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A miniature, readily available electrode pedestal for recording cerebral and other electrophysiological activity from several species.

A miniature, commercially available electrode pedestal with prewired and prenumbered leads was designed. It possesses long-term electrical reliability and can be applied to a wide range of animal species. It can be easily modified to record electroencephalograms, evoked responses, and related physiological measurements. The device is relatively small, with keyed and lock-down parts, and is resistant to damage.

Animals↗

Use of a bovine hemoglobin preparation in the treatment of cyclic ovarian hemorrhage in a miniature horse.

Anemia that was secondary to ovarian hemorrhage in a 4-year-old miniature horse mare was treated prior to laparotomy with polymerized ultrapurified bovine hemoglobin (PUBH). Two previous whole-blood transfusions had resulted in acute transfusion reaction, and a suitable blood donor could not be found among 9 horses, necessitating use of the blood substitute. Subsequent blood typing revealed the mare to be Aa-negative, with allo-antibodies against Aa in serum. Serious adverse reactions were not observed after infusion of PUBH, and the mare recovered. Although the safety and efficacy of using PUBH in horses has not been established, PUBH may prove to be an excellent alternative to whole-blood transfusions, when indicated.

Anemia↗

Development of a miniature intraventricular axial flow blood pump.

A new intraventricular axial flow blood pump has been designed and developed as a totally implantable left ventricular assist device (LVAD). This pump consists of an impeller combined with a guide-vane, a tube housing, and a DC motor. The pump is introduced into the LV cavity through the LV apex, and the outlet cannula is passed antegrade across the aortic valve. Blood is withdrawn from the LV through the inlet ports at the pump base, and discharged to the ascending aorta. Our newly developed axial flow pump system has the following advantages: 1) it is a simple and compact system, 2) minimal blood stasis both in the device and the LV cavity, 3) minimal blood contacting surface of the pump, 4) easy accessibility with a less invasive surgical procedure, and 5) low cost. A pump flow > 5 L/min was obtained against 100 mmHg differential pressure in the mock circulatory system. The pump could produce a passive pulsatile flow effect with a beating heart more efficiently than other non-pulsatile pumps because of minimal pressure drop and inertia along the bypass tract. Anatomic fit studies using dissected hearts of dilated cardiomyopathy (DCM) cadavers showed that this pump could smoothly pass through the aortic valve without any interference with mitral valve function. Recently, a dynamic pressure groove bearing and a miniature lip seal have been developed. The dynamic pressure groove bearing has a simple structure and acts as a pressure resistant sealing mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathy, Dilated↗

The effect of non-quantal acetylcholine release on quantal miniature currents at mouse diaphragm.

1. The amplitude and exponential decay time constant of miniature endplate currents (MEPCs) were measured in mouse diaphragms treated with anti-cholinesterase under conditions known to modulate non-quantal acetylcholine (ACh) release. 2. Anti-cholinesterase prolonged MEPC decay and the extent of this initial prolongation was not influenced by non-quantal release. When non-quantal release was present, the decays of MEPCs became increasingly faster over several hours. This increased decay did not occur in the absence of non-quantal release. 3. Potentiation of the non-quantal release by zero Mg2+ and 1 x 10(-5) M choline, on the other hand, led to acceleration of MEPC shortening. 4. Increase of temperature from 15 to 26 degrees C and the presence of the desensitization-promoting drug proadifen (5 x 10(-6) M) accelerated the rate of MEPC shortening. 5. These observations are consistent with increased receptor desensitization due to non-quantal release. Repetitive binding of ACh to postsynaptic receptors which prolongs the time course of MEPC in anti-cholinesterase-treated endplates leads to progressive desensitization in the presence of non-quantal release and to the subsequent shortening of the quantal responses.

Acetylcholine↗

Effects of met-enkephalin on GABAergic spontaneous miniature IPSPs in organotypic slice cultures of the rat hippocampus.

