Biomedical subjects

L C Anderson

Publications and source records attributed to L C Anderson.

At least 19 recordsLinked to original sources

PubMed1998

Salivary concentrations of atrazine reflect free atrazine plasma levels in rats.

The protein binding of atrazine in plasma and its effect on salivary excretion of atrazine was determined in male Sprague-Dawley rats. The degree of protein binding of atrazine was determined at 3 steady-state plasma concentrations, 50, 150, and 250 microg/L, using an ultrafiltration technique. In total, 48 arterial blood samples were collected from 18 rats; 38 of 48 blood samples had their time-matched whole saliva samples. The average protein binding of atrazine ranged from 18% to 37%; however, it was not significantly different across the 3 steady-state plasma concentrations nor among the individual rats. Overall, 26% of atrazine was bound to plasma proteins and not available for transport from blood into saliva. Protein binding of atrazine in plasma was not correlated with total atrazine plasma concentration nor with free atrazine plasma concentration, which indicates that the protein-bound fraction of atrazine is independent of plasma concentration within the range measured in this study (30-400 microg/L). The average saliva/plasma (S/P) concentration ratio of atrazine increased from 0.7 using total atrazine plasma concentration to 0.94 (S/fP) when free atrazine plasma concentrations calculated as 26% of protein binding was used. Salivary concentration was highly correlated with free atrazine plasma concentration. The results suggest that salivary concentration of atrazine not only reflects its total plasma level but accurately measures the portion of atrazine (free atrazine) in plasma, which may be of toxicological significance.

Animals↗

PubMed1998

NGF depletion reduces ipsilateral and contralateral trigeminal satellite cell reactions after inferior alveolar nerve injury in adult rats.

Following peripheral nerve injury, neuronal cell functions in sensory ganglia shift from normal maintenance and neurotransmission toward survival and regeneration. A rapid modulation of glial cell activity, which is related to changes in neuronal-support cell interaction, also occurs after nerve injury. Nerve growth factor (NGF) is required for the survival and maintenance of specific populations of sensory and sympathetic neurons, and changes in neuronal gene expression after axonal injury are due in part to a loss of NGF retrograde transport from the periphery to the cell body. A similar role for NGF in modulating support cell responses to peripheral nerve injury, however, has not been demonstrated. Using an autoimmune model, we assessed the effects of NGF depletion in adult rats on the injury-induced expression of glial fibrillary acid protein immunoreactivity (GFAP-IR) in the ipsilateral and contralateral trigeminal ganglia (TG). Unilateral inferior alveolar nerve crush resulted in a bilateral, NGF-dependent trigeminal satellite cell response. In control rats there was a widespread induction of GFAP-IR in the ipsilateral as well as the contralateral TG. In contrast, GFAP-IR was reduced to the mandibular division of the ipsilateral TG in NGF-depleted rats, and the contralateral up-regulation of GFAP-IR was entirely abolished. Bilateral sympathectomy failed to mimic the effects of autoimmunization. Our results provide evidence that NGF depletion inhibits injury-induced satellite cell responses, independent of its effects on sympathetic nerve function.

Animals↗

PubMed1997

Animal rights.

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Adolescent↗

PubMed1997

Nerve growth factor depletion by autoimmunization produces thermal hypoalgesia in adult rats.

Nerve growth factor (NGF) plays a role in mechanisms of inflammation and hyperalgesia in adult animals. We sought to determine if NGF depletion produced by autoimmunization of adult rats altered their thermal sensitivity to an acute noxious thermal stimulus. Anti-NGF IgG was not detected in the cerebrospinal fluid of any tested samples. Only those rats with the highest anti-NGF serum titers showed significant (P < 0.05) thermal hypoalgesia measured using the hot plate test (52 degrees C): the mean (+/-S.D.) hind paw lick latency of rats in the high anti-NGF titer group was 18.0 +/- 4.6 s compared to means of 10.8 +/- 4.3 s, 9.2 +/- 2.6 s and 10.1 +/- 3.0 s in the medium, low and control groups, respectively. Thus, NGF depletion by autoimmunization is a useful model for investigating the role of NGF in behavioral responses of adult rats to noxious stimuli, providing high titers of antibody are present.

