The bioavailability of iron from foods is ultimately determined by interactions between iron and other components in the digestive milieu. Perhaps the most important factor is the concentration of Fe2+ during transit through the duodenum. During in vitro simulations of human digestion it is possible to probe the concentration of Fe2+, the rate of Fe2+ formation, and total iron concentration using ferrous chromogens. It is crucial, of course, that the chromogen not interfere with the redox reactions occurring during digestion. Accordingly, ferrozine was examined with regard to its ability to reduce complexes Fe3+, alter rates of Fe3+ production, detect Fe2+ present in the digestive mixture and differentiate the effects of chelating and reducing agents in the mobilization of iron from pinto beans. The chromogen was found to be free from apparent artefacts and to be a sensitive and reproducible probe of the state of iron in digestive mixtures.

Biological Availability↗

PubMedDate not supplied

Effects of kynurenic acid on amygdaloid kindling in the rat.

The anticonvulsant properties of the endogenous excitatory amino acid antagonist, kynurenic acid (KYA), were studied in prepubescent and adult rats using the amygdaloid kindling model of epilepsy. Treatment with intracerebroventricular KYA (360 nmoles (adult dose) or 240 nmoles (prepubescent dose] prior to administration of the electrical kindling stimulus significantly reduced the rate of kindling in both age groups. However, there was no significant difference between the KYA-treated and the controls in mean afterdischarge threshold in either age group. The results of this study indicate that with the kindling model KYA has a significant anticonvulsant effect in both prepubescent and adult rats.

Age Factors↗

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Transfer following rapid kindling in the prepubescent rat.

In order to investigate the transfer effect following rapid kindling in the immature animal, prepubescent rats were initially kindled in the amygdala using interstimulus intervals of 5 min followed by transfer kindling in the contralateral amygdala at age 100 days using twice daily kindling. A second group of rats were kindled in the prepubescent period with hourly stimulations followed by transfer kindling at age 100 days using twice daily stimulations. A control group underwent sham-kindling in the prepubescent period followed by twice daily kindling at age 100 days. While a transfer effect was seen in both the rapidly kindled and hourly kindled groups, the transfer effect was greater in the animals kindled with the longer interstimulus interval. While rapid kindling produces a long-standing change in brain excitability, the effect is less pronounced than with hourly kindling techniques.

Age Factors↗

PubMedDate not supplied

Failure of neocortical transplants to alter seizure susceptibility in previously kindled rats.

Transplantation of embryonic tissue into the brains of host animals has been demonstrated to totally or partially correct functional lesions and neurohormonal deficits in a variety of animals. This study evaluated the hypothesis that "naive" embryonic neural tissue implanted into previously kindled animals will alter subsequent seizure susceptibility. At age 16 days, male rats were electrically kindled in the right amygdala (AM). Following kindling (age 19 days), rats underwent either transplants of embryonic neocortical tissue into the left dorsal hippocampus or a sham procedure. At age 84 days, both groups underwent transfer kindling in the left AM. In addition, two other groups of 19-day-old pups that had had electrode implantation in the right AM without subsequent kindling received either embryonic neocortical implants in the left dorsal hippocampus or a sham procedure and were kindled in the left AM for the first time at age 84 days. There were no differences in rate of kindling between the animals that received successfully grafted transplants and those that underwent sham procedures. Using the kindling model, transplantation of embryonic neocortical tissue into the hippocampus does not significantly alter seizure susceptibility in the host animal.

Animals↗

PubMedDate not supplied

Behavioral effects of kainic acid administration on the immature brain.

Prepubescent male rats with an amygdaloid electrode in place were administered kainic acid (KA) intraperitoneally (i.p.) while controls received phosphate-buffered saline (PBS). All KA-treated animals developed status epilepticus with bilateral forelimb clonus and ictal discharges on the EEG. The rats were then tested as adults for learning, memory, emotionality, social interaction, and activity level using the T maze, water maze, handling test, home cage intruder test, and open field test. KA-treated rats learned at a slower rate in the water maze and T maze than the controls. In addition, KA-treated rats had evidence of impaired memory during spatial bias testing in the water maze. In the home cage intruder test, KA-treated animals were more submissive and less aggressive than control animals. Finally, KA-treated animals were significantly more active than control animals in the open field test. This study demonstrates that KA administration to the immature brain, in a convulsant dose, results in permanent changes in behavior, learning, and memory.

Age Factors↗

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Genetically epilepsy-prone rats are characterized by altered tissue trace element concentrations.

