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Biomedical subjects

J M Carney

Publications and source records attributed to J M Carney.

At least 19 recordsLinked to original sources
PubMed2001

Can HIV-1-contaminated syringes be disinfected? Implications for transmission among injection drug users.

Bleaching of syringes has been advocated to prevent HIV-1 transmission among injection drug users (IDUs). Bleach is frequently distributed by needle exchange, outreach, and educational programs targeting IDUs. We applied a sensitive HIV-1 microculture assay to determine the effectiveness of bleach in disinfecting syringes contaminated with HIV-1. This study demonstrates that in a laboratory environment designed to replicate injection behaviors, undiluted bleach is highly effective in reducing the viability of HIV-1 even after minimal contact time. However, it did not reduce the HIV-1 recovery to zero. Furthermore, three washes with water were nearly as effective as a single rinse with undiluted bleach in reducing the likelihood that contaminated syringes harbored viable HIV-1. Given the reality that IDUs share syringes and may not have access to a new, sterile syringe for each injection, the results suggest that they should be encouraged through harm reduction interventions to clean their syringes, preferably with undiluted bleach.

Disinfectants↗
PubMed2001

Caloric restriction mimetics: metabolic interventions.

Caloric restriction (CR) retards diseases and aging in laboratory rodents and is now being tested in nonhuman primates. One way to apply these findings to human health is to identify and test agents that may mimic critical actions of CR. Panel 2 focused on two outcomes of CR, reduction of oxidative stress and improved glucoregulation, for which candidate metabolic mimics exist. It was recommended that studies on oxidative stress should emphasize mitochondrial function and to test the efficacy of nitrone and other antioxidants in mimicking CR's effects. Studies should also focus on the long-term effects of compounds known to lower circulating glucose and insulin concentrations or to increase insulin sensitivity. Also, four other developing areas were identified: intermediary metabolism, response to infection, stress responses, and source of dietary fat. These areas are important because either they hold promise for the discovery of new mimetics or they need to be explored prior to initiation of CR trials in humans. Other recommendations were that transgenic approaches and adult-onset CR should be emphasized in future studies.

Animals↗
PubMed2000

Oxidative stress leading to loss of critical proteases in Alzheimer's disease. An alternative view of the etiology of AD.

An alternative view of the etiology of Alzheimer's disease is suggested which focuses on the relationship between oxidative stress and the decrease in proteases seen in aging. Proteases act to govern the acceleration of the pathology of aging and, as damage from oxidative stress increases, the loss of proteases in at-risk persons leads to symptoms of AD. Controlling the damage to proteases or controlling the generator(s) of oxidative stress may help to control the onset or progression of Alzheimer's disease.

Alzheimer Disease↗
PubMed2000

Prolonged episodes of persistent asthma: A distinct clinical pattern with characteristic clinical features.

STUDY OBJECTIVES: To investigate a clinical pattern of unexplained persistent asthma that is episodic in nature and lasts for months to years. This pattern of prolonged episodes of unexplained, persistent asthma was not defined previously. DESIGNS: Investigating the clinical features using a retrospective cohort design. SETTING AND PATIENTS: Eighteen subjects (ages, 13 to 64 years) from an allergy practice in a large prepaid health maintenance organization who had two or more prolonged episodes of unexplained persistent asthma lasting >/= 2 months during a 12-year period. RESULTS: These subjects accounted for 39 asthmatic episodes lasting from 2 to 74 months (median, 7 months). The duration of the episodes positively correlates with the severity of asthma (p = 0.02) at the initial part of the episodes. All episodes demonstrated a similar pattern, with symptom severity greatest at the onset and gradually diminishing until recovery. The relatively symptom-free intervals between the episodes ranged from 1.5 to 63 months (median, 13 months). Fifty-six percent of the episodes (95% confidence interval [CI], 40% to 72%) were associated with symptoms very suggestive or suggestive of an infection of the upper respiratory tract at the onset of the episodes; 33% of the episodes (95% CI, 19% to 50%) had possible symptoms suggestive of an infection; whereas only 10% of the episodes (95% CI, 3% to 24%) had questionable or no symptoms suggestive of an infection of the upper respiratory tract. Thirty-four episodes had the onset between September and March, whereas only 5 episodes occurred between April and August (p < 0. 001). CONCLUSIONS: These observations indicate that prolonged episodes of unexplained, persistent asthma lasting for months to years constitute a distinct clinical pattern of asthma with characteristic clinical features.

