Rate-sensitive glucocorticoid feedback inhibition of adrenocorticotropin and beta-endorphin/beta-lipotropin secretion in rats

In the present study, we present physiological evidence for rate-sensitive, fast feedback inhibition of secretion of ACTH and beta-endorphin (beta END)-related peptides. We used a 2 min restraint stress to physiologically increase plasma corticosterone, then examined the plasma responses of immunoreactive ACTH and beta END plus beta-lipotropin (beta END/beta LPH) to a subsequent restraint stress. After onset of this stress, plasma corticosterone increased from 2.5-10 min at a rate of 120 nM min-1, then remained at a peak from 10-15 min. A single 2 min restraint stress produced peak plasma levels of ACTH and beta END/beta LPH 2.5 min after onset of the stress, and these plasma concentrations declined after this initial stress at rates of 2.7 and 7.4 pM min-1, respectively. Application of a second restraint stress at the time of the peak corticosterone response produced plasma ACTH and beta END/beta LPH responses similar to those after the first stress. Application of a second stress during the period of significant rate-rise of corticosterone in plasma did not result in decreased incremental responses of plasma ACTH or beta END/beta LPH. However, the rates of decline of plasma ACTH and beta END/beta LPH of 7.6 and 32 pM min-1, respectively, from peak levels, were significantly greater after this second stress applied during the period of significant increase in plasma corticosterone concentration than the corresponding rates of decline observed after the initial stress or after a subsequent stress applied at the peak of plasma corticosterone. These differences in rates of decline of plasma ACTH or beta END/beta LPH appear to reflect differences in secretion rate rather than clearance, since disappearance of [125I]ACTH1-24 was not different after an initial vs. subsequent stress. In contrast to these data from intact rats, initial and subsequent stresses did not show different rates of decline of plasma ACTH or beta END/beta LPH in adrenalectomized rats. In conclusion, the stress-induced rate rise of glucocorticoid provides a negative feedback signal which serves to terminate and limit the duration, but not the peak, of the responses of POMC-derived peptides to subsequent stress.     

The use of urinary diagnostic indices in pre-eclampsia-associated oliguria

A case is presented of severe pregnancy-induced hypertension that was complicated by oliguria and managed with the aid of a pulmonary artery catheter. This case illustrates that urinary diagnostic indices may be unreliable in predicting the etiology of oliguria. Although urinary diagnostic tests are advocated routinely as reliable in the nonobstetric literature, possible misinterpretation of these values in severe pre-eclampsia with oliguria may require confirmation with hemodynamic data obtained from a pulmonary artery catheter.     

A randomized multicenter study to determine the efficacy of activity restriction for preterm labor management in patients testing negative for fetal fibronectin.

OBJECTIVE: To assess the impact of activity restriction (AR) on the incidence of preterm birth in women treated for preterm labor testing negative for fetal fibronectin (fFN). STUDY DESIGN: Women who were diagnosed with preterm labor and tocolyzed with magnesium sulfate were concurrently screened with fFN for the purpose of subsequent management. Included were consenting patients with negative fFN, gestational age 23 0/7-33 6/7 weeks, cervical dilation < or =3 cm, and minimal vaginal bleeding. Patients were randomized to AR or no AR. Primary study outcome was incidence of preterm delivery and interval from randomization to delivery. RESULTS: A total of 73 women with negative fFN were randomized (36 with AR, 37 without AR). The overall preterm birth rate was 40%, with 44.4% of patients with AR and 35.1% of patients without AR delivering preterm, p=0.478. CONCLUSION: Maternal AR did not impact pregnancy outcome. The incidence of preterm birth in symptomatic women testing fFN negative was higher than previously reported.     

Rapidly growing breast cancer: results of a retrospective analysis with a study of prognostic factors

Between January 1977 and December 1982, 66 consecutive patients have been treated for unilateral, rapidly progressing, non metastatic breast cancer. They were divided into three groups: Group A (n = 10): tumor whom volume had increased during the 2 months before diagnosis; Group B (n = 30): inflammatory signs (erythema, skin oedema, elevated local temperature) involving less than one half of the breast; Group C (n = 26): inflammatory signs involving more than one half of the breast. All patients where managed similarly: 3 to 4 courses of chemotherapy (CMF: n = 24; AVCF: n = 42), then loco regional irradiation therapy with cobalt 60, followed by maintenance chemotherapy, only if the first chemotherapy had proved effective (CMF: n = 13; AVCF: n = 27). Nine patients with residual tumor after radiotherapy underwent mastectomy with axillary dissection. The actuarial 5 years survival for the whole group is 29%, and respectively 49%, 38% and 9% for the groups A, B and C. The median disease free intervals are 43, 29 and 12 months respectively. Fifteen prognostic factors likely to influence overall survival or disease free survival were evaluated. With univariate analysis, 8 factors were found to be of individual prognostic value: extent of initial erythema, erythema present after initial chemotherapy, erythema present after radiotherapy, non menopaused status, tumor diameter greater than 10 cms, residual breast tumor (clinical or radiographic) after maintenance chemotherapy, supra clavicular adenopathy (N3). Age at the diagnosis, type of chemotherapy, or performance of a radical mastectomy did not influence the prognosis. Multivariate analysis using the Cox-model isolated 3 factors of bad prognosis: erythema involving the whole breast at initial diagnosis, erythema present at the end of initial chemotherapy, N3.     

