Cholesterol lowering treatment restores blood global DNA methylation in chronic kidney disease (CKD) patients.

BACKGROUND AND AIMS: Chronic kidney disease (CKD) is characterized by increased oxidative stress (OS). In consideration of the well-known link between OS and DNA methylation we assessed DNA methylcytosine (mCyt) concentrations in CKD patients at baseline and during cholesterol lowering treatment. METHODS AND RESULTS: DNA methylation and OS indices (malonyldialdehyde, MDA; allantoin/uric acid ratio, All/UA) were measured in 30 CKD patients randomized to three cholesterol lowering regimens for 12 months (simvastatin 40 mg/day, ezetimibe/simvastatin 10/20 mg/day, or ezetimibe/simvastatin 10/40 mg/day) and 30 age- and sex-matched healthy controls. DNA methylation was significantly lower in CKD patients vs. controls (4.06 ± 0.20% vs. 4.27 ± 0.17% mCyt, p = 0.0001). Treatment significantly increased mCyt DNA concentrations in all patients (4.06 ± 0.04% at baseline; 4.12 ± 0.03% at 4 months; 4.17 ± 0.03% at 8 months; and 4.20 ± 0.02% at 12 months, p = 0.0001 for trend). A trend for a greater effect on DNA methylation was observed with combined treatment ezetimibe/simvastatin 10/40 mg/day (+5.2% after one year treatment). The treatment-associated mCyt increase was significantly correlated with the concomitant reduction in MDA concentrations and All/AU ratios. CONCLUSION: Our results demonstrate that CKD patients have a lower degree of DNA methylation and that cholesterol lowering treatment restores mCyt DNA concentrations to levels similar to healthy controls. The treatment-associated increase in DNA methylation is correlated with a concomitant reduction in OS markers. The study was registered at clinicaltrials.gov (NCT00861731).

Impact of cholesterol lowering treatment on plasma kynurenine and tryptophan concentrations in chronic kidney disease: relationship with oxidative stress improvement.

BACKGROUND AND AIM: Tryptophan (Trp) degradation via indoleamine (2,3)-dioxygenase (IDO), with consequent increased in kynurenine (Kyn) concentrations, has been proposed as marker of immune system activation. Oxidative stress (OS) might contribute to the pro-inflammatory state in chronic kidney disease (CKD) through the activation of NF-kB, with consequent activation and recruitment of immune cells. METHODS AND RESULTS: Serum concentrations of Trp and Kyn, oxidative stress indices malondialdehyde (MDA) and allantoin/uric acid (All/UA) ratio and anti-oxidant amino acid taurine were measured in 30 CKD patients randomized to 40 mg/day simvastatin (group 1), ezetimibe/simvastatin 10/20 mg/day (group 2) or ezetimibe/simvastatin 10/40 mg/day (group 3) and treated for 12 months. Baseline Kyn and Kyn/Trp ratio were higher in CKD patients vs. healthy controls (1.67 ± 0.62 µmol/L vs 1.25 ± 0.40 µmol/L, p < 0.01 and 0.036 ± 0.016 vs 0.023 ± 0.010, p < 0.001 respectively). Both Kyn and Kyn/Trp ratio significantly decreased after cholesterol lowering treatment, to values comparable with healthy controls after one year treatment (1.67 ± 0.62 µmol/L vs 1.31 ± 0.51 µmol/L, p < 0.0001 and 0.036 ± 0.016 vs 0.028 ± 0.012 p < 0.0001, respectively). This was paralleled by a significant decrease in MDA (218 ± 143 nmol/L vs 176 ± 123 nmol/L, p < 0.01) and All/UA ratio (1.47 ± 0.72 vs 1.19 ± 0.51, p < 0.01) in CKD patients. CONCLUSIONS: Amelioration of both oxidative and inflammation status after cholesterol lowering treatment in CKD might be mediated by restoration of antioxidant taurine concentrations during therapy (from 51.1 ± 13.3 µmol/L at baseline to 63.1 ± 16.4 µmol/L, p < 0.001 by ANOVA), suggesting that improvement of both oxidative and inflammation status in CKD patients could be explained, at least partly, by the cholesterol lowering effects.

