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PubMedDate not supplied

Atypical antipsychotic drug use and diabetes.

Recently, there has been increased concern about the occurrence of diabetes associated with the use of atypical antipsychotic (AAP) drugs. The relationship between diabetes, schizophrenia, and antipsychotic drugs is complex and intriguing, as untreated patients with schizophrenia are known to suffer from diabetes more often than the general population. Thirty individual case reports of clozapine-, 26 cases of olanzapine- and a few others of seroquel- and risperidone-associated diabetes mellitus, hyperglycemia and diabetic ketoacidosis were found by a Medline search. The case reports do not provide the incidence of diabetes in patients treated with AAP drugs, but they suggest that AAP drugs may cause hyperglycemia. Further research is needed to identify the cause of the susceptibility of the schizophrenic population, and to elucidate the mechanisms by which the antipsychotic drugs either cause diabetes or precipitate its onset. Which antipsychotic drugs have a higher and which have a lower potential to induce diabetes is not conclusively answered at present. However, the findings that 50% of the patients completely improve upon drug discontinuation, and that hyperglycemia promptly recurs upon reinstitution of the incriminated drug indicate that this side effect is reversible and is drug related. African Americans are particularly susceptible to AAP drug-induced diabetes. Until the new research data become available, AAP drug treatment of schizophrenic patients aims at prevention, institution of vigilant screening procedures, and management of hyperglycemia.

Antipsychotic Agents↗
PubMed2006

Measuring attachment representation in an FMRI environment: a pilot study.

This exploratory study is the first to examine the neural correlates of attachment status in adults. The study examined the feasibility of assessing attachment narratives in the functional magnetic resonance imaging (fMRI) environment by challenging subjects to tell attachment stories to specific attachment pictures from the Adult Attachment Projective (AAP) while being scanned. We investigated theoretically derived hypotheses regarding predicted differences in the brain activation patterns of individuals whose attachment status was organized (resolved) versus disorganized (unresolved) with respect to attachment trauma (e.g., as associated with loss through death, abuse, threat of abandonment). Adult attachment was assessed using the AAP, a new representational attachment measure that we thought might be suitable for use in the fMRI environment. This measure was used to obtain a preliminary picture of the neural processes associated with the activation of attachment in 11 healthy female adults. Results are reported from a second-level analysis (p < 0.001 uncorrected) and confirm that the AAP is a feasible measure for use in a neuroimaging environment. Cerebral activation during continuous speech yielded results consistent with the literature. Brain activation was demonstrated in expected visual and semantic brain regions. Furthermore, we found that the rate of articulation was positively correlated with activation in the right superior temporal gyrus. The results of theoretically derived attachment hypotheses showed no differences at the chosen level of significance when comparing the 'all attachment pictures' effect between both groups (resolved vs. unresolved). More interestingly, we found a significant interaction effect between the sequence of pictures and attachment category. Only the unresolved participants showed increasing activation of medial temporal regions, including the amygdala and the hippocampus, in the course of the AAP task. This pattern was demonstrated especially at the end of the AAP task where the pictures are drawn to portray traumatic situations. We interpret these results as confirming our hypothesis, linking unresolved attachment to emotional dysregulation of the attachment system. These results are discussed in relation to assessing attachment in an fMRI environment and future research in this area.

Adult↗
PubMed1984

Demonstration of a free elastolytic metalloenzyme in human lung lavage fluid and its relationship to alpha 1-antiprotease.