Since trace element abnormalities have been found in the human epileptic population, trace element concentrations were determined in blood and tissues of genetically epilepsy-prone rats both exposed to an unexposed to seizure-inducing stimuli and in genetically related epilepsy-resistant rats. Half of the epilepsy-prone group were exposed to seizure-inducing sound twice daily for 3 weeks. Food intake and weight gain were monitored for each animal. Genetically epilepsy prone rats with induced seizures consumed significantly less food and gained less weight than did the epilepsy resistant group. Seizure prone rats without seizures consumed the same amount of food as the resistant rats but gained less weight than the resistant strain but more than the seizure-induced animals. Epilepsy-prone animals had significantly altered trace element concentrations in tissues as compared with the resistant animals independent of seizure induction. Brain and liver iron, liver copper, and brain and heart manganese levels were all significantly lower in the seizure-prone rats as compared with the seizure-resistant rats. In the seizure-prone rats, induction of seizures resulted in an increase in brain and heart zinc levels and a decrease in whole blood manganese levels. These results demonstrate that both genetic factors relevant to susceptibility to seizures and the seizures themselves are associated with changes in trace element concentrations.

Acoustic Stimulation↗

PubMedDate not supplied

Effects of age on seizure susceptibility in genetically epilepsy-prone rats (GEPR-9s).

To study the effect of age on seizure latency, intensity, reproducibility, and mortality in genetically epilepsy-prone rats of the severe colony (GEPR-9s), 472 seizure-naive rats, ranging in age from 14 to 65 days, received a series of three audiogenic stimulations. Both the percentage of rats having one or more seizures and the percentage of seizures that were stage 9 generally increased with advancing age of the animal at the time of the first stimulation. Mean latency to seizure onset decreased while seizure intensity increased with increasing age of the animal. Reproducibility of seizure stage also increased with advancing age of the animal. The effects of senescence on seizure susceptibility were also investigated in an additional 18 prepubescent rats (25-35 days) who received three audiogenic stimulations and were tested again between the ages of 480 and 540 days with identical testing procedures. No significant changes occurred with either latency to seizure onset or seizure intensity in rats tested during prepubescence and again at senescence. Although GEPR-9s provide an excellent model of inherited seizures, latency to seizure onset, seizure intensity, and seizure reproducibility is dependent on age of the animal. Once established, however, audiogenic-induced seizures persist throughout life.

Acoustic Stimulation↗

PubMedDate not supplied

Age-dependent cognitive and behavioral deficits after kainic acid seizures.

The long-term behavioral and cognitive effects of seizures at different ages were studied using the kainic acid (KA) seizure model. Rats of postnatal (P) ages (in days) 5, 10, 20, 30, and 60 were administered KA intraperitoneally (i.p.), which induced status epilepticus for several hours, or an equivalent volume of saline. Occurrence of spontaneous recurrent seizures (SRS) was then monitored for 3 months by a closed-circuit videotaping system. Rats began behavioral testing on P80; a separate group of rats that received KA on P60 began testing on P120. Behavioral tests included the Morris water maze (visuospatial learning and memory), the open field test (response to a novel environment), and the handling test (emotionality). When tested on P80, KA-treated P5 and P10 rats had no demonstrable deficits on any test as compared with controls. KA-Treated P20 rats differed from controls only on the water maze spatial bias test. KA-Treated P30 rats had deficits in spatial bias, were more active in the open field, and were more aggressive when handled. KA-Treated P60 rats, whether tested on P80 or P120, had deficits in learning platform position and spatial bias in the water maze, were more active in the open field, and were more aggressive when handled. P60 rats with SRS performed poorer in water maze place learning and spatial bias testing, although the number of SRS did not correlate with overall task acquisition. Our findings suggest age-related behavioral and cognitive deficits after KA-induced seizures. Pubescents and adults had alterations in learning, memory, exploratory behavior, and response to handling, whereas younger animals had no obvious behavioral or cognitive deficits.

Age Factors↗

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Frequency and determinants of microembolic signals on transcranial Doppler in unselected patients with acute carotid territory ischemia. A prospective study.

BACKGROUND AND PURPOSE: Few data exist regarding to the occurrence of microembolic high-intensity transient signals (HITS) on transcranial Doppler ultrasound (TCD) in unselected acute stroke patients. The aim of this study was to investigate prospectively the frequency and determinants of HITS in acute carotid territory ischemia. We hypothesized that carotid artery disease, cardiac abnormalities, and nonlacunar infarcts were independent predictors of HITS in acute stroke. METHODS: We investigated 145 consecutive patients with acute internal carotid artery territory ischemia. The median time interval between stroke and TCD examination was 2 days. TCD monitoring was performed for 30 min on each middle cerebral artery. The frequency of HITS was cross-classified with carotid artery status, potential cardiac sources of embolism, and nonlacunar infarct subtype. Multivariate logistic regression models determined the independent relationship of these variables to HITS. RESULTS: Microembolic signals were detected in 35 patients (24.1%), Ipsilateral carotid artery disease was significantly and independently associated with HITS (odds ratio 3.3, 95% confidence interval 1.4-7.8, p = 0.007), whereas potential cardiac sources (OR 1.07, 95% CI 0.48-2.4, p = 0.84) and infarct subtype (OR 0.84, 95% CI 0.29-2.4, p = 0.75) were not. CONCLUSIONS: High-intensity transient signals can be found in almost 25% of patients with acute anterior cerebral circulation ischemia and are significantly more prevalent among those with symptomatic carotid artery disease. Future clinical studies are required to determine whether HITS are a marker of increased stroke recurrence and can help to clarify stroke etiology in patients with competing stroke mechanisms.

