In vivo and in vitro studies of the site of inhibitory action of omeprazole on adrenocortical steroidogenesis

Summary The site of omeprazole inhibition of adrenal steroidogenesis has been sought in vivo by analyzing the patterns of urinary steroid metabolite excretion after 6 days of treatment with placebo/omeprazole.Excretion rates of androsterone, aetiocholanolone, dehydroepiandrosterone, 11 hydroxyandrosterone, tetrahydrocortisone, tetrahydrocortisol and cortolone were reduced, indicating a block at an early step in steroidogenesis, possibly cholesterol side-chain cleavage. In vitro studies have confirmed this finding by measuring conversion of added precursors to cortisol in isolated bovine adrenocortical cells. Cortisol synthesis from added 20 hydroxycholesterol was inhibited by 83% in the presence of 100 µg omeprazole/ml. Conversion from pregnenolone and progesterone and their 17 hydroxylated derivatives was inhibited by 20–40% whereas cortisol production from added 11 deoxycortisol was not affected.These data suggest that omeprazole primarily inhibits cholesterol cleavage and does not inhibit 3 hydroxysteroid dehydrogenase, 17 hydroxylase or 11 hydroxylation; 21 hydroxylase activity may be marginally attenuated.     

Effect of moderate exercise on salivary immunoglobulin A and infection risk in humans

The incidence of upper respiratory tract infections (URTI) and salivary immunoglobulin A concentrations [IgA_s] of nine individuals were examined during 12 weeks of moderate exercise training, and compared to ten sedentary controls. Changes in maximal oxygen uptake were assessed at initial, mid-point and final evaluations (T1–3), while changes in [IgA_s] and salivary immunoglobulin concentration-salivary albumin concentration ratio ([IgA_s]:[Alb_s]) were monitored at T1 and T3. During the 12 week period, symptoms of URTI were self-recorded daily. During the period of training the level of fitness significantly increased (P<0.05) in the exercise group. The number of days recording symptoms of influenza, but not of cold, and total light URTI symptoms was significantly reduced in the exercise group during the last weeks of training. A significant increase in [IgA_s] and in [IgA_s]:[Alb_s] was found in the exercise group after training. Both [IgA_s] and [IgA_s]:[Alb_s] were significantly related to the number of days showing symptoms of influenza (P<0.01) and the total number of days of sickness (P<0.05). These data provide quantitative support for the belief that regular, moderate exercise results in an increased [IgA_s] at rest and [IgA_s]:[Alb_s], which may contribute to a decreased risk of infection. Electronic Publication     

Childcare as a stabilizing influence on HPA axis functioning: a reevaluation of maternal occupational patterns and familial relations

The influence of family relations, maternal occupational characteristics, and childcare1The UK terms "childcare," childcare centres' and "nurseries" are used throughout this paper to define group care for children prior to starting their first year of formal schooling at age 4 years and are used synonymously with the American terms "day-care" and "preschool." This form of group care is provided in a formal setting, outside the family home and excludes "childminding" (i.e., childcare that may be group based and offered at the home of the care provider/childminder). In the UK, this form of childcare is offered from zero to 4 years old. Children are separated according to their age into small groups usually consisting of 10-15 children. In the present study, all children were in the preschool-aged group (3-4 years old). Where childcare of a different or more generic form is referred to, then this has been made clear in the context or stated in the text. utilization on preschool children's cortisol production were investigated in 56 mother-child dyads. Family characteristics and maternal employment, childcare and child temperament were reported by mothers. Morning and evening levels of children's salivary cortisol were obtained. Children in highly expressive or reserved families exhibited higher cortisol levels compared to children in moderately expressive families. Elevated levels of cortisol were detected in children of mothers reporting low levels of job role quality or high levels of emotional exhaustion. Frequent childcare use was found to protect children against the physiological effects of low maternal job role quality and emotional exhaustion. Findings underscore the pervasive role of the family as set within an external support system and highlight the potential physiological impact of these interacting contexts for children. Further research is needed to fully understand current findings and to develop appropriate psycho-physiological interventions.     