Animals↗

PubMed1997

Determination of atrazine levels in whole saliva and plasma in rats: potential of salivary monitoring for occupational exposure.

Current biological monitoring techniques are often unable to provide accurate estimates of pesticide dose in exposed worker populations. This study was conducted to investigate the feasibility of pesticide biomonitoring using saliva. Atrazine [2-chloro-4-ethylamino-6-(isopropylamino)-s-triazine], a member of the triazine herbicides, was selected to investigate salivary excretion following direct gastric administration in rats. Concentrations of atrazine in whole saliva and arterial plasma samples were determined by enzyme-linked immunosorbent assay (ELISA). Atrazine reached its highest level in both arterial plasma (238 micrograms/L) and whole saliva (157 micrograms/L) 35 min after administration of 105 mg/kg of atrazine, and then decreased with time in a parallel fashion. Although saliva atrazine levels were lower than levels in arterial plasma, there was a very high correlation between whole saliva and arterial plasma atrazine concentrations (r2 = .95). In addition, pharmacokinetic analysis suggested that salivary levels of atrazine can be used to predict concentrations of atrazine in plasma. The mean whole saliva/arterial plasma atrazine concentration ratio (S/P) was 0.66 +/- 0.11 (n = 20). The S/P ratios did not vary significantly over time, and were not affected by salivary flow rate. This study demonstrates that atrazine is transported into saliva, and that a relatively constant concentration ratio between whole saliva and arterial plasma is maintained. Because the salivary concentrations of atrazine are independent of variation in salivary flow rate, salivary monitoring of atrazine in humans may prove useful and practical. Finally, this study suggests that other pesticides with chemical and physical properties similar to those of atrazine can be monitored in saliva.

Animals↗

PubMed1997

The action of perchlorate on malignant-hyperthermia-susceptible muscle.

To better understand the altered skeletal muscle excitation-contraction (E-C) coupling that occurs in malignant hyperthermia, we have examined the potentiating actions of perchlorate in intact muscle fiber bundles, isolated sarcoplasmic reticulum (SR) vesicles, and the purified ryanodine receptor/Ca2+ release channel (RyR) isolated from malignant-hyperthermia-susceptible (MHS) and normal porcine muscle. The concentration of perchlorate that half-maximally potentiated twitch tension (2.5-3.5 mM) was not significantly different for MHS and normal muscles. The effect of perchlorate on fractional twitch force was significantly greater for normal than for MHS muscle, although the absolute twitch potentiation was similar for both muscle types. The K-contracture threshold of MHS muscle bundles is significantly lower than that of normal bundles; perchlorate shifted the K-contraction activation curves of both MHS and normal muscle bundles to lower K+ concentrations. Perchlorate both increased ryanodine binding to MHS and normal SR vesicles and increased single-channel open probability of the purified MHS and normal RyR. In both cases, the percentage increase was greater for normal than for MHS preparations; however, the absolute increase in activity was not different for MHS and normal RyR indicating that there is no difference in the perchlorate sensitivity of MHS and normal SR Ca2+ release channels. Thus, the greater absolute responses of the MHS Ca2+ release channel in the presence of perchlorate is likely to be due to the greater basal activity of the MHS release channel and does not reflect an underlying defect in the site of action of perchlorate on the MHS skeletal muscle Ca2+ release channel.

Animals↗

PubMed1997

Correspondence of salivary and plasma concentrations of atrazine in rats under variable salivary flow rate and plasma concentration.

The stability of the saliva/plasma (S/P) concentration ratio of atrazine was determined under varying conditions of salivary flow rate and plasma concentration of atrazine in Sprague-Dawley rats. In the salivary flow study, whole saliva samples were collected at different salivary flow rates while the plasma concentration of atrazine was maintained at a steady-state level of approximately 150 micrograms/L. In the plasma level study, whole saliva samples were collected at two steady-state plasma concentrations of atrazine (50 and 250 micrograms/L), while salivary flow rate was maintained at a relatively constant level. In both studies, atrazine concentrations in whole saliva and arterial plasma demonstrated a consistent relationship, but salivary concentrations were always lower than those of arterial plasma. Linear regression analysis demonstrated that the S/P concentration ratio of atrazine was not significantly different for salivary flow rates ranging from 23 to 92 microL/min/kg body weight, and did not vary for atrazine plasma concentrations between 30 and 433 micrograms/L. The S/P concentration ratio of atrazine was relatively constant throughout each experimental period (0.68 +/- 0.1 and 0.70 +/- 0.11 for salivary flow and plasma level studies, respectively) and did not differ significantly between rats. When data from both studies were pooled, salivary concentrations were highly correlated with plasma concentrations (r2 = .94). It is concluded that under these experimental conditions, the stability of the S/P concentration ratio of atrazine is not affected by variations in salivary flow rate or atrazine plasma concentrations. The results from this study support the conclusion that atrazine salivary concentrations can be used to predict plasma levels of atrazine in rats.

