Exploring glycine root uptake dynamics in phosphorus and iron deficient tomato plants during the initial stages of plant development.

BACKGROUND: Phosphorus (P) and iron (Fe) deficiencies are relevant plants nutritional disorders, prompting responses such as increased root exudation to aid nutrient uptake, albeit at an energy cost. Reacquiring and reusing exudates could represent an efficient energy and nitrogen saving strategy. Hence, we investigated the impact of plant development, Fe and P deficiencies on this process. Tomato seedlings were grown hydroponically for 3 weeks in Control, -Fe, and -P conditions and sampled twice a week. We used Isotope Ratio Mass-Spectrometry to measure δ13C in roots and shoots after a 2-h exposure to 13C-labeled glycine (0, 50, or 500 µmol L-1). Plant physiology was assessed with an InfraRed Gas Analyzer and ionome with an Inductively Coupled Plasma Mass-Spectrometry. RESULTS: Glycine uptake varied with concentration, suggesting an involvement of root transporters with different substrate affinities. The uptake decreased over time, with -Fe and -P showing significantly higher values as compared to the Control. This highlights its importance during germination and in nutrient-deficient plants. Translocation to shoots declined over time in -P and Control but increased in -Fe plants, suggesting a role of Gly in the Fe xylem transport. CONCLUSIONS: Root exudates, i.e. glycine, acquisition and their subsequent shoot translocation depend on Fe and P deficiency. The present findings highlight the importance of this adaptation to nutrient deficiencies, that can potentially enhance plants fitness. A thorough comprehension of this trait holds potential significance for selecting cultivars that can better withstand abiotic stresses.

Speckle Tracking Echocardiography in Non-ST-Segment Elevation Acute Coronary Syndromes.

Non-ST-segment elevation acute coronary syndromes (NSTE-ACSs) are a group of clinical conditions characterized by acute myocardial ischemia. Conventional echocardiography is generally used to evaluate cardiac function using wall motion analysis and left ventricular ejection fraction but may be insufficient to explore all the complex features of NSTE-ACSs, which may vary substantially from patient to patient in terms of severity of ischemia and extent of involved myocardium. In the last years, speckle tracking echocardiography (STE) has become a widely available technique for the non-invasive assessment of cardiac function and has been repeatedly applied in the setting of NSTE-ACSs. In this review we summarize current evidence about the use of STE in patients with NSTE-ACSs, trying to underline advantages and limitations in comparison with conventional echocardiography for: diagnosis of NSTE-ACS, differential diagnosis, identification of high-risk patients, and prediction of outcome.

Role of external beam radiotherapy in the treatment of relapsing meningioma.

The role of radiotherapy in the treatment of relapsing meningiomas is not well established. Data of patients treated with radiotherapy for a relapsing meningioma were retrospectively analyzed. Overall survival (OS) was the primary endpoint of the analysis. Local control and acute and late toxicity rates have been also reported. From April 1986 to February 2011, 37 patients with a diagnosis of recurrent meningioma were treated. Median age was 64 years (range 36-79). A total of 18, 10, 5 and 4 patients were affected by relapsing benign, atypical, malignant meningiomas and meningiosarcomas, respectively (WHO classification). Median dose was 60 Gy (range 46-66 Gy). The median follow-up was 42 months (range 3-300 months). OS at 1, 3, 5 and 8 years was 81, 55.6, 43.9 and 25.8%, respectively (median OS 45 months). A strong statistical trend was observed toward better OS rates in patients treated with radiotherapy at first recurrence compared to those treated at the second (or more) recurrence (OS 50.5 vs. 30.8%, p=0.055). A statistical impact of the histology (WHO I vs. II, III and IV) on 5-year OS was also observed (OS 60 vs. 30%, 0 and 0%, p=0.010). Radiotherapy has been well tolerated, with no G2-4 neurological toxicity (RTOG toxicity score). Conventional radiation therapy has an important role in multidisciplinary approach in the treatment of recurrence of meningiomas. The histological type and the timing of the radiotherapy are prognostic factors in terms of survival.