Adolescent↗
PubMed2000

Survival of HIV-1 in syringes: effects of temperature during storage.

In a previous paper we demonstrated that HIV-1 survival in syringes was strongly associated with the volume of blood remaining and with the duration of storage at room temperature. The current study was performed to determine the effects of storage temperature upon the survival of HIV-1 inside syringes. At 4 degrees C, 50% of all syringes contained viable HIV-1 at 42 days of storage, the longest storage duration tested. At room temperature (20 degrees C), the last day that syringes with 2 microL of infected blood were positive was Day 21, and viable HIV-1 was recovered from 8% of syringes. The last day on which syringes with 20 microL were positive was Day 42, and viable HIV-1 was recovered from 8% of syringes. Above room temperature (27, 32, and 37 degrees C), the likelihood of encountering syringes with viable HIV-1 when periods of storage exceeded 1 week decreased to less than 1%. The temperatures at which drug injectors are likely to store their used syringes will vary according to climate, season, and circumstances faced by the injector. The survival of HIV-1 in contaminated syringes varied over a range of temperatures, and this may be a factor influencing the syringe-borne transmission of HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Adriamycin-induced changes of creatine kinase activity in vivo and in cardiomyocyte culture.

Adriamycin (ADM) is an anthracycline anti-neoplastic agent, whose clinical effectiveness is limited by severe side effects, including cardiotoxicity. The toxic effects of ADM are likely to be the consequence of the generation of free radicals. This study demonstrates that ADM induces significant changes in the activity of the oxidative sensitive enzyme creatine kinase (CK) in the heart in vivo and in a cardiomyocyte culture model. The changes observed are likely to reflect the ability of ADM to damage the plasma membrane of cardiac cells and to induce the direct inactivation of CK. The role for ADM-derived free radicals is one of the possible mechanisms for the CK inactivation observed during the ADM treatment.

Animals↗
PubMed1999

Antioxidants protect against reactive oxygen species associated with adriamycin-treated cardiomyocytes.

Adriamycin (ADM) is a broad-spectrum antineoplastic antibiotic used to treat cancer patients. However, the usefulness of this drug is presently limited by the development of a dose-dependent cardiotoxicity. A current hypothesis for the ADM-induced cardiotoxicity is the production of reactive oxygen radicals by the drug. We utilized the fluorescent indicator 2',7'-dichlorodihydrofluorescein diacetate (DCFH/DA), in which fluorescence appears if reactive oxygen species (ROS) are present, to investigate the ability of ADM to generate reactive oxygen species and the potential protective effect of antioxidants in a cultured cardiomyocyte model. All three of the antioxidants (alpha-phenyl-tert-butyl nitrone (PBN), trolox, and 5-aminosalicylic acid (5-ASA)) tested in our ADM-treated myocytes provided protection against the oxidative stress induced by the drug. These findings suggest that antioxidants modulate ADM-induced oxidative stress, and they are discussed in terms of a possible therapeutic strategy in the prevention of cardiotoxicity resulting from ADM administration.

Animals↗
PubMed1999

Elevated oxidative stress in models of normal brain aging and Alzheimer's disease.

Age-associated neurodegenerative disorders are becoming more prevalent as the mean age of the population increases in the United States over the next few decades. Both normal brain aging and Alzheimer's disease (AD) are associated with oxidative stress. Our laboratory has used a wide variety of physical and biochemical methods to investigate free radical oxidative stress in several models of aging and AD. Beta-amyloid (A beta), the peptide that constitutes the central core of senile plaques in AD brain, is associated with free radical oxidative stress and is toxic to neurons. This review summarizes some of our studies in aging and A beta-associated free radical oxidative stress and on the modulating effects of free radical scavengers on neocortical synaptosomal membrane damage found in aging and A beta-treated systems.

Aging↗
PubMed1999

Amyloid beta-peptide inhibits Na+-dependent glutamate uptake.

