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Biomedical subjects

Christopher Bell

Publications and source records attributed to Christopher Bell.

18 recordsLinked to original sources
PubMed2006

Chronic olanzapine treatment causes differential expression of genes in frontal cortex of rats as revealed by DNA microarray technique.

Recent emerging biochemical data indicate that several important neuroregulatory genes and proteins may be involved in the etiology of schizophrenia and bipolar disorder. Additionally, the same genes appear to be targets of several psychotropic medications that are used to treat these disorders. Recent DNA microarray studies show that genes involved in synaptic neurotransmission, signal transduction, and glutamate/GABA regulation may be differentially regulated in brains of subjects with schizophrenia. We hypothesized that chronic administration of olanzapine to rats would alter expression of various genes that may be involved in the etiology of schizophrenia and mood disorders. Rats were administered olanzapine (N=20, 2 mg/kg/day) or sterile saline intraperitoneally (N=20) daily for 21 days. Control and olanzapine-treated frontal cortices were analyzed using cDNA microarray technology. The results showed significant downregulation of 31 genes and upregulation of 38 genes by greater than two-fold in the drug-treated brains vs controls. Our results provide evidence for altered regulation of genes involved with signal transduction and cell communication, metabolism and energy pathways, transport, immune response, nucleic acid metabolism, and neuronal growth factors. Real-time quantitative RT-PCR analysis verified the direction and magnitude of change in six genes of interest: calbindin 3, homer 1, regulator of G-protein signaling (RGS) 2, pyruvate kinase, Reelin and insulin 2. Western blotting showed significant upregulation in protein products for Reelin 410 and Reelin 180 kDa and downregulation for NMDA3B and RGS2. Our results show for the first time that olanzapine causes changes in levels of several important genes that may be involved in the etiology and treatment of schizophrenia and other psychiatric disorders.

Animals↗
PubMed2006

Predictors of recurrence in veteran patients with umbilical hernia: single center experience.

BACKGROUND: Different medical and social conditions have been associated with primary and recurrent hernias. Possible predictors of recurrence after elective umbilical hernia repair have not been defined clearly. The aim of this study was to determine factors that predict recurrence in patients after elective repair of umbilical hernias. METHODS: A 6-year retrospective review of patients with elective umbilical hernia repair at the Dallas VA Medical Center was performed. Clinical and pathologic data were evaluated by univariate analysis to identify predictive factors for recurrence. RESULTS: A total of 244 patients underwent elective hernia repair within the study period (male, 96%; mean age, 56 y; Caucasian, 74%; African American, 14%; Hispanic, 8%). Because 15 patients were not compliant with follow-up requirements, 229 were eligible for the study. Ninety-seven underwent suture repair (42.4%) and 132 underwent mesh repair (57.3%). Eleven recurrences were identified (4.8%): 7 in the suture repair group (7.7%) and 4 in the mesh repair group (3%). Univariate analysis showed that patients likely to develop recurrences were as follows: African American (15.6% vs. 3.5%; P = .017), type II diabetics (14.2% vs. 2.6%; P = .002), patients with hyperlipidemia (9.2% vs. 2.6%; P = .028), and human immunodeficiency virus-positive patients (66.6% vs. 3.9%; P = .000). CONCLUSIONS: Smoking, obesity, size of hernia, type of repair, or chronic obstructive pulmonary disease do not seem to predict recurrence of hernias in our VA population. African Americans, patients with type II diabetes, hyperlipidemia, and positive for human immunodeficiency virus, may have a higher risk for recurrence after elective umbilical hernia repair.

Adult↗
PubMed2006

Baroreflex gain in normotensive and GH hypertensive rats before and after early gonadectomy.

The authors have assessed arterial baroreflex gain in urethane-anesthetized normotensive and New Zealand genetically hypertensive (GH) rats and investigated the effect of gonadectomy in adult animals at 3 weeks of age postnatally. No gender differences in resting blood pressures existed for either normotensive or GH strains. In normotensive animals, bradycardic gain was greater than tachycardic gain and was lower in females than in males. Tachycardic gain was similar in GH and normotensive rats of either sex, but bradycardic gain was lower in GH. Gonadectomy had no effect on baroreflex gain in male or female animals of either strain.