The prevalence of nasal polyps and the corresponding urinary LTE4 levels in severe compared to mild and moderate asthma.

BACKGROUND: Several comorbid conditions may contribute to worsening asthma symptoms, including nasal polyps (NPs). Cysteinyl leukotrienes (Cys-LTs) play a crucial role in asthma pathophysiology, and specific receptors for CysLTs are reported as upregulated in nasal polyp tissues. The aim of the present study was to assess the prevalence of nasal polyps in severe vs. mild and moderate asthma, and to compare the corresponding levels of urinary Leukotriene E4 (LTE4). MATERIALS AND METHODS: A cohort of 386 asthma patients were studied: n=166 with mild, n=146 with moderate and n=74 severe asthma. All patients performed a nasal endoscopy and urine were collected in the morning for the quantitative LTE4 immunoenzimatic assay (Cayman Chemical, MI, USA). Intolerance to ASA was also assessed by means of a nasal provocation test with L-ASA. RESULTS: The prevalence of NPs was the following: 8 cases (4.8%) in mild; 14 (9.6%) in moderate, and 33 (44.6%) in severe asthma. Mean urinary LTE4 levels were increasing according to the disease severity. ASA-intolerance was assessed in 1 patient in mild asthma (0.6%), 14 in moderate asthma (9.6%) and 28 in severe asthma (37.8%). CONCLUSIONS: Nasal polyps represent a comorbid which is highly frequent in severe asthma. Both their prevalence and the corresponding mean LTE4 levels in urine proved in strict, direct relationship with asthma severity. In severe asthma, nasal polyps represent a condition which is associated with the highest excretion of urinary LTE4 and ASA intolerance.

The costs of treatment of early and chronic Pseudomonas aeruginosa infection in cystic fibrosis patients.

The aim of cystic fibrosis (CF) care is to improve both the life expectancy and quality of life of patients. However, rising costs and limited resources of health services must be taken into account. There are many different antibiotic strategies for therapy of Pseudomonas aeruginosa infection in CF patients. In this 5-year retrospective study we found that the cost of treatment of initial infection is considerably lower than the cost of treating chronic P. aeruginosa infections. The percentage distribution of costs of antibiotic treatment in relationship to the administration route was considerably different between outpatients and inpatients. We observed an increase in antibiotic costs with the age of the patient and the decrease in FEV(1)values. The implementation of early eradication treatment, in addition to decreasing the prevalence of patients chronically infected by P. aeruginosa, might also bring about a notable decrease in costs.

Urinary LTE4 is higher after nasal provocation test with L-ASA in bronchial than in only nasal responders.