Although the human alveolar macrophage in tissue culture can secrete an elastolytic metalloenzyme that is not inactivated by alpha 1-antiprotease (AAP), levels of this proteolytic activity and its relationship to AAP in human lung lavage fluid ( HLF ) are unknown from previous studies. Therefore, we measured elastolytic activity in concentrated (20- to 30-fold) HLF from 15 smokers and 10 nonsmokers and related results to measurements of AAP in these fluids. Activity (mean +/- SEM) against a C elastin substrate (expressed as nanograms of porcine pancreatic elastase equivalents per milligram of lavage fluid protein) in smokers, 18.9 +/- 6.7, significantly exceeded (p = 0.05) levels present in nonsmokers, 4.4 +/- 1.8. With the synthetic elastin-like chromophore substrate succinyl-trialanine-nitroanilide ( SLAPN ), activity in individual samples was reduced 79% by EDTA, a metalloproteinase inhibitor, whereas activity was reduced by only 29% in the presence of PMSF, a serine proteinase inhibitor. In addition, using a pooled sample of HLF and C elastin substrate, 80% of activity against the elastin substrate was eliminated by EDTA, whereas 51% was eliminated by PMSF. The activity measured with C elastin substrate correlated inversely with antigenic AAP (r = -0.05, p = 0.01), but no correlations were found between this activity and HLF cell number, cell viability, differential count, or subject smoking history. The detection of activity with C elastin in HLF , with primarily a metalloenzyme inhibitor profile, in the presence of antigenically detectable AAP, may have pathogenetic relevance for emphysema in humans.

Adult↗
PubMed2006

Management of neonatal hyperbilirubinemia: pediatricians' practices and educational needs.

BACKGROUND: Early detection and treatment of neonatal hyperbilirubinemia is important in the prevention of bilirubin-induced encephalopathy. In this study, we evaluated the New Jersey pediatricians' practices and beliefs regarding the management of neonatal hyperbilirubinemia and their compliance with the recommendations made by the American Academy of Pediatrics (AAP) in 1994. METHODS: A survey questionnaire was mailed to a random sample of 800 pediatricians selected from a list of 1623 New Jersey Fellows of the AAP initially in October 2003 and then in February 2004 for the non-respondents. In addition to the physicians' demographic characteristics, the questionnaire addressed various aspects of neonatal hyperbilirubinemia management including the diagnosis, treatment, and follow up as well as the pediatricians' beliefs regarding the significance of risk factors in the development of severe hyperbilirubinemia. RESULTS: The adjusted response rate of 49.1% (n = 356) was calculated from the 725 eligible respondents. Overall, the practicing pediatricians reported high utilization (77.9%) of the cephalocaudal progression of jaundice and low utilization (16.1%) of transcutaneous bilirubinometry for the quantification of the severity of jaundice. Most of the respondents (87.4%) identified jaundice as an indicator for serum bilirubin (TSB) testing prior to the neonate's discharge from hospital, whereas post-discharge, only 57.7% felt that a TSB was indicated (P < 0.01). If the neonate's age was under 72 hours, less than one-third of the respondents reported initiation of phototherapy at TSB levels lower than the treatment parameters recommended by the AAP in 1994, whereas if the infant was more than 72 hours old, almost 60% were initiating phototherapy at TSB lower than the 1994 AAP guidelines. Most respondents did not regard neonatal jaundice noted after discharge and gestational ages 37-38 weeks as being significant in the development of severe hyperbilirubinemia. However, the majority did recognize the importance of jaundice presenting within the first 24 hours and Rh/ABO incompatibility. CONCLUSION: The pediatricians' practices regarding the low utilization of laboratory diagnosis for the quantification of jaundice after discharge and underestimation of risk factors that contribute to the development of severe hyperbilirubinemia are associated with initiation of phototherapy at lower than AAP recommended treatment parameters and recognition of neonatal hyperbilirubinemia as an important public health concern.

Adult↗
PubMed2003

The role of apoptosis in acetaminophen-induced injury.

Apoptosis plays a critical role in acetaminophen (AAP)-induced hepatic injury, since inhibiting apoptosis also prevents the development of acute liver failure. In this study, the mechanism of apoptosis induction by AAP was investigated in the human hepatoblastoma cell line HuH7. AAP caused marked cytotoxicity in HuH7 cells as a result of apoptosis. Processing of execution caspases to their corresponding active fragments and cleavage of cytokeratin-18 were observed, supporting a role of caspases in AAP-induced apoptosis. The manifestation of apoptosis was preceded by a translocation of cytochrome c from mitochondria to the cytosol. In conclusion, AAP induces apoptosis in human hepatoblastoma HuH7 cells through mitochondrial cytochrome c release and caspase activation.

