In vivo effects of chicken interferon-gamma during infection with Eimeria

Newly hatched chickens are highly susceptible to infection by opportunistic pathogens during the first 1 or 2 weeks of life. The use of cytokines as therapeutic agents has been studied in animal models as well as in immunosuppressed patients. This approach has become more feasible in livestock animals, in particular poultry, with the recent cloning of cytokine genes and the development of new technologies, such as live delivery vectors. We have recently cloned the gene for chicken interferon-gamma (Ch-IFN-gamma). Poly-HIS-tagged recombinant Ch-IFN-gamma was expressed in Escherichia coli, was purified by Ni chromatography, and was found to be stable at 4 degrees C and an ambient temperature for at least several months and Several weeks, respectively. Ch-IFN-gamma was capable of protecting chick fibroblasts from undergoing virus-mediated lysis, induced nitrite secretion from chicken macrophages in vitro, and enhanced MHC class II expression on macrophages. Administration of recombinant Ch-IFN-gamma to chickens resulted in enhanced weight gain over a 12-day period. Furthermore, the therapeutic potential of Ch-IFN-gamma was assessed using a coccidial challenge model. Birds were treated with Ch-IFN-gamma or a diluent control and then infected with Eimeria acervulina. Infected birds treated with Ch-IFN-gamma showed improved weight gain relative to noninfected birds. The ability of Ch-IFN-gamma to enhance weight gain in the face of coccidial infection makes it an excellent candidate as a therapeutic agent.     

Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders

We evaluated the association between attention deficit hyperactivity disorder (ADHD) and the age of onset of psychoactive substance use disorders (PSUD) in adults with ADHD. We hypothesized that ADHD and psychiatric comorbidity would be risk factors for early onset PSUD. We compared 120 referred adults having a clinical diagnosis of childhood-onset ADHD with 268 non-ADHD adults. All diagnoses were obtained using DSM-III-R based structured psychiatric interviews. We used group comparisons of age at onset and Cox proportional hazard models to examine the development of PSUD over time. ADHD was associated with earlier onset of PSUD independently of psychiatric comorbidity. Conduct and juvenile bipolar disorders conferred a significantly increased risk for early onset PSUD independently of ADHD. Psychiatric disorders commonly emerged before the onset of PSUD in both groups. Persistent ADHD with and without psychiatric comorbidity was associated with adolescent onset PSUD. In addition, comorbidity with conduct and juvenile bipolar disorders predicted very early onset PSUD in both ADHD and non-ADHD individuals. These findings confirm and extend previous findings documenting important associations between PSUD and psychiatric comorbidity including persistent ADHD.     

Use of iohexol to quantify hemodialysis delivered and residual renal function: technical note

BACKGROUND: Classically, urea (molecular wt = 60) is used to determine the urea reduction ratio (URR) or clearance, based on volume of distribution (Kt/V). These methods are subject to many errors. The purpose of this study was to determine whether iohexol (Io; molecular wt = 821) could be used instead of urea and provide better information as well as middle molecule clearance data. METHODS: Ten hemodialysis (HD) patients were evaluated. All were dialyzed for three hours, and a single bolus of 100 ml of Io was injected immediately post-HD. For direct dialysis quantification (DDQ), the spent dialysate was collected in a drum, and urea and iodine (I) determined immediately prior to, at the end of, and 30 minutes post-HD. As routinely used, DDQ measures clearance directly rather than estimates the levels. RESULTS: Calculated Kt/V urea (1.21+/-0.05) significantly overestimated DDQ Kt/V urea (0.78+/-0.04, P < 0.001) whereas calculated and DDQ Kt/V Io were similar (1.44+/-0.10 vs. 1.36+/-0.05). The URR and iohexol reduction ratio (IoRR) were also different (0.63+/-0.02 vs. 0.69+/-0.02; P < 0.002) with a urea but not Io rebound (URR30 min 0.59+/-0.02, P < 0.05). Calculated urea clearance (C(urea)), 247+/-21 ml/min, significantly overestimated DDQ C(urea) (157+/-10 ml/min P < 0.001). Calculated CIo and DDQ CIo, however, were similar (109+/-8 vs. 104+/-7 ml/min). Total body clearance (TBC) in six anuric subjects was 2.5+/-0.3 ml/min, and in four oliguric subjects was 5.2+/-0.5 ml/min. In 10 additional patients, direct urine measurements demonstrated a non-renal clearance (NRC) of 2.97+/-0.18 ml/min, which was 4.0+/-0.3% of body wt. Use of this factor allowed an estimation of residual renal function (RRF) that accurately reflected measured RRF (1.32+/-0.53 vs. 1.42+/-0.55 ml/min) CONCLUSION: A single injection of Io can be used to determine Kt/V, RR, and RRF without rebound or the inconvenience of urine collection. It may also represent middle molecule clearance better than urea kinetics, and may serve as a superior method for determining HD delivered and dialysis adequacy.     

