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Biomedical subjects

S Baldi

Publications and source records attributed to S Baldi.

At least 19 recordsLinked to original sources
PubMed2005

Mechanisms of protection by pantoprazole against NSAID-induced gastric mucosal damage.

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) can be associated with severe adverse digestive effects. In clinical settings, proton pump inhibitors have proven to be effective in preventing and healing NSAID-induced gastroduodenal lesions. The present study investigates the mechanisms of protection afforded by pantoprazole against gastric injury induced by different NSAIDs in rats. Animals were orally treated with indomethacin (100 micromol/kg), diclofenac (60 micromol/kg), piroxicam (150 micromol/kg) or ketoprofen (150 micromol/kg). Thirty minutes before NSAIDs, animals received pantoprazole 6 or 60 micromol/kg orally. Four hours after NSAIDs, the following parameters were assessed: histomorphometric evaluation of gastric mucosal damage; gastric mucosal levels of myeloperoxidase (MPO), malondialdehyde (MDA), reduced glutathione as an index of non-proteic sulfhydryl compounds (GSH), and prostaglandin E2 (PGE2); mucosal cyclooxygenase-1 and -2 (COX-1, COX-2) mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). Separate experiments were carried out to assay the effects of pantoprazole on gastric acid secretion in pylorus-ligated rats. The in vitro influence of pantoprazole (1-10 microM) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate was also examined. All NSAIDs elicited mucosal necrotic lesions associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels, were detected in the gastric mucosa of indomethacin-, piroxicam- or ketoprofen-treated animals. Indomethacin enhanced mucosal COX-2 expression, while not affecting COX-1. At the oral dose of 6 micromol/kg pantoprazole did not affect NSAID-induced mucosal damage, whereas at 60 micromol/kg it markedly reduced injuries provoked by all test NSAIDs. Pantoprazole 60 micromol/kg also reversed the effects of NSAIDs on MPO, MDA, and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced COX-2 expression. However, at both doses, pantoprazole inhibited acid secretion in pylorus-ligated rats. Furthermore, pantoprazole concentration dependently reduced the in vitro oxidation of LDLs. Our results suggest that besides inhibiting acid secretion, the protection afforded by pantoprazole against NSAID-induced gastric damage depends on a reduction in mucosal oxidative injury, which may also account for an increment of sulfhydryl radical mucosal bioavailability. It is also suggested that pantoprazole does not influence the down-regulation of gastric prostaglandin production associated with NSAID treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms.

AIMS/HYPOTHESIS: Non-alcoholic fatty liver disease (NAFLD) has been associated with the metabolic syndrome. However, it is not clear whether insulin resistance is an independent feature of NAFLD, and it remains to be determined which of the in vivo actions of insulin are impaired in this condition. METHODS: We performed a two-step (1.5 and 6 pmol min(-1) kg(-1)) euglycaemic insulin clamp coupled with tracer infusion ([6,6-2H2]glucose and [2H5]glycerol) and indirect calorimetry in 12 non-obese, normolipidaemic, normotensive, non-diabetic patients with biopsy-proven NAFLD and six control subjects. RESULTS: In NAFLD patients, endogenous glucose production (basal and during the clamp) was normal; however, peripheral glucose disposal was markedly decreased (by 30% and 45% at the low and high insulin doses, respectively, p<0.0001) at higher plasma insulin levels (p=0.05), due to impaired glucose oxidation (p=0.003) and glycogen synthesis (p<0.001). Compared with control subjects, glycerol appearance and lipid oxidation were significantly increased in NAFLD patients in the basal state, and were suppressed by insulin to a lesser extent (p<0.05-0.001). The lag phase of the in vitro copper-catalysed peroxidation of LDL particles was significantly shorter in the patients than in the control subjects (48+/-12 vs 63+/-13 min, p<0.04). Lipid oxidation was significantly related to endogenous glucose production, glucose disposal, the degree of hepatic steatosis, and LDL oxidisability. CONCLUSIONS/INTERPRETATION: Insulin resistance appears to be an intrinsic defect in NAFLD, with the metabolic pattern observed indicating that adipose tissue is an important site.

3-Hydroxybutyric Acid↗
PubMed2005

Do children with developmental dyslexia have an implicit learning deficit?