UNLABELLED: Aspirin induced asthma (AIA) is a syndrome characterised by intolerance to acetylsalycilic acid (ASA), nasal polyps and bronchial asthma, being the metabolic shift of arachidonic acid toward the lipoxygenase pathway and hyper-production of cysteinyl-leukotrienes (cys-LTs) the current pathogenetic hypothesis. The research for both sensitive indicators and safe diagnostic tests is still attracting. Aim of the study was to compare the levels of urinary LTE4 in baseline and after Nasal Provocation Test (NPT) with L-ASA from subjects affected by aspirinin-Intolerance and characterized by only a nasal response to ASA to those from subjects with both a nasal and a bronchial response to the same challenge. METHODS: After their written consent, 74 subjects with mill to moderate AIA (16 male, mean age 45.3 years +/- 12.3 sd, mean basal FEV1 = 78.1% pred. +/- 6.2.4sd, FEV1 reversibility = 14.3% bsln +/- 2.1 ds after salbutamol 200 mcg) performed a NPT with L-ASA (total maximal dose 25 mg). Spirometry (FEV1), acoustic rinometry (nasal volume--VOL; nasal Resistance--Req; AR; TM Hood Lab., USA), and urinary LTE4 (Cayman Chemical, MI, USA, via Triturus System, Grifols, Spain) were checked in all subjects in basal conditions and 90' after NPT. STATISTICS: t test between means +/- sd, assuming p < 0.05, and linear regression between all variables considered. RESULTS: In 69 ASA-intolerant-asthmatics, mean FEV1 did not change significantly following NPT (78.7% pred. +/- 5.1 sd in baseline; 78.5% pred. +/- 4.1 sd after NPT, p = ns) even though in the presence of a significant decrease of VOL. (12.6 cm3 +/- 4.1 sd in baseline; 6.2 cm3 +/- 4.6 sd after NPT, p = 0.003); of a substantial increase in Req (0.9 cm H2O/l/min +/- 0.1 ds in baseline; 2.4 cmH2O/l/min +/- 0.2 after NPT, p = 0.04), and of urinary LTE4 excretion (333.0 pg/mg +/- 161.7 in bsln; 558.0 pg/mg +/- 171.690' after NPT with L-SA, p = 0.02). In only 5 subjects, the nasal response occurred concomitantly to a significant bronco-constriction after the NPT: mean FEV, changed from 77.9% pred. +/- 3.9 in bsln to 46.6% pred. +/- 4.3 after NPT (p < 0.001); mean VOL from 13.9 cm3 +/- 4.7 sd to 5.6 cm3 +/- 2.8 sd (p < 0.001); mean Req from 1.1 cmH2O/l/min +/- 0.2 in bsln to 2.5 cmH2O/l/min +/- 0.4 after NPT (p = 0.02) in these subjects. In ASA-intolerant bronchial responders, the severity of respiratory reactions proved related to the extent of urinary LTE4 response, which on the other hand, proved significantly higher than that observed in ASA-intolerant subjects with only nasal response and in ASA-tolerant subjects (LTE4 from 333.0 pg/mg +/- 161.7 in baseline up to 558.0 pg/mg +/- 171.6 90 min. following the NPT with L-ASA the nasal-responders, p = 0.04, but from 412.0 pg/mg +/- 102.8 in baseline up to 978.0 pg/mg +/- 108.7 after NPT in bronchial responders, p < 0.001 from baseline). CONCLUSIONS: Nasal challenge with ASA affects significantly both nasal VOL and Req, and LTE4 excretion in all ASA-intolerant subjects. During the nasal challenge, severity of respiratory reactions proves associated with the highest basal LTE4 synthesis. This feature reflects a spectrum of respiratory tract reactions where cysteinil-LTs can play a specific diagnostic role.

The therapeutic effects of inhaled long-acting beta2-adrenergics (LABA) and corticosteroids (ICS) are not affected by their inhalation sequence in moderate/persistent asthma.