The value of fine-needle aspiration biopsy in the cytodiagnosis of salivary gland lesions

Fine-needle aspiration cytology (FNAC) was performed on 195 cases of salivary gland lesions. The smears were technically adequate in 178 cases. Tissue examination was available for subsequent histocytologic correlation in 57 cases. The cytodiagnosis included inflammatory lesions (59) and benign (68) and malignant (51) tumors (total, 119). The accuracy of cytodiagnosis was 87.7% with a sensitivity of 80.9% and a specificity of 94.3%. Exact histologic typing was possible in 61.9% of the malignant tumors. Mucoepidermoid tumors and cellular-atypical pleomorphic adenoma posed difficulties in cytodiagnosis.     

Immunohistochemical and ultrastructural correlates of muscle-actin expression in pleomorphic adenomas and myoepitheliomas based on comparison of formalin and methanol fixation

Summary The degree and range of differentiation of the cells referred to as myoepithelial-like in pleomorphic adenomas and the tumour cells of myoepitheliomas are not definitely established. This type of information is critical for establishing reliable diagnostic criteria, such as expression of muscle-specific actin and ultrastructural identification of myofilaments, in these and other salivary gland tumours. Pleomorphic adenomas (18) and myoepitheliomas (5), of which 10 cases were fixed only in formalin and 13 cases where tissues were fixed in both formalin and methanol/acetic acid, were studied. Each tumour and normal accompanying parotid was immunostained with two monoclonal antibodies for smooth muscle actin, HHF35 and MSA. Staining of myoepithelial cells was absent in certain samples of normal gland with both HHF35 (15%) and MSA (69%) when formalin-fixed tissue was used. Using formalin-fixed tissue from 15 pleomorphic adenomas/myoepitheliomas, 2 (14%) had focal positivity with HHF35, while 8 cases (57%) were positive with MSA. However, a certain degree of false positivity was suspected since in samples of normal parotid, both acinar and duct cells were frequently stained, particularly with MSA. With methanol/ acetic acid-fixed tissue only 4 of 13 cases (31%) were positive with either MSA or HHF35 and 2 of these only had a minor proportion of the tumour cells expressing muscle-specific actin. Using alcohol-fixed tissue, myoepithelial cells were strongly stained in all examples of normal parotid gland with both anti-actin antibodies. In 5 cases examined by electron microscopy, there was no apparent correlation between immunohistochemical results and the presence or absence of cytoplasmic filament accumulation. The results indicate considerable tumour cell heterogeneity in muscle-specific actin expression and suggest that non-luminal cells in pleomorphic adenomas and the tumour cells in myoepitheliomas may differentiate as classical myoepithelial cells, as partially differentiated (i.e. modified myoepithelial cells) or as the counterpart of basal cells present in the intra- and interlobular ducts of normal salivary gland.     

Safety of nasal budesonide in the long-term treatment of children with perennial rhinitis

BACKGROUND: Intranasal budesonide is an efficacious treatment for perennial allergic rhinitis. Long-term effects on safety, particularly in children, need further investigation. OBJECTIVE: To investigate the long-term safety of intranasal budesonide in children. METHODS: In an open trial, 78 children (5-15 years) with perennial rhinitis were treated with intranasal budesonide pressurized metered dose inhaler 200 microg twice daily (delivered daily dose 256 microg) for 12 months; 43 children stayed in the study for 12 additional months and were switched to aqueous suspension (400 microg delivered daily dose) for 6 months. Statural growth, bone age, ophthalmologic and rhinoscopic status, cortisol and biochemical analyses in blood and urine were monitored during the first and second years, and adverse events (AEs) were continuously recorded. RESULTS: No significant effects on statural growth and bone age, compared with reference values, were observed. Morning plasma cortisol and 24-h urinary cortisol were not changed during treatment. Patients reported 195 AEs, most commonly nasal dryness (30%), blood-tinged secretions (21%) and, among non-nasal AEs, headache (13%). Rhinoscopy revealed no signs of mucosal atrophy, ulceration, or candidiasis but some nasal dryness. No treatment-related ophthalmological or biochemical aberrations were found. Reduction of blood eosinophils and nasal symptom scores, compared with pre-treatment values, indicated the efficacy of budesonide treatment. CONCLUSION: Long-term treatment for 1-2 years with intranasal budesonide 256-400 microg daily in children with perennial rhinitis revealed no negative effects on growth or endogenous cortisol production. Local side-effects were mild and patient symptoms decreased.     