OBJECTIVE: The purpose of this study was to investigate the effects of specific types of tasks on the efficiency of implicit procedural learning in the presence of developmental dyslexia (DD). METHODS: Sixteen children with DD (mean (SD) age 11.6 (1.4) years) and 16 matched normal reader controls (mean age 11.4 (1.9) years) were administered two tests (the Serial Reaction Time test and the Mirror Drawing test) in which implicit knowledge was gradually acquired across multiple trials. Although both tests analyse implicit learning abilities, they tap different competencies. The Serial Reaction Time test requires the development of sequential learning and little (if any) procedural learning, whereas the Mirror Drawing test involves fast and repetitive processing of visuospatial stimuli but no acquisition of sequences. RESULTS: The children with DD were impaired on both implicit learning tasks, suggesting that the learning deficit observed in dyslexia does not depend on the material to be learned (with or without motor sequence of response action) but on the implicit nature of the learning that characterises the tasks. CONCLUSION: Individuals with DD have impaired implicit procedural learning.

Child↗
PubMed2005

Nutritional status and airflow obstruction: two independent contributors to CO diffusing capacity impairment in COPD.

BACKGROUND: The association between weight loss and Chronic Obstructive Pulmonary Disease (COPD) has been recognised from many years. Based on the evidence that nutritional status reflects metabolic disturbances in COPD, the relationship between body mass index (BMI), severity of airflow obstruction and CO diffusing capacity (DL(CO)), that is the functional hallmark of emphysema, is relevant to the management of COPD phenotypes. METHODS: We reviewed 104 patients with COPD (82 males), aged 66 +/- 9 years (mean +/- SD). Height averaged 165 +/- 8 cm, weight 71 +/- 16 Kg, FEV1 50 +/- 18 (% of predicted), RV 169 +/- 49%, and DL(CO) 56 +/- 26%. Multiple linear regression was performed using BMI, FEV1 and RV, as explanatory variables for DL(CO). Patients were also classified into four groups according to BMI < or = 18.5 (low), > 18.5 and < or = 25 (ideal), > 25 and < or = 30 (overweight), > 30 (obese), and post-bronchodilator FEV1 < 50%. Using this categorisation, a two-factor analysis of variance, testing for interaction and main effects (BMI and FEV1) was performed as confirmatory analysis for the association between BMI (kg/m2), FEV1% and DL(CO)%. RESULTS: FEV1 and BMI were significantly and independently associated to DL(CO) according to the equation: DL(CO) = -18.32 + 0.65 x FEV1 + 1.59 x BMI (R2 = 0.40, p < 0.0001). The contribution of RV % to DL(CO) % was largely non-significant (p = 0.16). A close relationship was found between BMI (kg/m2) and DL(CO) %, for all of the four BMI groups segregated by post-bronchodilator FEV1 %, (p < .0001). No interaction was found between these two factors (p = 0.30). CONCLUSION: Nutritional status as assessed by BMI contributes substantially to impairment of DL(CO) independently of the severity of airflow obstruction. This data confirms the association between emphysematous process and weight loss in advanced COPD, independent of the airflow obstruction severity.

Adult↗
PubMed2004

Diagnosis of sleep apnea.

Obstructive sleep apnea syndrome (OSAS) is characterized by repeated oropharyngeal occlusions occurring during sleep. The prevalence of moderate OSAS (with an apnea-hypopnea index = or >15/h) is 9% and 4% in male and female, respectively. It is associated with an abnormally high frequency of cardiovascular disease (hypertension, stroke, coronary heart disease) and excessive daytime sleepiness responsible for an increased frequency of work and road accidents. Because the treatment of OSAS provides many benefits to patients and society, it is very important to obtain an early diagnosis. The diagnosis of OSAS is based on the combination of characteristic clinical features plus compatible findings on instrumental tests in which multiple physiologic signals are monitored simultaneously during a night of sleep. A full night polysomnography, conducted by a technologist in a sleep laboratory, is the gold standard for the diagnosis of suspected OSAS, but the capacity for performing polysomnography is limited. On the basis of the high incidence and prevalence of OSAS, of the limited number of sleep laboratories, long waiting times and high costs recommendations have been formulated for the use of unattended portable systems in the assessment of OSAS. The main clinical aspects of of OSAS, the diagnostic approach with full night polysomnography and unattended portable systems, the differential diagnosis and some examples of cardiorespiratory portable monitoring are presented in this paper.

Diagnosis, Differential↗
PubMed2003

The effect of lipoproteins on endothelial nitric oxide synthase is modulated by lipoperoxides.

