Role of mass spectrometry in steroid assays

In addition to protein hormones, steroids measurement constitutes the basis of modern endocrinology. Immunoassays have shown their limits in this field. In contrast, mass spectrometry shows an excellent sensitivity and specificity that make it the method of choice for steroids assays. The recent introduction of UHPLC-MS is a major advance which reinforces this position. In fact, mass spectrometry provides a lot of advantages such as determination of certain steroids in saliva, diagnosis of enzyme deficiencies, or measurement of molecules previously inaccessible like aldosterone. However, standardization is still needed to ensure good comparability of results between laboratories. In the future, mass spectrometry should not replace the immunoassays but rather complement it.     

Eosinophilic esophagitis: Update in diagnosis and management. Position paper by the Italian Society of Gastroenterology and Gastrointestinal Endoscopy (SIGE)

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized by symptoms related to esophageal dysfunction, as well as significant esophageal eosinophilia.The entity exists worldwide but has been most extensively studied in Western countries. However, a wide range of symptoms has been noticed such as chest pain or gastro-esophageal reflux disease-like symptoms. Upper gastro-intestinal endoscopy and esophageal biopsies are crucial for the diagnosis. Endoscopy might be normal or reveal typical patterns such as rings, furrows, exudates, edema, and stricture. Two to four biopsies should be performed both in the distal and in the proximal esophagus, and 15 eosinophils per high power field within the esophageal epithelium are the minimal threshold to diagnose eosinophilic esophagitis.Allergy testing is recommended, although its impact to orient treatment remains to be demonstrated. Eosinophilic esophagitis treatment includes medical treatment, diet and endoscopic dilation. Proton pump inhibitors are the first-line therapy as up to 50% of patients respond well to proton pump inhibitors irrespective of objective evidence of GERD. Topical viscous corticosteroids or elimination diet are the treatment of choice in case of unresponsiveness to proton pump inhibitors.     

Neuroprotective effects of testosterone on dendritic morphology following partial motoneuron depletion: Efficacy in female rats

Motoneuron loss is a significant medical problem, capable of causing severe movement disorders and even death. We have previously demonstrated that partial depletion of motoneurons induces dendritic atrophy in remaining motoneurons, with a concomitant reduction in motor activation. Treatment of male rats with testosterone attenuates the regressive changes following partial motoneuron depletion. To test whether testosterone has similar effects in females, we examined potential neuroprotective effects in motoneurons innervating muscles of the quadriceps of female rats. Motoneurons were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, some saporin-injected rats were given implants containing testosterone or left untreated. Four weeks later, surviving motoneurons were labeled with cholera toxin-conjugated HRP, and dendritic arbors were reconstructed in three dimensions. Compared to normal females, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons, and this atrophy was greatly attenuated by testosterone treatment. These findings suggest that testosterone has neuroprotective effects on morphology in both males and females, further supporting a role for testosterone as a neurotherapeutic agent in the injured nervous system.     

灯心草化学成分的研究(Ⅱ)

目的对灯心草Juncus effusus L.石油醚和醋酸乙酯提取物的化学成分进行研究。方法运用正相和反相硅胶柱层析对灯心草石油醚和醋酸乙酯提取物进行分离纯化,并用波谱技术鉴定其结构。结果从灯心草石油醚提取物分得2个甾体化合物stigmast-4-en-6β-ol-3-one(1),(24R)-stigmast-4-ene-3-one(2),从醋酸乙酯提取物分得两个二氢菲类化合物juncusol(3)和efffusol(4)。结论化合物1和2均为首次从灯心草属植物中分得。     

Serum Steroids and Success of Corticotropin Therapy in Infantile Spasms

ABSTRACT. Serum levels of 8 steroids and urinary Cortisol excretion were determined in 10 infants before and during corticotropin therapy for infantile spasms. High serum dehydroepiandrosterone-androstenedione concentration ratio distinguished the 6 infants with good therapeutic response from the 4 with poor response ( p =0.001). No such distinction was obtained directly by any of the serum steroid levels, 24-hour urinary Cortisol, or serum pregnenolone-proges-terone concentration ratio. This suggests that the therapeutic effect of corticotropin may be mediated by steroid factors other than Cortisol. Inhibition of the 3 β-hydroxysteroid dehydrogenase system in zona reticularis might be beneficial during the corticotropin therapy.     

