The effects of carnosine on oxidative DNA damage levels and in vitro lifespan in human peripheral blood derived CD4+T cell clones

Carnosine (beta-alanyl-L-histidine), an abundant naturally-occurring dipeptide has been shown to exhibit anti-ageing properties towards cultured cells, possibly due in part to its antioxidant/free radical scavenging abilities. In this paper the results of an investigation on the effects of carnosine, at the physiological concentration of 20 mM, on oxidative DNA damage levels and in vitro lifespan in peripheral blood derived human CD4+ T cell clones are reported. Under the culture conditions used (20% O(2)) long term culture with carnosine resulted in a significant increase in the lifespan of a clone derived from a healthy young subject. No such extension was observed when a T cell clone from a healthy old SENIEUR donor was similarly cultured. Culture with carnosine from the midpoint of each clone's lifespan did not have any effect on longevity, independent of donor age. Oxidative DNA damage levels were measured in the clones at various points in their lifespans. Carnosine acted as a weak antioxidant, with levels of oxidative DNA damage being lower in T cells grown long term in the presence of carnosine. The possibility that carnosine might confer anti-ageing effects to T cells under physiological oxygen tensions would appear to be worthy of further investigation.     

Multiplicity of allergens in peanuts

Crude peanut protein fractions from raw and roasted peanuts were examined in the RAST with 10 sera from patients showing clinical peanut sensitivity. The radioactive uptake results, which were generally high, did not reveal any distinguishable pattern. Two commercially available peanut proteins, peanut lectin and phospholipase D, gave poor RAST responses. Three purified peanut proteins, α-arachin, conarachin I, and concanavalin A-reactive glycoprotein, all gave significant RAST results that were generally lower than those obtained with the crude extracts. The extent of RAST inhibition obtained with these materials was inversely related to their abundance in the total peanut protein. Crossed immunoelectrophoresis with extracts from raw and roasted peanut indicated the presence of 22 and 10 anodically migrating antigens, respectively. Sixteen IgE binding antigens were revealed for raw peanut and seven for roasted peanut after incubation with a mixed serum from the 10 patients in crossed radioimmunoelectrophoresis (CRIE) using ¹²⁵I-labeled anti-IgE. CRIE plates treated with individual serum samples showed that all the patients had specific IgE for the major antigen peak, which has been tentatively identified as α-arachin. This major storage protein of peanut, which is known to be particularly heat resistant, may be of greater clinical significance than its apparently low RAST activity would seem to indicate.     

CT metrizamide myelography in syringomyelia: sensitivity and specificity

In a retrospective study of 32 patients with "proven" syringomyelia and 15 patients with an alternate proven diagnosis, a change in the caliber of the spinal cord with different positions ("collapsing cord sign or cord collapse") had a sensitivity of 38% and a specificity of 87%. Central cord enhancement ("bull's-eye") on delayed CT had a sensitivity and specificity of 91% and 87%, respectively. The positive predictive value of cord collapse was 87%, while the positive predictive value of central cord enhancement was 94%.     

Primary intraventricular hemorrhage in adults

Five adults with primary intraventricular hemorrhage are described. The presenting features included headache, confusion and drowsiness. Focal neurological signs were minimal or absent. All five had a history of hypertension, three patients had bilateral internal carotid occlusion at its origin, one had unilateral occlusion of the left internal carotid artery with severe stenosis of the contralateral siphon. Unilateral occlusion of the middle cerebral artery were present in the fifth patient. Pathological examination of the brain from one patient showed the presence of severe hemorrhagic "lacunar" infarcts adjacent to the left lateral ventricle, one showing direct continuity of blood in the lacune with the massive intraventricular hematoma. We hypothesize that such a finding illustrates one possible mechanism for this unusual type of hemorrhage. Patients with longstanding hypertension and severe occlusive disease of the internal carotid arteries may be predisposed to this unusual complication.     

Chemotherapeutic agent permeability to normal brain and delivery to avian sarcoma virus-induced brain tumors in the rodent: observations on problems of drug delivery

Four chemotherapeutic agents (cyclophosphamide, 5-fluorouracil (5-FU), methotrexate (MTX), and bleomycin) were given intravenously to rats harboring the avian sarcoma virus-induced glioma. Drug content in brain, tumor, and systemic tissue was measured. The uptake of drug and the consistency of drug levels in normal brain and tumor varied widely among these agents. [14C]Cyclophosphamide and its metabolites penetrated normal brain and, to a greater extent, brain tumor. [14C]5-FU and its metabolites also entered normal brain and brain tumor, but to lesser extent than [14C] cyclophosphamide and its metabolites. Immunoreactive MTX entry into tumor was variable, ranging from 30 to 1080 ng/g of tissue, with only minimal concentrations in normal brain. After conventional doses, immunoreactive bleomycin levels in tumor were also variable, ranging from 24 to 164 mu units/g of tissue, and little if any drug entered surrounding brain. In addition, the cerebrovascular permeability of 5-FU and MTX in normal rats was measured. Utilizing the method of Rapoport, the PA (product of permeability and capillary surface area) of 5-FU was found to be 6- to 12-fold greater than that of MTX. The PA of both drugs was increased 4- to 7-fold after osmotic blood-brain barrier opening. The variable "leakiness" of glial tumors, both experimentally and clinically, as well as the varied permeabilities of different water-soluble chemotherapeutic agents, makes the drug delivery problem in brain tumors a very complex issue.     