Aged↗

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Prospective study on the complication rate of carotid surgery.

BACKGROUND: Randomized trials of carotid endarterectomy for high-grade stenosis have shown a benefit for surgery under the condition of low perioperative complication rates. Concerns have been expressed that the complication rates of carotid surgery are higher in everyday practice and may vary considerably between centers. We prospectively established the complication rate for carotid surgery in a single institution. DESIGN: Prospective 2-year study. All patients received pre- and postoperative neurological evaluation. Laboratory tests included pre- and postoperative brain imaging, intracranial and neck vessel sonography, conventional angiography, magnetic resonance angiography, and intraoperative monitoring. PARTICIPANTS: 108 consecutive patients: 54 symptomatic patients fulfilling the inclusion criteria of the European Carotid Surgery Trial (ECST) and 54 asymptomatic patients fulfilling the inclusion criteria of the North American Trial on Asymptomatic Stenoses (ACAS). SETTING: Single academic center with a high volume of carotid endarterectomies (>50 per year). Participating center in ECST. MAIN OUTCOME MEASURES: Stroke or death as defined in the randomized trials. RESULTS: The overall complication rate was 8.3% (95% CI 4.1-15.6%). Complications were more frequent in patients with symptomatic stenosis (11.1%, CI 4.6-23.3%) than in asymptomatic cases (5.6%, CI 1.5-16.4%). Three patients died (2 strokes, 1 myocardial infarction). Disabling strokes were found in 2 patients (Rankin scale scores 3 and 4). Nondisabling strokes (Rankin scale score 1 and 2) occurred in 4 patients. The complication rates for symptomatic and asymptomatic patients were higher than the ones reported in the randomized trials, but 95% confidence intervals showed that the differences were not statistically significant. The point estimates of complication rates still supported a benefit of surgery for patients with symptomatic stenosis, but denied a positive effect of endarterectomy for patients with asymptomatic stenosis. CONCLUSION: In this center, a beneficial effect of carotid surgery for asymptomatic stenoses cannot be safely assumed.

Adult↗

PubMedDate not supplied

Transcranial Doppler waveform blunting in severe extracranial carotid artery stenosis.

OBJECTIVE: To investigate the frequency of transcranial Doppler (TCD) waveform blunting in patients with severe (80-99%) symptomatic or asymptomatic extracranial carotid artery stenosis. BACKGROUND: Severe carotid artery stenosis has been identified as a risk factor for ischemic stroke. Blunted Doppler flow waveforms (reduced systolic flow velocity and pulsatility) of the middle cerebral artery (MCA) are inferred to reflect hemodynamic impairment, possibly indicating an increased risk of stroke. METHODS: The 114 consecutive patients (mean age 72.4 years, SD 9.0 years; 37% women; 46 clinically symptomatic, 68 asymptomatic) with 80-99% stenosis of the extracranial internal carotid artery (ICA), as determined by duplex sonography, were examined with TCD. Flow velocities, pulsatility index, and spectral waveforms of the MCA distal to the ICA stenosis were assessed blinded to the clinical status of the ICA: Doppler waveform blunting was defined as loss of the characteristic systolic peak. Odds ratios with 95% confidence intervals and chi(2) statistics were used to describe the association between waveform blunting and the symptomatic status of the ICA stenosis. RESULTS: Among symptomatic patients, 23 (50%) had completed strokes, and a further 23 (50%) had transient neurologic deficits in the territory of the stenotic ICA. Blunted spectral waveform was found in 37 (80%, 95% CI 68-92%) of the symptomatic and 25 (37%; 95% CI 25-49%) of the asymptomatic patients. Symptomatic patients had significantly increased odds of having blunted TCD waveforms (OR 7.5, 95% CI 3.1-18.1, p < 0.001). CONCLUSIONS: Our findings suggest that TCD waveform blunting in the MCA as here described may be an additional risk factor in the setting of severe extracranial carotid artery stenosis. A prospectively designed study to confirm our results seems warranted.

Aged↗