Endogenous gonadal hormones modulate behavioral and neurochemical responses to acute and chronic cocaine administration

Recent evidence demonstrates that there are sex differences in behavioral responses to cocaine. Further, reproductive gonadal hormones (estrogen, progesterone and testosterone) have been further implicated in mediating some of the cocaine-induced alterations. To better understand sex differences and the role of gonadal hormones in cocaine-induced locomotor and stereotypic behavior, intact and gonadectomized male and female Fischer rats were randomly assigned to either chronic cocaine (15 mg/kg) or saline treatments for 14 days followed by a challenge administration (7 days after the last cocaine/saline administration). Locomotor (ambulatory and rearing) and stereotypic activities were measured on days 1, 7 and 14 as well as after withdrawal/challenge with cocaine. Overall, intact female rats consistently showed a rapid (acquired by day 7) and longer lasting (persistent through the challenge dose) sensitization for all locomotor behaviors than any of the other groups. In contrast, intact males developed sensitization of these locomotor activities only in response to chronic cocaine administration, and after withdrawal and drug challenge the sensitization to cocaine-induced locomotor activity was no longer present. In female rats, gonadectomy affected ambulatory activity but not total and rearing responses after acute, sub-acute, chronic and challenge response to cocaine. On the other hand, castrated male rats were affected in cocaine-induced ambulatory activity but not rearing activity. In intact male rats, cocaine-induced stereotypic activity was rapidly and persistently sensitized after 7 days of cocaine administration, where gonadectomized male rats developed sensitization to cocaine-induced stereotypic activity only after a challenge cocaine administration. Although cocaine induced stereotypic activity, no statistically significant differences were observed between intact and ovariectomized female rats or throughout the different lengths of cocaine administration. After a challenge of cocaine, corticosterone levels were induced in all experimental groups. Moreover, no differences in levels of benzoylecgonine, a cocaine metabolite, were observed. Similar to our previous observations after acute cocaine administration, after challenge of cocaine, an increase in progesterone and a decrease in testosterone levels were observed in intact females and males, respectively. In summary, endogenous hormones seem to be involved in the behavioral activation and development of sensitization to cocaine.     

Steroid resistant nephrotic syndrome

Steroid Resistant-Nephrotic Syndrome (NS) is a chronic, progressive disorder affecting upto 10% of all children with NS. It causes morbidity and mortality due to persistent edema, hypertension, hyperlipidemia, thrombosis and infection. Progression to renal failure was thought to be inevitable in survivors. Recent insights into the pathogenesis of the disease has identified several responsible genes and proteins. Studies have shown that long term aggressive therapy with combinations of steroids, alkylating agents and cyclosporine, cause complete or partial remission in 20–80% patients. The use of nonspecific renal protective agents such as the angiotensin converting enzyme inhibitors, angiotensin 2 receptor blockers, and anti-lipid agents retard disease progression. Although these are indications of significant improvement in outcome, further multicentre controlled studies are required to determine the optimum drugs and regimens to be used.     

The response of phimosis to local steroid application

The effectiveness of topical steroid application in relieving phimosis was studied in 63 boys treated with local application of steroid ointment to the foreskin. Betamethasone valerate 0.05% (42 patients), hydrocortisone 1% (18 patients), or hydrocortisone 2% (3 patients) was applied three times daily for 4 weeks. Thirty-seven of the patients treated with 0.05% betamethasone valerate ointment (half-strength Betnovate) showed an initial improvement and circumcision was performed on 5 non-responders. Six patients showed initial improvement but later redeveloped phimosis: they were given a further course of treatment, resulting in 2 satisfactory responses and 4 failures requiring circumcision. Two patients using 2% hydrocortisone and 16 using 1% hydrocortisone ointment showed improvement, but 2 of the latter group ultimately required circumcision. Overall, a permanent improvement was achieved in 51 of the 63 patients, with the ability to retract the foreskin after one or more treatments. The remaining 12 boys required circumcision. Local application of steroid ointment to the foreskin results in resolution of phimosis in the majority of cases, but if the foreskin has a circumferential white scar, it is slightly less likely to respond. Following cessation of steriods, phimosis redevelops in a proportion of patients. Correspondence to: S. W. Beasley     

Mycobacterium intracellulare infection of the shoulder and spine in a patient with steroid-treated systemic lupus erythematosus

Atypical mycobacterial infections of bone are rare. A patient with systemic lupus erythematosus treated with steroids developed an M. intracellulare infection of the shoulder and spine. These infections are insidious and diagnosis is difficult. Marked involvement of one joint, large effusion, or aspirated small synovial fragments suggest an atypical tuberculous joint infection.