Evaluation of anti-inflammatory, anti-nociceptive, and anti-ulcerogenic activities of novel synthesized thiazolyl and pyrrolyl steroids

Developing new therapeutic agents that can overcome gastrointestinal injury and at the same time could lead to an enhanced anti‐inflammatory effect becomes an urgent need for inflammation patients. Thiazolyl and pyrrolyl steroids were synthesized via straight forward and efficient methods and their structures were established based on their correct elemental analysis and compatible IR, ¹H‐NMR, ¹³C‐NMR, and mass spectral data. The dihydrothiazolyl‐hydrazonoprogesterone 12 and the aminopyrrolylprogesterone 16a showed anti‐inflammatory, antinociceptive, and anti‐ulcerogenic activity with various intensities. Edema were significantly reduced by both doses of tested compounds (25 and 50 mg/kg) at 2, 3, and 4 h post‐carrageenan. The high dose of compound 16a was the most effective in alleviating thermal pain. Gastric mucosal lesions, caused in the rats by the administration of ethanol or indomethacin (IND), were significantly inhibited by each of the two tested compounds. These results provide a unique opportunity to develop new anti‐inflammatory drugs which devoid the ulcerogenic liabilities associated with currently marketed drugs.     

A study of some practical aspects of high temperature liquid chromatography in pharmaceutical applications

In the pharmaceutical industry fast and efficient separation techniques play an increasing role among analytical methods because the samples to be investigated grow both in complexity and number, and there is an increasing time pressure to complete the analysis. Reducing the analysis time without decreasing the efficiency is possible using higher pressures, elevated temperatures, smaller particle sizes, or a combination of these approaches. Recently developed chromatographic techniques such as the UHPLC (ultra high performance liquid chromatography) and HTLC (high temperature liquid chromatography) are highly promising in meeting these demands. In this study, high temperature liquid chromatography (HTLC) with a zirconia-based column and temperatures elevated up to 150°C was used. We investigated the chromatographic behaviour of a steroid active pharmaceutical ingredient (levonorgestrel) and its structurally related impurities as model compounds. The effect of the temperature in the range of 50-150°C and the flow-rate in the range of 0.5-3.0 ml/min, and using methanol as an organic modifier, were studied for optimisation of the separation method.     

小剂量地塞米松对体外循环心内直视手术术后恢复的影响

目的应用术后恢复质量QoR-40评分系统,探讨小剂量地塞米松对体外循环心内直视手术术后恢复的影响。方法体外循环下单瓣膜置换患者80例,随机分为地塞米松组(D组)和对照组(C组),每组40例。D组术中给予地塞米松20 mg(4 mL)、C组给予生理盐水4 mL。术后应用QoR-40对恢复质量及恶心呕吐、疲劳程度、寒战等进行评分。结果 D组在术后第1天及第2天,身体舒适、情绪状态、疼痛及总分上均优于C组(P<0.01)。D组术后第1天及第2天疲劳水平均较C组轻(P<0.05);D组恶心呕吐发生率术后2 d均低于C组(P<0.01),且前者术后第1天恶心呕吐水平显著低于后者(P<0.05)。D组术后第1天及第2天寒战比率均小于C组(P<0.01)。结论小剂量地塞米松能够明显提高体外循环心内直视手术术后恢复质量。     

A pooled analysis of FEV1 decline in COPD patients randomized to inhaled corticosteroids or placebo

BACKGROUND: There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV(1). METHODS: The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting >/= 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV(1) decline in COPD patients, and whether this relationship is modified by gender and smoking. RESULTS: There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (+/- SE) relative increase in FEV(1) of 2.42 +/- 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV(1) decline (-0.01 +/- 0.09%; p = 0.86). The initial treatment effect was dependent on smoking status and gender. Smokers who continued to smoke had a smaller increase in FEV(1) during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV(1) with ICS therapy than did male ex-smokers. CONCLUSIONS: We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV(1) among those who completed these randomized clinical trials.     

Lack of effect of corticosteroid injection at the shoulder joint on blood glucose levels in diabetic patients

The effect of systemic glucocorticosteroids on the metabolism of glucose is well known; however, there are no reports on the effect of intraarticular steroids on the metabolism of glucose in diabetic patients. Controlled or near controlled diabetic patients who have self-monitoring devices for home monitoring of blood glucose with shoulder pain were offered an intraarticular crystalloid steroid injection of 35 mg of methylprednisolone acetate (MPA) at the shoulder joint after failure of pharmacological and physical therapy. Patients were asked to record blood glucose levels before and 2 h after breakfast, lunch, and supper (six times a day) every other day during 1 week before the injection and during the day of the injection, the next day and every other day for 2 weeks after the injection. Fructosamine levels were obtained just before the injection and 2 weeks after the injection. Wilcoxon signed rank test was used to compare the mean glucose levels before with those after the injection. Paired t test was used to compare the mean fructosamine values after the injection with those before the injection. Eighteen patients completed the study. Fifteen had adhesive capsulitis. The mean glucose levels before injection were 165.5, 195.5, 184.6, 199.4, 182.8, and 200.7 mg% before and 2 h after breakfast, lunch, and supper, respectively. There was no significant change between the mean glucose values before and after meals after the injection compared to those before the injection, respectively, except on a few occasions only throughout the study period. Mean fructosamine level before injection was 279 μmol/l±49.8 compared to 275 μmol/l±50.9 after the injection (P=0.125). Intraarticular injection of MPA at the shoulder joint in diabetic patients with shoulder pain has no significant effect on blood glucose levels.     