Acetaminophen↗
PubMed1990

Dose-dependent pharmacokinetics and first-pass metabolism of acetaminophen in rats.

In order to investigate the in vivo first-pass metabolism of acetaminophen (AAP) following the oral and intraduodenal administration in rats, a pharmacokinetic compartment model including absorption process was developed. Using the parameters for the disposition kinetics of AAP and its metabolites, sulfate and glucuronide, which were determined in the separate study, the extent of the first-pass metabolism and the contribution of sulfation and glucuronidation to the total first-pass metabolism in vivo were quantitatively estimated. As for the results, the first-pass metabolism of AAP following the oral and intraduodenal administration was mainly attributable to the sulfo-conjugation pathway in rats. The sulfation of AAP in the intestine and/or in the liver during the first-pass was proved to be a saturable process. Then, the sulfation in the first-pass metabolism showed the dose- and absorption rate-dependent kinetics. Thus, the pharmacokinetic model including the absorption process proposed in the present study was proved to be valid and useful for the estimation of in vivo first-pass metabolism of AAP in rats.

Acetaminophen↗
PubMed1978

Comparison of effects of acetaminophen on liver microsomal drug metabolism and lipid peroxidation in rats and mice.

Studies were conducted to determine the in vivo effect of acetaminophen (AAP) on the lipid peroxidation, drug metabolizing enzyme activity and microsomal electron transfer system of rat and mouse liver. AAP was found to inhibit ethylmorphine N-demethylase activity in the presence of NADPH and this inhibition of the enzyme was due to decrease in cytochrome P-450 content, but not due to change in lipid peroxidation in liver microsomes. Kinetical data showed that AAP administration had no effect on Km values of ethylmorphine N-demethylase, however, a decrease in the Vmax values was seen in rats and mice. There was no significant effect of AAP on both NADPH-cytochrome c reductase and the content of cytochrome b5 3 hours after this administration to rats and mice. On the other hand, AAP induced a significant decrease in NADH-ferricyanide reductase in mice, but not in rats. The greatest decrease in cytochrome P-450 observed among the components of the liver microsomal electron transfer system of rats and mice.

Acetaminophen↗
PubMedDate not supplied

Improving guideline adherence for the diagnosis of ADHD in an ambulatory pediatric setting.

BACKGROUND: The American Academy of Pediatrics (AAP) has published clinical practice guidelines for the diagnosis of Attention Deficit Hyperactivity Disorder (ADHD). However, implementation of guidelines has been notoriously difficult to achieve in the wider context of changing individual physicians' clinical practice. OBJECTIVE: Implement a formalized diagnostic protocol for ADHD and study whether this protocol improved adherence of pediatric residents and faculty to published guidelines for the diagnosis of ADHD. METHODS: Quasi-experimental retrospective record review of 63 pediatric patients evaluated for ADHD by pediatric residents and faculty in an outpatient pediatric clinic before (n = 25) and after (n = 38) implementation of a formal diagnostic process for ADHD. The key elements of the new diagnostic process include completion of a semistructured interview and mandatory rating scales for home and school. The published AAP guidelines include 1) documentation of Diagnostic and Statistical Manual for Mental Disorders (DSM) IV criteria; 2) evidence of core symptoms obtained directly from home and 3) from school; and 4) assessment for coexisting conditions. Adherence was assessed to each criterion individually (yes/no) and was summarized in a single score. RESULTS: Only 4% of clinicians and nurse practitioners diagnosing children in the before group adhered to all 4 AAP guidelines, compared to 82% in the after group (P < .001). Significant improvement was observed across each of the 4 criteria in the AAP guidelines. Moreover, the improvement in adherence to all 4 guidelines was noted for residents and faculty. CONCLUSION: A significant improvement in adherence to AAP guidelines was obtained for all providers through implementation of a structured diagnostic approach to ADHD.

Ambulatory Care↗
PubMed1998

Management of acute gastroenteritis in children in Israel.

