Histamine and tryptase modulate asthmatic airway smooth muscle GM-CSF and RANTES release.

Degranulating mast cells are increased in the airway smooth muscle (ASM) of asthmatics, where they may influence ASM function. The aim of the present study was to determine whether histamine and tryptase modulate ASM cell granulocyte-macrophage colony-stimulating factor (GM-CSF) and RANTES (regulated on activation, normal T-cell expressed and secreted) release and also to examine which receptors are involved in this release. Confluent, quiescent ASM cells from asthmatic and nonasthmatic donors were treated with histamine (1 microM-100 microM) with and without histamine receptor antagonist pre-treatment, or the protease-activated receptor (PAR)-2 agonists tryptase (0.5-5 nM) and SLIGKV (100 and 400 microM). The cells were then stimulated with interleukin (IL)-1beta and/or tumour necrosis factor (TNF)-alpha (10 ng.mL(-1)) or left unstimulated for 24 h. Release of GM-CSF and RANTES was determined by ELISA and prostaglandin (PG)E(2) measured by enzyme immunoassay. Neither histamine nor tryptase induced ASM GM-CSF or RANTES secretion. However, histamine increased IL-1beta-induced GM-CSF release and markedly reduced TNF-alpha-induced RANTES release by both asthmatic and nonasthmatic cells to a similar extent, but did not modulate PGE(2) release. All changes involved activation of the histamine H1 receptor as they were partially or fully blocked by chlorpheniramine, but not ranitidine. Tryptase, via its proteolytic activity, also potentiated GM-CSF, but not RANTES, release from asthmatic and nonasthmatic ASM cells induced by both cytokines. PAR-2 involvement in the tryptase potentiation was unlikely because SLIGKV had no effect. In conclusion, mast cells, through histamine and tryptase, may locally modulate airway smooth muscle-induced inflammation in asthma.     

Occular loiasis in a Zambian woman

Asymptomatic infection with Loa loa, an eye worm, is reported in a 32-year old Zambian woman. The patient revealed up to 28% eosinophilia but microfileraemia was not noticed. One gravid female parasite 56 X 0.56 mm, extracted from lower lid of left eye of the patient, is described. Treatment with diethylcarbamazine (DEC) extended over three weeks was successful against another parasite in tissues.     

Diagnosing abuse: a systematic review of torn frenum and other intra-oral injuries.

INTRODUCTION: A torn labial frenum is widely regarded as pathognomonic of abuse. METHODS: We systematically reviewed the evidence for this, and to define other intra-oral injuries found in physical abuse. Nine studies documented abusive torn labial frena in 27 children and 24 [corrected] were fatally abused: 22 were less than 5 years old. Only a direct blow to the face was substantiated as a mechanism of injury. RESULTS: Two studies noted accidentally torn labial frena, both from intubation. Abusive intra-oral injuries were widely distributed to the lips, gums, tongue and palate and included fractures, intrusion and extraction of the dentition, bites and contusions. CONCLUSIONS: Current literature does not support the diagnosis of abuse based on a torn labial frenum in isolation. The intra-oral hard and soft tissue should be examined in all suspected abuse cases, and a dental opinion sought where abnormalities are found.     

Corpectomy for multi-level cervical spondylosis and ossification of the posterior longitudinal ligament

The choice of a surgical approach for multi-level cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL) is still a controversial issue. While most of the surgeons are still performing decompression by laminectomy some are doing multi-level anterior decompression. Few neurosurgeons are performing decompression by corpectomy. We have treated 26 patients by median cervical corpectomy during the last 4 years. These patients were followed up for a mean period of 25 months. Twenty one (80%) patients had a good outcome, 2 patients remained unchanged and 3 expired. Review of the literature and our experience indicates that patients with CSM and OPLL should be operated by median cervical corpectomy (anterior approach).     

Cervical status as a predictor of preterm labour.

A study was conducted on 140 pregnant women at and after 28 weeks of pregnancy for finding out the relationship of cervical length and position with onset of preterm labour. Incidence of preterm labour was significantly higher (p < 0.001) in women with central position of cervix (54.67%) than that with posterior position of cervix (10.77%). Onset of preterm delivery was closely related to cervical length of 2.5 cm or less irrespective of central (82.75%) or posterior (20%) position of cervix (p < 0.001).     