Maintenance of asthma control by once-daily inhaled ciclesonide in adults with persistent asthma

BACKGROUND: Inhaled corticosteroids (ICS) are recommended therapy for persistent asthma, although side effects can limit appropriate use. Ciclesonide, a novel ICS, is activated in the lung, thereby reducing systemic activity and side effects. This 12-week, double-blind, randomized, parallel-group, placebo-controlled study evaluated the efficacy and safety of ciclesonide in adults with persistent asthma. METHODS: After a 2-week baseline period in which current ICS treatment was continued, 329 patients were randomized to receive ciclesonide 160 microg (n = 107) or 640 microg (n = 112) (ex-actuator doses, equivalent to 200 and 800 microg ex-valve, respectively), or placebo (n = 110) once daily in the morning. Efficacy was monitored by asthma symptom scores, rescue medication use, morning and evening peak expiratory flow (PEF) measurements, spirometry, and probability of study completion without experiencing lack of efficacy. RESULTS: Morning PEF remained stable with either ciclesonide dose but decreased with placebo; the differences were significant (P < 0.0001) for both ciclesonide doses vs placebo. The forced expiratory volume in 1 s and forced vital capacity decreased significantly with placebo (P < 0.005), but were unchanged with ciclesonide. Lack of efficacy was significantly greater for patients switched to placebo (63%) than it was for those treated with ciclesonide 160 microg (30%) (P < 0.0001 vs placebo) or ciclesonide 640 microg (31%) (P < 0.0001 vs placebo). There were no significant differences between the two tested doses of ciclesonide with respect to efficacy and safety. Serum and 24-h urine cortisol were unaffected by ciclesonide treatment. Both doses of ciclesonide were well tolerated with no cases of oral candidiasis. CONCLUSION: Ciclesonide (160 or 640 microg) once daily in the morning effectively maintains asthma control, does not affect cortisol levels, and has an adverse event profile comparable with placebo in adults with primarily mild to moderate asthma.     

腹部良性疾病患者手术前后血清Cortisol、PRL及GH测定的临床意义

目的：探讨腹部良性疾病患者手术前后血清Cortisol、PRL、GH水平的变化,以评价不同阶段的应激情况。方法：Cortisol和PRL采用化学免疫发光法,GH采用放射免疫分析。结果：32例患者Cortisol水平在手术前24h抽血测定结果与对照组比较略有升高,但统计差异无显著性（P〉0.05）;麻醉前的血清标本测定结果则升高较为显著,与对照组比较有显著差异（P〈0.05）;术后24h的血清标本测定数值升高幅度更为明显,较对照组比较差异极为显著（P〈0.01）。PRL含量在术前24h抽血测定血清浓度也稍有上升,与对照组比较无统计学意义（P〉0.05）;上手术台后麻醉前抽取的血清标本测定结果则明显升高,与对照组比较有显著差异（P〈0.05）;术后24h的血清标本测定结果PRL水平升高更加明显（P〈0.01）。GH水平在术前24h抽血测定时与上述2项指标的情况基本相同;其余麻醉前和手术后24h的2次血标本测定统计情况亦与上2种指标大致相同（P〈0.05,P〈0.01）。结论：本文患者三项血清指标的变化证实患者存在明显的应激反应;如这种反应过度,则提醒临床应对患者实施必要的处理。     

Salivary cooling,escape reaction and heat pain in capsaicin-desensitized rats

Salivary thermolytic mechanism (weight of salivary glands, effect of desalivation on water intake and body temperature, grooming activity) as well as escape behaviour and reaction to heat pain were studied in capsaicin-desensitized and control rats exposed to various warm ambient temperatures. Body temperature of the desensitized rats increased more than the controls at all the ambient temperatures studied (32, 34 and 36°C); however, significant differences in the mechanism of salivary cooling were obtained only at 34 and 36°C. Central impairment of saliva spreading in desensitized rats seems evident. Complete surgical desalivation did not increase hyperthermia of control and desensitized animals in warm environments. Therefore other mechanisms, primarily vasodilatatory, must also be involved in the rat's thermolytic normal response. Although desensitized rats did not show a tendency to escape from the warm environment their response to heat pain was normal. In conclusion, it is suggested that heat perception in desensitized animals is impaired; however, the existence of some capsaicin-insensitive thermolytic mechanisms (prone extension of the body) cannot be excluded.Supported by the Scientific Research Council, Ministry of Health, Hungary /4-05-0303-04-2/0/ and MTA-OM-MÉM-EÜM 70.211/79