Anna Loraschi

Simvastatin treatment in subjects at high cardiovascular risk modulates AT1R expression on circulating monocytes and T lymphocytes.

Objective Angiotensin II, through the activation of angiotensin II type 1 receptors, plays a crucial role in atherosclerosis. Statins may interfere with the effects of angiotensin II. Methods We have investigated the expression of angiotensin II type 1 receptor, angiotensin II type 2 receptor and angiotensinogen on circulating monocytes and T-lymphocytes from subjects at high risk for vascular events before and during simvastatin treatment, and healthy controls. In-vitro experiments were also performed to assess the ability of simvastatin to interfere with angiotensin II signalling. Results In comparison with controls, high-risk subjects had similar angiotensin II type 1 receptor expression on the cell membranes but significantly higher angiotensin II type 1 receptor mRNA levels at least in monocyte subsets whereas their expression on T cells was similar. Angiotensin II type 2 receptor mRNA expression was higher than controls in both monocytes and T lymphocytes. No differences were observed in angiotensinogen expression on monocytes while T lymphocytes of high-risk subjects show higher expression. One-month treatment of high-risk subjects with simvastatin resulted in a reduction of angiotensin II type 1 receptor mRNA without affecting angiotensin II type 2 receptor whereas angiotensinogen mRNA expression was reduced at least in monocytes. Incubation in vitro with simvastatin reduces the expression of angiotensin II type 1 receptor mRNA levels on monocytes from untreated subjects. Conclusion Simvastatin induces down-regulation of the angiotensin II type 1 receptor, interferes with angiotensin II activity in immune cells and contributes to the anti-inflammatory profile of statins that can explain the therapeutic effects of these drugs.

Hepatotoxicity after high-dose methylprednisolone for demyelinating disease.

Liver toxicity, although not mentioned among the possible adverse effects of corticosteroids, has been occasionally reported in literature. We observed 2 cases of hepatotoxicity after a high-dose methylprednisolone treatment of a demyelinating disease and evaluated the potential relationship in the light of available evidence. The first patient developed a histologically documented acute hepatitis and recovered after 3 weeks. In the second patient, a mild augmentation of liver enzymes occurred, followed by normalization in a few days. The causal relationship between hepatotoxicity and methylprednisolone treatment was deemed probable in both cases. Careful review of the literature suggests that corticosteroid-induced liver damage may be more frequent than commonly believed.

Dietary supplement and drug use and doping knowledge and attitudes in Italian young elite cyclists.

Objective:To explore use and attitudes toward drugs and dietary supplements (DS) and knowledge concerning doping in cycling. Design:Retrospective cross-sectional study. Setting:Professional cycling. Participants:Elite under-23 male cyclists. Intervention:Anonymous semistructured questionnaire administered during race periods. Main Outcome Measures:Use and attitudes toward DS and drugs, and doping knowledge. Results:Forty cyclists aged 19 to 23 years and practicing for 14 to 30 h/wk were interviewed. Previous use (last 3 months) of drugs or DS occurred in 33 of 40 (82.5%) and 39 of 40 (97.5%) cyclists, respectively. Almost all the subjects named at least 1 doping agent (range, 1-10). Within a fixed list of 18 substances (among which only 14 were doping agents), participants recognized 3 to 18 of them as doping agents. They recognized tramadol and sildenafil as doping agents, which are not doping agents, and failed to recognize probenecid and albumin, which actually are. Doping knowledge correlated with drug use (r2 = 0.1614; P = 0.01). Participants deemed doping prevalence high among cyclists in general but not in their own team (P < 0.0001). Conclusions:Use of prescription drugs and DS was a common occurrence. Doping knowledge was poor and biased, and its relationship with drug use deserves consideration. Educational interventions are needed to improve knowledge and awareness about prescription drugs and DS use, as well as about doping.

Pain perception, blood pressure levels, and peripheral benzodiazepine receptors in patients followed for differentiated thyroid carcinoma: a longitudinal study in hypothyroidism and during hormone treatment.

BackgroundElevated blood pressure levels that are associated with hypalgesia and hypothyroidism have major influences on the cardiovascular system. The potential modulation of pain sensitivity by thyroid hormones is largely undetermined. Moreover, a few experimental studies show that peripheral benzodiazepine receptors (PBRs), which may be altered in hypothyroidism, seem to be related with pain perception. MethodsDental pain threshold and tolerance were evaluated in 19 patients followed for differentiated thyroid carcinoma (1) in severe short-term hypothyroidism (phase 1) and (2) during thyroid stimulating hormone-suppressive LT4 treatment (phase 2). PBR expression (cytofluorimetric evaluation) on peripheral blood mononuclear cells was also investigated in the 2 phases. ResultsPain perception differed throughout the study, the dental pain threshold was higher in phase 1 (P<0.05) whereas pain tolerance was higher but not significantly (P=0.07). Although the systolic blood pressure was higher during hypothyroidism (P<0.01), no relationship was found between blood pressure changes and pain sensitivity variations. Moreover, the multiple regression analysis showed an independent association of the clinical phase with pain sensitivity (r=−2.61, P=0.029), while accounting for systolic blood pressure. The intensity of PBRs was significantly higher in the first phase of the study (P=0.047) whereas the ratio did not significantly differ. However, no relationship was observed between pain sensitivity and PBRs. DiscussionIn conclusion, in athyreotic patients, the pain sensitivity is related to the thyroid status and is independent of the increase in blood pressure induced by thyroid hormone deprivation. The PBRs do not seem to have major influence on pain sensitivity changes in hypothyroidism.

