Effects of wearing and removing dentures on oropharyngeal motility during swallowing.

Wearing dentures and dysphagia are common in older individuals; however, it is still unknown how dentures affect oral and pharyngeal swallowing. The purpose of this study was to reveal the effects of wearing and removing dentures on oropharyngeal movements during pharyngeal swallowing in the feeding sequence of solid food. Participants were 25 edentulous volunteers (nine men, 16 women; mean age 76·2 years) who wore complete dentures. The test food was minced agar jelly containing barium sulphate. Subjects were instructed to feed and swallow the test food with or without dentures during observation using videofluorography. We quantitatively evaluated the range, distance and duration of oropharyngeal movements during pharyngeal swallowing. When dentures were absent, the range of mandible and hyoid movements were significantly expanded in the anterosuperior direction, and the range of laryngeal movement was significantly expanded in the anterior direction. Additionally, the posterior pharyngeal wall contraction and upper oesophageal sphincter opening significantly increased. In addition, the distances of the mandible, hyoid and laryngeal movements and the mandibular duration were significantly extended when dentures were absent. No significant differences were observed in the duration of movements of other organs between wearing and removing dentures. The hyoid bone, larynx, posterior pharyngeal wall and upper oesophageal sphincter do not change their duration of movements when dentures were removed but, rather, expand their range of movement. This might be a spatial change of oropharyngeal movement to avoid temporal changes in pharyngeal swallowing when dentures were absent in edentulous older individuals.

Effects of physical and morphometric factors on nutrient removal properties in agricultural ponds.

Effects of physical and morphometric factors on nutrient removal properties were studied in small agricultural ponds with different depths, volumes, and residence times in western Japan. Average residence time was estimated to be >15 days, and it tended to decrease from summer to winter because of the increase in water withdrawal for agricultural activity. Water temperature was clearly different between the surface and bottom layers; this indicates that thermal stratification occurred in summer. Chlorophyll-a was significantly high (>20 µg/L) in the surface layer (<0.5 m) and influenced by the thermal stratification. Removal ratios of dissolved total nitrogen (DTN) and dissolved total phosphorus in the ponds were estimated to be 53-98% and 39-98% in August and 10-92% and 36-57% in December, respectively. Residence time of the ponds was longer in August than in December, and DTN removal, in particular, was more significant in ponds with longer residence time. Our results suggest residence time is an important factor for nitrogen removal in small agricultural ponds as well as large lakes.

Development of a targeted gene panel for the diagnosis of Gorlin syndrome.

Gorlin syndrome is a rare autosomal dominant disease caused by mutations in the PTCH1, PTCH2, and SUFU genes. Each symptom of the disease has a different time point of onset, which makes early diagnosis based solely on symptoms challenging. In this study, a gene panel was developed to overcome the challenges in the diagnosis of Gorlin syndrome and allow diagnosis using a single test. A custom panel was generated for four genes associated with Gorlin syndrome: PTCH1, PTCH2, SMO, and SUFU. Twenty-seven samples from 12 patients with Gorlin syndrome and three asymptomatic blood relatives of the patients were examined. This panel was highly reliable with a high Q30 quality score, on-target ratio, and coverage. The panel was time- and cost-efficient and enabled the detection of more mutations than whole-exome sequencing for the same patient. Pathogenic mutations in both PTCH1 and PTCH2 were detected in five of the 12 patients with Gorlin syndrome who were diagnosed based on clinical symptoms. Using this panel, the same mutation was identified in the patients and their blood relatives. In summary, this panel facilitated the highly reliable genetic diagnosis of Gorlin syndrome at a low cost, using only blood samples.

DNA vaccination targeting macrophage migration inhibitory factor prevents murine experimental colitis.

Previous studies have shown that neutralization of macrophage migration inhibitory factor (MIF) by anti-MIF antibody reduces intestinal inflammation in mice. In this study we tested whether or not anti-MIF autoantibody induced by DNA vaccine targeting MIF protects mice against experimental colitis. Mice were administered a MIF-deoxyribonucleic acid (DNA) vaccine by introducing oligonucleotides encoding helper T epitope into the cDNA sequence of murine MIF by in vivo electroporation. Preventive effects of this method against dextran sulphate sodium-induced (DSS) colitis were evaluated. Mice administered with MIF-DNA vaccine raised values of autoantibody significantly. The clinical and histological findings of colitis induced by 3·0% DSS solution were ameliorated significantly in mice treated with MIF-DNA vaccine compared with saline or pCAGGS-treated mice given DSS. Myeloperoxidase activity, infiltration of F4/80-positive staining cells and the levels of proinflammatory cytokines were suppressed in the colon of MIF-DNA vaccine treated mice compared with saline or pCAGGS-treated mice exposed to DSS. Our results suggest that immunization with helper T epitope DNA-vaccine targeting MIF may be a useful approach for the treatment of colitis including inflammatory bowel diseases.

