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Background: Traumatic brain injury (TBI) is a major risk factor for Alzheimer’s disease (AD). Although the mechanisms that lead to AD after a TBI are unclear, we hypothesize that changes in amyloid-β (Aβ) metabolism and abnormal tau phosphorylation are reasonable candidates.Objective: To investigate Aβ and tau dynamics in the chronic phase of TBI.Methods: We evaluated Aβ1-42, total tau (t-tau), and phosphorylated tau (p-tau) levels in the cerebrospinal fluid (CSF) of 15 patients who developed a prolonged disorder of consciousness after a severe TBI (mean time from TBI 271.6 ± 176.5 days).Results: Reduced Aβ1-42 levels (median 258 pg/ml, range 90–833.6) were observed in 14/15 patients (93.3%) with severe post-TBI disorders of consciousness. These CSF analysis data did not correlate with time since TBI or with the patients’ level of consciousness as determined by the Coma Recovery Scale Revised. Normal t-tau levels (median 95.2 pg/ml, range 52–256.9) were found in all patients. Normal p-tau levels (...

Traumatic brain injury (TBI) is a major risk factor for Alzheimer disease (AD). Although the mechanisms that lead to AD after a TBI are largely unknown, changes in amyloid- β (A β ) metabolism and abnormal tau phosphorylation are probably involved. In this study, we evaluated A β 1 - 42 , total tau (t-tau), and phosphorylated tau (p-tau) levels in the cerebrospinal fluid (CSF) of 15 patients who developed a prolonged disorder of consciousness after a severe TBI (mean time from TBI 271.6 ± 176.5 days; range 92–578 days). Reduced A β 1 - 42 levels (cohort median value 258 pg/ml, range 90–833.6 pg/ml) were observed in 14/15 patients (93.3%) with severe post-TBI disorders of consciousness. Normal t-tau levels (median 95.2 pg/ml, range 52–256.9 pg/ml) were found in all patients. Normal p-tau levels (median 22.2 pg/ml, range 14–72 pg/ml) were observed in 14/15 patients, while 1 patient had a p-tau level slightly increased. In conclusion, the present findings show that reduced CSF A β levels are not paralleled by significant changes in t-tau and p-tau levels; these results suggest that treatments aimed to prevent chronic neurodegeneration and AD risk after a severe TBI may be better targeted on A β than tau.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that influences neuronal plasticity throughout life. Emergence from a vegetative state (VS) after a traumatic brain injury (TBI) implies that the brain undergoes plastic changes. A common polymorphism in the BDNF gene—BDNF Val66Met (referred to herein as BDNFMet)—impairs cognitive function in healthy subjects. The aim of this study was to determine whether the BDNFMet polymorphism plays a role in the recovery of consciousness and cognitive functions in patients in a VS after a TBI. Fifty-three patients in a VS 1 month after a TBI were included in the study and genotyped for the BDNFMet polymorphism. Scores of levels of cognitive functioning (LCF) at 1, 3, 6, and 12 months post-TBI were retrospectively compared in patients without (Val group), and with (Met group), the BDNFMet polymorphism. The BDNFMet polymorphism was detected in 20 out of the 53 patients. The mean LCF scores in the Val and Met groups were 1.6 – 0.5 and 1.4 – 0.5 at 1 month, 2.3 – 0.7 and 2.5 – 1.2 at 3 months, 3.3 – 1.7 and 3.5 – 1.7 at 6 months, and 4 – 1.9 and 3.9 – 1.8 at 12 months, respectively ( p > 0.05). The percentages of patients in the Val and Met groups who emerged from the VS were 36.4% and 30% at 3 months, 66.3% and 70% at 6 months, and 70% and 87.5% at 12 months ( p > 0.05), respectively. These findings provide evidence that the BDNFMet polymorphism is not involved in cognitive improvement in patients with a VS following TBI. Future studies should focus on the role of other BDNF polymorphisms in the recovery from a VS.