BACKGROUND AND AIM: The effect of low-density lipoproteins (LDLs) on endothelial nitric oxide synthase (eNOS) is debated. By coupling in vivo and in vitro experiments we evaluated the role of oxidized lipid substrates in the modulation of eNOS activity by LDLs. MATERIALS AND METHODS: Plasma lipids, nitrite/nitrates (NO2/NO3), and malondialdehyde (MDA) were measured in 14 controls, and in 13 patients with familial hypercholesterolemia (FH) before and after 12 weeks of treatment with atorvastatin (20 mg u.i.d.). Nitric oxide synthase in cell lysate and NO2/NO3 into the medium were measured in human microvascular (HMEC-1) and umbilical vein (HUVEC) endothelial cells after 24 h of incubation with increasing concentrations of mildly oxidized LDLs with and without atorvastatin and in HMEC-1 with and without vitamin C. In HMEC-1, NO2/NO3 was also determined after exposure to more intensively oxidized LDLs. RESULTS: At baseline, plasma NO2/NO3 (56 +/- 7 vs. 35 +/- 3 micro M) and MDA (5.6 +/- 0.7 vs. 2.9 +/- 0.3 micro M), were significantly (P < 0.02 for both) higher in the FH patients. In the whole study group, NO2/NO3 was more strongly correlated with plasma MDA (Rho = 0.70) than LDL-cholesterol (Rho = 0.57). In the FH patients, atorvastatin induced a significant decline in plasma total and LDL-cholesterol (-3.1 +/- 0.5 and -2.9 +/- 0.5 mM, respectively), NO2/NO3 (-35 +/- 8 microM) and MDA (-3.4 +/- 0.7 microM) (P < 0.001 for all). Changes in plasma NO2/NO3 were related to the concomitant changes in plasma MDA (Rho = 0.79, P < 0.006) and not to changes in LDL-cholesterol. In HMEC-1 and in HUVEC, mildly oxidized LDLs stimulated both e-NOS and NO2/NO3 accumulation; the effect on e-NOS was potentiated by vitamin C in HMEC-1. Atorvastatin had no effect in HMEC-1 while it stimulated eNOS but not NO2/NO3 in HUVEC. The accumulation of NO2/NO3 in HMEC exposed to increasing concentrations of more intensively oxidized-LDLs showed a nonlinear dose-response curve. CONCLUSIONS: In uncomplicated patients with FH, plasma NO2/NO3 concentrations are elevated; the cross-sectional data, intervention study and in vitro experiments indicate that oxidized lipids exert a tonic stimulatory action on e-NOS and NO2/NO3 generation not mediated through superoxide anion formation. Atorvastatin amplify this eNOS response in HUVEC, but not in HMEC, and this effect is not associated with a parallel increased NO2/NO3 generation.

Adult↗
PubMed2002

Defective regulation and action of atrial natriuretic peptide in type 2 diabetes.

Increased plasma atrial natriuretic peptide (ANP) levels and impaired ANP action have been reported in patients with diabetes or insulin resistance. The aim of this study was to assess the interaction between insulin and ANP in type 2 diabetes. In 12 normotensive, normoalbuminuric type 2 diabetics, we infused insulin at a high (6.6 pmol/min/kg) or, on a different day, at a low rate (0.6 pmol/min/kg) during 4 hours of isoglycemia under isovolumic, isoosmolar conditions. The normal response was established in 12 healthy volunteers using an identical protocol. Despite higher baseline ANP levels (17.7 +/- 2.8 vs. 10.8 +/- 1.8 pg/ml, p = 0.04), urinary sodium excretion was similar in diabetics and controls (113 +/- 8.5 vs. 102 +/- 8.8 mEq/24 hours, p = ns). In both groups, hyperinsulinemia caused a decrease in blood volume (0.33 +/- 0.10 l, p < 0.01), diastolic blood pressure (6 %, p < 0.02), and natriuresis. However, plasma ANP decreased in controls (from 12.7 +/- 1.9 to 8.6 +/- 1.4 pg/ml, p = 0.01) but not in type 2 diabetics (15.1 +/- 2.7 vs. 17.2 +/- 3.8 pg/ml, p = ns). We conclude that ANP release is resistant to volume stimulation in type 2 diabetic patients, and natriuresis is resistant to ANP action. This dual disruption of ANP control may play a role in blood pressure regulation in diabetes.