Animals↗
PubMed2006

Management of hepatic and intracardiac echinococcal cysts: case report and review of the literature.

BACKGROUND: Infection with Echinococcus granulosus affects the liver commonly, but disseminated involvement is rare. We describe a 63 year-old man with echinococcal infection producing both hepatic and cardiac involvement that was managed surgically after failed percutaneous hepatic treatment. METHODS: This report is a case study of a unique surgical problem. Various treatment modalities are reviewed. RESULTS: The patient was a 63 year-old man from Iraq who immigrated to the United States after becoming infected with Echinococcus granulosus. He had undergone percutaneous management and albendazole therapy prior to presentation for treatment of hepatic hydatid cysts. He continued to have abdominal pain and fever and was referred to our institution. Imaging revealed persistence of the hepatic hydatid cysts, as well as a new finding of an intracardiac hydatid cyst. The patient underwent successful treatment of his complicated hepatic hydatid cysts with pericystectomy and repair of a biliary fistula. The cardiac cyst was removed as well. The patient made an uneventful recovery, and his symptoms resolved. CONCLUSION: Although rare, echinococcal infection may be encountered in the United States as travel increases to and from regions of the world where the disease is endemic. It is important for surgeons to be familiar with the multiple options for treatment of hydatid disease.

Echinococcosis↗
PubMed2005

Thermogenic responsiveness to beta-adrenergic stimulation is augmented in exercising versus sedentary adults: role of oxidative stress.

Beta-adrenergic receptor (beta-AR) modulation of resting and postprandial energy expenditure (EE) is augmented in regularly exercising compared with sedentary adults, but the underlying physiological mechanisms are unknown. Differences in thermogenic responsiveness to beta-AR stimulation, perhaps secondary to reactive oxygen species (ROS) bioactivity, may be involved. To determine habitual exercise-related differences in beta-AR thermogenic responsiveness and the possible influence of ROS, we measured the percentage increase in EE (DeltaEE%; indirect calorimetry, ventilated hood method) above resting EE in response to non-specific beta-AR stimulation (intravenous isoproterenol (isoprenaline): 6, 12 and 24 ng (kg fat-free mass)-1 min-1) in 25 sedentary (11 males; 51+/-4 years; body mass index 25.0+/-0.8 kg m-2, maximal oxygen uptake 29+/-1 ml kg-1 min-1 (mean+/-s.e.m.)) and 14 habitually aerobic exercising (9 males, 46+/-6 years, 23.1+/-0.7 kg m-2, 44+/-3 ml kg-1 min-1) healthy adults under normal (control) conditions and during acute intravenous administration of a potent antioxidant, ascorbic acid (vitamin C; 0.04 g (kg fat-free mass)-1). DeltaEE% was greater (P=0.02) in the habitually exercising (8.6+/-1.2, 12.9+/-1.2, 20.0+/-1.4) versus sedentary (6.3+/-0.7, 10.4+/-0.8, 16.0+/-1.0) adults. Ascorbic acid increased (P=0.01) DeltaEE% only in the sedentary adults (to 9.5+/-0.9, 12.4+/-0.7, 18.5+/-0.8), abolishing baseline group differences. DeltaEE% was not related to the amount of body fat, sex, or any other baseline characteristic. Thermogenic responsiveness to beta-AR stimulation is augmented in habitually exercising adults. The mechanism is ascorbic acid dependent, suggesting that it may be linked to decreased ROS bioactivity. Our findings advance a novel mechanism by which habitual physical activity may modulate EE in humans, with potential implications for energy balance and body weight control.

Adolescent↗
PubMed2005

Thermogenic responsiveness to nonspecific beta-adrenergic stimulation is not related to genetic variation in codon 16 of the beta2-adrenergic receptor.