Analysis of Variance↗

PubMed1996

Sequential secretion of rat submandibular kallikrein and peroxidase during intermittent sympathetic stimulation.

Secretion of peroxidase from acinar cells, true tissue kallikrein (rK1) from granular tubules and total protein have been assessed in sequential samples of rat submandibular saliva formed during intermittent periods of sympathetic stimulation in bursts of 50 Hz 1 s every 10 s at 5 V, for 1 or 2 min each with 2 min intervals between periods. This protocol was repeated twice after 1 h rest pauses. The salivary flow remained greater throughout than when using ongoing burst stimulation. Protein secretion was considerable in the first 2 samples (1 min followed by 2 min) reaching the remarkable concentration of 285 +/- 14.4 mg/ml, then it gradually decreased with little recovery after 1 h pauses. rK1 outputs followed a similar pattern. Peroxidase, however, showed no greater output in initial samples and continued steadily in similar amounts throughout. When intermittent stimulations were used for 1 sequence only (total stimulation time = 9 min) the glands showed 84 +/- 2.6% depletion of rK1 compared to the control glands. A correspondingly large depletion of granules occurred from the granular tubules on the stimulated side, which was greater than with ongoing burst stimulation for 1 h (Garrett et al., 1991). Thus, secretion of rK1 from the granules in granular tubules occurs most efficiently with short sharp bursts of high frequency sympathetic stimulation but soon diminishes. In contrast, peroxidase secretion from acinar cells continues steadily and more modestly for long periods of time undiminished.

Animals↗

PubMed1996

Differential dose-response to oral xemilofiban after antecedent intravenous abciximab. Administration for complex coronary intervention.

BACKGROUND: Placebo-controlled randomized trials of parenteral platelet glycoprotein (GP) IIb/IIIa receptor antagonists have demonstrated reduced ischemic complications of coronary angioplasty. Orally active GP IIb/IIIa blockers are being developed to allow more sustained receptor antagonism with potential for long-term secondary prevention. Sequential therapy with abciximab followed by an oral IIb/IIIa antagonist has not previously been reported. The clinical safety and pharmacodynamics of a sequential therapeutic strategy are unknown. METHODS AND RESULTS: Of 74 consecutive patients enrolled in a placebo-controlled, dose-ranging pharmacokinetic/pharmacodynamic study of xemilofiban, a new oral nonpeptide GP IIb/IIIa antagonist, after elective intracoronary stent placement, 17 patients received abciximab during stent deployment as a weight-adjusted intravenous bolus and 12-hour infusion at the discretion of the investigator. Ex vivo platelet aggregation in response to 20 mumol/L ADP and 4 micrograms/mL collagen was measured over time after the first dose of either xemilofiban (5, 10, 15, or 20 mg) or placebo (ticlopidine) administered 8 to 18 hours after termination of abciximab and again after 1 week of twice-daily oral administration of study drug. At baseline, patients who had received abciximab had lower platelet aggregation in response to both agonists (P < .001). A significant dose-response relationship to xemilofiban was observed. Patients who had received abciximab had lower ADP-induced (P < or = .010) and collagen-induced (P < or = .029) platelet aggregation after xemilofiban. This pharmacodynamic interaction was no longer evident at 1 week. No significant clinical bleeding events or blood product transfusions were observed in this trial. CONCLUSIONS: Both the magnitude and the duration of pharmacodynamic response to xemilofiban were enhanced by prior abciximab treatment. The potentiated pharmacodynamic response was not evident after 1 week. This observation has implications for the safety and efficacy of sequential parenteral-oral GP IIb/IIIa blockade therapy and may be useful in deriving dose regimens for orally administered compounds.

