[Evaluating fitness to work and occupational invalidity/ disability in respiratory diseases].
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Disability Evaluation↗
Biomedical subjects
P Cejudo
Publications and source records attributed to P Cejudo.
Human hepatic stellate cells secrete adrenomedullin: potential autocrine factor in the regulation of cell contractility.
BACKGROUND/AIMS: Hepatic stellate cells (HSCs) are perisinusoidal pericytes which have receptors for vasoactive factors, such as endothelin-1, which can regulate cell contractility in an autocrine manner. It is unknown whether human HSCs have receptors for and are able to synthesize the vasodilator peptide adrenomedullin (ADM), a peptide produced by most contractile cells. METHODS AND RESULTS: Stimulation of HSCs with ADM resulted in a dose-dependent raise in cAMP concentration (radioimmunoassay) and markedly blunted the endothelin-induced increase in [Ca2+]i and cell contraction, as assessed in cells loaded with fura-2 using a morphometric method. The existence of the receptor CRLR for ADM and their associated proteins RAMP-1 and RAMP-2 was demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR). Moreover, activated human HSCs spontaneously secreted ADM in the culture medium in a time-dependent manner. ADM secretion was markedly enhanced by tumour necrosis factor-alpha and interleukin-1beta. Specific mRNA for ADM (RT-PCR and Northern blot) was detected in HSCs and increased after incubation of cells with cytokines. CONCLUSIONS: Human HSCs have functional receptors for ADM, the stimulation of which blunts the contractile effect of endothelin-1. Cultured human HSCs secrete ADM in baseline conditions. This secretion is markedly increased by cytokines. These results suggest that ADM can regulate HSCs' contractility in an autocrine manner.
Adrenomedullin↗
Long-term aquaretic efficacy of a selective nonpeptide V(2)-vasopressin receptor antagonist, SR121463, in cirrhotic rats.
Water retention in experimental cirrhosis can be reversed by blocking V(2)-vasopressin (AVP) receptors with the nonpeptide antagonist OPC-31260 or by using the kappa-opioid receptor agonist niravoline, a compound inhibiting central AVP release. However, reluctance to use these drugs in human beings has emerged because the former loses aquaretic efficacy in rats after 2 days of treatment and the latter may have adverse effects in humans. Recently, a new potent and selective nonpeptide V(2)-AVP receptor antagonist, SR121463, has been developed that could be useful for the treatment of dilutional hyponatremia in human cirrhosis. The current study assessed the aquaretic efficacy of 10-day chronic oral administration of SR121463 (0.5 mg/kg/day) in cirrhotic rats with ascites and impaired water excretion after a water load (minimum urinary osmolality >160 mOsm/kg and percentage of water load excreted <60%). Urine volume (UV), osmolality (U(Osm)V), and sodium excretion (U(Na)V) were measured daily. At the end of the 10-day treatment, mean arterial pressure also was measured. In basal conditions cirrhotic rats showed ascites, sodium retention, and impaired water excretion. UV, U(Osm)V, and U(Na)V did not change throughout the study in cirrhotic rats receiving the vehicle. In contrast, SR121463 increased UV and reduced U(Osm)V during the 10-day treatment. This resulted in a greater renal ability to excrete a water load and normalization in serum sodium and osmolality. During the first 6 days of treatment, SR121463 also increased U(Na)V without affecting mean arterial pressure. These data suggest that SR121463 could be of therapeutical value for chronic management of human cirrhosis.
Animals↗
Vascular endothelial growth factor production in peritoneal macrophages of cirrhotic patients: regulation by cytokines and bacterial lipopolysaccharide.
Vascular endothelial growth factor (VEGF) is an angiogenic peptide with vascular permeability and relaxing properties. This study assessed whether peritoneal macrophages of cirrhotic patients can be up-regulated to produce VEGF under proper stimulatory conditions. Macrophages were isolated from ascites. VEGF protein secretion and mRNA expression were measured in basal conditions and after stimulation with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), and interleukin-1 (IL-1). These substances induced a time- and dose-dependent increase in both VEGF production and transcript expression. Assays with actinomycin D showed that VEGF mRNA induction is secondary to both higher VEGF gene transcription and mRNA stability. Ascites and plasma concentration of VEGF was also measured in cirrhotic patients with (n = 15) and without (n = 10) spontaneous bacterial peritonitis (SBP). Plasma values did not differ between both groups of patients. However, ascites VEGF levels were higher in SBP patients than in noninfected cirrhotic patients (710 +/- 183 vs. 94 +/- 15 pg/mL; P <.025). These results indicate that cytokines and LPS markedly increase VEGF protein secretion and mRNA expression in macrophages of cirrhotic patients, and suggest that this substance could be an important mediator of the pronounced arterial vasodilation frequently occurring in SBP patients.
Ascites↗
[Peripheral muscle strength in stable COPD patients: correlation with respiratory function variables and quality of life].
The aim of this study was to assess peripheral muscle strength in patients with chronic obstructive pulmonary disease (COPD) using a simple test and to look for correlation with function variables, physiological strength variables and quality of life parameters. Twenty-three COPD patients with moderate to severe air-flow limitation (FEV1 = 39 +/- 12%) in stable phase but displaying inability to carry out daily tasks were enrolled. Peripheral muscle strength was assessed in all patients by measuring the maximum load in a single repetition of five simple upper and lower extremity exercises performed at a multi-gymnastics station. Results were compared to respiratory function variables (FVC, FEV1, FEV1/FVC and gasometry), to results of an exercise test on a cycle ergometer with monitoring of respiratory gases (VEmax, VO2max and Wmax), to endurance (minutes) to dyspnea (Mahler's scale) and to quality of life (Chronic Respiratory Disease Questionnaire-CRDQ). No relation between functional parameters and endurance in minutes was found. Minute ventilation (VE) proved to be significantly related to oxygen intake (VO) and maximum work in the stress test. Dyspnea on Mahler's scale was unrelated, but fatigue variables and emotional function variables on the CRDQ were related. We conclude that peripheral muscle strength is unrelated to level of flow limitation or exercise tolerance in COPD patients. Peripheral muscle strength is related, however, to maximum work load and some aspects of quality of life.
Aged↗
[Efficacy of a program for tobacco use cessation with a combined substitution treatment of nicotine (patches plus chewing gum) at 6 months of follow-up].
Our aim was to assess the efficacy after 6 months of combined smoking cessation therapy using nicotine substitution with both chewing gum and patches. Sixty-six (25 women, 41 men) heavy smokers (38.04 packs/year and 8.42 mean score on Fagerström test) were followed between September 1995 and March 1997. Most patients were referred by respiratory, cardiology or ear-nose-and-throat outpatient clinics. The patients were prescribed 24-hour nicotine substitution therapy with 21 mg patches, plus chewing gum providing 2 mg of nicotine (3 to 10 per day) for a minimum of 8 weeks and a maximum of 12, with gradually decreasing doses. The patients were checked 1, 2, 4, 8, 12 and 24 weeks after enrollment. Expired air carbon monoxide was measured to confirm abstinence at each checkup and a simple questionnaire was filled in to assess abstinence syndrome and detect the presence of treatment side effects. Rate of abstinence achieved with this protocol after six months of follow-up was 37.9%. The failure rate was highest in the first week (33%) but gradually decreased until week 12. No patients had to abandon treatment due to side effects.
Administration, Cutaneous↗