The purpose of this review is to summarize much of the work on the inhibition of the astroglial glutamate transporter in relation to excitotoxic neurodegeneration, in particular, inhibition of uptake by the beta-amyloid peptide (A beta) found in the Alzheimer's disease (AD) brain. There is evidence for oxidative stress in the AD brain, and A beta has been found to generate reactive oxygen species (ROS), thus adding to the stress or possibly initiating it. The oxidative inhibition of the glutamate transporter protein by A beta increases the vulnerability of glutamatergic neurons, and by rendering them susceptible to the excitotoxic insult that results from impaired glutamate uptake, A beta can be directly connected to the neurodegeneration that follows.

Alzheimer Disease↗
PubMed1999

Oxidative alterations in Alzheimer's disease.

There is increasing evidence that free radical damage to brain lipids, carbohydrates, proteins, and DNA is involved in neuron death in neurodegenerative disorders. The largest number of studies have been performed in Alzheimer's disease (AD) where there is considerable support for the oxidative stress hypothesis in the pathogenesis of neuron degeneration. In autopsied brain there is an increase in lipid peroxidation, a decline in polyunsaturated fatty acids (PUFA) and an increase in 4-hydroxynonenal (HNE), a neurotoxic aldehyde product of PUFA oxidation. Increased protein oxidation and a marked decline in oxidative-sensitive enzymes, glutamine synthetase and creatinine kinase, are found in the brain in AD. Increased DNA oxidation, especially 8-hydroxy-2'-deoxyguanosine (8-OHdG) is present in the brain in AD. Immunohistochemical studies show the presence of oxidative stress products in neurofibrillary tangles and senile plaques in AD. Markers of lipid peroxidation (HNE, isoprostanes) and DNA (8-OHdG) are increased in CSF in AD. In addition, inflammatory response markers (the complement cascade, cytokines, acute phase reactants and proteases) are present in the brain in AD. These findings, coupled with epidemiologic studies showing that anti-inflammatory agents slow the progression or delay the onset of AD, suggest that inflammation plays a role in AD. Overall these studies indicate that oxidative stress and the inflammatory cascade, working in concert, are important in the pathogenetic cascade of neurodegeneration in AD, suggesting that therapeutic efforts aimed at both of these mechanisms may be beneficial.

Alzheimer Disease↗
PubMed1998

Detection of HIV-1 nucleic acid and HIV-1 antibodies in needles and syringes used for non-intravenous injection.

BACKGROUND: HIV antibodies and HIV DNA have been detected in needles and syringes that have been used for intravenous injections in HIV-infected persons. During intravenous injection, blood is typically aspirated into the lumen of the syringe. During intramuscular or subcutaneous injection, however, blood is not usually introduced into the syringe. OBJECTIVES: To investigate the presence of HIV antibodies, HIV proviral DNA, HIV RNA, and human DNA in needles and syringes that had been used for intramuscular or subcutaneous injection in persons known to have HIV infection. METHODS: Discarded disposable needles and syringes used by health-care personnel for medically indicated intramuscular or subcutaneous injections of HIV-infected patients were collected. Residual material was extracted from the syringes. The extracts were analyzed by enzyme immunoassay for the presence of HIV antibodies. PCR was conducted to detect HIV and human DNA, as well as HIV RNA. RESULTS: HIV antibodies were detected in 16 (6.2%) out of 260 syringes. Human DNA or HIV-specific DNA were not detected. A second set of 80 syringes was collected to examine the presence of HIV RNA. HIV RNA was detected in three (3.8%) out of 80 syringes. CONCLUSION: This analysis demonstrates that the risk of transmitting HIV from syringes that have been used for intramuscular or subcutaneous injection may be low, but is not zero.

DNA, Viral↗
PubMed1998

Effects of mitochondrial respiratory stimulation on membrane lipids and proteins: an electron paramagnetic resonance investigation.