Synthesis of Indole-Containing 2-Thiobarbituric Acid Derivatives

The synthesis of barbituric acid derivatives containing α-phenylskatyl residues substituted at C(5) is described. The initial compound was α-phenylnorgramine, which had been previously successfully used for the alkylation of a series of CH-acids, in particular, for the synthesis of diethyl-1H-indol-3-yl(phenyl)methylmalonate. This compound has been used to obtain a series of 2-thiobarbituric acid derivatives, which are expected to possess antioxidant, membrane protector, and radioprotector properties.__________Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 1, pp. 29 – 33, January, 2005.     

Alternaria alternata NADP-dependent mannitol dehydrogenase is an important fungal allergen.

BACKGROUND: Alternaria alternata is one of the most important allergenic fungi worldwide. Mannitol dehydrogenase (MtDH) has previously been shown to be a major allergen of Cladosporium herbarum and cross-reactivity has been demonstrated for several fungal allergens. OBJECTIVE: The present study's objective was to clone the MtDH from an A. alternata cDNA library, express and purify the recombinant non-fusion protein and test its IgE-binding properties. Methods A cDNA library prepared from A. alternata hyphae and spores was screened for mannitol dehydrogenase by DNA hybridization with the radioactively labelled C. herbarum homologue as a probe. The resulting clone was sequenced and heterologously expressed in Escherichia coli as a recombinant non-fusion protein, which was purified to homogeneity and analysed for its IgE-binding capacity. RESULTS: The coding sequence of the full-length cDNA clone comprises 798 bp encoding a protein with a molecular mass of 28.6 kDa and a predicted pI of 5.88. Protein sequence analysis revealed an identity of 75% and a homology of 86% between the MtDHs of A. alternata and C. herbarum. The functional mannitol dehydrogenase was expressed in the E. coli strain BL21(DE3) transformed with the vector pMW172 and purified to homogeneity. The enzyme catalyses the NADPH-dependent conversion of d-fructose to d-mannitol. In IgE-ELISA and immunoblots, MtDH is recognized by 41% of A. alternata-allergic patients. In vivo immunoreactivity of the recombinant MtDH was verified by skin prick testing. Finally, inhibition-ELISA experiments confirmed cross-reactivity between the MtDHs of A. alternata and C. herbarum. CONCLUSION: Mannitol dehydrogenase (Alt a 8) represents an important new allergen of the ascomycete A. alternata that might be suitable for improving diagnostic and therapeutic procedures.     

Healthcare worker competencies for disaster training

Background  

Although training and education have long been accepted as integral to disaster preparedness, many currently taught practices are neither evidence-based nor standardized. The need for effective evidence-based disaster training of healthcare staff at all levels, including the development of standards and guidelines for training in the multi-disciplinary health response to major events, has been designated by the disaster response community as a high priority. We describe the application of systematic evidence-based consensus building methods to derive educational competencies and objectives in criteria-based preparedness and response relevant to all hospital healthcare workers.     

Evaluation of tissue response to MTA and Portland cement with iodoform.

OBJECTIVE: The aim of this study was to evaluate the biocompatibility of Portland cement with the addition of iodoform, compared to MTA (ProRoot). STUDY DESIGN: Eighteen Wistar albino rats were divided into 3 groups of 6 animals each. Polyethylene tubes were filled either with freshly mixed MTA or Portland cement mixed with iodoform (20% wt/wt) and implanted subcutaneously. An empty tube served as control. After 7, 30, or 60 days, the implants together with the surrounding tissues were removed in blocks. Sections were evaluated for the presence and thickness of a fibrous capsule, presence of granulation tissue, and the severity of inflammatory response. Data were submitted to nonparametric statistical analysis with individual comparisons between groups at a significance level of P < 0.05. RESULTS: There were no differences between inflammatory responses at 7 and 30 days. After 60 days from surgical removal, there was significantly more tissue reaction to the MTA and Portland cement compared to the control group. CONCLUSION: There were no significant differences regarding inflammatory responses between MTA and Portland cement with iodoform after 7, 30, or 60 days. After 60 days, the fibrous capsule around the Portland cement appeared more organized than tissue surrounding MTA implants. After 60 days, there was still a significantly increased tissue reaction to the 2 cements compared to the empty polyethylene tubes.