UNLABELLED: Bronchial asthma is defined as "a chronic inflammatory disease of the airways involving many cells" and inhaled corticosteroids have therefore become the fundamental drugs for the long-term management of the disease. In moderate and severe persistent asthma the use of a long-acting bronchodilator is recommended in order to control symptoms and to enhance the efficacy of corticosteroids. Although not based on scientific evidence, it has been assumed that the, 2 adrenergic and the inhaled steroid should be administered in a strict inhalation sequence: the bronchodilatator first and then the steroid. The aim of the study was to assess the effects of this assumption experimentally, common indeed since long ago. MATERIALS AND METHODS: Twelve subjects with moderate-persistent asthma (7 males, aged 18-64, basal FEV1 = 65.59% pred. +/- 7.59 ds; reversibility = + 14.8% +/- 8.3 ds from baseline after Salbutamol 200mg), symptomatic despite the regular home treatment with Fluticasone p. 250mg bid and beta 2 short-acting prn for over 6 weeks, were initially treated with combined SM/FP 50/250mg bid from an unique Diskus" device, for 6 weeks. After this initial phase, the treatment continued according to a randomised, double-blind, cross-over design: all subjects received the same drugs, from two different Diskus" inhalers, and according to two different sequences of administration: 1) SM first and FP 20' later for 4 weeks, and then FP first and SM 20' later for a further 4 weeks; 2) vice versa. No wash-out period was included between these two phases of cross-over treatment. FEV1 (% pred.); morning PEF (L/min), the use of short-acting beta 2 as required (n/week); the number of awakenings at night (n/week), and the daytime asthma symptom score were measured. STATISTICS: The t paired test and anova (Duncan test) were used for statistical comparisons: a p<0.05 was accepted as the minimum level of significance. RESULTS: After the first six weeks of treatment with combined Salmeterol/Fluticasone, 50/250 mg FEV1 changed from 69.6% pred. +/- 7.59 ds to 79.8% pred. +/- 10.1 ds (p>0.005), whilst the morning PEF changed from 282.2 l/min : 64.1 ds to 333.4 l/min +/- 55.5 ds (p<0.02). Furthermore, the consumption of beta 2 adrenergic prn dropped from 4.4 (no./week) +/- 7.3 ds to 1.2 +/- 0.9 ds (p<0.001); the number of night-time awakenings decreased from 1.6 (no./week) +/- 0.2 ds to 0.2 +/- 0.3 ds (p<0.001), and the daytime symptom score changed from 3.4 +/- ds 0.8 to 1.9 +/- 0.7 ds (p<0.001). This therapeutic performance was maintained over the two subsequent 4-week periods of treatment from two distinct devices independently of the inhalation sequence. In particular, by both using salmeterol first or using fluticasone first, the therapeutic effects proved quite identical: FEV1: 80.7 % pred. +/- 9.5 ds and 80.3 +/- 7.4 ds; morning PEF: 336.5 l/min +/- 55.4 ds and 338.6 l/min +/- 67.1 ds; consumption of beta 2 adrenergic as required: 0.9 (no./week) +/- 0.6 ds and 0.9 (no./week) +/- 0.8 ds; number of awakenings: 0.3 (no./week) +/- 0.3 and 0.2 (no./week) +/- 0.3 ds; day-time/night-time symptom score: 1.7 +/- 0.5 ds and 1.8 +/- 0.6 ds, respectively (anova = ns). CONCLUSIONS: Both in terms of lung function and of clinical outcomes the efficacy of SM and FP administration proved completely independent of the particular sequence for their separate inhalation and quite superimposable to thatachieved b y their combined inhalation from an unique device.

Resistance to Passion fruit woodiness virus in Transgenic Passionflower Expressing the Virus Coat Protein Gene.

We report the use of the coat protein (CP) gene from Passion fruit woodiness virus (PWV) to produce resistant transgenic plants of yellow passion fruit. A full-length CP gene from a severe PWV isolate from the state of São Paulo, Brazil (PWV-SP) was cloned into pCAMBIA 2300 binary vector, which was further introduced into Agrobacterium tumefaciens strain EHA 105. Leaf disks were used as explants for transformation assays, e.g., 2,700 and 2,730 disks excised from plants from the Brazilian cultivars IAC-275 and IAC-277, respectively. In vitro selection was performed in kanamycin. After transferring to the elongation medium, 119 and 109 plantlets of IAC-275 and IAC-277, respectively, were recovered. Integration of the PWV CP gene was confirmed in seven of eight plants evaluated by Southern blot analysis, showing different numbers of insertional events for the CP gene. Three transgenic plants (T3, T4, and T7) expressed the expected transcript, but the 32 kDa PWV CP was detected by Western blot in only two plants (T3 and T4). The results of three successive mechanical inoculations against the transgenic plants using three PWV isolates showed that the primary transformant T2 of IAC-277 was immune to all isolates.

Montelukast 10 mg improves nasal function and nasal response to aspirin in ASA-sensitive asthmatics: a controlled study vs placebo.

