Impairment of chemoattractant-stimulated hexose uptake in neonatal neutrophils

Neonatal neutrophils (polymorphonuclear leukocytes [PMN]) exhibit a well-documented deficiency in chemotaxis, the nature of which has not been fully elucidated. To determine whether impaired ability of neonatal PMN to increase hexose uptake in response to chemoattractants could contribute to this defect, we compared uptake of 2-deoxy-D- glucose (2-DOG) in stimulated versus resting PMN from neonates (cord blood) and healthy adults. Compared with unstimulated values; N-formyl- methionyl-leucyl-phenylalanine (fMLP) (optimal at 10 nmol/L) caused a threefold to fourfold increase in 2-DOG uptake by adult PMN. Unstimulated 2-DOG uptake by neonatal PMN was slightly higher than that for adult cells, but fMLP caused only a minimal (less than twofold) increase, and optimally stimulated uptake was significantly lower than for adult PMN (P < .01 for adult versus neonatal stimulated uptake; n = 6). Findings were similar when ionomycin or C5a was used as a stimulus. Optimal fMLP stimulation of adult PMN was associated with a marked decrease in the Km for 2-DOG uptake, from 0.74 +/- 0.11 to 0.23 +/- 0.03 mmol/L (delta Km = -0.51 +/- 0.12 mmol/L; n = 6). In contrast, there was relatively little fMLP-induced change in the Km for uptake of 2-DOG by neonatal PMN (from 0.44 +/- 0.04 mmol/L to 0.32 +/- 0.019 mmol/L n = 6); delta Km = -0.12 +/- 0.04 mmol/L; P = .011 for adult versus neonatal delta Km. Stimulation with fMLP was not accompanied by a significant change in the Vmax for 2-DOG uptake with either adult or neonatal PMN, and the respective values for Vmax were similar. We conclude that the chemoattractant-induced increase in hexose uptake by PMN is deficient in neonates compared with adults and that this deficiency involves mechanisms that determine the Km for this process. This impairment may contribute to defective chemotaxis in neonatal PMN.     

Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety

Background and purpose:

Thrombus formation is commonly associated with pulmonary arterial hypertension (PAH). Thrombin may thus play an important role in the pathogenesis and pathophysiology of PAH. Hence, we investigated the contractile effects of thrombin and its mechanism in pulmonary artery.

Experimental approach:

The cytosolic Ca²⁺ concentrations ([Ca²⁺]_i), 20 kDa myosin light chain (MLC20) phosphorylation and tension development were evaluated using the isolated porcine pulmonary artery.

Key results:

Thrombin induced a sustained contraction in endothelium-denuded strips obtained from different sites of a pulmonary artery, ranging from the main pulmonary artery to the intrapulmonary artery. In the presence of endothelium, thrombin induced a transient relaxation. The contractile effect of thrombin was abolished by either a protease inhibitor or a proteinase-activated receptor 1 (PAR₁) antagonist, while it was mimicked by PAR₁-activating peptide (PAR₁AP), but not PAR₄AP. The thrombin-induced contraction was associated with a small elevation of [Ca²⁺]_i and an increase in MLC20 phosphorylation. Thrombin and PAR₁AP induced a greater increase in tension for a given [Ca²⁺]_i elevation than that obtained with high K⁺-depolarization. They also induced a contraction at a fixed Ca²⁺ concentration in α-toxin-permeabilized preparations.

Conclusions and implications:

The present study revealed a unique property of the pulmonary artery. In contrast to normal arteries of the systemic circulation, thrombin induces a sustained contraction in the normal pulmonary artery, by activating PAR₁ and thereby increasing the sensitivity of the myofilament to Ca²⁺. This responsiveness of the pulmonary artery to thrombin may therefore contribute to the pathogenesis and pathophysiology of PAH.     

肩周炎20例的综合疗效

1 临床资料 2004-04以来收治肩周炎20(男8,女10)例;年龄42～55岁19例,70岁1例;右侧16例,左侧4例;病史7 d～1.5 a,均无外伤史,患侧肩部活动受限,手臂上提小于40°,肩关节外展,外旋活动受限,不能自如穿、脱衣和梳理头发及摸背. 分型与药物组方见表1.     

Family and home correlates of children's physical activity in a multi-ethnic population: the cross-sectional child heart and health study in england (CHASE)

Background  

The influence of the family and home environment on childhood physical activity (PA) and whether this differs between ethnic groups remains uncertain. This paper investigates associations between family and home factors and childhood PA in a multi-ethnic population and explores whether associations differ between ethnic groups.     

