Ethanol Modulates the Hormone Secretory Responses Induced by Epidermal Growth Factor in Choriocarcinoma Cells

Analysis of clinical data has implicated ethanol (EtOH) as an embryotoxic agent and as an agent that disrupts normal placental structure and function. Because epidermal growth factor (EGF) is an important regulator of placental function, we have studied the effects of EtOH on EGF-induced hormone secretion using JEG-3 choriocarcinoma cells that serve as a model for trophoblast cells. EtOH at physiological (5-100 m m ) concentrations modulated effects of EGF in a time and dose-dependent manner. EGF-induced P₄ secretion was increased by 20–100 mM EtOH after a 2-day pretreatment of cells with EtOH, but not after a 6-day pretreatment. Preincubation with 50 mM EtOH doubled the P₄ responses to 50 and 100 ng/ml EGF. Although a 2- or 4-day preincubation of cells with 10–50 mM EtOH increased the secretion of E₂ in response to 20 ng/ml EGF, a 6-day preincubation inhibited the secretory response to EGF. Pretreatment of cells with 10–50 m m , but not 100 m m EtOH for 2 to 6 days enhanced the human chorionic gonadotropin (hCG) secretory response to EGF. At 50 mm EtOH, the secretion of hCG in response to EGF was increased 2-fold. EtOH also increased basal hCG secretion in a dose-dependent manner between 10–50 m m EtOH. These results suggest that EtOH may modulate EGF-stimulated hormone secretion from cells of placental origin. Such alterations, if they occur in vivo, may impact on the function of the placenta and could potentially explain the pathophysiology of alcohol toxicity during pregnancy.     

Common misconceptions about 5-aminosalicylates and thiopurines in inflammatory bowel disease

Misconceptions are common in the care of patients with inflammatory bowel disease(IBD).In this paper,we state the most commonly found misconceptions in clinical practice and deal with the use of 5-aminosalicylates and thiopurines,to review the related scientificevidence,and make appropriate recommendations.Prevention of errors needs knowledge to avoid making such errors through ignorance.However,the amount of knowledge is increasing so quickly that one new danger is an overabundance of information.IBD is a ...     

Acute onset autoimmune hepatitis: Clinical presentation and treatment outcomes

Introduction and aimAutoimmune hepatitis (AIH) may present acutely, which can rapidly progress to fulminant type. This pattern has been described worldwide but is generally under-reported. We aim to describe the clinical presentation and treatment outcomes of patients with acute onset AIH.Materials and methodsA multicenter retrospective cohort study of patients with acute onset AIH. Clinical, biochemical, and histological data were analyzed and the outcomes were reported.ResultsSeventy patients were included. The mean age was 33.8 ± 1.5 years and 58.6% were female. Upon initial presentation, 94% had jaundice, 44% had fatigue, 31% had pruritus, and 29% had abdominal pain. Biochemical analysis revealed elevated alanine transaminase (733 ± 463.6), aspartate transaminase (699 ± 423), and total bilirubin (210 ± 181.8). Antinuclear antibody (ANA) was positive in 61% of patients, anti-smooth muscle antibody (ASMA) in 69%, and both in 31%; immunoglobulin G (IgG) was elevated in 86% of patients. Advanced fibrosis was found in 39%. Complete remission was achieved in 74.3%, two patients required liver transplants and six died. No specific biomarkers were identified as predictive of remission; however, advanced age was associated with poor prognosis.ConclusionAcute onset AIH is a disease that requires early diagnosis and management. We confirmed that elevated transaminases are the hallmark of biochemical presentation of acute AIH. High IgG, ANA and ASMA are typically present in such patients upon presentation, however, their absence does not totally exclude the diagnosis. Initial response to treatment was excellent; however, the long-term mortality was higher than the general patient population.     

Effect of Age and Early Intervention with a Systemic Steroid,Intravenous Immunoglobulin or Amniotic Membrane Transplantation on the Ocular Outcomes of Patients with Stevens-Johnson Syndrome

Purpose

This retrospective observational case series of fifty-one consecutive patients referred to the eye clinic with acute-stage Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) from 1995 to 2011 examines the effect of early treatment with a systemic corticosteroid or intravenous immunoglobulin (IVIG) on the ocular outcomes in patients with SJS or TEN.

