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Correlation of miniature synaptic activity and evoked release probability in cultures of cortical neurons.

Spontaneous miniature synaptic activity is caused by action potential (AP)-independent release of transmitter vesicles and is regulated at the level of single synapses. In cultured cortical neurons we have used this spontaneous vesicle turnover to load the styryl dye FM1-43 into synapses with high rates of miniature synaptic activity. Automated selection procedures restricted analysis to synapses with sufficient levels of miniature activity-mediated FM1-43 uptake. After FM1-43 loading, vesicular FM1-43 release in response to AP stimulation was recorded at single synapses as a measure of release probability. We find that synapses with high rates of miniature activity possess significantly enhanced evoked release rates compared with a control population. Because the difference in release rates between the two populations is [Ca(2+)](o)-dependent, it is most likely caused by a difference in release probability. Within the subpopulation of synapses with high miniature activity, we find that the probabilities for miniature and AP-evoked release are correlated at single synaptic sites. Furthermore, the degree of miniature synaptic activity is correlated with the vesicle pool size. These findings suggest that both evoked and miniature vesicular release are regulated in parallel and that the frequency of miniature synaptic activity can be used as an indicator for evoked release efficacy.

Action Potentials↗

Prevalence of calcium oxalate uroliths in miniature schnauzers.

Epidemiologic data were evaluated from all dogs admitted to the University of Minnesota, Veterinary Teaching Hospital (UMVTH) between June 1981 and November 1989. Of 69,890 admissions, 2,077 were Miniature Schnauzers. Uroliths were retrieved from 63 of the 2,077 Miniature Schnauzers admitted. In 20 of the 63 urolith episodes, calcium oxalate was the predominant mineral identified. By comparison, calcium oxalate uroliths were identified in only 56 of the remaining 67,813 non-Miniature Schnauzer canine admissions. The odds that uroliths from Miniature Schnauzers were composed of calcium oxalate was 11.8 times greater than for other canine breeds evaluated at the UMVTH (95% confidence interval = 6.8 to 20.1). Data also were evaluated from files of uroliths retrieved from dogs and submitted to the Minnesota Urolith Center for quantitative mineral analysis, between June 1981 and November 1989. Of 3,930 uroliths analyzed, 615 (15.6%) uroliths were obtained from Miniature Schnauzers. of the 615 uroliths, 175 (28.4%) were calcium oxalate. By comparison, only 550 (16.6%) of the remaining 3,315 from dogs of breeds other than Miniature Schnauzers were calcium oxalate. The odds that uroliths submitted for analysis were composed of calcium oxalate was 2 times greater for Miniature Schnauzers than for dogs of other breeds (95% confidence interval = 1.6 to 2.4). Calcium oxalate uroliths were retrieved more frequently in males than females. The risk for males developing calcium oxalate uroliths was greater than 3 times the risk for females in both groups of data evaluated. The mean age of all Miniature Schnauzers admitted to the UMVTH with calcium oxalate uroliths was 9 years. Calcium oxalate uroliths were not detected in Miniature Schnauzers younger than 1.7 years.

Age Factors↗

[Study on masticatory muscles and tooth long axis of miniature pigs].

OBJECTIVE: The similarities of masticatory muscles and teeth orientations between miniature pigs and human beings were studied in order to evaluate the use of miniature pigs in oral biomechanics research. METHODS: By means of anatomy, the shapes, start-stop points and orientations of muscle of major masticatory muscles of miniature pigs were measured. Inclination of upper and lower teeth long axis was studied with lateral xray film of mandibles. RESULTS: The main masticatory muscles of miniature pigs include masseter muscle, temptory muscle, lateral pterygoid muscle, medial pterygoid muscle and zygomaticomandibular muscle. The angles of masticatory muscles and base plane are 63.9 degrees in massater muscle, 114.55 degrees in temple muscle, 64.4 degrees in medial pterygoidp muscle. The long axises of miniature pigs teeth are 6.1 degrees in the upper first molar, 6.5 degrees in the lower first molar, 7.3 degrees in the upper third premolar, 3.8 degrees in the lower third premolar. CONCLUSION: The masticatory muscles of miniature pigs are similar with human being in the shape, start-stop point and orientation of muscle force. The third premolar and the first molar of miniature pigs inclinate mesially, and are similar with the first premolar and the first molar of the human beings. Miniature pigs can be used as an animal models which can explain some problems of gnathostomatic system of human beings.