Administration of Brevibacillus laterosporus spores as a poultry feed additive to inhibit house fly development in feces: a new eco-sustainable concept.

The success of a microbial pesticide application against house flies developing in manure should accomplish the uniform mixing of active ingredients with this breeding medium, thus enhancing residual effects. The oral administration of the entomopathogenic bacterium Brevibacillus laterosporus to caged poultry species allows the homogeneous incorporation of its active ingredients with fly breeding media. Feces from treated broilers or hens show toxicity against exposed fly adults and larvae. Insecticidal effects are concentration-dependent with a lethal median concentration (LC50) value of 1.34 × 10(8) and 0.61 × 10(8) spores/g of feces for adults and larvae, respectively. Manure toxicity against flies was maintained as long as chickens were fed a diet containing adequate concentrations of B. laterosporus spores. Toxicity significantly decreased after spore administration to birds was interrupted. When poultry diet contained 10(10) spores/g, mortality of flies reared on feces exceeded 80%. The use of B. lateroporus spores as a feed additive in poultry production systems fostering a more integrated approach to farming is discussed.

Comparative applications of azadirachtin- and Brevibacillus laterosporus-based formulations for house fly management experiments in dairy farms.

The potential of two bioinsecticidal formulations containing Brevibacillus laterosporus spores and azadirachtin, respectively, was assayed in laboratory and in comparative field treatments for the management of immature house flies on dairy farms. As already known for B. laterosporus, preliminary laboratory experiments with azadirachtin evidenced a concentration-dependent effect. Azadirachtin median lethal concentration (LC50) value determined for second instar larvae was 24.5 microg/g diet. Applications in dairy farms were performed at dosages and concentrations predetermined in laboratory experiments, to employ the two formulations at an equal insecticidal potential. Repeated applications on the cow pen caused a significant fly development depression in areas treated with azadirachtin (63%) and B. laterosporus (46%), compared with the control. Formulations were applied at a dosage of 3 liters/m2, and concentrations of 2 x 10(8) B. laterosporus spores/ml and 25 microg azadirachtin/ml, respectively.

Enhancing ovarian cancer conventional chemotherapy through the combination with cannabidiol loaded microparticles.

In this work, we evaluated, for the first time, the antitumor effect of cannabidiol (CBD) as monotherapy and in combination with conventional chemotherapeutics in ovarian cancer and developed PLGA-microparticles as CBD carriers to optimize its anticancer activity. Spherical microparticles, with a mean particle size around 25 µm and high entrapment efficiency were obtained. Microparticles elaborated with a CBD:polymer ratio of 10:100 were selected due to the most suitable release profile with a zero-order CBD release (14.13 ± 0.17 µg/day/10 mg Mps) for 40 days. The single administration of this formulation showed an in vitro extended antitumor activity for at least 10 days and an in ovo antitumor efficacy comparable to that of CBD in solution after daily topical administration (≈1.5-fold reduction in tumor growth vs control). The use of CBD in combination with paclitaxel (PTX) was really effective. The best treatment schedule was the pre + co-administration of CBD (10 µM) with PTX. Using this protocol, the single administration of microparticles was even more effective than the daily administration of CBD in solution, achieving a ≈10- and 8- fold reduction in PTX IC50 respectively. This protocol was also effective in ovo. While PTX conducted to a 1.5-fold tumor growth inhibition, its combination with both CBD in solution (daily administered) and 10-Mps (single administration) showed a 2-fold decrease. These results show the promising potential of CBD-Mps administered in combination with PTX for ovarian cancer treatment, since it would allow to reduce the administered dose of this antineoplastic drug maintaining the same efficacy and, as a consequence, reducing PTX adverse effects.