Methods

All patients were classified by age (≤18 years vs. >18 years) and analyzed by treatment modality and early intervention with systemic corticosteroids (≤5 days), IVIG (≤6 days), or amniotic membrane graft transplantation (AMT) (≤15 days). The main outcomes were best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (logMAR) and ocular involvement scores (OIS, 0-12), which were calculated based on the presence of superficial punctate keratitis, epithelial defect, conjunctivalization, neovascularization, corneal opacity, keratinization, hyperemia, symblepharon, trichiasis, mucocutaneous junction involvement, meibomian gland involvement, and punctal damage.

Results

The mean logMAR and OIS scores at the initial visit were not significantly different in the pediatric group (logMAR = 0.44, OIS = 2.76, n = 17) or the adult group (logMAR = 0.60, OIS = 2.21, n = 34). At the final follow-up, the logMAR and OIS had improved significantly in the adult group (p = 0.0002, p = 0.023, respectively), but not in the pediatric group. Early intervention with IVIG or corticosteroids significantly improved the mean BCVA and OIS in the adult group (p = 0.043 and p = 0.024, respectively for IVIG; p = 0.002 and p = 0.034, respectively for corticosteroid). AMT was found to be associated with a significantly improved BCVA or OIS in the late treatment group or the group with a better initial OIS (p = 0.043 and p = 0.043, respectively for BCVA; p = 0.042 and p = 0.041, respectively for OIS).

Conclusions

Our findings suggest that patients with SJS or TEN who are aged 18 years or less have poorer ocular outcomes than older patients and that early treatment with steroid or immunoglobulin therapy improves ocular outcomes.     

Tuberculosis in patients with systemic rheumatic or pulmonary diseases treated with glucocorticosteroids and the preventive role of isoniazid: a review of the available evidence

Development of tuberculosis (TB) is a concern in patients who receive glucocorticosteroids for the treatment of chronic rheumatic or pulmonary diseases. However, the incidence of development of TB in such patients and the prophylactic role of isoniazid (INH) are unclear. We evaluated the available evidence from 20 relevant prospective and retrospective cohort and case–control studies identified in the PubMed and Cochrane databases. The frequency of development of TB in the populations studied varied from 0% to 13.8%. This figure was low in studies performed in countries with a low incidence of TB (0% in the USA and Greece, 0.6% in France and 1.35% in Spain). In contrast, the frequency of development of TB in the studied cohorts was high in studies performed in countries with a moderate to high incidence of TB (from 2.5% in South Korea to 13.8% in The Philippines). Isoniazid prophylaxis (INHP) was found to decrease the incidence of development of TB in two of four studies that examined this intervention. The available evidence suggests that patients who receive steroids for the treatment of chronic rheumatic or pulmonary diseases and who live in countries with a high incidence of TB have a high risk of development of TB in contrast to patients who live in countries with a low incidence of the infection. However, the role of INHP even for patients living in countries where TB is endemic is unclear because the effectiveness of INH in preventing TB development in such patients is not well established and there are cost-effectiveness and safety issues.     

Natural and gonadotropin-induced ovarian activity in tigers (Panthera tigris) assessed by fecal steroid analyses

Fecal samples were collected from female tigers (n = 17) to compare endocrine patterns associated with natural ovarian activity with those after chorionic gonadotropin ovulation induction and artificial insemination (AI). Baseline fecal estradiol concentrations were 65.77 +/- 3.61 ng/g with estrual peaks of 167.39 +/- 9.92 ng/g and an anovulatory cycle length of 17.96 +/- 0.70 days. Peak fecal estradiol was higher when females were housed with a male for breeding (262.30 +/- 41.43 vs. 165.30 +/- 3.67 ng/g; P < 0.05). The majority of animals showed some seasonal differences in fecal estradiol however, patterns were inconsistent. Fecal progestagens increased only after breeding confirming tigers are primarily induced ovulators. The non-pregnant luteal phase was 34.50 +/- 1.85 days in duration. In pregnant tigers, fecal progestagens remained elevated for 108 days until parturition and the diagnosis of pregnancy was possible based on the elevated fecal progestagens after 35 days of gestation. Tigers were administered equine chorionic gonadotropin (eCG) to stimulate follicular growth and human chorionic gonadotropin (hCG) to induce ovulation prior to AI [200 IU eCG/100 IU hCG (n = 5); 400 IU eCG/200 IU hCG (n = 2); 500 IU eCG/100 IU hCG (n = 2); 1000 IU eCG/750 IU hCG (n = 11); 1000 IU eCG/1000 IU hCG (n = 4)]. None of the tigers subjected to AI became pregnant (n = 9). Fecal endocrine patterns in gonadotropin-stimulated tigers were considerably different from those observed in naturally bred tigers. In particular, fecal estradiol concentrations were higher than those observed during natural estrus and remained elevated for longer periods of time in tigers administered the higher doses of gonadotropins typically used in conjunction with AI in this species. These abnormal endocrine patterns may help explain the poor success rate of AI in this species.     