Stimulation of beta-adrenergic receptors (beta-AR) by the sympathetic nervous system (SNS) modulates energy expenditure (EE), but substantial interindividual variability is observed. We determined whether the thermogenic response to beta-AR stimulation is related to genetic variation in codon 16 of the beta(2)-AR, a biologically important beta-AR polymorphism, and whether differences in SNS activity (i.e., the stimulus for agonist-promoted downregulation) are involved. The increase in EE (DeltaEE, indirect calorimetry, ventilated hood) above resting EE in response to nonspecific beta-AR stimulation [iv isoproterenol: 6, 12, and 24 ng/kg fat-free mass (FFM)/min] was measured in 46 healthy adult humans [Arg16Arg: 9 male, 7 female, 48 +/- 5 yr; Arg16Gly: 11 male, 4 female, 53 +/- 5 yr; Gly16Gly: 3 male, 12 female, 48 +/- 5 yr (means +/- SE)]. Neither FFM-adjusted baseline resting EE (P = 0.83) nor the dose of isoproterenol required to increase EE 10% above resting (P = 0.87) differed among the three groups (Arg16Arg: 5,409 +/- 209 kJ/day, 11.2 +/- 2.1 ng x kg FFM(-1) x min(-1); Arg16Gly: 5,367 +/- 272 kJ/day, 11.1 +/- 2.1 ng x kg FFM(-1) x min(-1); Gly16Gly: 5,305 +/- 159 kJ/day, 10.5 +/- 1.4 ng x kg FFM(-1) x min(-1)). Consistent with this, muscle sympathetic nerve activity and plasma norepinephrine concentrations were not different among the groups. Group differences in sex composition did not influence the results. Our findings indicate that the thermogenic response to nonspecific beta-AR stimulation, an important mechanistic component of overall beta-AR modulation of EE, is not related to this beta(2)-AR polymorphism in healthy humans. This may be explained in part by a lack of association between this gene variant and tonic SNS activity.

Adolescent↗
PubMed2005

Extending a home from hospital care programme for COPD exacerbations to include pulmonary rehabilitation.

The principals of rehabilitation medicine are to prevent muscle atrophy and improve mobility. Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with muscle atrophy and yet many patients do not undergo pulmonary rehabilitation until they have been in stable health for some time. We investigated the outcome of a supervised home exercise programme initiated immediately after hospitalisation for an exacerbation of COPD. Thirty-one patients were randomised into an exercise group (n=16, FEV(1) 0.94+/-0.34 L) and a control group (n=15, FEV(1) 1.08+/-0.33 L). The exercise group received a twice-weekly supervised exercise programme, in their homes, for 6 weeks. Spirometry, exercise capacity, isometric muscle strength, dyspnea level, quality of life at baseline and 6 weeks as well as subsequent exacerbations were quantified. At 6 weeks, the exercise group, improved the shuttle walk test (198 m+/-95-304+/-136 m) and increased 3 min step test capacity (119+/-40-163+/-26s) (both P<0.001). Knee extensor muscle strength and quality of life scores also increased. Neither exercise capacity nor muscle strength altered in the control group. Follow-up at 3 months showed that three of the control group and none of the exercise group had experienced subsequent exacerbations (P=0.06). Early rehabilitation via a home from hospital programme improved exercise tolerance, muscle strength, dyspnea scores, quality of life in COPD patients and reduced the number of subsequent exacerbations.

Aged↗
PubMed2005

A comparison of complications associated with colostomy reversal versus ileostomy reversal.

BACKGROUND: The incidence of complications after reversal of Hartmann's procedure is unknown. This study compares the morbidity of Hartmann's reversal versus loop ileostomy reversal. METHODS: Two groups of 20 patients were studied retrospectively over a 5-year period. One group underwent Hartmann's takedown, and the other underwent loop ileostomy takedown. Postoperative complications were compared between the 2 groups. RESULTS: Similar demographics were noted between each group. The most common initial indications for Hartmann's procedure were diverticulosis (11 patients, 55%) and colon cancer (4 patients, 20%). For patients who had undergone colectomy with primary anastomosis and ileostomy, colon cancer was the most common indication (12 patients, 60%) followed by diverticulosis (3 patients, 15%). Complications were more common after Hartmann reversal than loop ileostomy reversal (16 complications/11 patients versus 6 complications/4 patients, P = .047). CONCLUSION: Segmental colonic excision with anastomosis and loop ileostomy may be an attractive alternative to minimize morbidity with stoma reversal.

