[Regulatory T cells in kidney transplant recipients]. / Cellule T-regolatorie nel trapianto di rene.

Immunosuppressive drugs are essential for the prevention of acute transplant rejection but some may not promote long-term tolerance. Tolerance to self-antigens is ensured naturally by several mechanisms; one major mechanism depends on the activity of regulatory T lymphocytes (Treg), particularly CD4+CD25+ T cells. The transcription factor forkhead box protein 3 (Foxp3) has been identified as a molecular marker for Treg cells. The direct effects of immunosuppressive drugs on CD4+CD25+ cells are uncertain. In the clinical setting, basiliximab used in the induction phase of immunosuppression effectively reduced the number of acute rejection episodes. We studied the effects of the most widely used immunosuppressive induction regimens including cyclosporine, mycophenolate mofetil, steroids, and anti-CD25 monoclonal antibody (basiliximab) on the capacity to regulate human Treg in vivo. Twenty first cadaveric kidney transplant recipients (14 men, 6 women) were enrolled in the study. Blood samples were collected before kidney transplant and after one month. Blood sampling was done immediately before the administration of immunosuppressive therapy after an overnight fast. None of the transplant recipients presented laboratory or clinical signs of infection or acute rejection. The number and percentage of CD4+CD25+ and Foxp3+ T cells were determined by fluorescence activated cell sorter (FACS) analysis. Our results showed absence of both CD4+CD25+ and CD4+CD25+ Foxp3+ T cells one month after transplant. Peripheral CD4+CD25-Foxp3+ T cells significantly decreased after transplant but did not disappear. These preliminary data suggest that immunosuppressive induction therapy with basiliximab completely suppresses CD4+CD25+ regulatory cells and significantly reduces the total number of Foxp3+ lymphocytes.

Psychological Aspects and Psychopharmacologic Treatment in the Very Early Period After Kidney Transplantation: Role of a Multidisciplinary Approach.

BACKGROUND: In the context of kidney transplantation (KT), multidisciplinary interventions, including assessment and management of psychosocial aspects, are important to improve transplant's outcome. The aim of this study was to describe a multidisciplinary team approach to KT, with a specific focus on early detection and treatment of psychological distress and psychopathologic conditions in the early phase postsurgery. METHODS: The multidisciplinary team in kidney transplantation was implemented in January 2016. In this team approach, all transplant recipients are invited to 3 scheduled appointments for a multidisciplinary evaluation at 1, 3, and 6 months posttransplant, including a psychiatric interview, with the aim to assess the patient's adjustment after transplantation and provide support when necessary. RESULTS: This pilot study involved all 41 KT recipients consecutively referred for the first multidisciplinary appointment after transplantation. Five subjects (12% of the study sample) presented with a current psychiatric diagnosis. Psychopharmacologic treatment was confirmed or introduced for all these patients. Further psychological support was suggested to 4 other patients (10%). CONCLUSION: KT significantly improves patients' quality of life. However, the percentage of subjects receiving psychopharmacologic treatment and referred for further psychological and psychiatric support (22%) suggests the need for careful monitoring of psychosocial aspects over the long term.

Living Kidney Donation Is Recipient Age Sensitive and Has a High Rate of Donor Organ Disqualifications.