PIPERACILLIN (PP) is a wide-spectrum bactericidal ureidopenicillin. There have been a number of reports of cutaneous adverse reactions to PP, particularly in patients affected by cystic fibrosis. A cellmediated immunopathogenic mechanism has been demonstrated (on the basis of patch-test or delayed intradermal-test positivity) in only two cases of maculopapular reactions to PP (1,2). This report describes two cases of cutaneous reactions to PP that appear to have been caused by delayed hypersensitivity. Patient 1: A 38-year-old male immediately after a hemorrhoidectomy had been started on PP (Avocin 4 g/day intramuscularly), and after 6 days of treatment a generalized erythematous rash developed. The antibiotic was discontinued and after 7 days of corticosteroid therapy the skin lesions resolved. Patient 2: This 42-year-old male had undergone surgery for cranial trauma. Avocin (4 g/day intramuscularly) was administered during the postoperative period and a generalized maculopapular rash developed on the fourth day. The drug was then discontinued, and corticosteroid therapy was started. The rash resolved within 10 days, leaving generalized scaling. Neither patient had a personal or family history of allergic diseases. Two and seven months later, respectively, the patients underwent skin tests with penicilloylpolylysine (Allergopen, Reinbeck, Germany), minor determinant mixture (Allergopen), benzylpenicillin (BP), ampicillin (AM), amoxicillin (AX) and PP, as well as cefaclor and ceftriaxone, as previously described (3). AM, AX and PP were used at concentrations of 1 and 20 mg/ml in 0.9% NaCl, cephalosporins at 2 mg/ml. Both patients presented skin-test negativity after 20 min, and delayed intradermal reactions (after 24 h in case 1 and 48 h in case 2) only to AM, AX and PP: erythematous, indurated wheals larger than 10 mm, which began to fade after 72 h. Intradermal tests with PP were negative in 10 healthy control subjects, 4 of whom had previously tolerated PP. Patch tests were done with BP, AM, and AX (5% in petrolatum), as well as with PP, cefaclor and ceftriaxone (200 mg/ml in 0.9% NaCl) as previously described (3). Only those with AM, AX and PP were positive at the 48and 72h readings (patient 1:+++for all haptens; patient 2:+for all haptens). Single-blind challenges with BP (1000 000 IU), ceftriaxone (1 g) and cefaclor (500 mg) were also performed, the first two intramuscularly and the last orally. Increasing doses (0.01, 0.1 and 1.0 of the respective therapeutic doses indicated in parentheses) were administered at 1 week intervals, and were well tolerated. The characteristics of these two cases (i.e., cutaneous reactions appearing more than 48 h after the initiation of therapy, as well as patch-test and delayed intradermal-test positivity) are indicative of delayed hypersensitivity to PP. Patch tests and delayed-reading intradermal tests are a simple and effective means of diagnosing this type of reaction. Both of the previously described subjects displayed allergologic-test negativity to penicillin determinants as well as to AM and AX (1,2). Thus, their reactions were probably caused by a selective sensitization to PP; however, they were not challenged with other blactams to assess such selectivity. Our patients presented positive reactions to AM and AX, as well as to PP, but there were no reactions to penicillin determinants or to cephalosporins. The cross-reactivity between PP and the aminopenicillins may reflect the presence of antigenic structures shared by the side-chains of all three semisynthetic penicillins. However, considering that subjects tolerated cefaclor (an aminocephalosporin which shares the aminobenzyl side chain with AM and AX) recognition of the penicillin thiazolidin ring also appears to be important.

The extracellular matrix (ECM) is known to play an active role in numerous biological processes such as differentiation, apoptosis and cancer. Extensive alterations of epithelial basement membranes and of interstitial ECM are known to occur during the progression of most invasive carcinomas. Collagen, which represents the major component of the interstitial ECM, is primarily involved in the stromal changes at the site of tumor cell invasion. We have previously described the occurrence in breast and colon cancer ECM of an oncofetal form of collagen, characterized by an acidic chain distinct from those of type I and III collagen. In the present paper, we bring evidence that alpha2(I) collagen chains in colon cancer tissues expressing the acidic chains, are either overmodified or absent, both as protein and as regular mRNA transcripts. The results obtained strongly suggest that: i) the disorganisation of the collagen architecture and the phenomenon of fibril dispersion, which accompanies the lysis of basement membrane, is not only due to the enzymatic degradation of the collagen fibres, but presumably also to changes of the collagen molecules deposited in the stroma; ii) the neosynthesis of collagen occurring at tumor-host interface is deeply deregulated, and therefore to be considered the result of altered collagen gene expression correlated with the tumor progression, rather than as a mere defensive reaction of the host cells.

We investigated the mechanisms that regulate the efficacy of agonists in the arginine-vasopressin (AVP)/oxytocin (OT) receptor system. In this paper, we present evidence that AVP, a full agonist of the vasopressin receptors, acts as a partial agonist on the oxytocin receptor. We also found that AVP becomes a full agonist when two aromatic residues of the oxytocin receptor are replaced by the residues present at equivalent positions in the vasopressin receptor subtypes. Our results indicate that these two residues modulate the response of the oxytocin receptor to the partial agonist AVP.

A patient with maculopapular reactions to iopamidol needed to undergo angiography for a cerebral arteriovenous malformation. In vivo and in vitro tests were performed with ionic and nonionic contrast media, including iopamidol and iobitridol. All results were positive, demonstrating delayed hypersensitivity. The patient received 6-α-methylprednisolone and cyclosporine 1 week before and 2 weeks after four angiograms were obtained with the use of iobitridol, which was well tolerated. © RSNA, 2002