The action of met-enkephalin on GABAergic spontaneous miniature IPSPs (smIPSPs) was investigated in CA1 neurons from hippocampal slice cultures. In the presence of excitatory amino acid blockers (2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline, DL-2-amino-5-phosphonovaleric acid) and TTX, a continuous high-frequency bombardment of smIPSPs was recorded. The smIPSPs were blocked by the GABAA antagonist bicuculline. The occurrence of the smIPSPs was random and their amplitude distribution was skewed toward larger smIPSPs. Met-enkephalin (10-20 microM) reversibly reduced the frequency and changed the amplitude distribution of the smIPSPs. The proportion of "large" smIPSPs was reduced, but a loss of "small" smIPSPs also contributed to the reduction in smIPSP frequency. The selective mu-receptor agonist DAGO mimicked the effect of met-enkephalin and naloxone blocked the effect of DAGO. Hyperpolarization of the neuronal membranes, produced by reducing the extracellular K+ concentration, did not reduce the frequency of the smIPSPs, nor did it block the effect of DAGO. Reduction of the extracellular concentration of Ca2+ combined with an increase in extracellular Mg2+ or the addition of Cd2+ did not reduce the smIPSP frequency, nor did it block the effect of DAGO. These results suggest that CA1 pyramidal cells of hippocampal organotypic cultures are tonically inhibited by spontaneous release of GABA, through a release mechanism that is independent of propagated sodium action potentials. Met-enkephalin and DAGO reduce the tonic inhibition by reducing the frequency of the smIPSPs, through a direct action on the presynaptic GABAergic terminals. The effect was probably not mediated by hyperpolarization of the presynaptic membrane or by modulation of presynaptic Ca2+ currents.

Animals↗

Effect of treatment with a monoclonal antibody against equine tumor necrosis factor (TNF) on clinical, hematologic, and circulating TNF responses of miniature horses given endotoxin.

Tumor necrosis factor-alpha (TNF) is an important mediator of endotoxin-induced pathologic changes. To help define the role of TNF in equids with endotoxemia, the effects of pretreatment with a murine monoclonal antibody (MAB) against equine TNF were evaluated in Miniature Horses given endotoxin. Five horses were given TNF MAB at a dosage of 1.86 mg/kg of body weight, IV, and 5 were given control MAB. Five minutes later, lipopolysaccharide (LPS; Escherichia coli O55:B5), 0.25 microgram/kg, was given to all horses by bolus IV infusion. Clinical signs of disease were monitored at intervals up to 24 hours after LPS infusion, and blood was taken for determination of WBC count, PCV, plasma total protein concentration, plasma TNF activity, and serum MAB concentration. Reduction of plasma TNF activity in anti-TNF-treated horses was highly significant (P < 0.001), compared with that in control horses. Horses given TNF MAB had significantly improved clinical abnormality score (P < 0.010), lower heart rate (P < 0.001), and higher WBC count (P < 0.001), compared with horses given control MAB. Rectal temperature, respiratory rate, PCV, and plasma total protein concentration were not significantly different between groups. Serum MAB concentration peaked at 68 micrograms/ml 30 minutes after the end of antibody infusion in both groups. Neutralization of LPS-induced TNF activity reduced the hematologic and clinical responses of horses given LPS IV.

Analysis of Variance↗

Age and sex related changes of hematologic parameters in Sinclair(S-1) miniature swine.

Venous blood samples were collected monthly from 60 male and 60 female Sinclair(S-1) miniature swine from 1 through 36 months of age. Hematologic parameters evaluated included: erythrocyte count, packed cell volume, hemoglobin concentration, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, leukocyte count and differential leukocyte counts. Mean erythrocyte count increased from 3 through 9 months of age and declined thereafter. Mean packed cell volume and hemoglobin concentration decreased from 1 to 3 months of age, increased from 3 through 10 months of age and remained stable thereafter. From 7 through 36 months of age, females had greater mean packed cell volume and hemoglobin concentration than did males. Mean corpuscular volume and mean corpuscular hemoglobin increased linearly from 3 through 24 months of age and remained stable thereafter with females having greater mean corpuscular volumes and mean corpuscular hemoglobins than did males. Mean corpuscular hemoglobin concentration increased linearly from 1 through 30 months of age. Mean leukocyte count decreased from 1 through 9 months of age and remained stable thereafter. From 10 through 36 months of age, mean leukocyte count was greater for males than for females. From 6 through 24 months of age, mean per cent lymphocytes was greater for females than for males; whereas, mean per cent neutrophils was greater for males than for females.