Adult↗
PubMed2001

Relationship between extent of pulmonary emphysema by high-resolution computed tomography and lung elastic recoil in patients with chronic obstructive pulmonary disease.

We investigated the relationship between the extent of pulmonary emphysema, assessed by quantitative high-resolution computed tomography (HRCT), and lung mechanics in 24 patients with chronic obstructive pulmonary disease (COPD). The extent of emphysema was quantified as the relative lung area with CT numbers < -950 Hounsfield Units (HU). Patients with COPD had severe airflow obstruction (FEV(1) 35 +/- 15% pred) and severe reduction of CO diffusion constant (DCO/VA 37 +/- 19% pred). Maximal static elastic recoil pressure (Pst(max)) averaged 54 +/- 24% predicted, and the exponential constant K of pressure-volume curves was 258 +/- 116% predicted. Relative lung area with CT numbers < -950 HU averaged 21 +/- 11% (range 1 to 38%). It showed a highly significant negative correlation with DCO/VA (r = -0.84, p < 0.0001), a weak correlation with FEV(1)% predicted, and no correlation with either Pst(max) or constant K. A significant relationship was found between the natural logarithm of K and the full width at half maximum of the frequency distribution of CT numbers, taken as an index of the heterogeneity of lung density (r = 0.68, p < 0.0005). We conclude that currently used methods of assessing the extent of emphysema by HRCT closely reflect the reduction of CO diffusion constant, but cannot predict the elastic properties of the lung tissue.

Aged↗
PubMed2001

Fungal infections in lung transplantation. Incidence, risk factors and prognostic significance.

BACKGROUND AND AIM OF THE WORK: Fungal infections are frequent following lung transplantation and are associated with high mortality and morbidity. The study aims at 1) reporting our experience with fungal infections after lung transplantation; 2) identifying statistically significant correlations between the occurrence of fungal infections and bacterial infections, cytomegalovirus disease, rejection and steroid therapy; 3) assessing whether the presence of fungal infection has an impact on long-term survival. METHODS: 60 lung transplant recipients were studied with respect to incidence, pattern of presentation and median time to presentation of fungal infection after the transplant. Correlation analysis of the variables of interest was undertaken in 30 patients who had a minimum follow-up of 1 year following transplant. RESULTS: The prevalence of fungal infection was 44%; severe infections occurred in 5 patients (11%). The presence of Candida preoperatively was not associated with an increased risk of fungal infection. In a logistic regression analysis, a significant correlation was found between the occurrence of fungal infection and the following variables: respiratory bacterial infections (p = 0.0003), cytomegalovirus disease (p = 0.00001) and steroid therapy (p = 0.04). No statistically significant difference was found between patients who experienced a fungal infection and those who did not, either in univariate or multivariate survival analysis (p = 0.08). CONCLUSIONS: 1) fungal infections are frequent in lung transplant recipients and may be severe in more than 10% of the cases; 2) the presence of fungi preoperatively is not a contraindication to transplantation: an antifungal prophylaxis is probably indicated in such cases postoperatively; we recommend the use of the less nephrotoxic liposomal Amphotericin B by aerosol route; 3) a statistically significant association exists between fungal infections and both steroid therapy and CMV disease; this suggests that a similar antifungal prophylaxis is indicated in these clinical circumstances; 4) the presence of fungal infection is not an independent prognostic factor of long-term survival.

Adolescent↗
PubMed2000

Influence of obesity and type 2 diabetes on gluconeogenesis and glucose output in humans: a quantitative study.