Variation within the CLEC16A gene shows consistent disease association with both multiple sclerosis and type 1 diabetes in Sardinia.

Variation within intron 19 of the CLEC16A (KIAA0350) gene region was recently found to be unequivocally associated with type 1 diabetes (T1D) in genome-wide association (GWA) studies in Northern European populations. A variant in intron 22 that is nearly independent of the intron 19 variant showed suggestive evidence of association with multiple sclerosis (MS). Here, we genotyped the rs725613 polymorphism, representative of the earlier reported associations with T1D within CLEC16A, in 1037 T1D cases, 1498 MS cases and 1706 matched controls, all from the founder, autoimmunity-prone Sardinian population. In these Sardinian samples, allele A of rs725613 is positively associated not only with T1D (odds ratio=1.15, P one-tail=5.1 x 10(-3)) but also, and with a comparable effect size, with MS (odds ratio=1.21, P one-tail 6.7 x 10(-5)). Taken together these data provide evidence of joint disease association in T1D and MS within CLEC16A and underline a shared disease pathway.

Anti-PSMA 124I-scFvD2B as a new immuno-PET tool for prostate cancer: preclinical proof of principle.

BACKGROUND: Prostate cancer (PCa) is the second leading cause of cancer-related death in the Western population. The use in oncology of positron emission tomography/computed tomography (PET/CT) with emerging radiopharmaceuticals promises accurate staging of primary disease, restaging of recurrent disease and detection of metastatic lesions. Prostate-specific membrane antigen (PSMA) expression, directly related to androgen-independence, metastasis and progression, renders this tumour associate antigen a good target for the development of new radiopharmaceuticals for PET. Aim of this study was to demonstrate in a preclinical in vivo model (PSMA-positive versus PSMA-negative tumours) the targeting specificity and sensitivity of the anti-PSMA single-chain variable fragment (scFv) labelled with 124I. METHODS: The 124I-labeling conditions of the antibody fragment scFvD2B were optimized and assessed for purity and immunoreactivity. The specificity of 124I-scFvD2B was tested in mice bearing PSMA-positive and PSMA-negative tumours to assess both ex-vivo biodistribution and immune-PET. RESULTS: The uptake fraction of 124I-scFvD2B was very high on PSMA positive cells (range 75-91%) and highly specific and immuno-PET at the optimal time point, defined between 15 h and 24 h, provides a specific localization of lesions bearing the target antigen of interest (PSMA positive vs PSMA negative tumors %ID/g: p = 0.0198 and p = 0.0176 respectively) yielding a median target/background ratio around 30-40. CONCLUSIONS: Preclinical in vivo results of our immuno-PET reagent are highly promising. The target to background ratio is improved notably using PET compared to SPECT previously performed. These data suggest that, upon clinical confirmation of sensitivity and specificity, our anti-PSMA 124I-scFvD2B may be superior to other diagnostic modalities for PCa. The possibility to combine in patients our 124I-scFvD2B in multi-modal systems, such as PET/CT, PET/MR and PET/SPECT/CT, will provide quantitative 3D tomographic images improving the knowledge of cancer biology and treatment.

MR-based artificial intelligence model to assess response to therapy in locally advanced rectal cancer.

PURPOSE: To develop and validate an Artificial Intelligence (AI) model based on texture analysis of high-resolution T2 weighted MR images able 1) to predict pathologic Complete Response (CR) and 2) to identify non-responders (NR) among patients with locally-advanced rectal cancer (LARC) after receiving neoadjuvant chemoradiotherapy (CRT). METHOD: Fifty-five consecutive patients with LARC were retrospectively enrolled in this study. Patients underwent 3 T Magnetic Resonance Imaging (MRI) acquiring T2-weighted images before, during and after CRT. All patients underwent complete surgical resection and histopathology was the gold standard. Textural features were automatically extracted using an open-source software. A sub-set of statistically significant textural features was selected and two AI models were built by training a Random Forest (RF) classifier on 28 patients (training cohort). Model performances were estimated on 27 patients (validation cohort) using a ROC curve and a decision curve analysis. RESULTS: Sixteen of 55 patients achieved CR. The AI model for CR classification showed good discrimination power with mean area under the receiver operating curve (AUC) of 0.86 (95% CI: 0.70, 0.94) in the validation cohort. The discriminatory power for the NR classification showed a mean AUC of 0.83 (95% CI: 0.71,0.92). Decision curve analysis confirmed higher net patient benefit when using AI models compared to standard-of-care. CONCLUSIONS: AI models based on textural features of MR images of patients with LARC may help to identify patients who will show CR at the end of treatment and those who will not respond to therapy (NR) at an early stage of the treatment.