OBJECTIVE: Diarrheal diseases are a major cause of morbidity and mortality worldwide. Guidelines about the use of oral rehydration solutions (ORS) and dietary management of acute gastroenteritis (GE) were recently revised and published by the American Academy of Pediatrics (AAP). Study aims were to examine Israeli pediatricians' knowledge and implementation of the revised AAP guidelines, the effect of medical school (Israeli versus foreign medical graduates) on the physicians' practice, and the effect of the type of practice (community vs hospital-based) on the management of gastroenteritis. METHODS: A multiple-choice, written questionnaire was distributed at two pediatrics annual meetings. RESULTS: A total of 87 pediatricians completed the questionnaire. They were aware of 73% of the current AAP guidelines and followed 60% of the guidelines. Most pediatricians (83%) use ORS for treatment of dehydration in GE, but 60% of pediatricians believe that full-strength feeds are inappropriate in the presence of GE, and 67% of them do not recommend full-strength formulas. In addition, 37% of the pediatricians stop feeding temporarily in the presence of GE, in contrast to the 1996 AAP guidelines. There were no differences in knowledge and management practices among pediatricians graduating in Israel, Europe, or the United States, and no differences between pediatricians working in an ambulatory setting or in a hospital. CONCLUSIONS: Pediatricians in Israel, regardless of country of origin, medical school, or place of practice, are aware of the correct use of ORS but do not follow nutritional practices recommended recently by the AAP. These findings suggest that steps for implementing the guidelines are needed in Israel and most probably worldwide.

Acute Disease↗
PubMed1999

Pediatricians' response to the demand for school health programming.

OBJECTIVE: Because of the broad and increasing interest in school health, the American Academy of Pediatrics (AAP) surveyed its members to determine their awareness of school health education/programs, their level of participation, their desire to participate, and their resource needs to participate more effectively. METHODS: Self-administered questionnaires were mailed to a randomized representative sample of AAP members (N = 1602). Overall response rate was 64.5%. Some responses were stratified for analysis by gender; age (>45 years or </=45 years); practice area (urban, suburban, or rural); practice setting (solo, group, or hospital); and type of practice (general versus specialty). chi2 Tests were used to compare responses. RESULTS: Greater than half of the pediatricians who responded to the questionnaire were aware of school health education curriculum on risky adolescent behaviors in their community, counseling services (58%), school nursing services (63%), and screening services (71%); however, more than half were not aware of curriculum on injury/violence prevention, fitness, or whether a school health advisory council was available. Most pediatricians supported comprehensive school health education (pregnancy prevention, 82%; violence prevention, 77%; mental health, 56%). Also, respondents supported services (counseling, 76%; nutrition, 65%; screening/referral, 58%; school-based primary care, 58%). Although 22% of AAP pediatricians are currently working with local school programs, >70% wanted to become involved or more involved and needed information on how they may be able to participate. Only 25% believed they were adequately prepared. Two thirds believed school-based clinics were one of the best ways to reach underserved children and adolescents and should include preteens. CONCLUSION: AAP pediatricians want to become more involved with comprehensive school health programs. The ways in which they want to participate vary substantially. Most pediatricians thought they needed additional education. The AAP has developed recommendations for graduate medical education and continuing medical education for pediatricians to participate in integrated school health services.

Attitude of Health Personnel↗
PubMed2001

Barriers to domestic violence screening in the pediatric setting.