Abciximab↗

PubMed1996

Apical secretion of rat submandibular tissue kallikrein continues in the absence of external stimulation: evidence for a constitutive secretory pathway.

Sequential samples of saliva evoked by low frequency parasympathetic nerve stimulation were collected from cannulated submandibular ducts of anaesthetized rats following periods of varying length without stimulation. After such rest periods the first samples of saliva were found to contain much higher levels of tissue kallikrein (rK1) activity and protein than the ensuing samples from the same stimulation period and the latter contained levels similar to those found previously in parasympathetically-evoked saliva. rK1 activity in first samples increased with the length of the preceding interval, indicating that a continuous secretion of rK1 occurs from ductal cells into glandular lumina and accumulates there in the absence of stimulation or fluid secretion. The protein secretory pattern following rest pauses was unaffected by alpha-adrenergic receptor blockade and a high percentage of the proteinase activity was resistant to soya bean trypsin inhibitor, showing that the secretion was not caused by exocytosis of storage granules from ductal cells and therefore was likely to be a result of a constitutive secretion of newly synthesized enzyme. The pattern of continuous secretion into lumina detected for total protein in the absence of stimulation, suggests that other secretory proteins may also be secreted similarly but at different rates.

Animals↗

PubMed1996

Apical secretion of rat submandibular tissue kallikrein continues in the absence of external stimulation: evidence for a constitutive secretory pathway.

Sequential samples of saliva evoked by low frequency parasympathetic nerve stimulation were collected from cannulated submandibular ducts of anaesthetized rats following periods of varying length without stimulation. After such rest periods the first samples of saliva were found to contain much higher levels of tissue kallikrein (rK1) activity and protein than the ensuing samples from the same stimulation period and the latter contained levels similar to those found previously in parasympathetically evoked saliva rK1 activity in first samples increased with the length of the preceding interval, indicating that a continuous secretion of rK1 occurs from ductal cells into glandular lumina and accumulates there in the absence of stimulation or fluid secretion. The protein secretory pattern following rest pauses was unaffected by alpha-adrenergic receptor blockade and a high percentage of the proteinase activity was resistant to soya bean trypsin inhibitor, showing that the secretion was not caused by exocytosis of storage granules from ductal cells and therefore was likely to be a result of a constitutive secretion of newly synthesized enzyme. The pattern of continuous secretion into lumina detected for total protein in the absence of stimulation, suggests that other secretory proteins may also be secreted similarly but at different rates.

Animals↗

PubMed1996

Peroxidase and kallikrein in atropine-resistant secretion of submandibular saliva on parasympathetic nerve stimulation in anaesthetized rats.

Flow of submandibular saliva and the constituents secreted during chorda-lingual nerve stimulation at 40 Hz (3 x 10 min) were studied after alpha- and beta-adrenergic blockade, and in the absence (control) or presence of cholinergic blockade in anaesthetized rats. Peroxidase and true tissue kallikrein (rK1) were assessed to gain insight into the effects of the non-adrenergic, non-cholinergic (NANC) transmitters on protein secretion by acini and granular tubules, respectively. From control glands there was an overall mean flow of 181 +/- 15 microliters g-1 min-1, with no significant differences between the three periods. Secretion from atropinized glands was approximately 20% of that from control glands in the first 10 min, decreasing progressively to approximately 6% in the final period. Protein outputs from control glands showed no significant differences for the three periods (0.23 +/- 0.05 mg g-1 min-1). Protein outputs from atropinized glands were similar to controls in the first 10 min and then decreased significantly. Peroxidase output from control glands increased progressively (from 31 +/- 7 to 243 +/- 68 pmol dichlorofluorescein (DCF) g-1 min-1) but in saliva from atropinized glands the overall mean output was only 4.5 +/- 0.8 pmol DCF min-1 ml-1, with a progressive decrease between samples. Outputs of rK1 from control glands were similar for all samples (20.6 +/- 4.0 nmol AFC g-1 min-1), but there was a significantly smaller and decreasing output of rK1 from atropinized glands. In conclusion, NANC transmitters released from parasympathetic nerves during stimulation at high frequency appear to have little influence on the secretion of protein from rat submandibular acini and granular tubule cells when acting in isolation. This contrasts with their effects on amylase secretion from rat parotid glands under similar circumstances.