Heart block and hyperthyroidism. Report of two cases.

In two patients with hyperthyroidism who had no signs of heart disease, first-degree heart block with tall and large P waves occurred. In one patient, a left bundle-branch block and transient complete heart block with Stokes-Adams episodes also occurred, although there was no verifiable evidence of acute inflammatory disease.

Regression of Henoch-Schönlein disease with intensive immunosuppressive treatment.

OBJECTIVE: To assess the results of a new immunosuppressive cycle, which had given favorable results in other immune-mediated glomerulonephritides, in the treatment of Henoch-Schönlein disease. METHODS: Eight patients (seven male and one female; age range, 13 to 61 years) with biopsy-proved Henoch-Schönlein were treated with the following protocol: (1) induction with 250 to 750 mg intravenous methylprednisolone every day for 3 to 7 days plus 100 to 200 mg oral cyclophosphamide every day, (2) maintenance with 100 to 200 mg oral prednisone on alternate days plus cyclophosphamide, as before, for 30 to 75 days; (3) tapering, with prednisone reduced on average by 25 mg every month while the cyclophosphamide dose remained the same, and (4) discontinuation, after at least 6 months, with abrupt interruption of cyclophosphamide and slow tapering of prednisone. The results were assessed in terms of remission, improvement, progression of disease, kidney failure, and death, unambiguously defined. The follow-up extended up to 12 years. RESULTS: Seven of eight patients had a complete remission that was maintained indefinitely thereafter. Plasma creatinine levels decreased on average from 211 +/- 81 to 92 +/- 27 mumol/L (p < 0.01) and urine protein excretion decreased from 1.9 +/- 0.8 to 0.3 +/- 0.1 gm/day (p < 0.01). One patient died of intestinal infarction caused by atherosclerotic mesenteric artery thrombosis. CONCLUSIONS: Our data suggest that an intensive immunosuppressive regimen that combines prednisone and cyclophosphamide at high doses can be effective in healing Henoch-Schönlein disease.

Immunosuppressive treatment of Berger's disease.

BACKGROUND: The aim of our study was to determine whether immunosuppressive treatment is effective in preventing and reversing the evolution of Berger's disease toward chronic renal failure. METHODS: We studied 20 unselected, consecutive patients with biopsy-proven Berger's disease who met the criteria for disease progression. They had proteinuria, significant histologic changes, persistent hematuria, and red cell casts. The treatment consisted of prednisone in an alternate-day regimen and cyclophosphamide, either in a daily oral administration or in a monthly intravenous pulse injection, both given for a 6-month cycle. Five patients had chronic renal failure (as disclosed by plasma creatinine of 230 +/- 71 mumol/L), hypertension, and proteinuria (2.7 +/- 0.8 gm/day), whereas the remaining 15 patients had normal renal function (plasma creatinine, 97 +/- 18 mumol/L) and less severe proteinuria (1.9 +/- 1.1 gm/day). However, even these 15 patients had a significant number of risk factors heralding progression to chronic renal failure. RESULTS: Over an average follow-up of 8.7 +/- 3.7 years (range, 5 to 15 years), all patients but one had complete disease remission, including five patients with incipient chronic renal failure. Relapse occurred in two patients who were healed after a repeat treatment cycle. Over the entire follow-up period, no patient progressed to chronic renal failure and plasma creatinine concentration remained stable, even in subjects in whom it was high before treatment (257 +/- 79 versus 230 +/- 71 mumol/L; p > 0.05). CONCLUSION: The immunosuppressive treatment of patients with Berger's disease with high probability of progression appears to be effective in the prevention of end-stage renal disease.