OBJECTIVE: By surveying practitioners in our community, we hoped to determine what pediatricians and family physicians (FPs) perceive as barriers to the American Academy of Pediatrics (AAP) Recommendation on Domestic Violence Screening. BACKGROUND: When screened in the pediatric setting, as many as 40% of mothers will disclose domestic violence (DV) by their partner. Recognizing the profound effects of DV on children, the AAP recently recommended that all practitioners incorporate DV screening as a part of routine anticipatory guidance. Yet, there is little information about whether pediatricians have the training, the time to screen, or understand the magnitude of this problem. DESIGN/METHODS: A 22-question survey about attitudes, training, and current DV screening practice was sent to all general pediatricians and FPs with admitting privileges to Children's Hospital Medical Center in Cincinnati, Ohio. A copy of the AAP recommendation on screening was included. The vast majority of practitioners with an appreciable pediatric practice in the surrounding tri-state area of 1.8 million people have privileges at the institution. RESULTS: After 2 mailings, 310 (57%) of 547 of questionnaires were returned. The majority of practitioners (64%) were unaware of the AAP recommendation, but 51% of practitioners screened at least high-risk families for DV and 49% had identified a case of DV in their practice. Still, only 8.5% routinely screened for DV and 74% had received no specific DV training. Fifty-eight percent of practitioners estimated the incidence of DV to be <5% in their practice. The most commonly perceived barriers to screening were lack of education (61%), office protocol (60%), time (59%), and support staff (55%). FPs were significantly more likely to have DV training (64% vs 21%), more likely to screen at least high-risk women (79% vs 56%), and more likely to have identified a case of DV (92% vs 40%) than pediatricians. FPs were less likely to cite lack of education (46% vs 65%) and lack of time (50% vs 61%) than pediatricians. Physicians licensed in Ohio were less likely to have specific domestic violence training (23% vs 60%) as compared with Kentucky physicians, where domestic violence education is required for licensing. Kentucky physicians were less likely to cite lack of education as barrier to DV screening (20% vs 62%). When comparing the characteristics of those who screen to those who do not, those with DV training were 10.9 times (odds adjusted ratio) more likely to screen. CONCLUSIONS: Practitioners grossly underestimate the incidence of DV in their practices. Lack of education including knowledge of screening recommendations is a barrier to DV screening by pediatricians. Greater efforts are needed to educate pediatricians on DV for the AAP recommendations to be accepted.domestic violence, child abuse, screening, physician attitude.

Adult↗
PubMed2004

Referral patterns to a pediatric orthopedic clinic: implications for education and practice.

OBJECTIVE: Musculoskeletal medicine is becoming an increasingly essential part of primary care medicine. The American Academy of Pediatrics (AAP) Surgical Advisory Panel recently published voluntary guidelines to establish diagnoses that should be referred to a pediatric specialist rather than a general specialist (pediatric orthopedic surgery vs general orthopedic surgery). Given the crisis in pediatric orthopedic surgery manpower and resources, we believe that these guidelines are useful in defining appropriate referrals. The purpose of this study was to compare diagnoses that primary care pediatric providers believe commonly need referral to the AAP Guidelines for Referral to Pediatric Specialists recommendations for referral to pediatric orthopedic specialists. METHODS: A chart review of successive new referrals (n = 286) to the pediatric orthopedic clinic during a 12-month period was conducted. The following information was collected: 1) diagnosis from referring provider, 2) diagnosis and treatment plan by the pediatric orthopedic surgeon, 3) type of referring provider (eg, pediatrician, family practitioner, resident physician, physician assistant), and 4) patient age. The referring diagnosis, final orthopedic diagnosis, and treatment plan for each patient was compared against the AAP Guidelines for Referral to Pediatric Specialists. The terms "appropriate" and "inappropriate" were used to differentiate those diagnoses that matched versus those that did not match the AAP Guidelines, respectively. RESULTS: This analysis shows that a significant percentage (64.7%) of definitive diagnoses of referred cases were not consistent with the new AAP recommended guidelines for referral to pediatric orthopedic surgeons. In addition, a 23.8% (68 of 286) false-positive rate of referring diagnoses is noted. Cases that required no treatment or follow-up to monitor demonstrated a 32.8% (60 of 183) [(40 no treatment + 20 monitor inappropriate)/(116 no treatment + 67 monitor total)] false-positive rate. CONCLUSIONS: Inappropriate referrals create a large use of pediatric orthopedic resources, which delays care of other, more appropriate patients. A large proportion of referrals indicated either a lack of basic textbook knowledge or lack of examination skills and appropriate diagnostic tools as demonstrated by a high number of definitive diagnosis indicating normal variants.

Adolescent↗
PubMed2005

Community-level child health: a decade of progress.

