IL-8 and IFN-gamma in tear fluid of patients with cystic fibrosis.

Cystic fibrosis (CF) is inherited as an autosomal recessive disorder. It is caused by mutations in the protein-coding gene of chromosome 7, resulting in chronic pulmonary disease and pancreatic insufficiency. The disease affects all secretory epithelia, including the eye. The pathogenesis of ocular changes in CF is still unknown, but the involvement of immunologic processes in patients with CF has been studied in recent years. We measured interleukin-8 (IL-8) and interferon-gamma (IFN-gamma) levels in tears in a group of patients and a group of normal controls to determine if the levels of these cytokines are elevated in CF. The levels of these cytokines in tears and the clinical severity of CF and eye disease were compared. Tear samples were collected from 24 patients with CF at the department of pediatric diseases, Medical University of Bialystok, Poland. Cytokine levels were determined by ELISA. Ophthalmic examinations, including tests for keratoconjunctivitis sicca (dry eye), were used to study the ocular surface. The tear levels of IL-8 and IFN-gamma in the CF patients were significantly higher than those in controls. The clinical severity of CF correlated significantly with the IL-8 and IFN-gamma levels. We found positive correlation between the tear levels of IFN-gamma and dry eye findings in CF patients. Our results suggest that the inflammatory cytokines IL-8 and IFN-gamma may play key roles in the regulation of ocular surface inflammation and the immunologic reaction in patients with CF. The tear levels of IL-8 and IFN-gamma may be candidate markers for evaluation of the clinical status of CF and eye disease. These findings help to provide a new insight into the pathogenesis of dry eye in patients with CF and provide potential targets for therapy.     

Proton-observed carbon-edited NMR spectroscopy in strongly coupled second-order spin systems.

Proton-observed carbon-edited (POCE) NMR spectroscopy is commonly used to measure 13C labeling with higher sensitivity compared to direct 13C NMR spectroscopy, at the expense of spectral resolution. For weakly coupled first-order spin systems, the multiplet signal at a specific proton chemical shift in POCE spectra directly reflects 13C enrichment of the carbon attached to this proton. The present study demonstrates that this is not necessarily the case for strongly coupled second-order spin systems. In such cases NMR signals can be detected in the POCE spectra even at chemical shifts corresponding to protons bound to 12C. This effect is demonstrated theoretically with density matrix calculations and simulations, and experimentally with measured POCE spectra of [3-13C]glutamate.     

Arterial “inflammaging” drives vascular calcification in children on dialysis

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The TNF-derived TIP peptide activates the epithelial sodium channel and ameliorates experimental nephrotoxic serum nephritis

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Phosphate Kinetics During Weekly Cycle of Hemodialysis Sessions: Application of Mathematical Modeling

Both hyperphosphatemia and hypophosphatemia are associated with increased morbidity and mortality among patients on dialysis. The control of serum phosphate concentration is a considerable clinical problem. Our study aimed to improve understanding of phosphate kinetics in patients on dialysis using mathematical modeling. Three consecutive hemodialysis sessions with breaks of 2–2–3 days were monitored in 25 patients. Phosphate concentration was measured every hour and 45 min after the end of dialysis in blood serum and every 30 min in dialysate during each session. Volume of fluid compartments and body composition were assessed by bioimpedance. The pseudo one‐compartment model was applied to describe the profile of phosphate in blood serum during intra‐ and interdialytic periods of 1‐week cycle of three hemodialysis sessions. Model parameters, such as phosphate internal clearance (K_M) and the rate of phosphate mobilization (R_M), were correlated with the reduction of serum phosphate concentration during dialysis (C_post/C_pre) and with equivalent continuous clearance (ECC) for phosphate. K_M correlated negatively with predialysis serum phosphate concentration. There was significant positive correlation between R_M and age. Postdialysis volume of phosphate central compartment was lower than, but correlated to, extracellular water volume. Parameters of the pseudo one‐compartment model, phosphate internal clearance, and the rate of phosphate inflow to the central compartment (the one accessible for dialysis) from other phosphate body reservoirs correlated with the indices of dialysis adequacy, such as reduction of serum phosphate and ECC. The pseudo one‐compartment model can be successfully extended from a single hemodialysis to the standard weekly cycle of sessions and the model parameters strongly correlate with the adequacy parameters of dialytic removal of phosphate.     