Experimental dissociation of the effects of prostaglandins on renal sodium and water reabsorption by cyclo-oxygenase inhibitors in the rat.

1 The relative importance of the effect of prostaglandins on renal sodium and water reabsorption was assessed in rats. 2 Clearance experiments were performed on 24 anaesthetized rats divided into 3 groups. Each group was infused throughout either with Ringer solution at 9 ml/h (Protocol I), or at 3 ml/h (Protocol II) or with hypotonic fluid at 5 ml/h (Protocol III). Clearance periods were performed before and after intravenous injection of indomethacin (5 mg/kg) and then of aspirin (20 mg/kg). The natriuretic response to different degrees of volume expansion was not modified during the action of the inhibitors. 3 When baseline urine osmolality (Uosm) was high (Protocol II) no further increase occurred in the presence of prostaglandin inhibition. Conversely, Uosm rose from 771 +/- 134 to 1356 +/- 414 and from 575 +/- 245 to 841 +/- 407 mosm/kg (P less than 0.05) in Protocol I and Protocol III respectively, when antidiuretic hormone secretion was inhibited by the higher degree of volume expansion. 4 There was a significant correlation between the change in urine flow rate induced by cyclooxygenase inhibitors and the attendant variations in Na excretion, r = 0.42, n = 41, P less than 0.01. 5 Thus, prostaglandins affect Na loss during saline load as a side effect of their action on water permeability. They could play an important role in volume depletion by counterbalancing the large secretion rate of renal vasoconstrictors.

Effects of allogeneic bone marrow transplantation on pulmonary function in 80 children in a single paediatric centre.

We retrospectively reviewed the results of serial pulmonary function tests (PFT) after allogeneic bone marrow transplantation (BMT) performed in 80 children at a single institution over a 16-year period. We looked for associations linking PFT results to graft-versus-host disease (GVHD), conditioning regimen (total body irradiation (TBI) vs busulphan), and cytomegalovirus immune status. The median follow-up after BMT was 4 years. At 2 years after BMT, significant declines were found in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), as compared to baseline. Both FEV1 and the FEV1/FVC ratio showed significantly greater reductions in the group conditioned with busulphan (n=22) than in the group conditioned with TBI (n=49) and were significantly lower in the patients with (n=16) than without (n=64) chronic GVHD. Busulphan may be associated with greater long-term lung toxicity than TBI. The relevance of this finding to selection of conditioning regimens for BMT should be examined in the light of the overall pattern of side effects. Chronic GVHD was associated with airway obstruction.

IgM antibody response to the hepatitis C virus core protein in intravenous drug users.

To verify whether a solid-phase enzyme immunoassay for serum IgM antibodies to the hepatitis C virus (HCV) core protein (IgM anti-HCVcore) might be proposed as a surrogate test for serum HCV RNA, we studied 86 anti-HCV antibody-positive intravenous drug users. Serum HCV RNA was demonstrated by RT-PCR with primers derived from the 5' non-coding and the core region. IgM anti-HCVcore antibodies were found in 62/86 (72%) subjects; circulating HCV RNA was detected by the 5' noncoding assay in 53/86 samples (62%) and by the core region assay in 35/86 samples (41%). IgM anti-HCVcore reactivity was associated with core HCV RNA seropositivity (p < 0.05) but not with 5' noncoding HCV RNA seropositivity (p = NS). Patients infected by HCV type 1a were more-often positive for IgM anti-HCVcore (p < 0.05) and for core HCV RNA (p = 0.005) than patients infected by other HCV genotypes. IgM anti-HCVcore reactivity was significantly more common in subjects positive for core HCV RNA (p < 0.005) and in subjects aged > 30 years (p < 0.05). In conclusion, the IgM anti-HCVcore assay frequently tests positive in intravenous drug users, particularly when infected by HCV 1a, but is not a surrogate of testing for serum HCV RNA.

