Efficacy and limits of the bariatric surgery

Morbid obesity is associated with and increased risk of serious comorbidities, including type 2 diabetes, sleep apnoea, cardiovascular diseases, and orthopedic disabilities. Not operative treatments for superobese patients have not been shown to produce reliable long-term benefits, therefore surgical therapy has became the treatment of choice. The number of surgical procedures increased in the last year confirm these data. However, before recommended a specific surgical procedures to a superobese patients it is necessary to consider some variables, such as: patient, health structure, and multidisciplinary equipe. Since there are not recommended or condemned surgical procedures, in this paper the Authors tried to evaluate the effectiveness and limits of the most performed surgical procedures for the treatment of pathologic obesity: gastric by-pass, biliopancreatic diversion (duodenal switch), vertical gastroplasty, banding gastric. The Authors used some pointer of outcome to measure effectiveness and limits: five year post-operative percentage excess weight loss >/< 50, peri-operative >/< 1%, early and late complications >/< 15%, reoperation >/< 3%, improvement of quality of life. Thanks to new surgical technique, restrictive options are losing ground, while malabsorbitive bariatric procedures are collecting successful.     

Inhibition of the chemokine receptor CXCR2 prevents kidney graft function deterioration due to ischemia/reperfusion

BACKGROUND: Ischemia/reperfusion (I/R) injury after organ transplantation is a major cause of delayed graft function. Following I/R, locally produced CXC chemokines attract and activate granulocytes, which in turn promote graft damage. METHODS: We examined the involvement of granulocyte recruitment via the CXCR2 pathway in a rat model of 4 hours cold ischemia followed by kidney transplantation. Serum creatinine and intragraft granulocyte infiltration were monitored in the early phase posttransplant. A CXCR2 inhibitor, repertaxin, was given to recipients before transplantation (at -24 hours or -8 hours or -2 hours), immediately before reperfusion and 2 hours later. RESULTS: An increase of granulocyte chemoattractant CINC-1/interleukin-8 (IL-8) mRNA expression after I/R both in syngeneic and allogeneic transplantation was associated with a marked infiltration of granulocytes in renal tissue. In syngeneic transplantation, Lewis rats given 15 mg/kg repertaxin 24 hours before surgery had granulocyte graft infiltration and serum creatinine levels significantly reduced in respect to vehicle-treated animals. Intermediate effects were observed with 5 mg/kg, whereas the dose of 30 mg/kg had toxic effects. We found that reducing the pretreatment time to 8 hours before surgery was still effective. Prevention of granulocyte infiltration and serum creatinine increase was also obtained in allogeneic transplantation, when Brown Norway recipients of Lewis kidneys were given 15 mg/kg repertaxin starting 8 hours before surgery. CONCLUSION: Repertaxin treatment of the recipient animal was effective in preventing granulocyte infiltration and renal function impairment both in syngeneic and in allogeneic settings. The possibility to modulate I/R injury in this rat model opens new perspectives for preventing posttransplant delayed graft function in humans.     

Expression of the polycystin-1 C-terminal cytoplasmic tail increases Cl channel activity in Xenopus oocytes