Animals↗

Comparison of the inflammatory response between miniaturized and standard CPB circuits in aortic valve surgery.

OBJECTIVE: One of the complications of CPB is the systemic inflammatory response syndrome (SIRS). Recent developments tend to minimize the biological impact of CPB in using miniaturized closed circuit with reduced priming volume and less blood-air interface. The benefit of these miniaturized closed circuits in terms of inflammatory response has been proved in coronary surgery. However, in open heart surgery, the CPB circuit is no more closed and the benefit of the miniaturized set-up could disappear. The aim of the study is to compare the SIRS between standard and miniaturized circuits in aortic surgery. METHODS: Forty patients who underwent singular aortic valve replacement were randomly assigned either to a standard CPB (group A, n=20) or to a miniaturized CPB (group B, n=20). Pertinent clinical and surgical data were collected. Hematological parameters (leukocyte and neutrophil counts) and biochemical parameters (C-reactive protein, cytokine tests) were determined pre-, on and post-CPB. RESULTS: There were an increase in leukocyte and neutrophil counts and a decline in hematocrit in both groups. In both groups, there was a raise after CPB, in C-reactive protein, IL-6, TNF-alpha, neutrophil elastase, and IL-10. However, the raises of elastase and TNF-alpha were significantly lower after the weaning of miniaturized CPB (116+/-46 ng/ml and 10+/-4 pg/ml, respectively) compared to standard CPB (265+/-120 ng/ml, P=0.01 and 18+/-7 pg/ml, P=0.03). The raise of IL-10 is also lower with miniaturized circuit (15+/-6 pg/ml) compared to standard circuit (51+/-26, P=0.004). CONCLUSIONS: This study demonstrates in aortic surgery, the lesser inflammatory response of a miniaturized CPB compared to a standard CPB. However, there is always some inflammation after CPB and a small bio-reactive free perfusion circuit is still to be found in open heart surgery.

Aged↗

A novel phenotype for Lardon dwarfism in miniature Bos indicus cattle suggests that the expression of growth hormone receptor 1A in liver is required for normal growth.

Mutations within the growth hormone receptor (GHR) gene that lead to an inactivated or truncated GHR protein cause abnormal growth and small adult size in a variety of species (Laron dwarfism). We studied a line of miniature Bos indicus cattle that have phenotypic (small mature size) and endocrine (increased blood growth hormone and decreased blood insulin-like growth factor-I concentrations) similarities to Laron dwarfs. Liver mRNA from miniature and control cattle was used to amplify a cDNA within the coding region of the GHR. The miniature cattle had GHR mRNA size (determined by Northern blot) and cDNA sequence that were similar to control cattle and, therefore, were unlike most Laron dwarf genotypes in which the GHR gene is mutated. Amounts of mRNA from liver as well as muscle (superficial neck and longissimus) were analyzed by ribonuclease protection assay for IGF-I, total GHR, GHR 1A (inducible, liver-specific GHR mRNA), and GHR 1B (constitutive GHR mRNA). Four control and five miniature bulls were tested. As expected, liver IGF-I mRNA was decreased in the miniature cattle (approximately 12% of control; P < 0.01). The amount of the total GHR as well as GHR 1A mRNA were also decreased in liver (17% and 19% of control, respectively; P < 0.01). Other GHR mRNA, including GHR 1B mRNA, were similar for miniature and control cattle. In muscle, there was a tendency (P < 0.10) for decreased IGF-I mRNA and increased GHR mRNA in miniature compared with control cattle. In summary, a novel phenotype for Laron dwarfism in Bos indicus cattle was associated with underexpression of GHR 1A mRNA, but not other GHR mRNA variants in liver. In addition to decreased GHR 1A mRNA, the miniature cattle had decreased liver IGF-I mRNA. Full expression of GHR 1A in liver, therefore, may be required for full liver IGF-I expression and normal growth.

