Use of PABA test to check completeness of 24-h urine collections in elderly subjects.

The p-aminobenzoic acid (PABA) test has been successfully used as an indicator of completeness of 24-h urine collection in field studies of the general population. Our study was designed to investigate its validity for elderly people. Urinary excretion of fractionated oral doses of PABA was measured in 21 young control subjects (19-39 yr old) and 356 elderly (60-89 yr old) men and women. PABA excretion over 24 h was lower in elderly than in control subjects. Subjects aged greater than or equal to 70 yr had a lower recovery of the PABA dose than subjects aged 60-69 yr over the first 24 h, followed by a higher recovery over the next 24-48 h. The cumulative 48-h recovery was similar in all age classes of elderly subjects. However, 48% of the elderly subjects had a cumulative PABA recovery below the conventional cutoff for completeness (85%). These subjects also had consistently lower creatinine output and urinary volume. The lower 24-h urinary PABA recovery over 70 yr of age is interpreted to reflect the delayed renal clearance of the marker substance and indicates that the PABA test is unsuitable for this age group. The low 48-h cumulative recoveries found in all age classes of the elderly are thought to be caused by small unreported losses, which are recurrent in free-living populations.     

The response of NG2-expressing oligodendrocyte progenitors to demyelination in MOG-EAE and MS

Remyelination of primary demyelinated lesions is a common feature of experimental models of multiple sclerosis (MS) and is also suggested to be the normal response to demyelination during the early stages of MS itself. Many lines of evidence have shown that remyelination is preceded by the division of endogenous oligodendrocyte precursor cells (OPCs) in the lesion and its borders. It is suggested that this rapid response of OPCs to repopulate the lesion site and their subsequent differentiation into new oligodendrocytes is the key to the rapid remyelination. Antibodies to the NG2 chondroitin sulphate proteoglycan have proved exceedingly useful in following and quantitating the response of endogenous OPCs to demyelination. Here we review the literature on the response of NG2-expressing OPCs to demyelination and provide some new evidence on their response to the chronic inflammatory demyelinating environment seen in recombinant myelin oligodendrocyte glycoprotein (MOG) induced experimental allergic encephalomyelitis (EAE) in the DA rat. NG2-expressing OPCs responded to the inflammatory demyelination in this model by becoming reactive and increasing in number in a very focal manner. Evidence of NG2⁺OPCs in lesioned areas beginning to express the oligodendrocyte marker CNP was also seen. The response of OPCs appeared to occur following successive relapses but did not always lead to remyelination, with areas of chronic demyelination observed in the spinal cord. The presence of OPCs in the adult human CNS is clearly of vital importance for repair in multiple sclerosis (MS). As in rat tissue, the antibody labels an evenly distributed cell population present in both white and grey matter, distinct from HLA-DR⁺microglia. NG2⁺cells are sparsely distributed in the centre of chronic MS lesions. These cells apparently survive demyelination and exhibit a multi-processed or bipolar morphology in the very hypocellular environment of the lesion.     

Body growth in early diagnosed vesicoureteric reflux

Body growth was studied in 32 subjects with vesicoureteric reflux (VUR), diagnosed following the prenatal finding of urinary tract dilatation, who had normal renal filtration function and who received antibacterial prophylaxis by the first few days of life. They were followed for 1–5 years (mean 2.3 years). Most had persistent VUR during the 1st year of life. Body growth performance was compared with that of 94 subjects with VUR diagnosed and treated by us after the neonatal period. During the follow-up period, none of the patients with prenatally detected VUR had a height Z score below –2, nor a weight-for-height index below 90%, and 1 had variations in height Z score ≥1. The difference in the percentage of patients with prenatally detected VUR (1/32) and those with VUR diagnosed and treated after the neonatal period (20/94) who had variations in height Z score ≥1 was significant (P=0.035). Patients with prenatally detected VUR and normal renal filtration function, given antibacterial prophylaxis by the first few days of life, have normal body growth, although VUR still persists. Received: 19 March 1998 / Revised: 10 February 1999 / Accepted: 10 February 1999     

The conjugate Rituximab/saporin-S6 completely inhibits clonogenic growth of CD20-expressing cells and produces a synergistic toxic effect with Fludarabine.