In the late 1980s, the leadership of the South Carolina Chapter of the American Academy of Pediatrics (AAP) developed a growing awareness that there was a population of children in the state who frequented emergency departments and public health clinics but were not considered patients in any medical professional's office. Coincidentally, the commissioner of the South Carolina Department of Health and Environmental Control was struggling to expand resources needed to care for these children, who were crowding his facilities in search of primary care. Department of Health and Environmental Control clinic staff increasingly were unable to provide core public health services because of the need to treat illnesses and conduct well-child visits. Concurrently, with mounting concerns over the inadequacy and/or unavailability of quality health care for all children, the AAP embarked on the Access to Care campaign, a multiyear effort to improve access to care. The South Carolina Chapter of the AAP and Department of Health and Environmental Control subsequently launched an initiative, the Partnerships for Children program, to ensure that South Carolina children who were medically disenfranchised could have a medical home and all other services necessary for health and well-being. Although structured somewhat differently in various communities and practices, each of the >75 partnerships statewide focused on using public health professionals for specific care coordination and support that complemented physician office visits and encounters. These partnerships have gained substantial leverage through the expanding resources of the AAP Access to Care campaign. In reviewing claims for children <3 years old who were enrolled in Medicaid before the establishment of the Partnerships for Children program, <45% had evidence of a well-child visit. Data in the fourth year of the program indicate that 84% of children in this age group have had at least 1 well-child visit. Other data suggesting improved access to care are equally reassuring. In this report, I describe the evolution of the Partnerships for Children program, identify key ingredients for its success, and provide examples of effective strategies that bring community resources into pediatric practices to allow for more efficient and productive delivery of primary care. I also indicate the important role of the AAP Community Access to Child Health infrastructure in the maintenance and further development of this initiative.

Child↗
PubMed2005

The school nurse role in asthma management: can the action plan help?

Asthma is the most common chronic disorder in American schoolchildren, and school nurses play a valuable role in its management. A study was conducted in which school nurses were asked to describe their role in caring for students with asthma and their use of Asthma Action Plans (AAPs). The nurses indicated that they frequently provided direct care and education. They were comfortable with providing care to students with asthma and familiar with AAPs. Having an AAP increased their confidence in managing students with asthma. This emphasizes the need for continued education regarding the AAP and the development of policies that direct care and encourage use of an AAP at school.

Asthma↗
PubMed1995

Chloral hydrate sedation of children undergoing CT and MR imaging: safety as judged by American Academy of Pediatrics guidelines.

OBJECTIVE: The purpose of this prospective study was to determine the frequency of adverse events associated with supplemented and unsupplemented chloral hydrate sedation in a select group of children undergoing CT or MR imaging using the revised American Academy of Pediatrics (AAP) monitoring and management guidelines for pediatric sedation. The AAP guidelines do not recommend drug selection or dosages but define patient selection, discharge criteria, and monitoring standards for sedating children. SUBJECTS AND METHODS: This prospective study included 410 children 4 years of age or younger who were scheduled for CT and MR imaging as outpatients. Selected children were physical status 1 or 2 as determined by the American Society of Anesthesiologists physical status classification and had no contraindications to sedation per our institutional sedation policy. Children younger than 1 year old received only oral incremental doses of chloral hydrate. Children 1-4 years old received hydroxyzine plus incremental doses of chloral hydrate. Children between 2 and 4 years old who were not satisfactorily sedated 30 min after hydroxyzine plus incremental chloral hydrate were given 2 mg/kg meperidine intramuscularly, with a maximum dose of 50 mg. All children were monitored according to the revised guidelines recommended by the committee on drugs of the AAP. Vital signs and arterial hemoglobin oxygen saturation (SpO2) were monitored continuously by registered nurses trained in pediatric advanced life support from the time of sedative drug administration until the recommended discharge criteria were met. RESULTS: Mild hypoxia (SpO2, 90-95%) that resolved spontaneously without any therapeutic intervention was seen in 9% of the chloral hydrate group and in 5% of the chloral hydrate-hydroxyzine group. One child in the chloral hydrate group had severe hypoxia (SpO2, 85-89%), and one child in the chloral hydrate-hydroxyzine group had moderate hypoxia (SpO2, < 85%). Both required therapeutic intervention. In both cases, the severity of the underlying medical disease was underestimated at the time of presedation medical screening. The success rate of sedation was 100% for all the children having CT. For those having MR imaging, success was 100% for children 1-4 years old and 97% for children less than 1 year old. CONCLUSION: Use of supplemented and unsupplemented chloral hydrate sedation provides effective and safe sedation in children if the AAP guidelines for patient selection, monitoring, and management are followed. Careful medical screening and patient selection by knowledgeable medical personnel is important to exclude patients at high risk for life-threatening hypoxia. Monitoring with AAP guidelines is essential for prompt detection and management of life-threatening hypoxia.