Animals↗

Results of surgical treatment of colic in miniature breed horses: 11 cases.

OBJECTIVE: To report on the outcome of surgical treatment of acute abdominal crises in miniature breed horses. DESIGN: Retrospective case series of miniature horses presented to the University Veterinary Centre, Camden with an acute abdominal crisis. METHODS: Hospital records of all miniature horses that underwent ventral midline laparotomy for acute abdominal crisis between 1997 and 2001 were reviewed. The signalment, history, clinical signs, results of ancillary diagnostic procedures, location and type of intestinal lesion, treatment and outcome were retrieved from each case record. Long-term survival was determined by telephone interview of owners. RESULTS: Eleven miniature horses including five females and six males underwent ventral midline laparotomies for acute abdominal crisis during the study period. Ages ranged between 1 month and 19 years. Surgical findings included faecalith obstruction (seven horses), enterolith (one horse), strangulating lipoma of the descending colon (one horse), jejunal infarction (one horse), and caecal infarction (one horse). Long-term survival rate (minimum 12 months post surgery) was 55%. Six of eight horses with simple intraluminal obstructions survived, while the three horses with gastrointestinal lesions associated with vascular compromise were euthanased either at surgery (caecal infarction), or postoperatively, due to complications (strangulating lipoma of the descending colon, jejunal infarction). Postoperative complications in this study included impaction of the descending colon (two horses), diarrhoea (two horses), peritonitis (one horse), hyperlipaemia (two horses), incisional infection (two horses) and abdominal adhesions (one horse). Hyperlipidaemia was present in five of seven horses in which serum triglycerides were measured at presentation. CONCLUSIONS: Simple intraluminal obstructions of the large intestine were frequently encountered during exploratory laparotomy in miniature horses presented for acute abdominal crises, and their surgical treatment was associated with a good prognosis. In contrast, this study suggested that abdominal pain associated with vascular compromise of gastrointestinal tissues in miniature horses was associated with a poorer prognosis, consistent with reports in other horse breeds. Possible contributing factors to faecalith formation, including poor quality roughage, dental disease, and inadequate water consumption, should be recognised and avoided in miniature horses. Serum triglyceride concentrations should be measured in miniature horses presented for acute abdominal pain. If elevated, nutritional supplementation should be provided.

Abdominal Pain↗

Fibrocartilaginous embolic myelopathy in miniature schnauzers.

In large- and giant-breed dogs, fibrocartilaginous embolic myelopathy (FCEM) is a well-recognized syndrome of acute spinal cord infarction caused by embolization of fibrocartilage. The miniature schnauzer is reportedly the most frequently affected small breed, although clinical data from only six miniature schnauzers with FCEM is available in the literature. The purposes of this study were to determine the relative frequency of FCEM compared to other causes of myelopathy in miniature schnauzers, to characterize the clinicopathological features of FCEM in 38 miniature schnauzers, and to directly compare FCEM and intervertebral disk herniation in miniature schnauzers with respect to age at diagnosis; gender; neuroanatomical localization; and progression, asymmetry, and severity of neurological deficits. Fibrocartilaginous embolic myelopathy was the most common cause of myelopathy in miniature schnauzers. Age at diagnosis, asymmetry and severity of neurological deficits, and lack of progression of clinical signs after 24 hours assisted in distinguishing FCEM from intervertebral disk herniation. Fibrocartilaginous embolic myelopathy-related mortality in miniature schnauzers was significantly lower than mortality rates reported for affected large and giant breeds. Only 22% of miniature schnauzers were euthanized because of their disease, although the vast majority of survivors failed to achieve complete neurological recovery.

