Synergistic effect of low dose Cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation

Objective: Electroporation mediated transfer of plasmid DNA into peripheral muscle results in high transfection efficiency. The aim of this study was to investigate the effect of gene transfer of human IL-10 (hIL-10) into the tibialis anterior muscle (MTA) in combination with low dose Cyclosporine A (CsA) on acute rejection of lung allografts in the rat. Methods: Lung allotransplantation was performed from male BN donor to male Fisher F344 rats. Gene transfer was achieved by intramuscular injection into the MTA of the recipient followed by electroporation (4×20 ms impulses at 200 V/cm) 24 h prior to the transplantation. Group A (n=5) received CsA (2.5 mg/kg bw ip) for 5 days post-transplant and group B (n=5) 2.5 μg of PCIK hIL-10 (plasmid expression vector containing human CMV immediate early gene promoter and enhancer) and a low dose CsA (2.5 mg/kg bw i.p.). Graft function was assessed by blood gas at day 5 after exclusion of the native lung. Animals were sacrificed and blood was drawn to measure serum hIL-10 levels (ELISA) and tissue was sampled for histological grading of rejection. Results: Local expression of hIL-10 was confirmed at the mRNA level by in situ hybridization. All group A control animals showed severe signs of rejection. At day 5 all grafts in group B showed good gas exchange mean PaO2 233±123 mmHg, vs 44±8 mmHg in group A. Histological examination revealed moderate to severe rejection in all animals in group A (IIIB, ISHLT) in contrast to low moderate rejection in group B (II–IIIA). hIL-10 serum levels on day 5 were 14±7 pg/ml in group B vs. 0 in group A. Conclusions: Electroporation mediated hIL-10 overexpression in a peripheral muscle of the recipient in combination with low dose CsA reduces acute rejection in this model of rat lung allotransplantation.     

Transplacental carcinogenic effects of nickel(II) acetate in the renal cortex, renal pelvis and adenohypophysis in F344/NCr rats.

Nickel(II) acetate (NiAcet), a soluble nickel salt known to be an effective initiator of renal epithelial tumors in adult rats, was studied for possible transplacental carcinogenicity. Pregnant F344/NCr rats were given NiAcet i.p. either once a day on day 17 (90 mumol/kg body wt; group 1) or twice on days 16 and 18 of gestation (45 mumol/kg body wt/day; group 2). Offspring of these rats were further subdivided into groups 1A and B and 2A and B, respectively. Groups 1A and 2A received ordinary tap water while groups 1B and 2B received drinking water containing 500 p.p.m. sodium barbital (NaBB) during weeks 4-85 of age. Renal cortical epithelial and renal pelvic transitional epithelial tumors occurred in male offspring given NiAcet prenatally followed by NaBB postnatally (group 1B, 15 tumors in 8/15 rats; group 2B, 10 tumors in 7/15), but not in male offspring given NiAcet only (0/32) or in controls given prenatal sodium acetate (NaAcet) only (0/15) and rarely in males given NaAcet followed by the promoter NaBB (1/15). No renal tumors occurred in females. Pituitary tumor incidence was significantly higher in offspring of both sexes given NiAcet prenatally (NaAcet controls, 4/31, both sexes combined; group 1A, 14/33, P = 0.012; group 2A, 14/31, P = 0.008). Pituitary tumors appeared much earlier in rats given NiAcet prenatally, with or without postnatal NaBB, and often were malignant by cytologic and histologic criteria including pleomorphism and invasion of adjacent structures, unlike the well-differentiated adenomas that occurred less frequently in untreated rats. These results are the first evidence that Ni(II) is a potent transplacental initiator of epithelial tumors in fetal rat kidney and a complete transplacental carcinogen for rat pituitary.     

Spinal manipulation in a case of sacral fracture: presentation in a chiropractic office

A case is presented involving the successful management of symptoms following a sacral fracture. Treatment was primarily comprised of sacroiliac joint manipulation. The importance of accurate diagnosis, realistic risk/benefit assessment, and appropriate treatment is emphasized in considering contraindications of spinal manipulative therapy.     

Holographic analysis of displacement of the bovine cornea after disruption of intact structures]

Displacement of the surface of the cornea of bovine eyes after disruption of intact structures was investigated by means of holographic interferometry. Double-T-incisions of different depths were made with a diamond knife. Starting at about 80% of the incision depth there is a change in the central holographic interference fringe pattern. These effects can be clearly demonstrated by means of double-exposure holographic interferometry and real-time holographic interferometry. The stability of an existing corneal scar was analyzed by double-exposure holographic interferometry. The region of the scar showed a higher density of holographic interference fringes compared with the non-affected corneal areas, indicating a higher degree of elasticity. All eyes were investigated at an intraocular pressure of 1340 Pa (about 10 mmHg) and an intraocular pressure change of 10 Pa and 20 Pa. Further potential ophthalmic applications of holographic interferometry are discussed.     