Once-daily therapy for streptococcal pharyngitis with amoxicillin

OBJECTIVE: An orally administered antimicrobial regimen for the treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis given once rather than multiple times each day would be more convenient and might result in improved patient compliance. The purpose of this study was to evaluate the effectiveness of once-daily amoxicillin in the treatment of GABHS pharyngitis. PATIENTS: Children presenting to a private pediatric office with GABHS pharyngitis. DESIGN: Patients were randomly assigned to receive orally either amoxicillin (750 mg once daily) or penicillin V (250 mg three times a day) for 10 days. Compliance was monitored by urine antimicrobial activity. OUTCOMES: Outcomes were measured by impact on the clinical course, eradication of GABHS within 18 to 24 hours, and bacteriologic treatment failure rate as determined by follow-up throat cultures 4 to 6 and 14 to 21 days after completing therapy. GABHS isolates were serotyped to distinguish bacteriologic treatment failures (same serotype as initial throat culture) from new acquisitions (different serotypes). RESULTS: During the 16 months of this study, 152 children between 4 and 18 years of age (mean, 9.9 years) were enrolled; 79 children were randomly assigned to receive once-daily amoxicillin and 73 were assigned to receive penicillin V three times a day. The children in the two treatment groups were comparable with respect to age, duration of illness before initiation of therapy, compliance, and signs and symptoms at presentation. There was no significant difference in the clinical or bacteriologic responses of the patients in the two treatment groups at the 18- to 24-hour follow-up visit. Bacteriologic treatment failures occurred in 4 (5%) of the 79 patients in the amoxicillin group and in 8 (11%) of the 73 patients in the penicillin V group. CONCLUSIONS: These data demonstrate that once-daily amoxicillin therapy is as effective as penicillin V therapy given three times a day for the treatment of GABHS pharyngitis, and if confirmed by additional investigations, once-daily amoxicillin therapy could become an alternative regimen for the treatment of this disease.     

Localization of matrix metalloproteinases (MMPs‐2, 8, 9 and 20) in normal and carious dentine

Background: Dentine matrix metalloproteinases (MMPs) may participate in the destruction of dentine following demineralization by bacterial acids. This study investigated the localization of MMPs in carious dentine. Methods: Frozen sections of dentine caries were prepared without demineralization and immersed in monoclonal antibody against MMP‐2, ‐8, ‐9 and ‐20. The sections were labelled by IgG conjugated with gold colloidal particles, and observed under FE‐SEM. Labelling indexes (number of gold particles/μm²) of outer and inner carious dentine, respectively, with and without bacterial infection, were compared with that of normal dentine. Results: MMP‐2 was distributed in both carious and normal dentine; the level of MMP‐2 showed no significant difference among the outer caries, inner caries, and normal dentine. The labelling indexes of MMP‐8 and MMP‐9 both significantly decreased at the inner carious dentine compared with the level of normal dentine, but intensified again at the outer caries region. The labelling index of MMP‐20 was the highest at normal dentine. Conclusions: The localization of MMPs was visibly detected using immunogold labelling. The localization of MMP‐2 showed no significant difference among the three regions, while MMP‐8 and MMP‐9 showed significant reduction at the inner caries layer, and MMP‐20 reduced toward the outer caries.     

REVIEW ARTICLE: Paediatric nasopharyngeal rhabdomyosarcoma: A case series and literature review

Rhabdomyosarcoma (RMS) is the most common soft tissue tumour in children, with the head and neck region accounting for 35–40% of cases. Nasopharyngeal RMSs tend to grow rapidly and invade adjacent structures. Both the Intergroup Rhabdomyosarcoma Studies and the European Studies have established that the ideal management of this disease is multimodal, using a combination of surgery, chemotherapy and radiotherapy. This case series examines the role of radiotherapy in the management of paediatric nasopharyngeal RMSs, with particular reference to long-term morbidity and disease-free survival. The cases of five children with nasopharyngeal RMS were reviewed and a systematic review of the literature contained in the PubMed databases was conducted to establish 24 individually detailed cases. Management in all patients was multimodal, using a combination of chemotherapy, radiotherapy as well as surgery. External beam radiotherapy is an integral component of treatment for nasopharyngeal RMSs. With more patients surviving for longer periods, more long-term sequelae of radiotherapy have been reported. Complications include sensorineural deafness, endocrine manifestations following radiation of the pituitary gland, cranial nerve palsies, second malignancies within the radiation field, cataract formation, retinopathy and growth disturbance. Morbidity from radiotherapy may be considerable and depends on the field and dose of radiation. Current advances in radiotherapy are aimed at improving the rate of tumour control and reducing such complications. Recent improvements in imaging and conformal techniques have the potential to reduce the morbidity associated with radiotherapy in this cohort.