Age Factors↗

Calcium-dependent paired-pulse facilitation of miniature EPSC frequency accompanies depression of EPSCs at hippocampal synapses in culture.

Two forms of evoked neurotransmitter release at excitatory synapses between cultured hippocampal neurons have been described. After an action potential, it has been shown that transmitter initially is released synchronously, and this is followed by a period of "slow" asynchronous release. The "fast" synchronous component of release at these synapses has been found routinely to demonstrate paired-pulse and tetanic depression, whereas the short-term plasticity of asynchronous release has not been investigated. In the present experiments, we have used the whole-cell patch-clamp technique to record from pairs of neurons in a low-density hippocampal culture preparation to determine both the properties and underlying mechanisms of short-term plasticity of asynchronous release. It was found that an increase in miniature EPSC (mEPSC) frequency accompanied both single and multiple stimuli, and this mEPSC increase was facilitated during paired stimuli, even when the evoked synchronous release was depressed. In addition, both the activity-dependent depression of evoked EPSCs and facilitation of asynchronous mEPSC release were dependent on Ca accumulation in the nerve terminal. However, the Ca-dependent mechanisms underlying these two processes could be distinguished by the differential effects of two membrane-permeant calcium chelators, BAPTA-AM and EGTA-AM. Frequency-dependent depression of evoked EPSCs involves a rapid rise in intraterminal Ca, which likely triggers a process that proceeds in a Ca-independent manner, whereas the asynchronous release may be linked more directly to a sustained increase in intraterminal Ca.

Calcium↗

[Model of a miniature pig catheterized for pharmacokinetic and pharmacodynamic studies of anti-infective agents].

The miniature pig exhibits physiological and anatomical similarities to man. In addition, its reduced size and its docility make it appropriate for laboratory use. Curiously, this model remains seldom used in experimental pharmacokinetics. We present here in a chronic model of catheterized micropig allowing long term investigations of antiinfective agents. We work with Yucatan adult female micropigs weighing between 20 and 40kg. A catheter (60 cm x 2 mm) is placed in the external jugular vein under general anaesthesia and exits in the midline dorsal neck. The catheter is flushed every two days with heparinized saline to retain its potency. At the time of kinetic studies, the antiinfective agent is injected in an ear vein. Blood samples are obtained using the jugular catheter. The mean time of viability of the device is 13 weeks (SD: 10 weeks). Thrombosis was the main cause of arrest of the model. In conclusion, this chronic model of catheterized micropig is suitable for long term pharmacokinetic and pharmacodynamic investigations of antiinfective agents.

Adult↗

[Pharmacokinetic interaction between itraconazole and rifampin in Yucatan miniature pigs].

The objective of this study was to examine the effects of rifampin on itraconazole pharmacokinetics, at steady state, in three Yucatan miniature pigs. The pits received daily during three weeks oral itraconazole at a dosage of 200 mg at the beginning of the meal, then during the next two weeks oral itraconazole combined with an intravenous administration of rifampin at a dosage of 10 mg/kg/day. The coadministration of rifampin resulted in a 18 fold decrease of the Cmax of itraconazole [from 113.0 (SD: 17.2) to 6.2 ng/ml (SD: 3.9)], and in a 22 fold decrease of the AUC [from 1652.7 (SD: 297.7) to 75.6 ng.h/ml (SD: 30.01)]. The active metabolite of itraconazole, hydroxyitraconazole, was undetectable. This study demonstrates that rifampin considerably affects itraconazole kinetics at steady-state in this model of micropig, probably by inducing the hepatic metabolism of itraconazole.

Administration, Oral↗

Correlations between ganglioside storage degree and physiological characteristics of neuronal systems--experimental chloroquine intoxication in miniature pig.