Child, Preschool↗
PubMed2001

Comparison of bronchoalveolar lavage fluid obtained from Mannheimia haemolytica-inoculated calves with and without prior treatment with the selectin inhibitor TBC1269.

OBJECTIVES: To determine effects of selectin inhibitor TBC1269 on neutrophil infiltration, and neutrophil-associated injury during pneumonia induced by Mannheimia haemolytica and concentration of antimicrobial anionic peptide (AAP) in bronchoalveolar lavage fluid (BALF) as well as antimicrobial activity of BALF from healthy (control) neonatal calves, neonatal calves with M haemolytica-induced pneumonia, neonatal calves with prior treatment with TBC1269, and adult cattle. ANIMALS: Eighteen 1- to 3-day-old calves and 9 adult cattle. PROCEDURE: Calves were inoculated with M haemolytica or pyrogen-free saline (0.14M NaCl) solution into the right cranial lung lobe, and BALF was collected 2 or 6 hours after inoculation. Thirty minutes before and 2 hours after inoculation, 4 calves received TBC1269. The BALF collected from 9 adult cattle was used for comparison of BALF AAP concentration and antimicrobial activity. Protein concentration and neutrophil differential percentage and degeneration in BALF were determined. An ELISA and killing assay were used to determine BALF AAP concentration and antimicrobial activity, respectively. RESULTS: Total protein concentration was significantly decreased in BALF from calves receiving TBC1269. Similar concentrations of AAP were detected in BALF from all calves, which were 3-fold higher than those in BALF from adult cattle. However, BALF from neonates had little or no anti-M haemolytica activity. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that TBC1269 decreases pulmonary tissue injury in neonatal calves infected with M haemolytica. Although AAP is detectable in neonatal BALF at 3 times the concentration detected in adult BALF, neonatal BALF lacks antimicrobial activity for M haemolytica.

Animals↗
PubMed1981

Hepatic glutathione content and aryl hydrocarbon hydroxylase activity of acetaminophen-treated mice as a function of age.

Glutathione (GSH) plays an important role in cells as an antioxidant, and participates in the detoxification of drugs and foreign chemicals. The effect of age on hepatic glutathione (GSH) levels and aryl hydrocarbon hydroxylase (AHH) activity and the ability of these mice to respond to the acute administration of acetaminophen (AAP) has been studied. Female Swiss Webster mice at ages 3, 9, and 18 mo were treated i.p. with 500 mg/kg AAP, and hepatic GSH content and AHH activity were determined at 0, 0.5, 2, 4, 6, 8, 10, 12, and 24 hrs. The hepatic GSH levels and the AHH activity in 18 mo old mice were 43% and 36% lower, respectively, as compared to the 3 mo old animals. Maximum AAP-induced depletion of GSH occurred 2-4 hrs after treatment. Only in 18 mo animals did GSH fail to return to or exceed control levels 24 hr after AAP administration. Maximum decrease in hepatic AHH activity occurred in all age groups at 10 hr post-AAP administration, and had not returned to control values 24 hr after treatment. The results support the hypothesis that a decrease in GSH and mixed function oxidases may contribute to changes associated with aging as well as to the increased susceptibility to disease and drugs which occur with advanced age.

Acetaminophen↗
PubMed2000

In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract.

Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.

Acetaminophen↗