at different temperatures, with and without exposure to different concentrations of cigarette smoke. Body temperature, body weight, plasma corticosterone levels, and adrenal weights were recorded. Restraint using nosepieces at room temperature caused a time-dependent decrease in body temperature, which could be reversed by preheating the nosepieces to 37°C. Cigarette smoke dose-dependently caused an additional decrease, which was counteracted by controlling nosepiece temperature at 38°C. During 3 mo of exposure using heated nosepieces, Δ body temperature remained constant. Body weight gain did not differ between smoke-exposed and room air-breathing animals exposed using either heated or room-temperature nosepieces, but both groups gained significantly less weight, while adrenal weights were significantly and similarly increased, when compared to unrestrained littermates. Plasma corticosterone levels did not differ between the three groups. In conclusion, during restraint in nose-only exposure tubes with room temperature metal nosepieces, mice suffer a pronounced hypothermia. Preventing this by heating the nosepieces does not reduce the stress experienced by the animals.