An unusual systemic reaction associated with topical salicylic acid in a paediatric patient

Nongenital warts are generally harmless, self-limiting and often recover spontaneously; existing treatments usually require months to induce healing and recurrence is common [1]. Topical salicylic acid is widely use in wart removal; however, although generally well tolerated, it may elicit both local and systemic manifestations [2, 3]. Serious reactions to topical salicylate preparations so far reported are usually ascribed to percutaneous absorption of excessive amounts of salicylate ointment [3]. Here we present an unusual case of serious systemic illness arising in a child after the application of salicylic acid patches for a plantar wart. Parents sought advice for their 9-year-old son, after he had been complaining for 2 weeks of abdominal pain, nausea, constipation, increasing weakness and general illness. The abdominal pain started 2 days after beginning daily topical application of 15% salicylic acid patches (3.75 mg, 6 mm) for a plantar wart, and it was followed by the other symptoms a few days later. Familiarity with atopy, personal history of previous atopic dermatitis, food allergy, asthmatic bronchitis and cutaneous eruptions following clarithromycin administration were reported by his parents. Laboratory data (haemocrome, creatininaemia, glycaemia, transaminases, amylase, antitransglutaminase IgA, anti-Helicobacter pylori IgG) were normal except for IgE levels (53 kU l−1, normal values < 25 kU l−1). Stool samples were negative for common gastroenteritis agents (Salmonella, Shigella, Campylobacter, Rotavirus, Adenovirus, common parasites) and for occult blood. Instrumental examinations (abdominal ecosonography and X-ray) showed delayed gastric empting and coprostasis. After 3 weeks of unsuccessful therapy with domperidone and fleet enemas, the general condition significantly worsened with the appearance of mildly impaired mental performance. Symptoms considerably improved only a few days after the suspension of salicylate patch application (1 month after the beginning of treatment) and worsened again a couple of days later, when a new patch was applied for a relapsing wart. Definitive cessation of the topical treatment was followed by progressive improvement of the patients condition and symptoms completely disappeared within 2 weeks. To the best of our knowledge, this is the first report of such a systemic clinical picture occurring after the application of salicylic acid-containing patches. Although the clinical picture described is complex and unusual, the close temporal relationship between patch application and occurrence of symptoms, together with positive dechallenge and rechallenge and with the exclusion of any other alternative explanation (e.g. gastroenteritis, coeliac disease, other drugs), strongly supports topical preparation as the causative agent of the adverse reaction. Salicylates can be absorbed percutaneously, and wounded skin can increase local and systemic concentrations [3]. In this case, however, the reaction may not necessarily have been triggered by systemic exposure, also in view of the very low amount of salicylic acid contained (3.75 mg) and the small diameter (6 mm) of the patches. Even though nausea and epigastric pain in our patient may be consistent with salicylism, only routine examinations were performed in view of the medium clinical severity of symptoms. Glycaemia was normal, whereas electrolyte balance, acid-base status, and serum salicylate levels were not evaluated. Nonetheless, other common features of salicylism, such as sweating, tinnitus, blurring of vision and tachypnoea, were not observed, therefore, systemic toxicity was deemed unlikely. Salicylic acid may also evoke pseudoallergic (‘salicylate intolerance’) reactions, which are non-immunological reactions related to overproduction of leukotriene metabolites and impaired prostaglandin (PG) synthesis due to cyclooxygenase-1 inhibition [4]. Interestingly, clinical evidence indicates that both food allergy and its non-immunological form, food intolerance, may be associated with abdominal pain, constipation and coprostasis [5, 6], the main symptoms observed in our patient. Moreover, non steroidal anti-inflammatory drug (NSAID) use may be a risk factor for chronic constipation, probably due to the inhibition of PG synthesis [7]. Thus, also in view of our patients atopic profile, which is considered a risk factor for NSAID hypersensitivity [8], we interpreted the clinical picture as a pseudoallergic reaction to topical salycilate involving the gastroenteric tract. The parents were advised not to use any salicylic acid preparation for their son, either topical or systemic, and, in case of need, to choose paracetamol as a safe alternative, since it had been used previously in this subject and was well tolerated. In conclusion, considering the usually benign nature as well as the high rates of spontaneous remission, the risks and benefits of topical salicylate in the treatment of nongenital warts should always be carefully evaluated.