Impaired fracture healing in macrophage migration inhibitory factor-deficient mice.

UNLABELLED: This study investigated the role of macrophage migration inhibitory factor (MIF) in fracture repair using MIF gene-deficient mice (MIF KO). Fracture healing was delayed in MIF KO, and this was mainly due to the delay in the mineralization of osteoid within the fracture callus. INTRODUCTION: We previously reported that the expression of macrophage migration inhibitory factor (MIF) was up-regulated during the fracture healing process in rats. However, its role in the pathophysiology of this process remained unclear. The aim of the present study was to clarify the role of MIF in the fracture healing process using MIF gene-deficient mice (MIF KO). METHODS: Bone repair in wild-type mice (WT) and MIF KO (n = 70, respectively) was investigated using a tibia fracture model. Radiographic, biomechanical, histological, bone histomorphometric, and molecular analyses were performed. RESULTS: Post-fracture biomechanical testing showed that maximum load and stiffness were significantly lower in MIF KO than in WT on day 42. However, similar levels were observed between the two groups on day 84. Bone histomorphometric analysis revealed significantly higher osteoid volume, a lower mineral apposition rate, and smaller numbers of osteoclasts in the MIF KO callus compared to the WT callus. The messenger ribonucleic acid expressions of matrix metalloproteinase (MMP)-2, membranous type 1-MMP, cathepsin K, and tissue nonspecific alkaline phosphatase were found to be significantly suppressed in the MIF KO callus. CONCLUSION: The results of the present study suggest that delayed fracture healing in MIF KO was mainly attributable to a delay in osteoid mineralization.

A novel DNA vaccine-targeting macrophage migration inhibitory factor improves the survival of mice with sepsis.

Sepsis is a common and frequently fatal condition and there is an urgent need for new therapies that will further reduce sepsis-induced mortality. Macrophage migration inhibitory (MIF) factor is important in the regulation of innate and adaptive immunity and is believed to play a key regulatory role in sepsis and autoimmune disease. As MIF deficiency or immunoneutralization protects mice or rats from fatal endotoxic shock or other inflammatory diseases, we examined whether DNA vaccination against this molecule would also be protective. DNA vaccines can stimulate both humoral and cellular immunity simultaneously and have been shown to be effective against a variety of pathogens or cytokine-driven pathologies. Mice were immunized with a MIF/tetanus toxin (TTX) DNA vaccine and sepsis was then induced by lipopolysaccharide or cecal ligation and puncture. The MIF/TTX DNA-vaccinated mice were protected from the lethal effect of sepsis compared with control-vaccinated mice in both models. Compared with the control-vaccinated mice, the MIF/TTX DNA-vaccinated mice also showed significantly lower serum tumor necrosis factor (TNF)-alpha protein levels and reduced mRNA expression of TNF-alpha, interleukin (IL)-1beta, IL-6, macrophage inflammatory protein-2 and Toll-like receptor-4 in the lungs. Thus, the MIF/TTX DNA vaccine may be useful for the prophylaxis of septic shock.

Vertical distribution of sediment phosphorus in Lake Hachirogata related to the effect of land reclamation on phosphorus accumulation.

The focus of this work is the change in sediment properties and chemical characteristics that occur after land reclamation projects. The results indicate a higher sedimentation rate in Lake Hachirogata after reclamation, with the rate increasing with proximity to the agricultural zone. In the west-side water samples, higher levels of dissolved total nitrogen and dissolved total phosphorus (DTP) were found in both surface and bottom waters. The increase in P (39-80%) was generally greater than that for N (12-16%), regarding the nutrient supply from reclaimed farmland in the western part of the lake. In the eastern part of the lake, the pore-water Cl- profile showed a decreasing vertical gradient in the sediment core. This indicates desalination of the lake water after construction of a sluice gate in 1961. In the western sediment-core sample, a uniform Cl- profile indicates the mixing of lake water and pore water after reclamation. Considering the sedimentation of P in the last 100 years, there is a trend of increasing accumulation of P and P-activities after the reclamation project. This appears to be an impact from change in the lake environment as a result of increased agricultural nutrients, desalination, and residence. A large amount of mobile phosphorus (42-72% of TP in the western core sample) trapped in sediment increases the risk of phosphorus release and intensification of algal blooms. High sediment phosphorus and phosphorus mobility should be considered a source of pollution in the coastal environment.

Down-regulation of protein kinase C potentiates atrial natriuretic peptide-stimulated cGMP accumulation in vascular smooth-muscle cells.