Adult↗
PubMed2005

Graft-associated hemorrhage from femoropopliteal vein grafts.

OBJECTIVE: The femoropopliteal vein (FPV) graft has been used extensively for large-caliber vascular reconstructions. To date, there have been no reports of anastomotic dehiscence or rupture leading to graft-associated hemorrhage (GAH). In the present report, we review our experience with GAH from FPV grafts to determine the incidence of this problem, to better understand the etiology, and to determine potential methods to prevent this complication. METHODS: All patients undergoing arterial reconstructions with FPV grafts were entered into a registry that included demographics, operative details, complications, and follow-up information. Episodes of GAH that occurred during the period from 1990 to 2004 were studied to determine etiologic factors and outcomes. RESULTS: During the study period, 574 FPV grafts were used for arterial reconstructions in 364 patients. GAH occurred in 11 patients (3%). Onset of GAH ranged from 1 hour to 180 days after operation. The mean blood transfusion requirement for GAH was 10 +/- 4 units. In three patients, the etiology of GAH was purely technical, resulting in a slipped or "popped" tie from a large side branch. In eight patients, the etiology was due to graft disruption secondary to uncontrolled infection and failure of anastomotic healing. Most of these patients were being treated for aortic graft infection. Special risk factors for this complication included malnutrition, ongoing polymicrobial and fungal infections, immunocompromised state, active cancer, steroid treatment, and ongoing graft contamination from gastrointestinal or pharyngeal leaks. Outcomes included four deaths and one stroke. CONCLUSIONS: GAH is a serious complication with high morbidity, mortality, and transfusion requirements. Although technical problems are preventable, FPV grafts, like all biologic grafts, can develop disruption with GAH from ongoing infection, especially in severely immunocompromised patients who are malnourished and have poor healing ability. Strategies for prevention and alternative treatment modalities are appropriate in patients at high risk for GAH.

Aged↗
PubMed2004

Ascorbic acid does not affect the age-associated reduction in maximal cardiac output and oxygen consumption in healthy adults.

Maximal aerobic capacity (Vo(2max)) decreases progressively with age, primarily because of a reduction in maximal cardiac output (Q(max)). This age-associated decline in Vo(2max) may be partially mediated by the development of oxidative stress that can suppress beta-adrenergic-receptor responsiveness and, consequently, reduce Q(max). To test this hypothesis, Vo(2max) (indirect calorimetry) and Q(max) (open-circuit acetylene breathing) were determined in 12 young (23 +/- 1 yr, mean +/- SE) and 10 older (61 +/- 1 yr) adults following systemic infusion of either saline (control) and/or the powerful antioxidant ascorbic acid (acute: bolus 0.06; drip 0.02 g/kg fat-free mass) and following chronic 30-day oral administration of ascorbic acid (500 mg/day). Plasma ascorbic acid concentration was not different between young and older adults and was increased similarly, independent of age [change (Delta) acute = 1,055 +/- 117%; Delta chronic = 62 +/- 19%]. Oxidized low-density lipoprotein concentration was greater (P < 0.001) in older (57 +/- 5 U/l) compared with young (34 +/- 3 U/l) adults and was reduced in both groups (P < 0.02) following acute (Delta = -6 +/- 2%) but not chronic (P = 0.18) ascorbic acid administration. Control (baseline) Vo(2max) and Q(max) were positively related (r = 0.76, P < 0.001) and were lower (P < 0.05) in older (34 +/- 2 ml.kg(-1).min(-1); 16.1 +/- 1.1 l/min) compared with young (43 +/- 3 ml.kg(-1).min(-1); 20.2 +/- 0.9 l/min) adults. Following ascorbic acid administration, neither Vo(2max) (young acute = 41 +/- 2; young chronic = 42 +/- 2; older acute = 34 +/- 2; older chronic = 34 +/- 2 ml.kg(-1).min(-1)) nor Q(max) (young acute = 20.1 +/- 0.9; young chronic = 19.1 +/- 0.8; older acute = 16.2 +/- 1.1; older chronic = 16.6 +/- 1.4 l/min) was changed. These data suggest that ascorbic acid administration does not affect the age-associated reduction in Q(max) and Vo(2max).