Animals↗

Identification of exogenous forms of human-tropic porcine endogenous retrovirus in miniature Swine.

The replication of porcine endogenous retrovirus subgroup A (PERV-A) and PERV-B in certain human cell lines indicates that PERV may pose an infectious risk in clinical xenotransplantation. We have previously reported that human-tropic PERVs isolated from infected human cells following cocultivation with miniature swine peripheral blood mononuclear cells (PBMC) are recombinants of PERV-A with PERV-C. Here, we report that these recombinants are exogenous viruses in miniature swine; i.e., they are not present in the germ line DNA. These viruses were invariably present in miniature swine that transmitted PERV to human cells and were also identified in some miniature swine that lacked this ability. These data, together with the demonstration of the absence of both replication-competent PERV-A and recombinant PERV-A/C loci in the genome of miniature swine (L. Scobie, S. Taylor, J. C. Wood, K. M. Suling, G. Quinn, C. Patience, H.-J. Schuurman, and D. E. Onions, J. Virol. 78:2502-2509, 2004), indicate that exogenous PERV is the principal source of human-tropic virus in these animals. Interestingly, strong expression of PERV-C in PBMC correlated with an ability of the PBMC to transmit PERV-A/C recombinants in vitro, indicating that PERV-C may be an important factor affecting the production of human-tropic PERV. In light of these observations, the safety of clinical xenotransplantation from miniature swine will be most enhanced by the utilization of source animals that do not transmit PERV to either human or porcine cells. Such animals were identified within the miniature swine herd and may further enhance the safety of clinical xenotransplantation.

Animals↗

Rapid miniaturized chromatography for technetium-99m-tetrofosmin.

UNLABELLED: The purpose of this investigation was to develop and evaluate a new and rapid miniaturized chromatography system that would accurately assess the radiochemical purity of 99mTc-tetrofosmin without the problems of solvent ratios and time requirements associated with the manufacturer's recommended procedure. METHODS: The migration of the radiochemical components of 99mTc-tetrofosmin was evaluated using various chromatography media with ethyl acetate as the solvent. After optimization of the miniaturized system, radiochemical purity assessments were performed simultaneously on 23 99mTc-tetrofosmin preparations using both recommended and miniaturized chromatography systems. RESULTS: A miniaturized chromatography system consisting of Whatman 1 chromatography paper with ethyl acetate was developed for the radiochemical purity assessment of 99mTc-tetrofosmin. Radiochemical purity results for 99mTc-tetrofosmin preparations were similar with both recommended and miniaturized chromatography methods, with a mean difference of 1.5% +/- 1.2% (s.d.). Differences in radiochemical purity results between the two chromatography systems were less than 2% (20 of 23 evaluations) with most preparations. CONCLUSION: Radiochemical purity results for 99mTc-tetrofosmin preparations were similar with both the manufacturer's recommended chromatography and miniaturized chromatography systems. The miniaturized chromatography system is easier to use, and the time required to perform radiochemical purity assessments is substantially reduced.

Acetates↗

Reproductive parameters of miniature stallions.