Central nervous neuronal patterns of chloroquine-induced ganglioside storage were investigated in miniature pigs. The systematic distribution of this process was first of all characterized by largely identical reproduction of the current storage patterns of native gangliosidosis. Loss of ganglion cells, cytoarchitectonic disintegration and other degenerative changes resulting in the inborn disease were, however, completely avoided by the experimental conditions. This allowed so far unknown clear-cut and much more comprehensive identification of the intensively as well as of gradually less storing neuronal systems. In this way conspicuous correlations between storage degree and physiological quality of certain neuronal systems became apparent. All identified types of the widely dispersed group of inhibitory interneurons were distinguished by particularly extreme residual body storage. These neurons are physiologically exceptional by their permanent activity which is indispensable for normal function of the nervous system. The most instructive counterpart was documented by extreme poor storage manifestations in the large neuronal perikarya of the nucleus mesencephalicus nervi trigemini. These neurons are comparatively very rarely stressed as they mediate the sensation for pain and temperature exclusively. The mentioned and numerous further experimentally ascertained examples substantiated the conclusion that the degree of ganglioside storage in a ganglion cell type in the experimental pig model might essentially be conditioned by frequency and intensity of its neurotransmission activity. The origin of this correlation could be traced back to the participation of ganglioside in the synaptic release of transmitters. The storage process in neuronal systems of the experimental pigs might hence essentially depend on the chloroquine-conditioned impairment in lysosomal degradation of gangliosided which had been involved in the latter process.

Animals↗

Cervical meningomyelocele associated with spina bifida in a hydrocephalic miniature colt.

Cervical meningomyelocele, spina bifida, and hydrocephalus were diagnosed in a newborn miniature colt that was unable to stand and had a cystic mass in the caudal portion of the dorsal cervical region. Results of physical examination and ultrasonographic imaging of the brain supported the diagnosis of hydrocephalus. Results of radiographic evaluation of the vertebral column were consistent with spina bifida at C5-C6. Fluid aspirated from the cervical mass resembled CSF. Radiography of the cervical region after injection of iohexol into the mass revealed herniation of the spinal cord through a large bony defect, supporting the diagnosis of spina bifida and meningomyelocele. Meningomyelocele, spina bifida, and hydrocephalus are interrelated congenital anomalies in other species. Meningomyelocele should be suspected in foals that have neurologic abnormalities, especially if they have other congenital anomalies and a fluid-filled mass along the dorsal midline.

Animals↗

Basic performance of a miniature intraventricular axial pump.

A miniature intraventricular axial pump for left ventricular (LV) support is under development. This pump was designed for placement in the LV cavity by insertion through the LV apex with the outlet located at the ascending aorta via the aortic valve. The basic hydrodynamic characteristics represented as a relationship between pump head (H) and flow (Q) showed a negative linear relationship under a constant head. This characteristic was generally the same as that obtained by other axial rotation pumps. However, the actual H-Q relationship was represented as anticlockwise "loops" caused by the contraction of the natural LV. The comparative in vitro data on these H-Q loops showed that the shape of the loops was changed drastically by the connecting condition between the pump and natural cardiovascular system.

Animals↗

Transesophageal echocardiography in critically-ill patients using a miniaturized probe: feasibility, efficacy and indications.

Transesophageal echocardiography (TEE) with standard probes may be unsuccessful in emergencies, and in critically-ill or non collaborative patients. A miniaturized pediatric probe was used to overcome these limitations. Thirty-nine patients (age 18-87 years, height 155-184 cm, weight 45-102 kg) were studied with the pediatric probe, and 21 of them were studied using both the pediatric and adult probes in a random sequence. Feasibility, efficacy and patient's compliance were assessed. The use of the pediatric probe was mandatory in 18 critically-ill and/or non collaborative patients for the following reasons: contraindication to sedation in 15 patients with respiratory failure and/ or with unstable hemodynamics (12 not intubated patients) or patients undergoing electroencephalographic monitoring (3 intubated patients); inability to advance the probe into the esophagus in 1 patient with esophageal compression from intrathoracic struma and in 2 patients with stenosing esophageal cancer. Imaging projections and diagnostic accuracy in a wide range of cardiac, aortic and mediastinal diseases were similar for both the pediatric and adult probes. Patient's compliance was much improved by the pediatric probe. In conclusion, TEE by pediatric probes can be used in critically-ill adult patients when the approach with the standard probe is unfeasible or when sedation is undesirable.

Adult↗

[An interstitial miniature antenna for localized in vivo P-31 MR spectroscopy].