Oxdralazine, a new peripheral vasodilator, combined with propranolol and hydrochlorothiazide: a rational approach to antihypertensive treatment.

Forty-three patients suffering from hypertension of different origin (chronic renal failure, gout, or idiopathic) were treated with propranolol (121 +/- 12 mg q.d.) plus hydrochlorothiazide (50 mg q.d.) for 75 +/- 9 days. Blood pressure did not return to normal limits in 15 patients, who were continued on the same protocol plus 10 to 50 mg oxdralazine q.d. After an average of 68 +/- 35 days blood pressure fell from 180/110 mm Hg to 145/90 mm Hg without orthostatism, significant side effects, or changes in GFR. This combination seems particularly successful since propranolol will prevent the undesired rise in cardiac output due to oxdralazine as well as the activation of the renin-angiotensin axis due to diuretics. Thus, the antihypertensive properties of each agent will be enhanced by a reduction in side effects by the associated drug, resulting in optimal blood pressure control.

Blunting of furosemide diuresis by aspirin in man.

Experiments were performed on humans to study the blunting on the diuretic action of furosemide by prostaglandin synthetase inhibitors. Maximal water diuresis was instituted. At the peak of urine flow, clearance periods were performed during baseline conditions and repeated after the injection of aspirin and, subsequently, of furosemide. Control subjects did not receive aspirin. Urine flow rate (V), Cosm, and Na excretion (UNa) . V were significantly lower when the administration of the diuretic had been preceded by that of aspirin. In the absence of furosemide, however, aspirin did not influence renal hemodynamics nor Na and water reabsorption. Therefore, the same experimental protocol was repeated in paired experiments where each normal subject served as his own control, being studied twice, in the presence and absence of aspirin, respectively. The average changes in water and Na excretion induced by furosemide were not different when the patients were pretreated with aspirin as compared with those measured in the absence of prostaglandin inhibition. Changes occurring in individual experiments were significantly correlated (r = 0.95, P less than 0.01) with those in calculated furosemide clearance. Since aspirin, indomethacin, and meclophenamate are secreted by the organic acid transport system of the proximal tubule, competition for a common secretory mechanism, rather than prostaglandin inhibition, could mediate the blunting of furosemide diuresis.

Effects of ubidecarenone in an exercise training program for patients with chronic obstructive pulmonary diseases.

A study was undertaken to determine the usefulness of ubidecarenone in pulmonary rehabilitation in exercise training programs in the management of chronic obstructive pulmonary disease (COPD). The subjects were 20 patients with COPD who had been participating in an exercise training program for at least four weeks. The patients were randomly assigned either to receive 50 mg of oral ubidecarenone daily or to enter a control group during the program. Oxygen consumption, expired volume, and heart rate were measured during exercise tests before and after training. Maximum oxygen consumption increased 13% in the ubidecarenone-treated patients and 7% in the controls, and maximum expired volume increased 10% in each group. The increases were significant in the ubidecarenone group but not in the controls. Heart rate increased 2% in both groups. It is concluded that ubidecarenone deserves further evaluation in exercise training programs for patients with COPD.

Urinary glycosaminoglycans in patients with systemic lupus erythematosus.