BACKGROUND: Living donor kidney transplantation (LDKT) is the best therapy for patients with chronic renal failure. Its advantages, compared with cadaveric transplantation, include the possibility of avoiding dialysis, the likelihood of best outcome, and donor pool expansion. Careful assessment of potential donors is important to minimize the risks and ensure success. However, the proportion of donors disqualified has been poorly investigated. The aim of this work is to describe our experience and present the main reasons for missed donation. METHODS: This was a single-center, retrospective study of all potential donors and recipients evaluated for LDKT between January 2008 and December 2017. RESULTS: During the period of study, 81 donor-recipient pairs were evaluated. Of these, 45.7% were disqualified and 37 LDKTs were carried out. LDKT was the first choice in 68% of cases and preemptive in 20%; 60% of transplants were among family members. Sex distribution revealed a prevalence of females in the donor group (69%) and males in the recipient group (70%). The mean living donor age was 53 ± 9.5 years; the mean recipient age was lower in recipients listed in the living transplant program than those listed for cadaver transplantation (45.8 ± 13.4 vs 54.2 ± 11.08; P < .0001). Reasons for denial included hypertension (18.9%), deceased donor transplant performed during the study period (16.2%), urologic pathology (13.5%), incompatibility (13.5%), withdrawal of consent by donor or recipient (13.5%), psychological unsuitability (8.1%), donor cancer (5.4%), and reduced renal clearance (2.7%). CONCLUSION: LDKT is considered an option especially for younger recipients. Of the potential kidney living donors, 45.7% were disqualified during the evaluation, with medical reasons being the primary cause.

[Lipoma of the parotid gland. Comments on a case]. / Lipoma della ghiandola parotide. Considerazioni su di un caso.

The authors present a case of parotid gland lipoma. They underline the clinical features, the unusual finding of it in the parotid lodge and the relationship with the surrounding tissues. After having shown the nosologic pattern of this neoplasm they underline the importance of the instrumental investigations by means of ET, TC and RM, that lead to a nearly sure pre-surgery diagnosis.

Poly(ethylene glycol)-mesalazine conjugate for colon specific delivery.

Chronic inflammatory bowel diseases (IBDs) are still waiting for improved and innovative therapeutic treatments, which can overcome the limits of the current approaches. Since IBDs affect mainly the lower tract of the intestine, a localized therapy in the colon tract will avoid most of the problems caused by systemic or poor selective therapies. Particularly promising are the advance drug delivery systems that can reach specific colon delivery, thus guaranteeing active agent release only at the site of action. This approach can meet two aims at the same time, first of all the drug will not affect healthy tissue and second a lower drug dose may be used because all the administered active agent will reach the target. To obtain a specific colon delivery we exploited the azoreductase enzymes, selectively present only in colon, by inserting an azo linker between a selected drug and a macromolecular carrier. The drug employed is mesalazine, a well know and used agent against IBDs. Poly(ethylene glycol) (PEG), of different molecular weights and structures, was used as carrier. Three different conjugates were synthesized and characterized, and the most promising one, with highest drug loading thanks to the use of diamino PEG of 4 kDa, was further investigated in vitro on mouse colonic epithelial cells (CMT-9) and in vivo on model mice with induced colitis. The data presented here demonstrate that PEG conjugation of mesalazine prevents drug release and absorption in upper intestine, after oral administration of the conjugates, and that the azo linker ensures a good drug release in the colon tract. The results in vivo take into consideration mice bodyweight gain, tissue histology and interleukin-2 beta as an index of inflammation. These parameters, all together, demonstrated the conjugate effectiveness against the controls.

Synthesis and biological in vitro evaluation of novel PEG-psoralen conjugates.

Psoralens are well-known photosensitizers, and 8-methoxypsoralen and 4,5',8-trimethylpsoralen are widely used in photomedicine as "psoralens plus UVA therapy" (PUVA), in photopheresis, and in sterilization of blood preparations. In an attempt to improve the therapeutic efficiency of PUVA therapy and photopheresis, four poly(ethylene glycol) (PEG)-psoralen conjugates were synthesized to promote tumor targeting by the enhanced permeability and retention (EPR) effect. Peptide linkers were used to exploit specific enzymatic cleavage by lysosomal proteases. A new psoralen, 4-hydroxymethyl-4',8-dimethylpsoralen (6), suitable for polymer conjugation was synthesized. The hydroxy group allowed exploring different strategies for PEG conjugation, and linkages with different stability such ester or urethanes were obtained. PEG (5 kDa) was covalently conjugated to the new psoralen derivative using four different linkages, namely, (i) direct ester bond (7), (ii) ester linkage with a peptide spacer (8), (iii) a carbamic linker (9), and (iv) a carbamic linker with a peptide spacer (12). The stability of these new conjugates was assessed at different pHs, in plasma and following incubation with cathepsin B. Conjugates 7 and 8 were rapidly hydrolyzed in plasma, while 9 was stable in buffer and in the presence of cathepsin B. As expected, only the conjugates containing the peptide linker released the drug in presence of cathepsin B. In vitro evaluation of the cytotoxic activity in the presence and absence of light was carried out in two cell lines (MCF-7 and A375 cells). Conjugates 7 and 8 displayed a similar activity to the free drug (probably due to the low stability of the ester linkage). Interestingly, the conjugates containing the carbamate linkage (9 and 12) were completely inactive in the dark (IC50 > 100 microM in both cell lines). However, antiproliferative activity become apparent after UV irradiation. Conjugate 12 appears to be the most promising for future in vivo evaluation, since it was relatively stable in plasma, which should allow tumor targeting and drug release to occur by cathepsin B-mediated hydrolysis.

