Plasma levels of neuropeptides in Alzheimer's disease.

BACKGROUND: In the central nervous system, several neuropeptides are believed to be involved in the pathophysiology of Alzheimer's disease (AD). Indeed, previous studies have documented that glucagon-like peptide 1 (GLP-1) possesses neurotropic properties and can reduce amyloid-beta peptide levels in the brain in vivo. Moreover, the concentrations of neuropeptide Y (NPY) seem to be altered in the cerebrospinal fluid of patients with AD and in subjects with major depression. Finally, among the modifications induced by aging, a dysregulation of the ghrelin-growth hormone (GH) system has been reported. METHODS: We investigated the plasma concentrations of these neuropeptides in 14 subjects with AD. Data obtained from these patients were compared with data from an age- and weight-matched healthy group. RESULTS: No significant differences were found between the two groups in relation to plasma levels of GLP-1, NPY, ghrelin and GH. Peripheral NPY concentrations were positively correlated with ghrelin levels in both groups, and with plasma GLP-1 concentration only in controls. CONCLUSION: On the basis of our results, peripheral levels of these neuropeptides seem not to serve as biochemical markers of AD.     

Coupling of lactose molecules to the carrier protein hinders the spleen and bone marrow uptake of doxorubicin conjugated with human albumin.

Several attempts have been made to enhance doxorubicin (DOXO) concentrations in tumour cells by drug conjugation with human albumin (HSA). HSA-DOXO has the drawback of causing DOXO accumulation in spleen and bone marrow, with a consequent leucopoenia not produced when lactose molecules are coupled to the carrier protein. In the present experiments we demonstrated that the effect of HSA lactosamination is not a consequence of a more rapid disappearance from the bloodstream of the lactosaminated conjugate (L-HSA-DOXO), which is rapidly internalized by the liver through the asialoglycoprotein receptor, but is due to a hindered uptake by spleen and bone marrow cells caused by the coupled lactose molecules. Experiments in vitro showed that HSA-DOXO produced an inhibition of murine macrophage proliferation not caused by L-HSA-DOXO. This result can be explained by higher amounts of the former conjugate entering in these cells and suggests macrophages as the cell type responsible for the spleen and bone marrow internalization of HSA-DOXO hindered by lactose coupling. Importantly, lactosamination of HSA did not reduce the marked uptake of HSA-DOXO by chemically induced rat hepatocellular carcinoma. L-HSA-DOXO, by avoiding DOXO accumulation in bone marrow is an attractive candidate for clinical trials against tumors which were found to actively internalize this conjugate in laboratory animals, such as hepatocellular carcinoma.     

Nephrotic syndrome in a mother and her infant: relationship with cytomegalovirus infection

This case report describes infantile nephrotic syndrome (NS) in a baby girl with a clinically severe cytomegalovirus (CMV) infection. Culture of the baby's urine was positive for CMV and IgM anti-CMV antibodies were detected. After an unsuccessful course of corticosteroids, gancyclovir treatment was started and a remission of cutaneous, pulmonary, and renal symptoms was achieved. As the mother also developed NS at the end of pregnancy, a common etiology could be postulated, although there were no signs of recent CMV infection in the mother, only anti-CMV IgG. The relationship between CMV infection and glomerular disease is still unclear: NS may represent another manifestation of CMV disease.     

Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB).

PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. INTRODUCTION: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. MATERIALS AND METHODS: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. RESULTS: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. CONCLUSIONS: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.     

Neridronate prevents bone loss in patients receiving androgen deprivation therapy for prostate cancer.

Today, androgen deprivation therapy is a cornerstone of treatment for advanced prostate cancer, although it presents important complications such as osteoporosis. Neridronate, a relatively new bisphosphonate, is able to prevent bone loss in patients with prostate cancer during androgen ablation. INTRODUCTION: Androgen-deprivation therapy (ADT) is a cornerstone of treatment for advanced prostate cancer. This therapy has iatrogenic complications, such as osteoporosis. The aim of our study was to evaluate the efficacy of neridronate, a relatively new bisphosphonate, to prevent bone loss during androgen ablation. MATERIALS AND METHODS: Forty-eight osteoporotic patients with prostate cancer, treated with 3-month depot triptorelina, were enrolled and randomly assigned to two different treatment groups: group A (n = 24) was treated with a daily calcium and cholecalciferol supplement (500 mg of elemental calcium and 400 IU cholecalciferol), and group B (n = 24) received in addition to the same daily calcium and cholecalciferol supplement, 25 mg of neridronate given intramuscularly every month. All patients also received bicalutamide for 4 weeks. Lumbar and femoral BMD was evaluated by DXA at baseline and after 1 year of therapy; moreover, deoxypyridinoline (DPD) and bone alkaline phosphatase (BALP) were determined at the beginning, midway through, and at the end of the study. RESULTS: After 6 and 12 months, whereas patients treated only with calcium and cholecalciferol (group A) showed a marked bone loss, with increased levels of DPD and BALP compared with baseline values, patients treated also with neridronate (group B) had substantially unchanged levels of these markers. After 1 year of treatment, lumbar and total hip BMD decreased significantly in patients treated only with calcium and cholecalciferol (group A), whereas it did not change significantly at any skeletal site in patients treated also with neridronate (group B). No relevant side effects were recorded during our study. CONCLUSIONS: Neridronate is an effective treatment in preventing bone loss in the hip and lumbar spine in men receiving ADT for prostate cancer.     