Previous studies have implicated mitochondria-derived reactive oxygen species (ROS) in both the aging process and age-related diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease etc. The current study, utilizing electron paramagnetic resonance (EPR) spectrometry, was designed to determine if mitochondrial respiratory stimulation, under state 4 conditions, caused extensive oxidative modifications to membrane cytoskeletal proteins and lipids in the brain. A mixed population of cortical synaptosomes and mitochondria, prepared by centrifugation techniques using rat brain cortex from adult (4-6 months) female Brown Norway rat brains, were labeled with the lipid-specific spin probe, 5-nitroxyl stearate (5-NS). Stimulation of the mitochondrial electron transport chain was accomplished using 20 mM succinate at 25 degrees C for 3 h. Mitochondrially derived free radicals, when reacted with the paramagnetic center of the spin probe, result in a loss of paramagnetism resulting in loss of intensity. A significant lowering (23%, P<0.0001) in the signal amplitude (B0) of 5-NS, indicative of generation of oxyradicals, was found. The order parameter, an inverse EPR-measure of membrane fluidity of the 5-NS spin labeled mitochondrial and synaptosomal membranes, also decreased following mitochondrial respiratory stimulation (P<0.005). Changes in the physical state of cytoskeletal and transmembrane proteins due to succinate oxidation were measured using MAL-6 (2,2,6, 6,-tetramethyl-4 maleimidopiperdin-1-oxyl), a thiol-specific nitroxide spin label. The ratio of the amplitudes of the weakly to strongly immobilized spin label reaction sites (W/S ratio) in the low-field region of the spectrum was used to determine any alteration in protein conformation. Previous studies in our laboratory have established that increased protein oxidation is associated with a decreased W/S ratio. In the current study, our results indicated significant lowering of the W/S ratio in cortex (30%, P<0.0001) upon stimulation of the mitochondria with 20 mM succinate. Thus, we conclude that respiratory stimulation of mitochondria, due to a hypermetabolic stress with succinate, caused significant oxidative modifications of cortical membrane lipids and proteins.

Animals↗
PubMed1998

Protein oxidation and enzyme activity decline in old brown Norway rats are reduced by dietary restriction.

The effect of aging and diet restriction (DR) on the activity of creatine kinase (CK), glutamine synthetase (GS) and protein carbonyl formation in the cerebellum, hippocampus and cortex of male and female brown Norway (BN) rats has been investigated. It was demonstrated that CK activity in three different regions of the rat brain declines with age by 30%. Age-related decrease of GS activity was only 10-13% and did not reach statistical significance. Consistent with previously published studies, age-related increase of protein carbonyl content in each brain area studied has been observed. Preventive effects of a caloric restricted diet on the age-associated protein oxidation and changes of the activity of CK and GS in the brain was observed for both aging male and female BN rats. DR delayed the accumulation of protein carbonyls. Age-related changes of CK activity in rat brain were abrogated by DR. The activity of GS in the brain of old rats subjected to the caloric restricted diet was higher than that in the brain of young animals fed ad libitum. The results are consistent with the notion that DR may relieve age-associated level of oxidative stress and lessen protein damage.

Aging↗
PubMed1998

Opioids disrupt Ca2+ homeostasis and induce carbonyl oxyradical production in mouse astrocytes in vitro: transient increases and adaptation to sustained exposure.

Pharmacologically distinct subpopulations of astroglia express mu, delta, and/or kappa opioid receptors. Activation of mu, delta, or kappa opioid receptors can destabilize intracellular calcium ([Ca2+]i) in astrocytes leading to cellular hypertrophy and reactive injury. To assess whether acute or sustained opioid exposure might adversely affect astroglial function by disrupting Ca2+ homeostasis or by producing reactive oxygen species, fura-2 and a novel fluorescent-tagged biotin-4-amidobenzoic hydrazide reagent, respectively, were used to detect [Ca2+]i and carbonyl oxidation products within individual murine astrocytes. Acute (3 h) exposure to mu; (H-Tyr-Pro-Phe (N-Me) -D-Pro-NH2; PLO17), delta ([D-Pen2, D-Pen5]-enkephalin), and kappa (trans-(+/-)-3, 4-dichloro-N-methyl-N-[2-(1-pyrr olidinyl) cyclohexyl] benzeneacetamide methanesulfonate; U50,488H) opioid agonists caused significant mean increases in [Ca2+]i and in the levels of oxidative products in astrocytes. In contrast, following 72 h of continuous opioid exposure, [Ca2+]i and carbonyl levels returned to normal, irrespective of opioid treatment. These preliminary findings indicate that opioids initially destabilize [Ca2+]i and increase reactive oxygen species in astrocytes; however, astrocytes later recover and adapt to sustained opioid exposure.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1998

Adriamycin induces protein oxidation in erythrocyte membranes.