Infection-related morbidity and mortality in patients with connective tissue diseases: a systematic review

Patients suffering from connective tissue diseases (CTDs) constitute an important subgroup of immunosuppressed patients at risk for developing serious infections. Prophylactic antibiotic administration may decrease infection-related morbidity and mortality burden in patients with CTD, though one needs first to evaluate the overall effect of infection on morbidity and mortality in such patients and the presence of adequate prognostic/risk factors for infection development. Studies focusing on infection-related morbidity and mortality in patients with CTD were reviewed. Data on disease type, therapeutic regimens used, including corticosteroid dose and method of administration as well as other immunosuppressive agents, and outcome were extracted to evaluate the existence of specific treatment patterns predisposing to infection as well as infectious disease-related morbidity and mortality in patients with CTD. Thirty-nine studies focusing on infection incidence and/or outcome in patients with CTD were identified and analyzed; the majority of the reviewed studies (20) included patients with systemic lupus erythematosus (SLE). The mortality attributed to infection was 5.2%, while the overall mortality was 20%. There were no adequate data on the specific effect patterns of corticosteroid and immunosuppressant treatment on infection risk. Pneumocystis jiroveci (carinii) pneumonia, evaluated independently, exhibited significant mortality in patients with Wegener’s granulomatosis, polymyositis/dermatomyositis, and SLE. In conclusion, infectious diseases are a major cause of mortality in patients with CTD. However, treatment-related factors predisposing to serious infections have not been adequately outlined. In addition, there are no data regarding the effect of prophylactic practices involving antibiotic administration in morbidity and mortality.     

Synthesis and anabolic/androgenic evaluation of novel 9α-fluorosteroids

3β,11β-Dihydroxy-9α-fluor-5α-androstane-17-one (2), 3β-acetoxy-9α-fluor-11β-hydroxy-5α-androstane-17-one (3), 3β-acetoxy-9α-fluor-11β,17β-dihydroxy-5α-androstane (4), 3β,17β-diacetoxy-9α-fluor-11β-hydroxy-5α-androstane (5), 3β-acetoxy-9α-fluor-11β-hydroxy-5α-androstane 17β-propionate (6), 3β-acetoxy-9α-fluor-11β-hydroxy-5α-androstane 17β-enanthate (7), 3β-acetoxy-9α-fluor-11β-hydroxy-5α-androstane 17β-isobutyrate (8) were synthesized in the present study. Compounds 2 and 8 exhibited higher anabolic activity than the rest of the synthesized compounds. The structure of all these newly synthesized compounds was confirmed by analytic spectral data (mass, ¹H NMR and ¹³C NMR).     

Medical comorbidities predict the need for colectomy for complicated and recurrent diverticulitis

Objective

The objective of this study was to identify risk factors for recurrent or complicated diverticulitis requiring colectomy.

Methods

A total of 112 patients were admitted to the West Haven Veterans Affairs Medical Center with the diagnosis of colonic diverticular disease from January 1998 to December 2006. Patients' records were assessed for demographics, past medical history, and physical and biochemical features of presentation. Student t tests, analysis of variance, and chi-square analysis were used to compare binary and categoric data.

Results

The medical records of 112 patients admitted to the West Haven Veterans Affairs hospital with the diagnosis of diverticulitis were analyzed retrospectively. A total of 97.3% were male (n = 109), with a mean age of 63.3 years, and a significant smoking history greater than 30 pack-years was present in 70.5% (n = 79) of patients. Eighty-four percent (n = 94) of patients presented with localized abdominal pain and 69.6% (n = 78) had abdominal tenderness without peritoneal signs. Computed tomography was performed in 85.7% (n = 96) of cases. A total of 23.2% (n = 26) of patients proceeded to laparotomy, with free perforation being the most common indication (38.4%, n = 12) followed by a history of 2 or more antecedent attacks of diverticulitis (23.1%, n = 6). Analysis of variance showed that serum albumin levels were significantly lower in the group undergoing colectomy compared with those who did not (3.4 vs 4.1 mg/dL; P = .016). The need for colectomy owing to complicated or recurrent attacks correlated with glucocorticoid use (P < .001) and a history of chronic obstructive pulmonary disease (P < .038), but not with diabetes mellitus, collagen vascular disease, or inflammatory bowel disease.

Conclusions

The rules regarding the treatment of diverticulitis are evolving. Comorbid conditions such as hypoalbuminemia, chronic obstructive pulmonary disease, and glucocorticoid use may predispose patients to recurrent or complicated attacks of diverticulitis requiring colectomy. Stratification and reduction of risks may reduce the overall morbidity and mortality of diverticulitis.     

Sex steroids and libido

The effects of steroidal hormones on sexual desire and motivation are a question still under debate. This paper reviews up-to-date knowledge regarding physiological imprinting and activation by endogenous hormones of central nervous system areas involved in libido during intrauterine life and puberty. The endocrine environment probably continues to play a role during fertile life and the postmenopausal period, but this effect is often overridden by psychological and social factors. The impairment of sexual interest during estrogen—progestin treatment is an infrequent but relevant side-effect whose possible underlying mechanisms are discussed. Both endocrine and psychorelational elements may interact. From the biological point of view, androgen and oxytocin level modification and loss of estrogen fluctuations have been considered, but also the history of hormone-related mood changes could be a risk factor. On the psychological side, both the profound repercussions of the contraceptive choice and consequent responsibility, as well as the high value attributed to sexual experience are probably facilitating elements in the loss of libido under treatment.