UNLABELLED: Aspirin-induced asthma (AIA) is a clinical syndrome characterized by acute airway reaction to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDS). The most recent etiological hypothesises is that an overexpression of the enzyme LTC(4) synthase occurs in AIA, with the consequent production of sulfidopeptide leukotrienes (LTs). AIM: Aim of the present study was to assess the effect of Montelukast, a selective cys-LT receptor antagonist, on nasal function, nasal reactivity to ASA and blood markers of eosinophilic inflammation in mild-to-moderate AIA. MATERIAL AND METHOD: Thirty-six nonsmoker subjects with AIA (17 males, 22-52 years) performed a nasal provocation test (NPT) with lysine-aspirin (L-ASA) in baseline and after a 4-week Montelukast 10 mg or placebo treatment. Nasal function was assessed by the acoustic rhinomanometry, and they also performed a lung function test (forced expiratory volume in 1 s), and a blood sample for the eosinophil count and the eosinophil cationic protein (ECP) plasma measurements. After both treatments, all subjects repeated the NPT, the lung function, and the ECP and the eosinophil blood count. STATISTICAL ANALYSIS: t-Test was used to compare mean values +/- SD between groups, and P < 0.05 was assumed as the level for statistical significance. RESULTS: Airway patency was never affected by the NPT with L-ASA. In baseline, NPT with L-ASA precipitated a nasal reaction in all subjects, with a substantial increase in nasal resistance (calculated resistance [REQ]; from 0.89 +/- 0.18 to 2.2 +/- 0.17 cmH(2)O/l/min in group M, P < 0.001; and from 0.91 +/- 0.48 to 2.3 +/- 0.21 cmH(2)O/l/min in group P, P < 0.001); and a significant reduction in total nasal volume in at least one nostril (volume [VOL]; from 11.1 +/- 3.2 to 8.1 +/- 4.1 cm(3) in the group M, P < 0.001, and from 12.3 +/- 4.1 to 7.9 +/- 4.5 cm(3) in the group P, P < 0.001). The nasal reaction to L-ASA remained unchanged following placebo, but it was completely minimized following a 4-week treatment with Montelukast. Also nasal function, the nasal symptom score, and the markers of eosinophilic inflammation proved significantly affected and improved by the active drug only. CONCLUSIONS: Montelukast 10 mg daily for 4 weeks, but not placebo, improves nasal function and nasal response to Aspirin substantially in ASA-sensitive asthmatics.

A functionally active RARalpha nuclear receptor is expressed in retinoic acid non responsive early myeloblastic cell lines.

Although all-trans retinoic acid (ATRA) can restore the differentiation capacity of leukemic promyelocytes, early leukemic myeloblasts are conversely not responsive to ATRA induced granulocytic differentiation. To assess whether this resistance to ATRA is related to an impaired function of the Retinoic Acid Receptor alpha (RARalpha), we performed an analysis of RARalpha expression and transactivation activity, in several myeloid leukemic cell lines, representative of different types of spontaneous acute myeloid leukemias. Our results indicate that a functionally active RARalpha nuclear receptor is expressed in all the analyzed cell lines, regardless of their differentiation capacity following exposure to ATRA. The observation that ATRA treatment is able to induce the expression of retinoic acid target genes, in late- but not in early-myeloblastic leukemic cells, raises the possibility that the differentiation block of these cells is achieved through a chromatin mediated mechanism. Acetylation is apparently not involved in this process, since the histone deacetylase inhibitor trichostatin A, is not able to restore the differentiation capacity of early leukemic myeloblasts. Further investigation is needed to clarify whether myeloid transcription factors, distinct to RARalpha, play a role in the resistance of these cells to ATRA treatment.

Tolerance to lipopolysaccharide is related to the nitric oxide pathway.

Repeated administration of lipopolysaccharide (LPS) induces a refractory state to its usual pyrogenic effects which is called endotoxin tolerance. We tested the hypothesis that nitric oxide (NO) participates in the endotoxin tolerance. Single injection of LPS resulted in an elevation in body temperature (Tb), whereas a significant reduction of the thermoregulatory response to LPS was observed to repeated administration of LPS (administered at 48 h intervals). Intracerebroventricular (i.c.v.) injection of L-NAME (a non-selective NO inhibitor of nitric oxide synthesis) markedly enhanced the febrile response to LPS in tolerant rats. The data suggest that NO pathway in the central nervous system plays a role in endotoxin tolerance.