Adrenergic alpha-Antagonists↗

PubMed1995

Differential secretion of proteins by rat submandibular acini and granular ducts on graded autonomic nerve stimulations.

1. The influence of graded parasympathetic and sympathetic nerve stimulations on the secretion of protein from rat submandibular gland was studied. Peroxidase was used as a marker for the acini and rat tissue kallikrein (official nomenclature rK1) as the marker for granular ducts. Tonin (rK2) was also measured, and the ratio of rK2:rK1 was calculated as an indication of the cellular route of secretion. 2. Continuous parasympathetic nerve stimulation caused a copious flow of saliva that had a low protein content. The secretion of peroxidase (acini) showed a gradual moderate increase as the frequency increased. However, the concentrations of rK1 and rK2 (granular ducts) showed little change throughout, and the ratio of rK2:rK1 remained relatively constant. 3. Graded sympathetic stimulation was applied against a background of parasympathetic stimulation. Secretion of peroxidase was increased by the addition of 0.1 Hz continuous sympathetic stimulation. The amount increased thereafter up to 2 Hz, but showed no further increase if the stimulation was applied as bursts of 10 or 20 Hz. In comparison, the secretion of proteinase activity showed little change with superimposed continuous sympathetic stimulation, and the rK2:rK1 ratio was similar to that in saliva produced by parasympathetic stimulation alone. Sympathetic stimulation applied in bursts, however, caused a large increase in the secretion of proteinase activity, and with 20 Hz burst stimulation the rK2:rK1 ratio was indistinguishable from that of sympathetic saliva per se. There was an augmented secretion of both peroxidase and kallikrein when 20 Hz burst stimulation was combined with parasympathetic stimulation. The effects of sympathetic stimulation were abolished by alpha- and beta-adrenoceptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Revision total hip replacement using the S-ROM femoral component.

The proximally porous-coated, modular S-ROM femoral component was used in 52 complex total hip revisions done in 48 patients. These patients had severe bone loss, leg length inequality, and instability. Twenty-two patients required structural femoral allografts; 8 had previous resection arthroplasties for sepsis. The mean number of previous hip operations was 3. The stem was press fit, and the metaphyseal sleeve was selectively cemented to the allograft. The preoperative Harris rating was 44 points; at a mean of 3 years, followup was 82 points. Eighty-four percent of the patients were satisfied with their outcomes. No radiographic or histologic evidence of fretting at the modular sleeve-stem junction or along the stem was seen. Significant thigh pain persisted in 2 patients and was directly related to stem diameters > 17 mm. Complications in these complex cases were not infrequent, reflecting the need for allograft augmentation, and included greater trochanter bursitis and nonunion in 20 hips, minor nonpropagating fracture in 13 hips, and 12 dislocations. Mechanical loosening occurred in 5 hips. There were no complications attributable to the S-ROM modular femoral component, and the prosthesis has proven to be versatile and did well in these very difficult cases.

Adult↗

PubMed1994

Transcranial magnetic evoked potentials used to monitor the spinal cord during neuroradiologic angiography of the spine.

A current topic in intraoperative monitoring of the spinal cord is the inability of the somatosensory evoked potentials (SSEP) to adequately document anterior spinal cord function. Transcranial magnetic stimulation (TMS) of the cortex for assessing corticospinal (efferent) pathways is a developing modality. The authors demonstrate a potential application of TMS as a monitoring medium for use in the neuroradiology suite. Limitations of intraoperative applications of cortical magnetic stimulation associated with cortical suppression are caused by anesthetics and neuromuscular blockers. These limitations generally are not an issue in the neuroradiology suite. In this report, motor improvement was correctly predicted by magnetic evoked potential amplitudes, whereas an SSEP remained unchanged during neuroradiologic angiography.

Arteriovenous Malformations↗

PubMed1994

Morphological effects of diabetes on the granular ducts and acini of the rat submandibular gland.