Breeding soundness evaluation (BSE) of stallions is a routine component of stud farm practice. Guidelines for assessing satisfactory breeding potential have been developed using data derived from stallions of full-size breeds. In view of the increasing popularity of miniature stallions, knowledge of normal semen parameters of these stallions is important. Therefore, testicular measurements and semen parameters from 216 sexually rested miniature stallions were obtained. Semen was collected twice, 1.5 to 3 h apart, using an artificial vagina. Values were averaged over the 2 collections because of the sexual inexperience of the stallions. The smaller stallions (Group A, 72 to 86 cm; Group B, 87 to 96 cm) had smaller testicles (P<0.05), and Group A stallions had the lowest ejaculate volume (P<0.05) compared with Group C (97 to 104 cm) stallions. Thus, although there was no difference in the concentration of spermatozoa per milliliter between groups of stallions, Group A stallions had fewer total spermatozoa in their ejaculate than Group C stallions (4.31+/-0.47x10(9) vs. 5.41+/-0.30x10(9), P<0.05). Moreover, miniature stallions had smaller testicles and fewer total spermatozoa in their ejaculate than is commonly accepted as normal in full-size stallions. Average total scrotal width of miniature stallions was found to be 7.13, 7.38 and 7.95 cm for Groups A, B and C, respectively. The average total number of spermatozoa in the ejaculates of miniature stallions in this study was 4.94+/-0.22x10(9) cells, with 1.75+/-0.09x10(9) total normal, motile spermatozoa. When only stallions <96.5 cm in height were considered (conforming to requirements of the American Miniature Horse Association Registry), the average total number of spermatozoa in the ejaculates was 4.59+/-0.30x10(9) cells, with 1.70+/-0.11x 10(9) total normal, motile spermatozoa. Based on these findings, different criteria should be used to evaluate the potential breeding soundness of miniature stallions than are commonly applied to full-size stallions.

Animals↗

Inhibitory miniature potentials in the stretch receptor neurons of crayfish.

Intracellular microelectrodes inserted into the soma of crayfish stretch receptor neurons record frequent fluctuations of the membrane potential. Time course, amplitude, and interval distribution indicate that they are miniature potentials. At the average resting potential the polarity of the miniature potentials depends on the anion used in the microelectrode: KCl electrodes record depolarizing, K citrate or K(2)SO(4) electrodes, hyperpolarizing miniature potentials. The inhibitory postsynaptic potentials (i.p.s.p.'s) show a similar polarity change. The reversal potentials of i.p.s.p.'s and miniature potentials are equal and within 10 mv of the resting potential, more negative with K citrate (or K(2)SO(4)), less negative with KCl electrodes. Reversal can be accomplished by changing the membrane potential by stretching or by current passing. Injection of Cl(-) into the soma or replacement of external Cl by propionate results in an abrupt increase of the amplitude of the miniature potentials lasting for several minutes. The miniature potentials like the i.p.s.p.'s are reversibly abolished by the application of picrotoxin and gamma-aminobutyric acid. They are not affected by tetrodotoxin, nor by acetylocholine, eserine, or atropine. It is concluded that the miniature potentials represent a spontaneous quantal release of transmitter substance from inhibitory nerve terminals, and that the transmitter substance predominantly increases the Cl(-) permeability of the postsynaptic membrane. The effect of the spontaneously released transmitter on the behavior of the receptor neuron is considerable. The membrane conductance is increased by up to 36% and the excitability is correspondingly depressed.

Acetylcholine↗

Effects of adrenergic drugs on miniature contractions of isolated dog urinary bladder.

Isolated dog urinary bladder showed spontaneous miniature contractions under a steady state. In dome preparations, norepinephrine and isoproterenol decreased the frequency of miniature contractions, while epinephrine produced biphasic responses on it; increase by low concentration and decrease by high concentrations. The height of miniature contractions was decreased by these drugs. In trigone preparations, norepinephrine and epinephrine increased the frequency of miniature contractions, while isoproterenol decreased it. These drugs decreased the height of miniature contractions. In both preparations, phentolamine enhanced the decreases in frequency and height by norepinephrine, epinephrine and isoproterenol, while propranolol depressed or reversed them. A computer analysis showed positive and significant correlations between changes in tension development of bladder and frequency and height of miniature contractions. Results indicate that miniature contractions in both dome and trigone of isolated dog urinary bladder are increased by activation of alpha-adrenoceptors and decreased by activation of beta-adrenoceptors.

Animals↗

Inheritance of congenital cataracts and microphthalmia in the Miniature Schnauzer.