Induction of a functional vitamin D receptor in all-trans-retinoic acid-induced monocytic differentiation of M2-type leukemic blast cells.

Different types of acute myeloid leukemia blast cells were induced to differentiate in vitro with all-trans-retinoic acid (ATRA) and vitamin D3 (VD). M0/M1 leukemic cells are not sensitive to differentiating agents, whereas M3 leukemic cells are induced to undergo granulocytic differentiation after ATRA treatment but are not sensitive to VD. M2 leukemic blast cells behave differently because they undergo monocytic differentiation with both the differentiation inducers. To gain some insight into the maturation of M2-type leukemic cells, we studied the molecular mechanisms underlying monocytic differentiation induced by ATRA and VD in spontaneous M2 blast cells as well as in Kasumi-1 cells (an acute myeloid leukemia M2-type cell line). Our results indicate that ATRA as well as VD efficiently increases the nuclear abundance of VD receptor (VDR) and promotes monocytic differentiation. VDR is functionally active in ATRA-treated Kasumi-1 cells because it efficiently heterodimerizes with retinoid X receptor, binds to a DR3-type vitamin D-responsive element, and activates the transcription of a vitamin D-responsive element-regulated reporter gene. Consistent with these findings, VD-responsive genes are induced by ATRA treatment of Kasumi-1 cells, suggesting that the genetic program underlying monocytic differentiation is activated. The molecular mechanism by which ATRA increases the nuclear abundance of a functional VDR is still unknown, but our data clearly indicate that the M2 leukemic cell context is only permissive of monocytic differentiation.

Antisense inhibition of Bax mRNA increases survival of terminally differentiated HL60 cells.

Cell sensitivity to programmed cell death is primarily modulated by members of the Bcl-2 family, as the balance of homodimer or heterodimer formation between proapoptotic and antiapoptotic members defines apoptosis susceptibility in the great majority of cellular contexts. It is, therefore, important to clarify if the Bax protein is limiting for activation of the genetic program of programmed cell death or can be complemented by different Bcl-2 family members, such as Bak or Bad. To gain some insight into the role of Bax in the molecular mechanisms of apoptosis of myeloid cells, we inhibited this gene in all-trans-retinoic acid (ATRA)-treated HL60 cells using the methodology of antisense oligodeoxynucleotides (AS-ODN). Our results indicate that Bax inhibition has no effect on the proliferation and differentiation capacity of HL60 cells. Instead, the survival rate of terminally differentiated Bax-inactivated HL60 (Bax(-) HL60) cells is almost three times higher in respect to control cultures, indicating that in mature granulocytes Bax is not efficiently complemented by others members of the Bcl-2 family proteins.

Influência do Episódio Depressivo Maior na Manifestaçäo da Pneumonia / Influence of depression in the outcome of pneuminia

Vários pesquisadores têm avaliado que o Episódio Depressivo Maior interfere no início, curso e progressäo de doenças reguladas imunologicamente. OBJETIVO: Analisar se o Episódio Depressivo Maior, ocorrido nos últimos seis meses, pode constituir um dos fatores de risco para o desenvolvimento da pneumonia adquirida na comunidade em pacientes ambulatoriais, sem comorbidade associada. MATERIAIS E MÉTODOS:O grupo caso foi composto de 13 pacientes(9 feminino e 4 masculino), entre 18 a59 anos, acometidos por Resultadpneumonia, que frequentavam o Ambulatório de Pneumologia do Hospital das Clínicas (UEL). A partir do grupo-caso, foi selecionado o grupo-controle, no Hemocentro do Hospital Universitário (UEL), que deveria ser semelhante quanto ao sexo, idade, raça, estado civil e condiçöes sócio-econômicas. Em ambos os grupos, foram aplicados questionários baseados nos critérios diagnósticos do DSM-IV (Diagnosis Statistics Manual - 4ª ed.) para depressäo. RESULTADO: A idade média do grupo-casofoi de 44,23 anos e do grupo-controle, 40,53. Depressäo foi diagnosticada em 26,92 por cento das pessoas. Nos pacientes-caso, 46,15 por cento apresentaram um ou mais episódios de depressäo, enquanto qque nos pacientes-controle, apenas 7,69 por cento. CONCLUSAO: No presente estudo verificou-se que o Episódio Depressivo Maior pode influenciar na suscetibilidade a infecçäo por pneuminia adquirida na comunidade, sem comorbidade, em pacientes ambulatoriais. Espera-se que, no futuro, a detecçäo da depressäo precoce da depressäo pelo clínico, seu correto tratamento c/ou encaminhamento adequado ao especialista possam, desta forma, reduzir as complicaçöes imunológicas decorrentes da depressäo