Adaptation, Physiological↗
PubMed2004

Aortofemoral bypass in young patients with premature atherosclerosis: is superficial femoral vein superior to Dacron?

PURPOSE: Previous studies have documented poor patency rates in "young" patients (age 55 years or younger) with premature atherosclerosis undergoing aortofemoral bypass (AFB) to treat aortoiliac occlusive disease. Given the high reported graft patency rates with superficial femoral vein (SFV) grafts performed because of aortic graft infection, we evaluated the role of SFV grafts for AFB as primary therapy for premature atherosclerosis in a case-control study. METHODS: Over 10 years 31 patients aged 55 year or younger underwent AFB with use of SFV (V-AFB). Case controls consisted of all patients 55 years of age or younger who underwent AFB with use of Dacron (D-AFB) during the same period (n = 80). In all cases this was the initial therapy (no repeat operations). The two groups were well matched for age, sex, weight, preoperative ankle-brachial index, and the comorbid conditions of smoking, coronary artery disease, chronic obstructive pulmonary disease, hyperlipidemia, hypertension, and renal insufficiency. There were more patients with diabetes in the V-AFB group (34% vs 16%; P =.05). Patients in the V-AFB group had more advanced disease, and the surgical indication was more frequently critical ischemia compared with the D-AFB group (90% vs 46%; P <.001). RESULTS: There was only one perioperative death in each group. There were no differences in cardiac, pulmonary, or gastrointestinal complications. However, fasciotomy occurred more frequently with V-AFB (44% vs 1%; P <.001). Surgery time was longer with V-AFB (7.3 vs 4.5 hours; P <.001). Despite these short-term drawbacks, V-AFB proved superior at long-term follow-up. The 5-year primary patency rate was significantly higher with V-AFB than with D-AFB (100% vs 56%; P =.013). There was also a trend for higher limb salvage at 5 years (90% vs 62%). Four graft infections occurred with D-AFB, and none with V-AFB (P =.32). CONCLUSIONS: AFB performed with SFV grafts is a far more durable operation than standard D-AFB in young patients with aortoiliac occlusive disease. However, V-AFB is far more likely to require lower extremity fasciotomy, and takes almost twice as long to perform.

Age Factors↗
PubMed2004

High energy flux mediates the tonically augmented beta-adrenergic support of resting metabolic rate in habitually exercising older adults.

The sympathetic nervous system contributes to resting metabolic rate (RMR) via beta-adrenergic receptor (beta-AR) stimulation of energy metabolism. RMR and beta-AR support of RMR are greater in habitually exercising compared with sedentary older adults possibly due to greater energy flux (magnitude of energy intake and energy expenditure during energy balance). In 10 older adults regularly performing aerobic endurance exercise (mean +/- se, 66 +/- 1 yr) compared with baseline, a reduction in energy flux (via abstention of exercise and proportional reduction in dietary intake) decreased (P < 0.05) energy expenditure (7746 +/- 440 vs. 9630 +/- 662 kJ.d(-1)), caloric intake (7808 +/- 431 vs. 9433 +/- 528 kJ.d(-1)), RMR (5192 +/- 167 vs. 5401 +/- 209 kJ.d(-1)), and skeletal muscle sympathetic nervous system activity (36 +/- 2 vs. 42 +/- 2 bursts.min(-1)). Significant beta-AR support of RMR was observed at baseline (167 +/- 42 kJ.d(-1)) but not during reduced energy flux. The change in RMR from baseline to reduced energy flux was related to the corresponding change in beta-AR support of RMR (r = 0.77, P = 0.009). No changes were observed in seven time controls (69 +/- 3 yr) who maintained energy flux. High energy flux is a key mechanism contributing to the elevated RMR and beta-AR support of RMR in habitually exercising older adults. Maintenance of high energy flux via regular exercise may be an effective strategy for maintaining energy expenditure and preventing age-associated obesity.