In vitro attachment of human gingival fibroblasts to endosseous implant materials

In recent years, the focus of dental implant research has been the nature of the bone-implant interface associated with osseointegration, yet the transgingival portion of endosseous dental implants has received little attention. The purpose of this study was to determine the attachment of human gingival fibroblasts to three different implant materials: commercially pure titanium, non-porous hydroxyapatite, and porous hydroxyapatite. Cell attachment was quantified by radiolabeling gingival fibroblasts with tritiated thymidine and counting attached cells by liquid scintillation following incubation for periods of 20, 40, and 60 minutes. Additional studies coating implant surfaces with fibronectin were also performed. The nature of the implant material itself appeared to affect the number of attached cells. Determined on a surface area basis, fibroblast attachment was greatest to titanium followed by non-porous hydroxyapatite. Porous hydroxyapatite demonstrated the least amount of fibroblast attachment. When incubated with fibronectin at a concentration of 50 micrograms/ml, no increase in the number of cells attached to the various implant materials was observed. A small but statistically significant increase in the number of fibroblasts attached to porous hydroxyapatite at 40 minutes was observed when implant materials were pre-treated with fibronectin.     

Encephalopathy due to capillary leak syndrome

Systemic capillary leak syndrome (SCLS) is characterized by intermittent attacks of leakage of intravascular fluids into the extravascular space. Hypovolemia, hemoconcentration, weakness, edema, and visceral congestion are resulting manifestations of SCLS. Most patients with SCLS have clear mentation during attacks, and encephalopathy is not a known manifestation of the syndrome. We report a patient with acute idiopathic capillary leak syndrome manifested in an acute encephalopathy. The possibility of SCLS should be considered in patients who have an encephalopathy and hemoconcentration.     

Physiological and pathological roles of interleukin-6 in the central nervous system

The cytokine interleukin-6 (IL-6) is an important mediator of inflammatory and immune responses in the periphery. IL-6 is produced in the periphery and acts systemically to induce growth and differentiation of cells in the immune and hematopoietic systems and to induce and coordinate the different elements of the acute-phase response. In addition to these peripheral actions, recent studies indicate that IL-6 is also produced within the central nervous system (CNS) and may play an important role in a variety of CNS functions such as cell-to-cell signaling, coordination of neuroimmune responses, protection of neurons from insult, as well as neuronal differentiation, growth and survival. IL-6 may also contribute to the etiology of neuropathological disorders. Elevated levels of IL-6 in the CNS are found in several neurological disorders including AIDS dementia complex, Alzheimer's disease, multiple sclerosis, systemic lupus erythematosus, CNS trauma, and viral and bacterial meningitis. Moreover, several studies have shown that chronic overexpression of IL-6 in transgenic mice can lead to significant neuroanatomical and neurophysiological changes in the CNS similar to that commonly observed in various neurological diseases. Thus, it appears that IL-6 may play a role in both physiological and pathophysiological processes in the CNS.