Effect of oral and intravenous heparin tetrasaccharide on allergic airway responses: Critical role of N-sulfation

We have shown that inhaled heparin (hep) oligosaccharides attenuate allergic airway responses in sheep and that this anti-allergic activity resides in a tetrasaccharide sequence. Here we determined: (a) the anti-allergic activity of oral and intravenous hep-tetrasaccharide on allergic airway responses in the sheep model of asthma; and (b) the role of N-sulfation in mediating this anti-allergic activity. Ascaris suum-induced early (EAR) and Late (LAR) airway responses and airway hyperresponsiveness (AHR) to carbachol were measured in allergic sheep without and after treatment with different doses of oral or intravenous hep-tetrasaccharide. At doses of 0.06 mg/kg, 0.125 mg/kg, and 0.25 mg/kg, oral hep-tetrasaccharide caused a dose-dependent inhibition of EAR and LAR. Post-antigen AHR was also inhibited dose dependently. The same doses of intravenous hep-tetrasaccharide yielded comparable inhibition of EAR, LAR and AHR, confirming that orally delivered hep-tetrasaccharide has good bioavailability. The protection by hep-tetrasaccharide on EAR and LAR was dependent on N-sulfation, as N-desulfated/N-acetylated tetrasaccharide had a markedly reduced effect. However, inhibition of the post-antigen AHR was independent of N-sulfation. These results demonstrate that orally administered hep-tetrasaccharide inhibits allergic airway responses in the sheep model of asthma. Hep-tetrasaccharide has good oral bioavailability and its anti-allergic activity is critically dependent on N-sulfation of the glucosamine ring.     

Activity of the Bcl-2 family inhibitor ABT-263 in a panel of small cell lung cancer xenograft models

PURPOSE: The purpose of this study was to characterize the activity of the Bcl-2 protein family inhibitor ABT-263 in a panel of small cell lung cancer (SCLC) xenograft models. EXPERIMENTAL DESIGN: A panel of 11 SCLC xenograft models was established to evaluate the efficacy of ABT-263. Single agent activity was examined on a continuous dosing schedule in each of these models. The H146 model was used to further evaluate dose and schedule, comparison to standard cytotoxic agents, and induction of apoptosis. RESULTS: ABT-263 exhibited a range of antitumor activity, leading to complete tumor regression in several models. Significant regressions of tumors as large as 1 cc were also observed. The efficacy of ABT-263 was also quite durable; in several cases, minimal tumor regrowth was noted several weeks after the cessation of treatment. Antitumor effects were equal or superior to that of several clinically approved cytotoxic agents. Regression of large established tumors was observed through several cycles of therapy and efficacy was retained in a Pgp-1 overexpressing line. Significant efficacy was observed on several dose and therapeutic schedules and was associated with significant induction of apoptosis. CONCLUSIONS: ABT-263 is a potent, orally bioavailable inhibitor of Bcl-2 family proteins that has recently entered clinical trials. The efficacy data reported here suggest that SCLC is a promising area of clinical investigation with this agent.     

Effects of Sucrose and Trehalose on the Preservation of the Native Structure of Spray-Dried Lysozyme

Purpose. To investigate the effects of sucrose, trehalose, sucrose/dextran mixtures, and sucrose/trehalose mixtures on the preservation of the native structure of spray-dried lysozyme in the solid state. Methods. The intensity of the -helical band and the melting enthalpies (H_m ) of spray-dried lysozyme in the dried form and in aqueous solution were obtained using second derivative FTIR and differential scanning calorimetry (DSC) respectively. Results. The intensity of the -helical band and the H m of spray-dried lysozyme obtained were linearly correlated and both suggest that the stabilization of lysozyme in the dried form was excipient concentration-dependent with a close to maximum stabilization being conferred by sucrose or trehalose at a mass ratio 1–2 (sugar:enzyme). Sucrose appeared to be more effective than trehalose on a weight by weight basis whilst stabilizing effects of dextran/sucrose or trehalose/sucrose mixtures were found to be additive. Conclusion. Dehydration during spray drying was considered the main stress to the denaturation of lysozyme. A major effect of the sugars in protecting lysozyme against dehydration was attributable to hydrogen bonding between the sugar and protein molecules, which lead to an increase in the change in the negative value of the free energy between native and denatured states.     