Determinants of attrition in a pediatric healthy lifestyle intervention: The CIRCUIT program experience

IntroductionAttrition in pediatric weight management programs is notoriously high. Greater understanding of its determinants is needed to inform retention strategies. We identified determinants of attrition in CIRCUIT, a healthy lifestyle intervention program for youth at risk of cardiovascular disease.MethodsA one-arm intervention study of children aged 4-18 years who initiated the CIRCUIT program in the first five years of its existence (N = 403). We defined attrition as attending the baseline visit but ceasing attendance prior to the 1-year follow-up. Potential determinants of dropout included the child’s age, sex, ethnicity, body mass index (BMI) z-score, family socio-demographic characteristics, and estimated driving time to the program, all measured at baseline. Associations were estimated bivariately, using chi-squared- and t-tests, and simultaneously in a multivariable logistic regression model.ResultsOf the 403 participants who started the program, 198 (49%) dropped out within 12 months of enrollment. Youth who dropped out were older (mean age 12.8y vs. 11.3y; p < 0.01), were less likely to live with both parents (62% vs. 71%; p = 0.05), and to have mothers who had completed high school (79% vs. 88%; p = 0.01). No group differences were observed for sex, ethnicity, baseline BMI z-score, fathers’ education, or driving time to the program. In multivariate models, only older age at initiation of the intervention (OR: 1.2; CI: 1.1,1.3) and lower maternal education (OR: 2.0; CI: 1.0,3.8) were associated with dropout.ConclusionImproved tailoring of interventions to older pediatric participants and to families of lower maternal education may help reduce attrition in CIRCUIT and similar lifestyle intervention programs.     

Longitudinal Examination of Prenatal Tobacco Switching Behaviors and Birth Outcomes,Including Electronic Nicotine Delivery System (ENDS) and Dual Use

Maternal and Child Health Journal - In the US, approximately 8% of pregnant women smoke, and 5–11.9% currently use ENDS products. The health effects of ENDS use are debated; however, most...     

Antitrust exemption: are health providers crying wolf?

Demands by health providers for relief from federal antitrust law have reached a new high as they examine the likely impact of managed competition on the way they do business. Indeed, the American Medical Association endorsed managed competition on the condition that doctors get an antitrust exemption; the Pharmaceutical Manufacturers Association recently said that drug makers needed to discuss prices before they could hold back increases. But the Federal Trade Commission, an independent agency, has shown no signs of revising its antitrust measures to reflect the enormous changes that lie before the health industry.     

Trust is the prescription for hospital/physician relations under health care reform

Hospitals are reacting to health care reform by forming collaborative physician/hospital organizations and other ventures. The success of these new partnerships depends on what shape the reformed system takes and establishing trust between all players.     

Basal glucose turnover inPsammomys obesus

The aim of this study was to examine wholebody glucose turnover and glucose uptake into individual tissues inPsammomys obesus. The animals were classi-fied according to the level of circulating glucose and insulin in the fed state: group A was normoglycaemic and normoinsulinaemic (glucose <8.0 mmol/l, insulin <150 mU/l), group B was normoglycaemic and hyperinsulinaemic (glucose <8.0 mmol/l, insulin 150 mU/l), and group C was hyperglycaemic and hyperinsulinaemic (glucose 8.0 mmol/l, insulin 150 mU/l). The animals were deprived of food for 6 h, after which they were anaesthetized and cannulated, using the jugular vein for infusions and the carotid artery for blood sampling. Whole-body glucose turnover was measured using a primed-continuous infusion of 6-[³H]-glucose and saline to quantitatively assess hepatic glucose production (HGP), glucose disposal (Rd), and the metabolic clearance rate of glucose (MCR). Following the 2-h infusion period, the glucose metabolic index (Rg) of individual tissues was measured using a fixed-dose bolus of 2-deoxy-[¹⁴C]glucose. Under the steady-state conditions of the experiment, HGP was assumed to be equal to Rd, and both variables were found to be significantly correlated to the fasting glucose concentration (r=0.534,P<0.05,n=19). On the other hand, MCR was found to be inversely correlated to the fasting plasma glucose concentration (r=0.670,P<0.01,n=19). When the animals were divided into three groups as described above, HGP in group C animals was significantly elevated compared with group A (20.8±2.6 vs 12.7±0.6 mg · kg^–1 · min^–1;P<0.05), and MCR showed a tendency to be lower in group C than group A, although the difference was not statistically significant. HGP and MCR were not significantly different between groups A and B. Measurement of the glucose metabolic index in individual tissues showed that group C animals had significantly higher Rg values in muscles and adipse tissues compared with those in group A (P<0.05). In addition, Rg in group B white gastrocnemius and soleus were significantly higher than in group A despite similar rates of HGP and levels of glycaemia. These findings suggest that an early increase in skeletal muscle glucose uptake and hyperinsulinaemia can be demonstrated in group BPsammomysobesus before significant hyperglycaemia.