Linear birefringence measurements of the in vitro human cornea

This paper presents results of an in vitro investigation of the optical anisotropy of the human cornea. Computer controlled imaging polarimetry and the Jones formalism were used to investigate the distribution of the birefringence and the azimuth angle across the surface of 12 corneas taken from the corneal bank. Each map of the birefringence and the azimuth angle has no rotational symmetry and is different for each cornea. The minimal value of the birefringence always appears in the corneal centre and varies from 9 to 43 degrees for different corneas. Birefringence of the cornea increases monotonically more than one order in the direction of the corneal periphery. Close to the centre of the cornea the azimuth angle is almost constant and varies significantly away from the optical part of the cornea.     

Mechanism of action of anticandidal dipeptides containing inhibitors of glucosamine-6-phosphate synthase.

The mechanism of anticandidal action of novel synthetic dipeptides containing N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid (FMDP) residues was shown to be consistent with the "warhead delivery" concept. FMDP dipeptides were shown to be transported into Candida albicans cells by the di-tripeptide permease and subsequently hydrolyzed by intracellular peptidases, especially aminopeptidase. The anticandidal activity of the particular FMDP dipeptide was influenced by the rate of its transport and, to a lower extent, by the intracellular cleavage rate. A high transport rate accompanied by a high cleavage rate resulted in the high anticandidal activity of L-norvalyl-FMDP. The strong growth-inhibitory effect of this compound was the consequence of inhibition of the enzyme glucosamine-6-phosphate synthase by the released FMDP. The action of L-norvalyl-FMDP on exponentially growing C. albicans cells resulted in a sharp decrease of incorporation of 14C label from [14C]glucose into chitin, mannoprotein, and glucan. This effect, as well as the growth-inhibitory effect, was fully reversed by exogenous N-acetyl-D-glucosamine. Glucosamine-6-phosphate synthase was proved to be the only essential target for FMDP dipeptides. Scanning electron microscopy of C. albicans cells treated with L-norvalyl-FMDP revealed highly distorted, wrinkled, and collapsed forms. Cells formed long, bulbous chains, and partial lysis occurred.     

Health-related quality of life parameters as prognostic factors in a nonmetastatic breast cancer population: an international multicenter study.

PURPOSE: The purpose of this research was to evaluate whether baseline health-related quality of life (HRQOL) parameters are prognostic factors for survival in locally advanced breast cancer patients. Although the literature highlights the important role of HRQOL parameters in predicting survival in advanced metastatic disease, little evidence exists for earlier stages. PATIENTS AND METHODS: The overall sample consisted of 448 patients randomly assigned to receive cyclophosphamide, epirubicin, and fluorouracil versus epirubicin, cyclophosphamide, and granulocyte colony-stimulating factor. Patients were enrolled in 12 countries. HRQOL baseline scores were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap resampling technique was used to assess the stability of the outcomes. Bootstrap results were then applied for model averaging purposes as a means to account for the observed model selection uncertainty. RESULTS: The final multivariate model retained inflammatory breast cancer (T4d) as the only factor predicting overall survival (OS) with a hazard ratio of 1.375 (95% CI, 1.027 to 1.840; P =.03). The presence of inflammatory breast cancer lowers the median survival time from 6.6 to 4.2 years (36% reduction). None of the preselected HRQOL variables were prognostic for OS or disease-free survival, in either the univariate or multivariate analysis. CONCLUSION: Our findings suggest that baseline HRQOL parameters have no prognostic value in a nonmetastatic breast cancer population.     

Feasibility and clinical utility of real-time tele-echocardiography using personal mobile device-based pocket echocardiograph

IntroductionRecently introduced microUSB ultrasound probe, which can be connected to personal mobile device constitutes a new class of diagnostic pocket size imaging devices (PSID).The aim of this study was to assess the feasibility and clinical utility of real-time tele-echocardiography with the use such device.Material and methodsThe study group comprised 30 patients (18 men and 12 women; mean age: 54 ±14 years; mean body mass index: 27 ±6 kg/m²), admitted to various hospital departments (infectious diseases, internal medicine and cardiology). All patients underwent focused echocardiographic examination performed by an inexperienced operator using PSID and collaborating remotely in real-time with cardiologist by means of tele-consultation. Before commencing the examination, the operators underwent 1 h training in use of the PSID.ResultsIn most of patients PSID imaging provided sufficient diagnostic image quality. The dimensions of left ventricle, left atrium and the aorta obtained during the this examination showed good correlation with standard echocardiography (r = 0.89, r = 0.82, r = 0.92 respectively), but the correlation for TAPSE measurements was less pronounced (r = 0.52). The agreement in detection of pathologies (wall motion abnormalities, morphological and functional valvular abnormalities) between the tele-echocardiography and standard echocardiographic examination was good to very good (κ ranged from 0.648 to 0.823).ConclusionsPocket size imaging devices allows an inexperienced operator to perform a focused echocardiographic examination under a remote supervision of an experienced cardiologist. The introduction of new technology in the form of PSID with tele-echocardiography feature can revolutionize access to this imaging technique.