The contribution of gluconeogenesis (GNG) to endogenous glucose output (EGO) in type 2 diabetes is controversial. Little information is available on the separate influence of obesity on GNG. We measured percent GNG (by the 2H2O technique) and EGO (by 6,6-[2H]glucose) in 37 type 2 diabetic subjects (9 lean and 28 obese, mean fasting plasma glucose [FPG] 8.3 +/- 0.3 mmol/l) and 18 control subjects (6 lean and 12 obese) after a 15-h fast. Percent GNG averaged 47 +/- 5% in lean control subjects and was significantly increased in association with both obesity (P < 0.01) and diabetes (P = 0.004). By multivariate analysis, percent GNG was independently associated with BMI (partial r = 0.27, P < 0.05, with a predicted increase of 0.9% per BMI unit) and FPG (partial r = 0.44, P = 0.0009, with a predicted increase of 2.7% per mmol/l of FPG). In contrast, EGO was increased in both lean and obese diabetic subjects (15.6 +/- 0.5 micromol x min(-1) x kg(-1) of fat-free mass, n = 37, P = 0.002) but not in obese nondiabetic control subjects (13.1 0.7, NS) as compared with lean control subjects (12.4 +/- 1.4). Consequently, gluconeogenic flux (percent GNG x EGO) was increased in obesity (P = 0.01) and markedly elevated in diabetic subjects (P = 0.0004), whereas glycogenolytic flux was reduced only in association with obesity (P = 0.05). Fasting plasma glucagon levels were significantly increased in diabetic subjects (P < 0.05) and positively related to EGO, whereas plasma insulin was higher in obese control subjects than lean control subjects (P = 0.05) and unrelated to measured glucose fluxes. We conclude that the percent contribution of GNG to glucose release after a 15-h fast is independently and quantitatively related to the degree of overweight and the severity of fasting hyperglycemia. In obese individuals, reduced glycogenolysis ensures a normal rate of glucose output. In diabetic individuals, hyperglucagonemia contributes to inappropriately elevated rates of glucose output from both GNG and glycogenolysis.

Adipose Tissue↗
PubMed1999

Videothoracoscopic lung biopsy in the diagnosis of interstitial lung disease.

OBJECTIVE: Interstitial lung diseases (ILD) require lung biopsy for the diagnosis in more than 30% of patients. Open lung biopsy (OLB) was generally considered the most reliable method of biopsy and tissue diagnosis. This study tests the diagnostic accuracy and safety of the videothoracoscopic lung biopsy (VTLB) in the diagnosis of ILD. METHODS: During the last 5 years, 58 patients were submitted to VTLB under general anesthesia. The mean age was 49.6 +/- 12.0 years (range 21-69). All the biopsies were performed by an endostapler EndoPath 30 or 45. Conversion to minithoracotomy was necessary in only one patient because of extensive pleural sinfisis. All the specimens were sent to the microbiology and pathology department for microbiological and histopathological diagnosis. One chest-tube (28F) was positioned and connected to a drainage-system and placed on suction. RESULTS: The histopathological diagnosis was obtained for all patients and therefore the diagnostic accuracy of the procedure was 100%. No postoperative haemothorax occurred and only two patients experienced a prolonged air-leakage (3.4%). The median duration of the chest-drain was 3 days (range 1-7) and the median hospital stay was 4 days (range 2-7). CONCLUSION: VTLB provides adequate specimen volume for histopathologic diagnosis and achieves a very high diagnostic accuracy (100% in our series). The postoperative morbidity and mortality rates are lower than those related to OLB. We conclude that VTLB is an effective and safe procedure in the diagnosis of ILD.

Adult↗
PubMed1999

Insulin: new roles for an ancient hormone.

Recent research has greatly expanded the domain of insulin action. The classical action of insulin is the control of glucose metabolism through the dual feedback loop linking plasma insulin with plasma glucose concentrations. This canon has been revised to incorporate the impact of insulin resistance or insulin deficiency, both of which alter glucose homeostasis through maladaptive responses (namely, chronic hyperinsulinaemia and glucose toxicity). A large body of knowledge is available on the physiology, cellular biology and molecular genetics of insulin action on glucose production and uptake. More recently, a number of newer actions of insulin have been delineated from in vitro and in vivo studies. In sensitive individuals, insulin inhibits lipolysis and platelet aggregation. In the presence of insulin resistance, dyslipidaemia, hyper-aggregation and anti-fibrinolysis may create a pro-thrombotic milieu. Preliminary evidence indicates that hyperinsulinaemia per se may be pro-oxidant both in vitro and in vivo. Insulin plays a role in mediating diet-induced thermogenesis, and insulin resistance may therefore be implicated in the defective thermogenesis of diabetes. In the kidney, insulin spares sodium and uric acid from excretion; in chronic hyperinsulinaemic states, these effects may contribute to high blood pressure and hyperuricaemia. Insulin hyperpolarises the plasma membranes of both excitable and non-excitable tissues, with consequences ranging from baroreceptor desensitisation to cardiac refractoriness (prolongation of QT interval). Under some circumstances insulin is vasodilatory-the mechanism involving both the sodium-potassium pump and intracellular calcium transients. Finally, by crossing the blood-brain barrier insulin exerts a host a central effects (sympatho-excitation, vagal withdrawal, stimulation of corticotropin releasing factor), collectively resembling a stress reaction. Description and understanding of these new roles, their interactions, the interplay between insulin resistance and hyperinsulinaemia, and their implications for cardiovascular disease have only begun.