Congenital cataracts and microphthalmia in the Miniature Schnauzer were inherited as an autosomal recessive trait. Eighteen matings of affected X affected Miniature Schnauzers resulted in 87 offspring with congenital cataracts and microphthalmia (49 males/38 females). Two matings of congenital cataractous and microphthalmic Miniature Schnauzers (2 females) X a normal Miniature Schnauzer (1 male) yielded 11 clinically normal Miniature Schnauzers (7 males/4 females). Eighteen matings of congenital cataractous and microphthalmic Miniature Schnauzers (6 males) X carrier Miniature Schnauzers (9 females) produced 81 offspring; 39 exhibited congenital cataracts and microphthalmia (20 males/19 females) and 42 had clinically normal eyes (17 males/25 females).

Animals↗

Miniaturized membrane-based reversed-phase chromatography and enzyme reactor for protein digestion, peptide separation, and protein identification using electrospray ionization mass spectrometry.

A commonly used capillary fitting is employed for housing miniaturized membrane chromatography for performing reversed-phase peptide separations. By placing a hydrophobic and porous polyvinylidene fluoride membrane around the end of a polymer sleeve, the assembly of capillary fitting not only provides the stationary phase, but also establishes the necessary flow paths using capillary connections. The miniaturized membrane chromatography system is coupled with a micro-enzyme reactor containing immobilized trypsins for performing rapid protein digestion, peptide separation, and protein identification using electrospray ionization mass spectrometry. Separation performance of cytochrome c digest in miniaturized membrane chromatography is compared with the results obtained from micro-LC and capillary LC. The efficacy and the potentials of miniaturized membrane chromatography in tryptic mapping are reported. The use of miniaturized membrane chromatography allows significant reduction in sample consumption together with enhanced detection sensitivity. By minimizing the void volume in miniaturized membrane chromatography, the elution times of cytochrome c peptides are significantly shortened in this study in comparison with our previous results, and are comparable with those in micro-LC and capillary LC using considerably higher mobile phase flow-rates.

Animals↗

Induction of superovulation and recovery of fertilized oocytes in prepubertal miniature pigs after treatment with PG600.

The purpose of this study was to examine whether superovulation can be induced by hormonal treatment with PG600 (400 IU eCG and 200 IU hCG) at the prepubertal stage in miniature pigs. In Experiment 1, 14 prepubertal miniature pigs received 1, 1/2 or 1/4 vial of PG600, im on Day 0 (the first day of treatment). Presentation of estrus was monitored thereafter. On Days 10 to 13 (i.e., 6 to 8 d after estrus), the number of corpora lutea (CL) and residual follicles was counted by an exploratory laparotomy. Injection of 1/2 vial of PG600 effectively induced estrus and ovulation in the pigs. In Experiment 2, 15 prepubertal miniature pigs that received 1/2 vial of PG600 were artificially inseminated into the uterus by an exploratory laparotomy at 100 to 104 h after PG600 injection. Oocytes were recovered from the oviducts at 121 to 145 h after PG600 administration. The oocyte recovery rate was 66% (15 oocytes/pig, average), and 84% of these were at the 1-cell stage. In Experiment 3, 5 prepubertal miniature pigs that received 1/2 vial of PG600, followed by 100 IU hCG 70 h later, were artificially inseminated into the uterus. Oocytes were recovered synchronously at 120 to 122 h after PG600 treatment. The recovery rate was 80% (17 oocytes/pig, average) and 90% of the oocytes recovered were at the 1-cell stage. These results suggest that superovulation of prepubertal miniature pigs can be induced by 1/2 vial of PG600 injection, and by the combined treatment with PG600 and hCG injection, the fertilized ova can be synchronously recovered at around 120 h after PG600 injection. This procedure may provide a useful system for biomedical research using the miniature pigs, especially for producing transgenic animals for use in human disease models.

Animals↗

Production of transgenic miniature pigs by pronuclear microinjection.