Immunotoxins are chimeric proteins consisting of a toxin coupled to an antibody. To date, several clinical trials have been conducted, and some are still ongoing, to evaluate their anti-tumor efficacy. In this view, we chemically constructed an anti-CD20 immunotoxin with the mAb Rituximab and the type 1 ribosome-inactivating protein (RIP) saporin-S6, designed for B cells non-Hodgkin's lymphoma (NHL) therapy. This immunotoxin showed a specific cytotoxicity for the CD20+ cell lines Raji and D430B, evidenced by inhibition of protein synthesis, evaluation of apoptosis and clonogenic assay. Upon conjugation, saporin-S6 increased its toxicity on target cells by at least 2 logs, with IC(50) values of 0.1-0.3 nM. The percentage of AnnexinV+ cells was over 95% in both cell lines treated with 10 nM immunotoxin. A complete elimination of Raji clones was reached with the 10 nM immunotoxin, whereas a mixture of free RIP and mAb gave about 90% of clonogenic growth. Rituximab/saporin-S6, at 10 nM concentration, also induced apoptosis in 80% of lymphoma cells from NHL patients. Moreover, sensitivity of Raji to Rituximab/saporin-S6 was augmented when cells were coincubated with Fludarabine. The synergistic toxic effect of the two drugs led to a total elimination of the neoplastic population.     

Association between trauma and cancer of the testis: the importance of self-palpation of the testis for the early detection: two case reports

introduction: Cancer of the testis is not always early detected and recognised, both by the physician and by the patient: sometimes physicians do not make an accurate genitals exam while patients often underestimate this problem. Case reports: Case I: 42-year-old man accepted from another hospital's Emergency, because of pain and edema of the right testis after a recent trauma on the gonad. At US, evidence of increased volume of the right testis with a large intraparenchymal hematoma. The markers were higher than normal. We performed a right orchiecthomy. The pathologist noted the presence of a mixed cancer of the testis (95% embryonal, 5% seminoma). Case II: 49-year-old man with hematuria, accepted from Emergency. The abdominal US revealed the presence of a voluminous neoformation (diameter of 12 cm) of the right kidney with neoplastic thrombosis of the right kidney vein. At the general physical exam, we detected the presence of an increased right testis, that at the US appared to be suspicious for cancer. Tumor markers were normal with the exception of αFP. We performed right nephro-adrenalectomy, right orchiectomy and removal of local nodes. The definitive histological examination demonstrated the presence of a seminoma of the testis and papillary carcinoma of the kidney with node metastasis. Discussion: Current studies showed an association between trauma and cancer of the testis, even if some authors did not find this association because they consider that patients with trauma undergo US and in that occasion cancer is incidentally detected. Conclusions: The association between trauma and cancer of the testis is controversial in current studies. Furthermore screening for the cancer of the testis does not seem to be useful, even if the self- and the physician's palpation of the testis seem to be very important because in these two cases they should allow the early detection of the condition, with a resulting better prognosis.     

Saporin-S6: A Useful Tool in Cancer Therapy

Thirty years ago, the type 1 ribosome-inactivating protein (RIP) saporin-S6 (also known as saporin) was isolated from Saponaria officinalis L. seeds. Since then, the properties and mechanisms of action of saporin-S6 have been well characterized, and it has been widely employed in the construction of conjugates and immunotoxins for different purposes. These immunotoxins have shown many interesting results when used in cancer therapy, particularly in hematological tumors. The high enzymatic activity, stability and resistance to conjugation procedures and blood proteases make saporin-S6 a very useful tool in cancer therapy. High efficacy has been reported in clinical trials with saporin-S6-containing immunotoxins, at dosages that induced only mild and transient side effects, which were mainly fever, myalgias, hepatotoxicity, thrombocytopenia and vascular leak syndrome. Moreover, saporin-S6 triggers multiple cell death pathways, rendering impossible the selection of RIP-resistant mutants. In this review, some aspects of saporin-S6, such as the chemico-physical characteristics, the structural properties, its endocytosis, its intracellular routing and the pathogenetic mechanisms of the cell damage, are reported. In addition, the recent progress and developments of saporin-S6-containing immunotoxins in cancer immunotherapy are summarized, including in vitro and in vivo pre-clinical studies and clinical trials.     