Aged↗
PubMed2004

Clinical and epidemiologic burden of chronic myelogenous leukemia.

Chronic myelogenous leukemia represents 7-20% of all leukemia cases, with a worldwide incidence projected at less than one to two per 100,000 people. Approximately 85% of patients are diagnosed with chronic-phase chronic myelogenous leukemia and up to 40% are asymptomatic. Treatment strategies include chemotherapy, interferon-alpha therapy, transplantation (bone marrow/stem cell transplant) and imatinib mesylate (Gleevec), with the impact of treatment best realized during the chronic phase of the disease. Only transplantation has been clinically demonstrated to eradicate the Philadelphia chromosome, alter the natural course of the disease and cure patients diagnosed with chronic myelogenous leukemia. Interferon-alpha is currently considered for first-line treatment, however, the recent introduction of targeted therapy may change clinical practice. Ongoing research focused on new drug combinations and target therapies may eventually expand the armamentarium available to cure this disease.

Age Distribution↗
PubMed2004

Chronic sympathetic activation: consequence and cause of age-associated obesity?

Primary aging in adult humans is associated with a progressive, tonic activation of the peripheral sympathetic nervous system (SNS). The purpose of this SNS activation and its physiological impact are, however, unknown. We hypothesize that the chronic stimulation of the SNS with aging is driven in part by a progressive accumulation of body fat. This "error" is sensed by the central nervous system via increases in adiposity-sensitive humoral signals (e.g., leptin, insulin) that cross the blood-brain barrier, activate subcortical areas involved in the regulation of energy balance (e.g., ventromedial hypothalamus), and stimulate SNS outflow to peripheral tissues. The SNS activation is intended to increase beta-adrenergic thermogenesis in order to expend excess energy as heat rather than by storage of fat. Recent evidence, however, indicates that these adjustments are not effective in augmenting energy expenditure with aging. Indeed, older sedentary adults demonstrate reduced, not increased, beta-adrenergic stimulation of metabolic rate because of reduced tissue responsiveness, presumably mediated by SNS-induced impairment of beta-adrenergic signaling. As a result, age-associated SNS activation, initiated as a consequence of accumulating adiposity with the intent of preventing further fat storage, ironically, may in time evolve into a potential mechanism contributing to the development of obesity with aging.

Adipose Tissue↗
PubMed2003

Use of acetylene breathing to determine cardiac output in young and older adults.