Expression of the polycystin-1 C-terminal cytoplasmic tail increases Cl(-) channel activity in Xenopus oocytes. Background. Cyst expansion in autosomal-dominant polycystic kidney disease (ADPKD) is characterized by active Cl(-) secretion in excess of solute reabsorption. However, the connections between elevated epithelial Cl(-) secretion and loss-of-function or dysregulation of either ADPKD gene polycystin-1 (PC1) or polycystin-2 (PC2) remain little understood. Methods. Cl(-) transport in Xenopus oocytes expressing the CD16.7-PKD1 (115-226) fusion protein containing the final 112 amino acid (aa) of the PC1 C-terminal cytoplasmic tail, or in oocytes expressing related PC1 fusion protein mutants, was studied by isotopic flux, two-electrode voltage clamp, and outside-out patch clamp recording. Results. Expression in oocytes of CD16.7-PKD1 (115-226) increased rates of both influx and efflux of (36)Cl(-), whereas CD16.7-PKD1 (1-92) containing the initial 92 aa of the PC1 C-terminal cytoplasmic tail was inactive. The increased Cl(-) transport resembled CD16.7-PKD1 (115-226)-stimulated cation current in its sensitivity to ADPKD-associated missense mutations, to mutations in phosphorylation sites, and to mutations within or encroaching upon the PC1 coiled-coil domain, as well as in its partial suppression by coexpressed PC2. The NS3623- and 4, 4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS)-sensitive (36)Cl(-) flux was not blocked by injected ethyleneglycol tetraacetate (EGTA) or by the cation channel inhibitor SKF96365, and was stimulated by the cation channel inhibitor La(3+), suggesting that CD16.7-PKD1 (115-226)-associated cation conductance was not required for (36)CI(-) flux activation. Outside-out patches from oocytes expressing CD16.7-PKD1 (115-226) also exhibited increased NS3623-sensitive Cl(-) current. Conclusion. These data show that CD16.7-PKD1 (115-226) activates Cl(-) channels in the Xenopus oocyte plasma membrane in parallel with, but not secondary to, activation of Ca(2+)-permeable cation channels.     

Relevance of Toll-like receptor-4 polymorphisms in renal transplantation

BACKGROUND: Polymorphisms in Toll-like receptor-4 (TLR4) have been reported to be associated with a blunted immune response to microbial pathogens, as well as a decreased risk of atherosclerosis in the general population. We assessed the impact of the two TLR4 variants on the risk of severe infection, the incidence of acute rejection, and the occurrence of atherosclerotic complications in renal transplant recipients (RTR). METHODS: TLR-4 polymorphisms were assessed in a cohort of 238 RTR. Post-transplant atherosclerotic events, acute rejection, severe bacterial infection, cytomegalovirus (CMV) disease, and opportunistic infections were evaluated as outcomes. RESULTS: The patients were followed for a mean duration of 95 +/- 29 months after transplant. TLR4 polymorphism was observed in 27 (11.3%) RTR. Subjects with TLR4 polymorphisms were less likely to experience post-transplant atherosclerotic events (RR 0.44; 95% CI 0.21 to 0.93; P= 0.02) and acute rejection (RR 0.41; 95% CI 0.30 to 0.83; P= 0.01), but presented severe bacterial infections (RR 1.33; 95% CI 1.12 to 1.67; P= 0.01) and opportunistic infections (RR 3.03; 95% CI 1.72 to 8.29; P= 0.008) more frequently. TLR4 polymorphism was marginally associated with CMV disease (RR 1.47; 95% CI 0.95 to 2.64; P= 0.08). CONCLUSION: RTR with TLR4 polymorphism present a lower risk of post-transplant atherosclerotic events and acute allograft rejection, but experience severe infectious episodes more frequently. This subset of RTR may benefit from a less potent immunosuppression regimen, along with increased preventive measures against infectious agents.     

Successful management of concomitant omphalocele, accessory hepatic lobe, and biliary atresia in a 44-day-old boy

We report the second case in literature of a boy with the association of large omphalocele, accessory hepatic lobe, and biliary atresia, and the first successful treatment. The patient was submitted to a surgical treatment at 44 days of life, including Kasai procedure, correction of the remnant abdominal wall defect, and removal of a hepatic accessory lobe. The boy evolved with normalization of hepatic function tests. After 15 years of follow-up, the patient is completely healthy, weights 45 kg, and is 1.64 m tall.     