Estradiol and tryptophan depletion interact to modulate cognition in menopausal women.

Despite an abundance of data in animals, there is little research in humans regarding how estrogen and serotonin (5-HT) may interact to influence cognition. Through the use of estrogen treatment (ET) and tryptophan depletion (TRP-D) in a within-subject design involving healthy menopausal women, we have manipulated both estrogen and 5-HT in order to evaluate their individual and joint effects. Although neither manipulation influenced visuospatial learning, a significant interaction suggested that estrogen exerted a protective effect on verbal memory, such that TRP-D impaired performance to a greater extent before the administration of ET. In consonance with this finding, ET was associated with a small, but positive mood effect on the day following active TRP-D. In addition, ET significantly improved letter-cued verbal fluency with and without TRP-D. Finally, time since last menstrual period was significantly associated with verbal memory scores, such that longer length of hypogonadism resulted in decreased verbal memory performance. These data support the interaction of estrogen and 5-HT in nonreproductive behavior in humans as well as highlight the role of ovarian steroids in cognition.     

Lymphocyte responses in acute coronary syndromes: lack of regulation spawns deviant behaviour.

The inflammatory and immune systems are abnormally activatedduring the acute phases of coronary atherosclerotic disease.^1,2In particular, an unusual population of effector cells, lackingcostimulatory molecule CD28, is transiently expanded in parallelwith the occurrence of the waxing phases of atheroscleroticcoronary disease.³ The origin of the lymphocyte response in acute coronary syndromeshas been a matter of debate in the last decade. Questions stillovercome the answers. It has been demonstrated that the T-cellresponse can be directed to restricted antigens within the     

Non-specific bronchial hyper-responsiveness in children with allergic rhinitis: Relationship with the atopic status

An increased prevalence of bronchial hyper-responsiveness (BHR) has been demonstrated in children from a general population, and in non-asthmatic adults with allergic rhinitis. Thus, also children with allergic rhinitis are expected to be at higher risk of BHR. We evaluated the prevalence of BHR in a sample of non-asthmatic children with allergic rhinitis by means of the methacholine (Mch) bronchial challenge, and by monitorizing the airway patency using the daily peak expiratory flow variability (PEFv). Fifty-one children (ranged 6–15 years of age) with allergic rhinitis, ascertained by skin prick test to inhalant allergens, underwent a 14-day peak expiratory flow monitoring, and a Mch bronchial provocation challenge. Thirty healthy children matched for age, and sex served as control group. Thirty-one children in the rhinitis group (61%), and six (20%) in the control group were Mch+ (Mch provocative dose causing a 20% fall of forced expiratory volume in 1 s respect to baseline <2250  μ g, equivalent to 11.50  μ mol). In rhinitic children the PEFv did not significantly differ between Mch+ and Mch− subjects, but the total serum immunoglobulin E (IgE) were higher among Mch+. The persistent form of rhinitis was significantly associated to Mch positivity. Non-asthmatic children with allergic rhinitis displayed a high prevalence of BHR. The BHR was significantly associated with persistent rhinitis and with higher total IgE levels. Nevertheless, the spontaneous changes in airway patency, as expressed by PEFv, were within normal limits both in Mch+ and Mch− children.     

The psychiatric services in cremona: A case study of the Italian reform law

Italy's mental health law of 1978 provided for the gradual phasing out of psychiatric hospitals (PH) and the creation of comprehensive community-based systems. However, these changes have taken place at different times and in different forms. There are now three different organizational and care models operating in Italy: in the first, common in Southern Italy, the former PH and the new general hospital general wards (GHPW) coexist; in the second, outpatient departments complement the above facilities, but the hospital activity remains central; in the third model, a community model has been given priority-the so-called community priority. While many reports have been published describing the activity of some of the services adhering to the third model, no report has been published specifically describing the activity of services which work according to the second model, such as Cremona. In this paper, the activity of the Cremona psychiatric services is described, and the consequences of the reform law and the problems related to an hospital-based activity are emphasized.     

Distribution of 2-naphthol sulphotransferase and its endogenous substrate adenosine 3′-phosphate 5′-phosphosulphate in human tissues

The activity of sulphotransferase towards 2-naphthol and the concentration of its endogenous substrate, adenosine 3'-phosphate 5'-phosphosulphate (PAPS), have been measured in five specimens of human liver, lung, and kidney, and the mucosa from the ileum and the ascending, descending and sigmoid colon. The activity of 2-naphthol sulphotransferase (mean nmol.min-1.mg-1 protein) was 1.82 (liver); 0.034 (kidney); 0.19 (lung); 0.64 (ileum); 0.47 (ascending colon); 0.50 (descending colon); 0.40 (sigmoid colon). The concentration of PAPS (mean nmol.g-1 wet tissue) was 22.6 (liver); 4.8 (kidney); 4.3 (lung); 12.8 (ileum); 8.1 (ascending colon); 7.5 (descending colon); 6.2 (sigmoid colon). The concentration of PAPS and the activity of 2-naphthol sulphotransferase were higher in the liver than in the extrahepatic tissues. There was significant difference between ileum and ascending colon, both the activity of sulphotransferase and the concentration of PAPS being higher in the former. 2-Naphthol sulphotransferase activity and the concentration of PAPS have consistent distribution patterns. Differences between the tissues studied were more marked for sulphotransferase than for its endogenous substrate.