Presence of a functional vitamin D receptor does not correlate with vitamin D3 phenotypic effects in myeloid differentiation.

Although VDR is expressed in all the acute myeloid leukemia cell populations studied, most of these leukemias do not exhibit any phenotypic response when exposed to VD. To determine whether VD resistance is related to an altered VDR function, we performed an analysis of VDR expression, phosphorylation, DNA binding capacity and transactivation activity in several leukemic myeloid cell lines arrested at different levels of maturation. Our results indicate that VD induces a clear phenotypic effect, i.e. terminal monocytic differentiation, only in leukemic cells of M2/M3 (intermediate myeloblasts) and M5 (monoblasts) types but not in erythroid precursor cells, early leukemic myeloblasts (M0/M1 type) and promyelocytes (M3 type). VDR expression and function are evident in all the nuclear extracts obtained from the different myeloid cell lines after 12 h of VD treatment, but VD activation of monocytic differentiation is limited to a narrow differentiation window characterized by the M2 type myeloid cellular context.

Antisense inhibition of c-fes proto-oncogene blocks PMA-induced macrophage differentiation in HL60 and in FDC-P1/MAC-11 cells.

To gain some insight into the role of c-fes in macrophage differentiation, we have analyzed the ability of HL60 leukemic promyelocytic cells and FDC-P1/MAC-11 murine myeloid precursor cells to differentiate in response to phorbol esters after inhibition of c-fes function. Fes inactivation has been obtained by using oligodeoxynucleotides (ODN) complementary to the 5' region of c-fes mRNA and to 5' splice junctions of c-fes primary transcript. After 5 days (d) in culture, in several separate experiments performed with different ODN preparations, a complete inhibition of c-fes expression was observed in HL60 and in FDC-P1/MAC-11 cells. No perturbation of cell growth was evident in our experimental conditions in both cell lines after c-fes inhibition. Furthermore, in HL60 cells lacking c-fes product, an almost complete downregulation of the alpha 4 beta 1 fibronectin receptor occurred. However, in both cell lines, the induction of macrophage differentiation by phorbol esters resulted in an almost complete maturation arrest as evaluated by morphological, cytochemical, immunological criteria, and by the cytofluorimetric cell cycle analysis. A loss of the adhesion capacity of both myeloid cell lines, when compared to terminally differentiated macrophages, was also observed. These results suggest that HL60 and FDC-P1/MAC-11 cells, when treated with phorbol 12-myristate 13-acetate, require c-fes protein expression to activate the genetic program underlying macrophage differentiation.

Calcitonin nasal spray in patients with chronic asthma: a double-blind crossover study vs placebo.

The study, which was of a double-blind, crossover type vs placebo in 12 subjects suffering from postmenopausal osteoporosis and chronic asthma, evaluates the effects of acute, prolonged administration of salmon calcitonin (sCT) nasal spray on respiratory function (FEV1, MMEF, V25). No significant changes in bronchomotor tone were observed as a result of prolonged treatment with sCT nasal spray, thereby confirming the complete tolerability of the formulation.

Rifampicin-isoniazid and delayed elimination of theophylline: a case report.

This paper reports a case of tuberculosis relapse and chronic obstructive lung disease treated with rifampicin and isoniazid. The subsequent introduction of slow-release theophylline therapy revealed a delay in the theophylline elimination kinetics resulting in a toxic plasma level. Interference with hepatic microsomal enzymes is considered to occur.