Medida do desempenho físico por testes de campo em programas de reabilitação cardiovascular: revisão sistemática e meta‐análise

Introduction

The literature concerning the effects of cardiac rehabilitation (CR) on field tests results is inconsistent.

Serotonin transporter polymorphism modifies the association between depressive symptoms and sleep onset latency complaint in elderly people: results from the ‘InveCe.Ab’ study

Previous studies have documented the involvement of the central nervous system serotonin in promoting wakefulness. There are few and conflicting results over whether there is an actual association between bearing the short allele of serotonin transporter promoter polymorphism (5‐HTTLPR) and worse sleep quality. This study examined whether sleep onset latency complaint is associated with the 5‐HTTLPR triallelic polymorphism in the SLC6A4 gene promoter and whether this polymorphism influences the relationship between sleep onset latency complaint and depressive symptoms in elderly people. A total of 1321 community‐dwelling individuals aged 70–74 years were interviewed for sleep onset latency complaint and for sleep medication consumption. Participants’ genomic DNA was typed for 5‐HTTLPR and rs25531 polymorphisms. Depressive symptoms were evaluated with the Geriatric Depression Scale Short form and general medical comorbidity was assessed by the Cumulative Illness Rating Scale. The presence of a past history of depression was recorded. The S′ allele of the 5‐HTTLPR triallelic polymorphism was associated with sleep onset latency complaint. This association was maintained after adjusting for depressive symptoms, sex, age, history of depression and medical comorbidity. After stratification for 5‐HTTLPR/rs25531, only in S′S′ individuals high depressive symptoms were actually associated with sleep onset latency complaint. These data indicate that the low‐expressing 5‐HTTLPR triallelic polymorphism is an independent risk factor for sleep onset latency disturbance. Furthermore, the 5‐HTTLPR genotype influences the association between depressive symptoms and sleep onset latency complaint.     

In vitro anti-tumour activity of anti-CD80 and anti-CD86 immunotoxins containing type 1 ribosome-inactivating proteins

Immunotoxins specific for the CD80 and CD86 antigens were prepared by linking three type 1 ribosome-inactivating proteins (RIPs), namely bouganin, gelonin and saporin-S6, to the monoclonal antibodies M24 (anti-CD80) and 1G10 (anti-CD86). These immunotoxins showed a specific cytotoxicity for the CD80/CD86-expressing cell lines Raji and L428. The immunotoxins inhibited protein synthesis by target cells with IC50s (concentration causing 50% inhibition) ranging from 0.25 to 192 pmol/l as RIPs. The anti-CD80 immunotoxins appeared 1-2 log more toxic for target cells than the anti-CD86 ones. Immunotoxins containing saporin and bouganin induced apoptosis of target cells. The toxicity for bone marrow haemopoietic progenitors of these conjugates was also evaluated. Bouganin and related immunotoxins at concentrations up to 100 nmol/l did not significantly affect the recovery of committed progenitors or of more primitive cells. The saporin-containing immunotoxins at concentrations >/= 1 nmol/l showed some toxicity on colony-forming unit cells (CFU-C). The expression of the CD80 and CD86 molecules is prevalently restricted to antigen-presenting cells and is also strong on Hodgkin and Reed-Sternberg cells in Hodgkin's disease. Present results suggest that immunotoxins targeting type 1 ribosome-inactivating proteins to these antigens could be considered and further studied for the therapy of Hodgkin's disease or other CD80/CD86-expressing tumours.