Animals↗
PubMed1999

Inducing placebo respiratory depressant responses in humans via opioid receptors.

Several lines of evidence indicate that placebos produce analgesia through the activation of endogenous opioid systems. Recently, we showed that placebos may also produce respiratory depressant responses, a typical side-effect of narcotics, when a subject had a prior experience of respiratory depression in the course of narcotic treatment. In the present study, we report that the placebo respiratory depression can be induced after repeated administrations of the partial opioid agonist buprenorphine. The placebo respiratory depressant effect that resulted from the buprenorphine conditioning was completely blocked by a dose of 10 mg of naloxone, indicating that it was mediated by endogenous opioids. These findings show that placebos act, via the activation of opioid receptors, not only on pain mechanisms but on the respiratory centres as well, thus mimicking a typical side-effect of narcotics. In addition, the experimental procedure we used did not produce any expectation of respiratory depression and, similarly, the subjects did not notice any sign of respiratory discomfort. Thus, the placebo respiratory depression elicited in the present study cannot be explained on the basis of cognitive or motivational mechanisms. Rather, it appears to be a sequence effect due to learning, thus suggesting a conditioning mechanism mediated by endogenous opioids.

Aged↗
PubMed1999

Evidence that acute insulin administration enhances LDL cholesterol susceptibility to oxidation in healthy humans.

Increased free radical production and hyperinsulinemia are thought to play a role in experimental and human atherosclerosis, but the relation between the 2 abnormalities has not been studied. In 23 healthy volunteers, we measured the susceptibility of circulating low-density lipoprotein (LDL) cholesterol particles to in vitro copper sulfate oxidation (measured as the lag phase) and cell-mediated oxidative modification (measured as malondialdehyde generation in LDL during incubation with human umbilical vein endothelial cells), as well as the vitamin E content of LDL cholesterol at baseline and after 2 hours of physiological hyperinsulinemia (euglycemic insulin clamp). The lag time of LDL oxidation decreased from control values of 108+/-3 and 107+/-3 minutes (at baseline and after 2 hours of saline infusion) to 101+/-3 minutes after 2 hours of clamping (P<0.0001). At corresponding times, cell-mediated malondialdehyde generation in LDL rose from 4.96+/-0.11 and 4.98+/-0.10 to 5.28+/-0.10 nmol/L (P=0. 0006), whereas the LDL vitamin E content decreased from 6.78+/-0.06 and 6.77+/-0.06 to 6.64+/-0.06 microg/mg (P<0.04). The insulin-induced shortening of the lag phase was directly related to the decrement of vitamin E in LDL; furthermore, in subjects with higher baseline serum triglyceride levels, insulin induced a greater shortening of the lag phase than in subjects with low baseline triglycerides. We conclude that in healthy humans acute physiological hyperinsulinemia enhances the oxidative susceptibility of LDL cholesterol particles. This effect may have pathogenic significance for atherogenesis in insulin resistant states.

Adult↗
PubMed1998

The specific effects of prior opioid exposure on placebo analgesia and placebo respiratory depression.

Although in most of the cases the placebo response appears to be unpredictable, several factors have been considered in order to explain the placebo analgesic effect. For example, it is widely recognized, albeit with little empirical evidence, that placebo analgesia is more likely to occur after a successful analgesic therapy. On the basis of this assumption, we tested the placebo response in a population of patients who were treated with buprenorphine the day before for relieving postoperative pain. However, due to the high variability of opioid responsiveness, buprenorphine was effective in some patients and poorly effective in some others. Similarly, buprenorphine produced respiratory depression with a large variability, ranging from mild depression to no effect. We found that the placebo analgesic response depended on the buprenorphine analgesic effectiveness of the previous day. Analogously, we found that a placebo respiratory depressant response was more pronounced in those patients with a respiratory depressant response to buprenorphine on the day before, irrespective of the analgesic effectiveness. These specific effects suggest that (1) the placebo effect is experience-dependent; (2) the mechanisms underlying placebo analgesia and placebo respiratory depression are independent from each other and, by considering the role of endogenous opioids in placebo analgesia, might involve different subpopulations of opioid receptors.

Analgesia↗