Comparative evaluation of commonly used laboratory tests for post-mortem diagnosis of rabies

Animal brain samples received at WHO Collaborating Centre laboratory at National Institute of Communicable Diseases (NICD) during the years 1991-2002 were tested by Seller's stain, Fluorescent Antibody Test (FAT) and Mouse Innoculation Test (MIT) as methods of rabies diagnosis. Negri bodies on Seller's staining could be detected in 52.5% of MIT positive brains, the concordance of this test with MIT was found to be 77.8%. FAT was positive in 91.5% of MIT positive brains, though it showed concordance of 95.7% with MIT results in the total samples. 12.2% of the samples were found positive by FAT of which 1/3rd also showed the presence of Negri bodies when MIT was negative i.e. showing that the virus is present in inactivated form. Thus emphasizing the need for timely and proper collection and transportation of specimens for testing. Seller's stain and FAT give reliable diagnosis of rabies in the brain samples in majority of the cases. MIT being time-intensive test, is of academic value only in decision making as regards initiation of Post Exposure Treatment (PET), it is recommended that in cases where Seller's stain and FAT have yielded negative results the decision to initiate PET should give due consideration to the nature and circumstances of the animal bite and other epidemiological features.     

Segregation of human immunodeficiency virus type 1 subtypes by risk factor in Australia

The aim of this study was to determine which human immunodeficiency virus type 1 (HIV-1) subtypes were circulating in Australia and to correlate the subtypes with risk factors associated with the acquisition of HIV-1 infection. DNA was extracted from peripheral blood mononuclear cells, and HIV-1 env genes were amplified and subtyped using heteroduplex mobility analysis, with selected samples sequenced and phylogenetic analysis performed. The HIV-1 env subtypes were determined for 141 samples, of which 40 were from female patients and 101 were from male patients; 13 samples were from children. Forty-seven patients were infected by homosexual or bisexual contact, 46 were infected through heterosexual contact, 21 were infected from injecting drug use (IDU), 13 were infected by vertical transmission, 8 were infected from nosocomial exposure, and 6 were infected by other modes of transmission, including exposure to blood products, ritualistic practices, and two cases of intrafamilial transmission. Five subtypes were detected; B (n = 104), A (n = 5), C (n = 17), E (CRF01_AE; n = 13), and G (n = 2). Subtype B predominated in HIV-1 acquired homosexually (94% of cases) and by IDU (100%), whereas non-subtype B infections were mostly seen in heterosexually (57%) or vertically (22%) acquired HIV-1 infections and were usually imported from Africa and Asia. Subtype B strains of group M viruses predominate in Australia in HIV-1 transmitted by homosexual or bisexual contact and IDU. However, non-B subtypes have been introduced, mostly acquired via heterosexual contact.     

Cytokines: the yin and yang of vitiligo pathogenesis

Introduction: Dysregulation of melanocyte function is associated with vitiligo, an idiopathic autoimmune hypopigmentary skin disorder, caused by the selective destruction of melanocytes. Cytokines, the key mediators of immune response, which are pivotal in maintaining immune homeostasis, are crucial in vitiligo pathogenesis. Several studies indicate that there is an imbalance between pro- and anti-inflammatory cytokines in the skin and serum of vitiligo patients.

Areas covered: In this comprehensive review, we have summarized the correlation of cytokine imbalance and vitiligo pathogenesis, its role in melanocyte biology, and its impact on vitiligo treatment. We have integrated various published reports on the levels of major cytokines from skin and serum samples of vitiligo patients. We have also discussed the role of endoplasmic reticulum and oxidative stress on cytokine imbalance and vice versa leading to destruction of melanocytes.

Expert commentary: The review reflects that dysregulation of cytokines is multifactorial, ranging from genetic predisposition to altered protein expression relevant to vitiligo pathogenesis. We emphasize that cytokine imbalance in systemic and skin microenvironment plays a crucial role in vitiligo pathogenesis and has promising potential as therapeutic targets for vitiligo.