Miniature pig is an attractive animal for a wide range of research fields, such as medicine and pharmacology, because of its small size, the possibility of breeding it under minimum environmental controls and the physiology that is potentially similar to that of human. Although transgenic technology is useful for the analysis of gene function and for the development of model animals for various diseases, there have not yet been any reports on producing transgenic miniature pig. This study is the first successful report concerning the production of transgenic miniature pig by pronuclear microinjection. The huntingtin gene cloned from miniature pig, which is a homologue of candidate gene for Huntington's disease, connected with rat neuron-specific enolase promoter region, was injected into a pronucleus of fertilized eggs with micromanipulator. The eggs were transferred into the oviduct of recipient miniature pigs, whose estrus cycles were previously synchronized with a progesterone analogue. A total of 402 injected eggs from 171 donors were transferred to 23 synchronized recipients. Sixteen of them maintained pregnancy and delivered 65 young, and one resulted in abortion. Five of the 68 offspring (three of which were aborted) were determined to have transgene by PCR and Southern analysis. The overall rate of transgenic production was 1.24% (transgenic/injected eggs). This study provides the first success and useful information regarding production of transgenic miniature pig for biomedical research.

Animals↗

Evaluation of miniature manometric techniques for the measurement of esophageal body pressure waves.

BACKGROUND AND AIMS: Perfused miniature manometric assemblies with lumina of 0.4-0.5 mm i.d. have been developed. Reduced luminal size offers the advantages of reduced assembly bulk and increased assembly complexity with greater numbers of lumina and lower manometric infusion volumes because of a slower perfusion rate. This study investigated the recording fidelity of miniature manometric assemblies in the measurement of esophageal peristalsis. METHODS: Four miniature manometric assemblies, each containing manometric lumina of either 0.4 or 0.5 mm i.d., were evaluated at 100 and 180 cm lengths. The fidelity of miniature manometric luminal recordings were evaluated in vivo during esophageal peristalsis by using a simultaneous comparison with the standard lumina and an intraluminal strain gauge. RESULTS: During esophageal peristalsis, miniature manometric lumina recorded the peak amplitude of pressure waves, with an accuracy at perfusion rates of 0.04 mL/min (0.4 mm, i.d.) and 0.15 mL/min (0.5 mm, i.d.). CONCLUSION: Miniature manometric assemblies of lengths that are practical for use in humans are suitable for recording esophageal peristalsis.

Adult↗

Development and evaluation of a miniaturized procedure for determining the bonding index: a novel prototype for solid dosage formulation development.

The purpose of this study was a comparative evaluation of miniaturized vs. University of Minnesota's (i.e., U of Minn. = Hiestand's) procedures for determining the tensile strength, indentation hardness, and bonding index (BI), one out of three Indices of Tableting Performance (ITP). Tableting properties of six direct compression placebo formulations were determined by using a compaction simulator and a Texture Analyser TA-XT2I, or by following the U of Minn. method, which included a specially designed triaxial compression device, a computer-controlled mechanical stress-strain analyzer, and a dynamic pendulum impact apparatus. Miniaturization of the procedures to determine the ITP, as well as the ability to differentiate between materials while operating compaction cycles more comparable to standard tablet production conditions, enabled proper evaluation of each material's inherent tableting properties. Indentation diameter calculated via an empirical equation appeared to correlate well with, and provided acceptable precision of accuracy to, the determination of indentation diameter via standard optical microscopy methods. The miniaturized and U of Minn. procedure exhibited a significant degree of correlation when comparing the BI. However, the tensile strength and indentation hardness values were somewhat different due to the use of triaxial decompression for the U of Minn. procedure vs. standard compaction profiling for the miniaturized procedure. The present direct compression placebo formulation data gathered from the miniaturized procedures and compared with the U of Minn. method for determining the ITP suggest that both techniques yield similar conclusions. However, discrimination of out-of-die compaction properties determined via the miniaturized procedures, such as tensile strength and indentation hardness, appeared to associate more precisely with changes in strain rate, thus allowing better discrimination of particle-particle interactions and ductile-to-brittle characteristics as a function of compaction speed and pressure.

Chemistry, Pharmaceutical↗