CT in low back and sciatic pain due to lumbar canal osseous changes.

In a consecutive series of 600 patients scanned by CT for various spinal diseases, those with low back and sciatic pain without disc herniation were selected for study. The causes proved to be joint facet degeneration (32 cases), stenosis of the neural foramina (13 cases), stenosis of the spinal canal (13 cases), lateral recess stenosis (6 cases) and spondylolisthesis (6 cases). The predominance of joint facet pathology as the underlying cause of low back and sciatic pain in the absence of disc herniation is confirmed. CT scanning of the soft tissues as well as of the skeletal structures is crucial to the aetiological diagnosis of the condition under study and hence to the proper planning of treatment.

Degenerative changes in hypophyseal adenomas: CT features.

16 patients with hypophyseal adenoma undergoing degenerative changes, namely necrotic-cystic changes, bleeding and calcification, were subjected to CT and the resulting density values studied. The cases were verified at operation and at histological examination. Evaluation of these features, despite the limitations of the method, proved to be very useful in differential diagnosis and in the planning of treatment.

[Neuro-AIDS: a multicenter neuroradiological study]. / Neuro-AIDS: studio neuroradiologico multicentrico.

The results are described of a retrospective multicentric CT/MR study of 141 neuro-AIDS patients (IV group CDC classification); 114 patients were drug addicted, 13 homosexual, 8 polytransfused, and 6 had other risk factors. The mean age was 29.6 years. The pathologic agent was identified in 47 cases by c.s. fluid examination, biopsy, autopsy or specific treatment response: it was HIV in 20 cases, toxoplasmosis in 11, cryptococcosis in 9, leishmaniasis, salmonella and papovavirus in single cases. In the follow up of 2 cases, a Kaposi's sarcoma and a primitive CNS lymphoma occurred. The main clinical features were AIDS-dementia complex (45% of cases) and focal neurologic manifestations (36%). The neuroradiological protocol consisted of 238 CT exams (97 controls), most of them with DDD (delayed double dose) technique, 7 MR exams (0.15 T) and 2 angiographies. CT findings were divided into 3 groups: negative (16%), atrophic (47%) and focal lesions (37%). In the first and second group, HIV and cryptococcal infections were the main pathologic agents. In the third group toxoplasma infections were discovered, and TB granulomas and other pathologic conditions, with ring-like or nodular enhancement, in cortical/cortico-medullary location. In follow-up patients a high tendency of evolution towards focal lesions was observed, even in negative cases. The DDD enhancement technique allowed in most cases both the demonstration of very small lesions and their grading. According to the literature CT, though a highly sensitive method, is inferior to MR imaging; however our experience in this field is currently insufficient. The specific diagnosis of pathologic agents of neuro-AIDS is difficult, due to the high number of opportunistic AIDS-related infections and neoplasms, with overlapping features: differential diagnostic criteria can be assessed only by comparing the clinical, microbiological, topographic, CT and MR findings. CT and MR exams are necessary to guide and monitor therapy and to plan stereotaxis biopsy.