Jaw fractures in Nigerian children: an analysis of 102 cases

OBJECTIVES: To present the prevalence and pattern of jaw fractures in children aged 15 years and below attending two hospitals serving as referral centres for facial injuries in North Eastern Nigeria. DESIGN: Retrospective Cross Sectional Study. SETTINGS: Department of Oral and Maxillofacial Surgery, University of Maiduguri Teaching Hospital, Borno State, Nigeria. SUBJECTS: One hundred and two patients with jaw fractures aged 15 years and below. MAIN OUTCOME MEASURES: Aetiological factors and pattern of jaw fractufes in children aged 15 years and below. RESULTS: We retrospectively reviewed 102 patients with jaw fractures aged 15 years and below seen over a five year period at two referral centres in Maiduguri, Northeastern Nigeria. This constituted 9.5% of the total 1,074 cases of maxillofacial injuries managed during the period. The male to female ratio was 7.5:1 and there was a male responderance in all age groups. The main causes of fractures were road traffic accident (n = 55, 53.7%) followed by falls (n = 26, 25%). Other etiological factors such as fights, sports and gunshots accounted for the remaining cases. The mandible was the commonest site with the body commonly fractured (n = 74, 72.5%). No Le Fort III fractures were identified in this study. CONCLUSION: Despite some limitations to our data, such as exclusion of patients who attended private clinics and lack of modern diagnostic methods, this report shows that there is obvious need for concern about the high prevalence of maxillofacial injuries in children caused by road traffic accidents in North Eastern Nigeria.     

Common allergens in shoe dermatitis: our experience in Lahore,Pakistan

BACKGROUND: Shoe dermatitis is a form of contact dermatitis resulting from exposure to shoes. Different chemicals, in conjunction with a hot and humid environment within the shoe, give rise to allergic or irritant dermatitis. Allergic shoe dermatitis is commonly caused by constituents of rubber, leather, adhesives, and rarely by linings and dyes. AIM: To determine the frequency of various allergens in shoe dermatitis in our patients. METHODS: One hundred and nine patients suspected of having contact dermatitis due to shoe allergens were included. All patients were patch tested with the Shoe series and European Standard series. Patches were applied on the upper back and removed after 48 h. Results were read at 48, 72, and 120 h and interpreted according to International Contact Dermatitis Research Group (ICDRG) criteria. RESULTS: Of the 119 patients, 87 (73%) reacted positively to various allergens, 48% of whom showed polysensitivity. Glues (33.6%), particularly para-tert-butylphenol formaldehyde resin (PTBP-FR) (26.9%), were the leading cause of shoe dermatitis. Other allergens were leather chemicals (26.4%), potassium dichromate (16.18%), rubber allergens (7.6%), and dyes (7.6%). Shoe scrapings tested positive in 26.3% of patients. Other common allergens were nickel sulfate (22.7%), neomycin sulfate (10.1%), and cobalt chloride (8.4%). CONCLUSIONS: Considering the diversity of allergens, all patients presenting with shoe dermatitis should be patch tested with the Shoe series and a standard series to determine the etiologic allergens.     

Perigraft to right atrial shunt by using autologous pericardium for control of bleeding in acute type A dissections

BACKGROUND: We report our experience with creating a perigraft to right atrial fistula by using autologous pericardium to control the inaccessible bleeding after aortic root repair in patients with acute type A aortic dissection. METHODS: Between 1994 and 2001, perigraft to right atrial fistula was used in 7 of 109 patients (mean age; 55 years) who underwent emergency operation for acute type A dissections. A chamber around the aortic graft was created by suturing a patch of pericardium to the right ventricular wall inferiorly, to the pulmonary artery medially, to the Teflon felt at the distal aortic anastomosis or innominate vein superiorly, and to the superior vena cava and right atrium laterally. A large stab wound was created on the medial aspect of the right atrium. The perigraft space was then closed expeditiously. RESULTS: None of these patients required reexploration for bleeding and they were discharged from the hospital without complications. The average blood and fresh frozen plasma requirement was 3.4 +/- 0.9 and 2.7 +/- 0.7, respectively. All underwent echocardiographic examination before discharge and no perigraft to right atrial shunt was detected. CONCLUSIONS: If intractable bleeding is encountered after the administration of protamine and thrombotic agents and a discrete bleeding site can not be found, then a perigraft to right atrial fistula using autologous pericardium can be created as a last resort. It provides primary and definite sternal closure and avoids the detrimental effects of a second pump run and continued bleeding.     

The effect of repeated leishmanin skin testing on the immune responses to Leishmania antigen in healthy volunteers

The leishmanin skin test (LST) is used in immunogenicity studies. The effect of multiple LSTs on immune responses was assessed. None of the volunteers converted to LST positive. IFN-gamma and IL-10 levels remained unchanged. Repetition of LST does not modulate the in vivo or in vitro immune responses to Leishmania antigen.