BACKGROUND: Phosphorus spectroscopy can be used to assess response in tumor therapy and to monitor response. An additional response parameter would be useful for individualization in oncological therapy. Methodical problems of localisation and contamination make it more difficult to interpret and reproduce the spectra. Interstitial and endoluminal spectroscopy antennas placed directly within or close to the tumor could provide help in this problem. MATERIAL AND METHOD: We developed an interstitial 31P MRS antenna together with a tuning network which can be used in thermometry catheters for hyperthermia within an internal lumen of 1.1 mm in diameter. A prototype of this type of miniature antenna suitable for use in Siemens MRI scanners at 1.5 T was described spectroscopically with regard to excitation profile, range and SNR. RESULTS: In terms of quality, the excitation profiles of the interstitial antennas in relation to orientation correspond to those of comparable but considerably larger endocavitary antennas and catheter coils for MR imaging and spectroscopy. Maximum sensitivity was achieved by aligning the coil normal perpendicular to the B0 field. Signal losses of up to 50% have to be reckoned with when using other orientations. The maximum range of the interstitial antenna was determined using spectroscopy and was found to be 5 mm, i.e. 9 times coil radius. The sensitivity (SNR, detection sensitivity) of the studied type of interstitial antenna allows in vivo 31P spectroscopy to be performed despite the unusually low axial dimension (coil radius r = 0.55 mm). The prototype of the described interstitial antenna was used to measure an in vivo spectrum from the back muscle of a rabbit in 10 min. Nevertheless, the detection volume of at least some ml necessary for 31P spectroscopy results mainly from the large antenna length. CONCLUSION: The sensitivity (SNR, detection sensitivity) of the interstitial antenna needs to be further improved in order to assess treatment response in patients. However, the construction principle is suitable for intracavitary 31P spectroscopy antenna with larger diameters, which can be used for advanced rectal, cervical and prostate carcinomas.

Animals↗

[Biological characteristics of miniature "Shiba" goats (author's transl)].

Practical informations of miniature "Shiba" goats, that have since long been bred for meat consumption in Kyushu District of Japan, were provided for using as laboratory animals. Nine years ago, some pairs of the goats, were introduced to Stock Farm of Tokyo University from a National Institute. Thereafter, they were successfully bred and increased in number and were distributed to many laboratories for researchers. The "Shiba" goat is white coloured, horned, and much smaller in size while sharing common characteristics with full size goats. The handling is much easier with less amount of food consumption. The body weight are 24 to 28 kg and 15 to 22 kg in males and females, respectively. They are obedient and have a strong resistance to diseases, including cerebral nematodiasis. The productive characteristics are as follows: 1) Continuous breeder, 2) Age at the first parturition: 13 months, 3) Gestation period: 5 months, 4) Litter size: 1.84, 5) Rate of raising: nearly all, 6) Delivery interval: 8 months, 7) No intersexality. Hematological data were also demonstrated.

Amprolium↗

Slow kinetics of miniature IPSCs during early postnatal development in granule cells of the dentate gyrus.

Whole-cell patch-clamp recordings were used to investigate the properties of GABAA receptor-mediated postsynaptic currents during development in dentate gyrus granule cells from neonatal [postnatal day 0 (P0)] to adult rats in brain slices. The frequency of miniature IPSCs (mIPSCs) was low at birth and increased progressively with age. The mIPSCs of all ages could be satisfactorily fitted with the sum of a single exponential rise and single exponential decay. From P0 to P14, both the rise time and the decay time constants were significantly longer than in the adult. The mIPSC rise and decay kinetics did not change during the first 2 postnatal weeks, but during the third week the kinetics sped up and by P21 attained adult values. In contrast, the amplitude of the mIPSCs did not change during development. The synaptic GABAA receptors in immature and adult cells showed differential sensitivity to modulators. The subunit-specific benzodiazepine agonist zolpidem increased the decay time constant of the IPSCs of immature granule cells with a reduced potency compared with the adult. Furthermore, zinc decreased the amplitude and decay time constant of mIPSCs from developing granule cells, whereas it had no effect on mIPSCs in adult neurons. The results reveal for the first time that until the end of the second postnatal week the synaptic GABAA receptor-mediated currents in dentate granule cells display slower rise and decay kinetics but similar amplitudes compared with adult, resulting in a net decrease in synaptic charge transfer during development.

Aging↗

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