OBJECTIVE: Several investigations indicate that glycosaminoglycans (GAG) are important components of the glomerular basement membrane (GBM) and that they play a remarkable role in the control of charge-selectivity in the glomerular capillary wall. In order to evaluate the possible use of GAG as a marker of glomerular disease, we evaluated urinary GAG excretion in 37 patients with systemic lupus erythematosus (SLE) grouped by disease activity and kidney involvement and in 17 healthy controls. METHODS: GAG were isolated from urine by using ion-exchange chromatography on DEAE Sephacel. GAG composition was determined by cellulose acetate electrophoresis and expressed as relative percentages by densitometric scanning of Alcian Blue stained strips. RESULTS: Total GAG levels were significantly increased only in active extra-renal SLE patients. Qualitative analysis of urinary GAG revealed the presence of a low sulphated chondroitin sulphate-protein complex (LSC-PG), whose frequency was higher in patients compared to controls. Moreover, inactive SLE was characterized by an alteration of the chondroitin sulphate/heparan sulphate ratio. CONCLUSION: These variations suggest the presence of an abnormal permeability of the renal filter in patients without other appreciable signs of kidney alteration. Therefore, qualitative-quantitative urinary GAG analysis could represent an additional diagnostic approach.

Bronchoalveolar lavage causes decrease in PaO2, increase in (A-a) gradient value and bronchoconstriction in asthmatics.

The aims of this study were to (1) record the changes of (arterial oxygen partial pressure) PaO2, (arterial carbon dioxide partial pressure) PaCO2, (percentage saturation of haemoglobin with oxygen in arterial blood) SaO2 and alveolar-arterial (A-a) oxygen gradiant resulting from bronchoalveolar lavage (BAL) in asthmatic and normal subjects; (2) measure changes in forced expiratory volume in 1 s (FEV1), vital capacity forced (FVC) associated with BAL; and (3) assess possible predictive factors for the degree of hypoxaemia and impairment of spirometry resulting from BAL. Bronchoscopy and BAL (150 ml) were performed in 24 asthmatics and 15 healthy subjects. Serial arterial blood samples (radial artery) were obtained in all subjects: T1 and before T2 after local anaesthesia; T3 at end of bronchoscopy; T4 after BAL and 5 min, 15 min, 1 h, 2 h, 8 h and 24 h (T5-T10) after the procedure, FEV1 and FVC were measured immediately before and 5 min afer bronchoscopy. Baseline PaO2 was lower in asthmatics (10.2 +/- 0.8 kPa) than in healthy subjects (10.8 +/- 0.8). Both groups showed a significant decrease in PaO2, and a significant widening in (A-a) oxygen tension gradiant at T3-9, with respect to T1 (P < 0.05). PaO2 reached a significantly lower value in asthmatics (7.1 +/- 0.6 kPa) than in HS (7.7 +/- 0.5; P < 0.05). In asthmatics, FEV1, FVC and the ratio FEV1/FVC decreased significantly after BAL (P < 0.001). In healthy subjects, FEV1 and FVC decreased significantly (P < 0.001), whereas FEV1/FVC did not. The fall in FEV1 after BAL was significantly greater in asthmatics (32.4 +/- 10.0%) than in healthy subjects (17.7 +/- 4.6; P < 0.001). Severity of asthma, basline FEV1 or initial PaO2 did not predict the degree of hypoxaemia or the fall of FEV1. It is concluded that BAL causes more severe hypoxaemia and a greater decrease in FEV1 in asthmatics compared to healthy subjects, strongly supporting the recommendation of special caution and careful monitoring when BAL is undertaken in asthmatics.

Inner ear pressure changes modify ADH secretion in freely moving guinea pig.

The present study was designed to elucidate the relationship between endolymphatic pressure and plasma ADH levels in conscious guinea pigs. Plasma ADH (pADH) was measured in basal conditions and after having applied positive or negative pressure of 20 cmH2O to the inner ear. The experimental protocol was designed to avoid any interference on ADH release caused by anesthesia and surgical stress. There was no change in blood pressure, heart rate, plasma Na (pNa) and osmolality (pOsm) after inner ear pressure (IEP) modifications. However, pADH was inversely related with IEP: pADH averaged 31.4 +/- 7.0 pg/ml (mean +/- S.D.) in basal conditions, rising to 48.8 +/- 19.3 when IEP was lowered and falling to 16.6 +/- 10.3 when IEP was raised. These results confirm that structures in the inner ear help control of ADH release.