Seasonal and altitudinal effects on glucocorticoid metabolites in a wild primate (Theropithecus gelada)

Behavioral ecologists are increasingly adopting sophisticated non-invasive methods for measuring glucocorticoids from “excreta” because samples are easy to collect, animals are left undisturbed, and measures may be more reflective of external events than serum samples. Some of the most common predictors for hormone profiles in wild animals are seasonal changes in ecology and behavior. For example, we might expect baseline glucocorticoid levels to track changes in food availability or other seasonal stressors such as unusually high or low temperatures. Geladas (Theropithecus gelada) are one of the few non-human primates that live at extremely high altitudes where nighttime temperatures often dip below freezing. However, the physiological effects of this relatively inhospitable environment have never been examined in this species. Here we validate a “field-friendly” method of hormone extraction from gelada feces and demonstrate that this method can be used to detect seasonal and altitudinal differences in glucocorticoid metabolites for this species. We use two years of climatological and hormonal data from a wild population of geladas to test the hypothesis that geladas exhibit elevated glucocorticoids under environmentally “challenging” conditions — mainly, when temperatures and rainfall are low and altitude is high. Our results indicate that cold temperatures and high altitude predicted elevated glucocorticoids, but low rainfall did not. Therefore, we suggest a metabolic hypothesis (as opposed to a nutritional hypothesis) to explain this result. However, at the present time, we cannot rule out a behavioral stress hypothesis.     

来氟米特合并小剂量激素治疗难治性肾病综合征疗效观察

目的:探讨来氟米特合并小剂量激素治疗难治性肾病综合征的临床疗效.方法:将54例难治性肾病综合征患者随机分为观察组和对照组,观察组28例,给予来氟米特合并小剂量激素治疗,对照组26例给予环磷酰胺合并小剂量激素,疗程6个月.结果:总有效率观察组为89.29%(25/28)明显高于对照组73.08%(19/26)(P＜0.0...     

Comparative endocrinological and clinical effects of percutaneous estradiol and oral conjugated estrogens as replacement therapy in menopausal women

Sixty-three healthy post-menopausal women participated in the study aimed at determining the efficiency of percutaneous administration of estradiol (E₂) giving physiological plasma levels of the estrogen to provide an efficient relief of climacteric and urogenital symptoms. Among these women, 31 had previous hysterectomy and were randomly allocated to one of the two estrogen replacement therapies while, similarly, the 32 women having an uterus were randomly divided between two groups who received in addition to estrogens, micronized oral progesterone. As estrogen, women received either E₂ by percutaneous administration (Oestrogel) or oral conjugated estrogens (Premarin). With Oestrogel, serum E₂ and estrone levels were within those seen during premenopause and showed a ratio close to 1.0. Climacteric symptoms were reduced or eliminated similarly in all groups. No change was noticed on the concentration of serum angiotensinogen with Oestrogel therapy while a 2.5-fold increase was found in women receiving Premarin. As indicated by the 24-week endometrial biopsy, the progestational response induced by oral progesterone at the dose used was sufficient in twenty out of thirty-two women to cause endometrial atrophy, thus suggesting the need for higher amounts of micronized progesterone in a proportion of women. The present data also indicate that Oestrogel provides efficient relief of climacteric and urogenital symptoms without exerting any detectable effect on hepatic function while maintaining the ratio of serum E₂/E₁ at the physiological value of 1.0.