PURPOSE: The aims of this investigation were: 1). to establish the day-to-day reproducibility of open-circuit acetylene breathing for measuring exercise cardiac output (Q(c)) in young and older adults; and 2). to compare estimates of Q(c) from open-circuit acetylene breathing with estimates of Q(c) from previously established closed-circuit acetylene rebreathing. METHODS: Twenty men (10 young: 28 +/- 1 yr; 10 older: 61 +/- 1 yr (mean +/- SE)) performed cycle ergometry exercise on 3 separate days. Q(c) was estimated using open-circuit acetylene breathing on 2 d, and closed-circuit acetylene rebreathing on 1 d. RESULTS: Open-circuit acetylene breathing was highly reproducible (young: standard error of measurement (SEM) = 1.52 L.min (-1) limits of agreement (LOA) = 0.2 +/- 4.2 L.min (-1), coefficient of variation 6% < CV < 8%, day 2 = (0.9 x day 1) + 2.4, r = 0.90, P< 0.001, r (2)= 0.82; older: SEM = 0.94 L.min (-1), LOA = 0.1 +/- 2.8 L.min (-1), 4% < CV < 10%, day 2 = (1.0 x day 1) + 0, r = 0.91, < 0.001, r(2) = 0.82). Estimates of Q(c) from open-circuit acetylene breathing demonstrated good agreement with closed-circuit acetylene rebreathing (young: SEM = 1.52 L.min (-1), LOA = 0.9 +/- 4.4 L.min (-1), 5% < CV < 10%, open-circuit = (1.0 x closed-circuit) + 1.5, r = 0.89, < 0.001, r (2) = 0.79; older: SEM = 1.13 L.min (-1), LOA = 0.1 +/- 3.2 L.min (-1), 5% < CV < 9%, open-circuit = (0.9 x closed-circuit) + 1.6, r = 0.88, < 0.001, r(2) = 0.78). CONCLUSION: These results demonstrate that open-circuit acetylene breathing provides reproducible measurements of Q(c) during exercise that demonstrate good agreement with values obtained from the acetylene rebreathing procedure in young and older healthy men.

Acetylene↗
PubMed2003

Oxidative stress does not modulate metabolic rate or skeletal muscle sympathetic activity with primary aging in adult humans.

Support of resting metabolic rate (RMR) by the beta-adrenergic receptors of the sympathetic nervous system is attenuated with age and contributes to declines in RMR. This may be mediated by an age-associated increase in oxidative stress that can suppress beta-adrenergic responsiveness and/or modulate sympathetic activity. To address these issues, RMR was determined in 12 young (23 +/- 1 yr, mean +/- SE) and 21 older (68 +/- 3 yr) adults before and during systemic infusion of ascorbic acid [bolus, 0.06 g/kg fat free mass (FFM); drip, 0.02]. Ascorbic acid increased plasma concentrations similarly in young (72 +/- 5 to 1107 +/- 114 micro mol/liter) and older (70 +/- 6 to 1022 +/- 63 micro mol/liter) adults, and reduced (P = 0.001) plasma concentrations of isoprostanes (young, -82.8 +/- 47; older, -107 +/- 29 pg/ml). Baseline RMR(FFM) was lower (5719 +/- 215 vs. 6703 +/- 328 kJ/d; P = 0.001) and muscle sympathetic nerve activity (MSNA) was greater (MSNA, 28 +/- 2 vs. 23 +/- 3 bursts/min; P < 0.05) in older compared with young. However, neither RMR(FFM) (young, +117 +/- 63; older, +163 +/- 48 kJ/d; P = 0.14) or MSNA (young, 0 +/- 2; older, -1 +/- 1 bursts/min; P = 0.71) changed in either age group during ascorbic acid infusion compared with saline control. These results indicate that increased oxidative stress: 1) is not a mechanism contributing to decreases in RMR with primary aging; and 2) does not modulate MSNA in healthy adult humans.

Adult↗
PubMed2002

Lithium ameliorates HIV-gp120-mediated neurotoxicity.

To investigate the protective effects of lithium against HIV-gp120-mediated toxicity in vivo, mice were exposed to lithium and gp120 and levels of the neuronal markers, microtubule-associated protein-2 and NeuN, and the astrocyte marker, glial fibrillary acidic protein, were determined. In addition, SH-SY5Y neuronal cells exposed to gp120 and lithium were assessed for cell viability. Lithium pretreatment protected the hippocampus of mice from gp120-mediated toxicity. Similarly, preexposure of neuronal cultures to lithium significantly reduced gp120-associated neurotoxicity. However, posttreatment with lithium had minimal neuroprotective effects against gp120, both in vivo and in vitro. The protective effects of lithium in vitro were blocked by LY294002, an inhibitor of the phosphatidylinositol 3-kinase/Akt pathway. Taken together, these results demonstrate that lithium might be neuroprotective against gp120-mediated toxicity and suggest that prophylactic treatment with lithium may prevent the onset/progression of HIV-associated cognitive impairments.

AIDS Dementia Complex↗