Biomedical subjects

Sandra Brunelleschi

Publications and source records attributed to Sandra Brunelleschi.

5 recordsLinked to original sources

PubMed2006

Gender differences in drug responses.

This review summarizes gender differences (GDs) in drug response. Although GDs have been described both in pharmacodynamics and pharmacokinetics, their role in clinical practice is not yet completely elucidated. The evidence that women have been less enrolled in clinical trials and that a gender-specific analysis usually is not included in the evaluation of results, contributes largely to this uncertainty. Consequently, adverse drug reactions (ADRs) are still higher in females than in males. Since sex is a fundamental biological variable that cannot be discounted, GDs in pharmacology have to be considered in order to improve drug safety efficacy and to optimize medical therapy both in men and women.

Cardiovascular System↗

PubMed2006

Macrophage-stimulating protein differently affects human alveolar macrophages from smoker and non-smoker patients: evaluation of respiratory burst, cytokine release and NF-kappaB pathway.

Macrophage activation is a key feature of inflammatory reactions occurring during bacterial infections, immune responses and tissue injury. We previously demonstrated that human macrophages of different origin express the tyrosine kinase receptor recepteur d'origine nantaise, the human receptor for MSP (RON) and produce superoxide anion (O(2)(-)) when challenged with macrophage-stimulating protein (MSP), the endogenous ligand for RON. This study was aimed to evaluate the role of MSP in alveolar macrophages (AM) isolated from healthy volunteers and patients with interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis), either smokers or non-smokers, by evaluating the respiratory burst, cytokine release and nuclear factor-kappa B (NF-kappaB) activation. MSP effects were compared with those induced by known AM stimuli, for example, phorbol myristate acetate, N-formyl-methionyl-leucyl-phenylalanine, lipopolysaccharide.MSP evokes O(2)(-) production, cytokine release and NF-kappaB activation in a concentration-dependent manner. By evaluating the respiratory burst, we demonstrate a significantly increased O(2)(-) production in AM from healthy smokers or smokers with pulmonary fibrosis, as compared to non-smokers, thus suggesting MSP as an enhancer of cigarette smoke toxicity. Besides inducing interleukin-1 beta (IL-1beta) and interleukin-10 (IL-10) production, MSP triggers an enhanced tumor necrosis factor-alpha release, especially in healthy and pulmonary fibrosis smokers. On the contrary, MSP-induced IL-10 release is higher in AM from healthy non-smokers. MSP activates the transcription factor NF-kappaB; this effect is more potent in healthy and fibrosis smokers (2.5-fold increase in p50 subunit translocation). This effect is receptor-mediated, as it is prevented by a monoclonal anti-human MSP antibody. The higher effectiveness of MSP in AM from healthy smokers and patients with pulmonary fibrosis is suggestive of its role in these clinical conditions.

Aged↗

PubMed2005

Expression of functional NK1 receptors in human alveolar macrophages: superoxide anion production, cytokine release and involvement of NF-kappaB pathway.

1 Substance P (SP) is deeply involved in lung pathophysiology and plays a key role in the modulation of inflammatory-immune processes. We previously demonstrated that SP activates guinea-pig alveolar macrophages (AMs) and human monocytes, but a careful examination of its effects on human AMs is still scarce. 2 This study was undertaken to establish the role of SP in human AM isolated from healthy smokers and non-smokers, by evaluating the presence of tachykinin NK(1) receptors (NK-1R) and SP's ability to induce superoxide anion (O(2)(-)) production and cytokine release, as well as activation of the nuclear factor-kappaB (NF-kappaB) pathway. 3 By Western blot analysis and immunofluorescence, we demonstrate that authentic NK-1R are present on human AMs, a three-fold enhanced expression being observed in healthy smokers. These NK-1R are functional, as SP and NK(1) agonists dose-dependently induce O(2)(-) production and cytokine release. In AMs from healthy smokers, SP evokes an enhanced respiratory burst and a significantly increased release of tumor necrosis factor-alpha as compared to healthy non-smokers, but has inconsistent effects on IL-10 release. The NK(1) selective antagonist CP 96,345 ((2S,3S)-cis-2-diphenylmethyl-N[(2-methoxyphenyl)-methyl]-1-azabicyclo-octan-3-amine)) competitively antagonized SP-induced effects. 4 SP activates the transcription factor NF-kappaB, a three-fold increased nuclear translocation being observed in AMs from healthy smokers. This effect is receptor-mediated, as it is reproduced by the NK(1) selective agonist [Sar(9)Met(O(2))(11)]SP and reverted by CP 96,345. 5 These results clearly indicate that human AMs possess functional NK-1R on their surface, which are upregulated in healthy smokers, providing new insights on the mechanisms involved in tobacco smoke toxicity.

Adult↗

PubMed2004

Anti-inflammatory drugs and tumor necrosis factor-alpha production from monocytes: role of transcription factor NF-kappa B and implication for rheumatoid arthritis therapy.

Inhibition of tumor necrosis factor-alpha (TNF-alpha) represents a relevant target in rheumatoid arthritis therapy. Besides inhibiting cyclooxygenase, anti-inflammatory drugs can affect the activation of transcription factors. We investigated the ability of dexamethasone, indomethacin, and rofecoxib to modulate nuclear factor-kappaB (NF-kappaB) activation and TNF-alpha release from human monocytes challenged with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA). Both stimuli induced NF-kappaB nuclear translocation and TNF-alpha secretion. Dexamethasone potently inhibited TNF-alpha release, indomethacin inhibited only PMA-evoked release, while rofecoxib had no effect. In the electrophoretic mobility shift assay, dexamethasone and rofecoxib dose-dependently inhibited the DNA binding activity of NF-kappaB in stimulated monocytes, whereas indomethacin failed to inhibit the LPS-evoked one. These results were further confirmed by evaluating the drugs' ability to reduce nuclear NF-kappaB subunits, as well as the amount of phosphorylated IkappaBalpha in cytosolic fractions. In conclusion, these results indicate that anti-inflammatory drugs differ largely in their ability to inhibit NF-kappaB activity and/or TNF-alpha release from human monocytes. These effects can be relevant to rheumatoid arthritis therapy.

Adult↗

PubMed2003

Risperidone-associated hyperprolactinemia: evaluation in twenty psychiatric outpatients.

Despite the lack of extrapyramidal side effects, some atypical antipsychotics can induce an increase in prolactinemia, as the conventional neuroleptics do. We decided to evaluate the effects of risperidone on serum prolactin levels and prolactin-related adverse effects in 20 outpatients of an Italian community psychiatric service. Patients enrolled in this study were on risperidone (2-8 mg per day; mean dose=4.15+/-0.4 mg per day) treatment in the period May-November 2002. The 20 patients, 13 women and 7 men (mean age=36.38+/-3.2 years for women and 29.7+/-2.2 for men) who accomplished inclusion criteria, participated in the study after giving informed written consent. Raised prolactin levels were observed in 13 (9 women and 4 men) out of 20 patients, but only 8 patients presented prolactin-related adverse effects, libido reduction being the most frequent. In this observational study, risperidone enhanced serum prolactin in 65% of patients. A good correlation was found between age and prolactin levels in pre-menopausal women, although no clear correlation among duration of treatment, dose used, prolactin levels and prolactin-related adverse effects could be established.

Adult↗