Repair of UV dimers in skin DNA of patients with basal cell carcinoma

Epidemiologic studies suggest that exposure to sunlight is the primary etiologic agent for basal cell carcinoma. Formation of UV-induced DNA damage is believed to be a crucial event in the process leading to skin cancer. In this study, repair of photoproducts in DNA was followed in the skin of patients with basal cell carcinoma and control subjects. The subjects were exposed to 800 J/m(2) Commission Internationale de 1'Eclairag of solar-simulating radiation on buttock skin. Biopsies were taken at 0 hour, 24 hours, and 3 weeks after the exposure. Two cyclobutane pyrimidine dimers, TT=C and TT=T, were measured using a sensitive (32)P-postlabeling assay. Initial levels of both TT=C and TT=T differed between individuals in both groups. The levels of TT=T in patients with basal cell carcinoma and controls were similar (9.9 +/- 4.0 and 9.2 +/- 2.9 products per 10(6) normal nucleotides), whereas the level of TT=C was significantly lower in controls than in patients with basal cell carcinoma (6.2 +/- 3.1 versus 10.9 +/- 4.5 products per 10(6) normal nucleotides). The fractions of TT=T remaining after 24 hours and 3 weeks were significantly higher in patients with basal cell carcinoma (72% and 11%) compared with controls (48% and 5%). A slower removal in patients with basal cell carcinoma than in controls was indicated also for TT=C (52% versus 42% remaining at 24 hours); however, the difference between groups was not significant. When including data from our previously reported small-scale study, the fraction of dimers remaining at 24 hours was significantly higher in patients with basal cell carcinoma for both TT=C and TT=T. The data suggest that patients with basal cell carcinoma have a reduced capacity to repair UV-induced DNA lesions.     

Gastric Bypass in Patients with BMI <40 but >32 Without Life-threatening Co-morbidities: Preliminary Report

Background: Surgical intervention is currently indicated for patients with BMI >40 or >35 with life-threatening comorbidities. Patients with BMI 32-40 without these comorbidities not only have the increased propensity to develop them but also suffer from similar psychosocioeconomic consequences. These patients may not respond to non-surgical treatment of obesity any better than those with BMI>40. The question has been raised whether to offer them surgical intervention. Methods: A study was carried out to determine outcome of surgery on patients with BMI >32 but <40 without life-threatening comorbidities but with either psychological, economic or social impairments affecting their quality of life. The approval of our Hospital Internal Review Board was obtained. In addition to routine evaluation for surgical intervention, these patients were required to have the approval of their primary care physician, be seen pre-operatively by a psychiatrist, and have a member of the family or a very close friend present at the time of discussion of operative risks and follow-up requirements. Patients committed to at least a 5-year follow-up. They were to be self-paying patients. The transected silastic ring vertical gastric bypass with a temporary gastrostomy was used. Results: 50 patients, 49 women and one man, were entered into the study between May 1, 1999 and April 30, 2000. 50% were self-pay, and the other 50% were able to obtain coverage through their insurance companies. There were few peri-operative complica tions and no deaths. The late complications include incisional hernias, dumping and transient alopecia. Hospital stay averaged 3.7 days. Follow-up has been 18-27 months. Weight loss has been excellent. Conclusion: Preliminary results of surgical intervention extended to patients with BMI 32-40 without life-threatening comorbidities but with psychosocioeconomic ramifications are very promising. Long term follow-up and comparison with other bariatric patients are planned.     

Inhibitory effect of melatonin on homocysteine-induced lipid peroxidation in rat brain homogenates

Oxidative damage is implicated in several pathologies including cardiovascular disease. As a model system to study the response of cells to oxidative insults, homocysteine toxicity was examined since it is an independent risk factor for atherosclerotic disease. The levels of malondialdehyde and 4-hydroxyalkenals were assayed as an index of oxidatively damaged lipid. In in vitro experiments, the increase of lipid peroxidation products induced by homocysteine were concentration- and time-dependent. To study the protective effect of melatonin on homocystine induced lipid peroxidation, brain homogenates were treated with different concentrations of melatonin. The accumulation of malondialdehyde and 4-hydroxyalkenals induced by homocysteine was significantly reduced by melatonin in a concentration-dependent manner. Additionally, a melatonin concentration of 1.5 mM reduced the levels of oxidatively damaged lipid products below those measured in control homogenates (no homocysteine, no melatonin). These data suggest that melatonin, an endogenous antioxidant may have a role in protecting cells from oxidative damage due to homocysteine and they support the idea that pharmacological concentrations could be used as a therapeutic agent in reducing cardiovascular disease where homocysteine may be a causative or contributing agent.     

Middle aortic syndrome caused by Takayasu's disease and treated by stent implantation: a report of medium-term follow-up

A 13-year-old girl with middle aortic syndrome caused by Takayasu's disease was treated by balloon angioplasty of the right renal artery stenosis and the implantation of 3 stents, 2 in the stenosed thoracic segment and 1 in the abdominal segment of the aorta. Spiral computed tomography one and two years after the stents were inserted showed that the disease had progressed despite treatment with immunosuppressants.