Pretransplant donor peripheral blood mononuclear cells infusion induces transplantation tolerance by generating regulatory T cells

BACKGROUND: It was suggested that maintenance of tolerance to organ transplantation may depend on the formation of T regulatory cells. METHODS: Lewis (LW) rats were made tolerant to a Brown Norway kidney by pretransplant donor peripheral blood mononuclear cells (PBMC) infusion. At greater than 90 days after transplantation, lymph node cells (LN) and graft-infiltrating leukocytes (GIL) alloreactivity was tested in mixed lymphocyte reaction (MLR), coculture, and transwell experiments. GIL phenotype was analyzed by FACS. mRNA expression of cytokines and other markers was analyzed on CD4+ T cells from LN. The tolerogenic potential of tolerant cells in vivo was evaluated by adoptive transfer. RESULTS: Tolerant LN cells showed a reduced proliferation against donor stimulators but a normal anti-third-party alloreactivity. In coculture, these cells inhibited antidonor but not antithird-party reactivity of na?ve LN cells. Interleukin (IL)-10 and FasL mRNA expression was up-regulated in tolerant CD4+ T cells, but an anti-IL-10 monoclonal antibody (mAb) only partially reversed their inhibitory effect. Immunoregulatory activity was concentrated in the CD4+ CD25+ T-cell subset. In a transwell system, tolerant T cells inhibited a na?ve MLR to a lesser extent than in a standard coculture. Regulatory cells transferred tolerance after infusion into na?ve LW recipients. CD4+ T cells isolated from tolerized grafts were hyporesponsive to donor stimulators and suppressed a na?ve MLR against donor antigens. CONCLUSIONS: Donor-specific regulatory T cells play a role in tolerance induction by donor PBMC infusion. Regulatory activity is concentrated in the CD4+ CD25+ subset and requires cell-to-cell contact. Regulatory CD4+ T cells accumulate in tolerized kidney grafts where they could exert a protective function against host immune response.     

Genetic and epigenetic features in radiation sensitivity

Recent progress especially in the field of gene identification and expression has attracted greater attention to the genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation, offering a better likelihood of cure for malignant tumours. Although only a small percentage of individuals are hypersensitive to radiation effects, all medical specialists using ionising radiation should be aware of the aforementioned progress in medical knowledge. The present paper, the second of two parts, reviews human disorders known or strongly suspected to be associated with hypersensitivity to ionising radiation. The main tests capable of detecting such pathologies in advance are analysed, and ethical issues regarding genetic testing are considered. The implications for radiation protection of possible hypersensitivity to radiation in a part of the population are discussed, and some guidelines for nuclear medicine professionals are proposed.Part I of this review article is available at     

Early and late effects of X-irradiation on submandibular gland: a morphological study in mice

BACKGROUND: Radiotherapy for head and neck cancers causes permanent salivary gland dysfunction and xerostomia. The aim of this study was to determine changes in mice submandibular glands after X-irradiation. METHODS: The submandibular glands of male C57BL/6 mice were locally X-irradiated in the head and neck region with a single dose of 7.5 or 15 Gy and analyzed morphologically and morphometrically at 1, 3, 6, 10, 40, and 90 days after irradiation. RESULTS: Two phases of gland reaction to irradiation have been noted. The first, early phase is observed up to 10 days after irradiation. The second, late phase was observed 90 days after irradiation. Also, a dose-related effect was noticed. The most prominent morphological changes were pyknotic nuclei, vacuolization of acinar cells and lysis of acini and granular convoluted tubules. Changes were detected at 3 and 6 days after irradiation followed by tissue regeneration. Ninety days after irradiation, prominent pathological changes (vacuolization and pyknotic nuclei of acinar cells, lysis of acini and granular convoluted tubules and edema) were detected, but the most remarkable change was disseminated mononuclear infiltration. Also, a statistically significant reduction in number of acinar cells was detected in both irradiated glands. CONCLUSIONS: Occurrence of disseminated mononuclear infiltration in gland during late post-irradiation phase makes the mouse model potentially better than the rat model for investigation of irradiation-induced salivary gland damage.