Effects of experimental diabetes on rat submandibular glands have been documented, but earlier reports suggested that diabetes caused an extensive cellular degeneration and a replacement of the parenchymal cells by fibrous connective tissue. Such observations, however, are difficult to reconcile with the relatively normal physiological responsiveness of the gland (Anderson and Suleiman, 1989). This study, therefore, reexamined the histological, histochemical and ultrastructural effects of streptozotocin-induced diabetes on rat submandibular glands. The tissues were examined at 3 weeks, and 3 and 6 months after the induction of diabetes, and compared with glands from age-matched controls by both light and electron microscopy. Light microscopically, the proportional volumes of the acini and granular ducts remained constant in control rats at about 48% and 38% respectively. In diabetic animals the volume density of the acini increased progressively to 62%, whereas that of the granular ducts decreased to 20%. The diameter and number of granular ducts were reduced in diabetic animals, but acinar cell profile area was only affected 6 months after the induction of diabetes. Ultrastructurally, there was an accumulation of lipid in the acinar cells and, with increasing duration of diabetes, the number of autophagic structures in both the acini and the granular ducts increased. Although there was evidence of some cellular degeneration it was never excessive. Morphometry showed that the volume density of secretory granules within the acinar cells was unaffected, but there was a significant reduction in the volume density of secretory granules within the granular ducts. Thus, in the rat submandibular gland the greatest effect of streptozotocin-induced diabetes was to cause hypotrophic changes in the cells of the granular ducts. The relative contributions of a direct effect of insulin insufficiency and the hypogonadal effects of diabetes, however, are not known.

Animals↗

PubMed1994

The effects of streptozotocin-induced diabetes on norepinephrine and cholinergic enzyme activities in rat parotid and submandibular glands.

Autonomic neuropathy is a common complication of diabetes mellitus, and both morphological and physiological data suggest that salivary gland function in diabetic rats is affected by neuropathies involving sympathetic and parasympathetic nerves. Therefore, glandular levels of the adrenergic neurotransmitter, norepinephrine (NE) and two cholinergic enzymes, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), were investigated in 6-month streptozotocin-diabetic rats. Significant, but variable, increases in total parotid NE (ng/gland) were observed in diabetic rats, whereas total submandibular NE was lower in diabetic animals than in controls. However, on a ng/mg tissue basis, NE levels in both the parotid gland, and less dramatically, in the submandibular gland were increased. Somewhat different results were observed for AChE and ChAT. AChE was marginally greater in the parotid glands of diabetic rats, whereas AChE and ChAT levels were significantly lower in diabetic than control submandibular glands. Expressed as enzymatic activity per mg tissue, submandibular gland ChAT, but not AChE, was increased. Short-term (3-day) insulin treatment of diabetic animals had no significant effects on total NE, AChE or ChAT in the parotid gland, but led to a further reduction in submandibular ChAT. With regard to function, changes in AChE appeared to be correlated with previously reported morphological assessments of parotid gland innervation in diabetic animals. Thus, the decreased response of the parotid gland in diabetic rats to parasympathetic stimulation may be related in part to the increase in AChE.

Acyltransferases↗

PubMed1994

The effects of streptozotocin diabetes on salivary-mediated bacterial aggregation and adherence.

Diabetic rats are known to have an increased susceptibility to dental caries and major alterations in parotid salivary composition. Salivary proteins play an important part in oral health maintenance; thus specific changes in salivary protein composition in diabetic animals might alter the ecological balance in favour of cariogenic bacteria, and toward the initiation and progression of the disease process. The ability of whole, parotid and submandibular salivas from control and streptozotocin-diabetic rats to mediate the aggregation and adherence to hydroxyapatite of mutans streptococci was examined. Salivary-mediated bacterial aggregating activity was significantly reduced in whole and parotid salivas from diabetic rats, but bacterial adherence to hydroxyapatite was unaffected. The aggregating and adherence activities of rat whole saliva were derived mainly from parotid saliva, which contains predominantly low molecular-weight proteins and glycoproteins (< 200 kDa), but rat parotid saliva was capable of interacting with the bacterial receptor for the high molecular-weight aggregating factor in human saliva. SDS-PAGE of parotid saliva revealed that a number of proteins, including the basic and acid proline-rich proteins, were altered in the salivas of diabetic animals. After incubation with either Streptococcus mutans or hydroxyapatite several protein bands were depleted, and thus a variety of proteins and glycoproteins may be responsible for the adherence and aggregating activity of rat parotid saliva.

Analysis of Variance↗