Adriamycin is an anthracycline antineoplastic agent whose clinical effectiveness is limited by severe side effects, including cardiotoxicity. A current hypothesis for adriamycin cardiotoxicity involves free radical oxidative stress. To investigate this hypothesis in a model system, we applied the technique of immunochemical detection of protein carbonyls, known to be increased in oxidized proteins, to study the effect of adriamycin on rat erythrocyte membranes. Erythrocytes obtained from adriamycin-treated rats demonstrated an increase of carbonyl formation in their membrane proteins. Yet, in separate experiments when adriamycin was incubated with rat erythrocyte ghosts, there was no significant increase of membrane protein carbonyls detected. In contrast, isolated erythrocytes incubated with an adriamycin-Fe3+ complex exhibited a robust carbonyl incorporation into their membrane proteins in a time-dependent manner. The level of carbonyl formation was dependent upon the concentration of Fe3+ known to form the adriamycin-Fe3+ complex. When the time course between protein carbonyl formation and lipid peroxidation was compared, protein carbonyl detection occurred earlier than lipid peroxidation as assayed by thiobarbituric acid reactive substances formation. These results are consistent with the notion that oxidative modification of membrane proteins may contribute to the development of the acute adriamycin-mediated toxicity.

Animals↗
PubMed1997

Free radical oxidation of brain proteins in accelerated senescence and its modulation by N-tert-butyl-alpha-phenylnitrone.

According to the free radical theory of aging, reactive oxygen species cause oxidative damage, proposed to be an underlying factor of the aging process. In the current study, we have used electron paramagnetic resonance spin labeling, measurements of protein carbonyl content, an index of protein oxidation, and determination of the activity of glutamine synthetase (an oxidatively sensitive enzyme) to report that cortical synaptosomal membranes from the senescence accelerated-prone (SAMP8) mouse showed structural characteristics of free radical oxidative stress relative to the senescence accelerated-resistant (SAMR1) mouse. The SAMP8 mouse exhibited a decrease in the relevant EPR parameter consistent with oxidative stress (P < 0.002), a decreased glutamine synthetase activity (P < 0.05), and an increased protein carbonyl content (P < 0.01) compared with these parameters in the SAMR1 mouse. Further, because free radical trapping compounds have been demonstrated to extend maximum life span and improve cognition in SAMP8 mice, we investigated the protective nature of the known free radical scavenger, N-tert-butyl-alpha-phenylnitrone (PBN), on the physical state of cortical synaptosomal membrane proteins. For 14 days, SAMR1 and SAMP8 mice were injected with 30 mg/kg PBN while the controls were injected with the corresponding volume of saline. Characteristic of less oxidized systems, cortical synaptosomal membranes from the PBN-injected SAMP8 mouse exhibited a return toward normal values of the relevant EPR parameter [the M1 = +1 low-field weakly immobilized line/M1 = +1 low-field strongly immobilized line (W/S) ratio of a protein-specific spin label] (P < 0.001) compared with that from saline-injected SAMP8 mice. In SAMR1 mice, in contrast to SAMP8, there was no significant change in the conformation of membrane proteins or protein carbonyl content of cortical synaptosomal membranes from the PBN-injected and saline-injected SAMR1 mice, showing that PBN itself did not induce conformational changes in cortical synaptosomal membrane proteins. The results are discussed with reference to the use of free radical scavengers as potential anti-aging agents.

Aging↗
PubMed1997

The expression of creatine kinase isoenzymes in neocortex of patients with neurodegenerative disorders: Alzheimer's and Pick's disease.

Creatine kinase (CK) activity was found decreased in the brains of patients with Alzheimer's disease (AD) and Pick's disease (PD). However, the decrease of total CK activity in AD was more pronounced than in PD. Analysis of the activity of two CK isoforms, BCK and ubiquitous mitochondrial CK, demonstrated that the decrease of total CK activity in AD and PD was related to the decrease of BCK activity. The decline of CK activity both in AD and PD correlated well with the decline of the content of immunoreactive BCK in brain extracts. The BCK mRNA level in AD and PD was not significantly different from control patients and could not be the primary reason for decreases in CK content and activity. The decreased level of BCK in AD and PD brains might be caused by posttranscriptional events, which could affect the translation of BCK mRNA and/or lead to the inactivation and degradation of the enzyme. Because CK is sensitive to oxidative modification, it is possible that the changes observed in this study result from free radical damage.

Aged↗