It has been reported that atrial natriuretic peptide (ANP) produces inositol phosphates and diacylglycerol in vascular smooth muscle cells (VSMC). The purpose of this study is to investigate whether diacylglycerol produced by ANP affects ANP-induced cyclic GMP (cGMP) accumulation through the activation of protein kinase C. Short-term (15 min) treatment of rat aortic VSMC with protein kinase C activating phorbol 12-myristate 13-acetate (PMA, 100 nM) decreased ANP (100 nM)-induced cGMP accumulation by 34.7% in the presence of IBMX (0.5 mM). However, the long-term (24 h) treatment to decrease the activity of protein kinase C led to an enhancement of the cGMP accumulation by 69.6% compared with that of control VSMC. There were no significant differences in Bmax and Kd for ANP and ANP-dependent particular guanylyl cyclase activity between long-term PMA-treated and control VSMC. In the present study, we show that the activation of protein kinase C attenuates the cGMP accumulation induced by ANP and that down-regulation of protein kinase C results in an enhancement of the cGMP accumulation. These data are consistent with the role of protein kinase C as a negative regulator in ANP-receptor/guanylyl cyclase pathway.

Circular dichroism and biochemical properties of the hepatitis B virus core antigen.

The hepatitis B virus (HBV) core antigen was purified by mild procedures, including hydroxyapatite column chromatography, with care taken to avoid the degradation of the particles. Circular dichroism (CD) of the HBV core particles in saline showed low intensities of negative ellipticities in the region dominated by amide bond absorption. Acid treatment of the particles induced a remarkable change in the CD spectrum, with the appearance of a positive extremum at about 208 nm. The amino acid composition and the COOH-terminal residue of the isolated core polypeptide (Mr 21,000-21,500) were shown to be essentially the same as those of the polypeptide deduced from the nucleotide sequences which had been proposed for the HBV core antigen by other laboratories. We failed to detect any NH2-terminal dansyl-derivatives from the core polypeptide by the dansyl-Edman method. We also showed by the method of fluorescein polarization that the core polypeptide conjugated with fluorescein isothiocyanate has an affinity for serum albumin. This may indicate a state of disassembled or non-assembled core polypeptide in sera.

Effect of aging on carotid artery stiffness and baroreflex sensitivity during head-out water immersion in man.

To examine the possible age-related blood pressure (BP) deregulation in response to central hypervolemia, we measured spontaneous baroreflex sensitivity (SBRS), carotid arterial compliance (CC), and R-R interval coefficient of variation (RRICV) during basal and thermoneutral resting head-out-of-water immersion (HOWI) in 7 young (YG = 24.0 +/- 0.8 years) and 6 middle-aged/older (OL = 59.3 +/- 1.3 years) healthy men. Compared with basal conditions (YG = 19.6 +/- 4.0 vs OL = 6.1 +/- 1.5 ms/mmHg, P < 0.05), SBRS remained higher in YG than OL during rest HOWI (YG = 23.6 +/- 6.6 vs OL = 9.3 +/- 2.1 ms/mmHg, P < 0.05). The RRICV was significantly different between groups (YG = 6.5 +/- 1.4 vs OL = 2.8 +/- 0.4%, P < 0.05) under HOWI. The OL group had no increase in CC, but a significant increase in systolic BP (basal = 115.3 +/- 4.4 vs water = 129.3 +/- 5.3 mmHg, P < 0.05) under HOWI. In contrast, the YG group had a significant increase in CC (basal = 0.16 +/- 0.01 vs water = 0.17 +/- 0.02 mm(2)/mmHg, P < 0.05) with no changes in systolic BP. SBRS was positively related to CC (r = 0.58, P < 0.05 for basal vs r = 0.62, P < 0.05 for water). Our data suggest that age-related vagal dysfunction and reduced CC may be associated with SBRS differences between YG and OL groups, and with BP elevation during HOWI in healthy older men.

Mechanism of the biphasic effect of ethylenediaminetetraacetate on lipid peroxidation in iron-supported and reconstituted enzymatic system.

The biphasic action of ethylenediaminetetraacetate (EDTA), depending on its concentration, on lipid peroxidation was examined in an iron-supported and reconstituted enzymatic system. In the presence of NADPH-cytochrome P450 reductase and NADPH, Fe(3+)-PPi or Fe(3+)-ADP, though not reducible in the absence of EDTA, was markedly reduced with increasing concentration of EDTA. Lipid peroxidation, in the reconstituted system containing negatively charged liposomes, showed the maximal rate at 0.5 molar ratio of EDTA/iron, but no peroxidation occurred in positively charged liposomes, suggesting production of a positively charged iron complex as the prooxidant. Isotachophoresis indicated production of net-negative charge, EDTA-Fe(3+)-PPi complex, from Fe(3+)-PPi and EDTA at 1.1 ratio of EDTA/iron. The complex quenched Fe(2+)-PPi-supported lipid peroxidation. We suggest that EDTA-iron complexes of different charges are generated, depending on the amount of EDTA in the enzymatic system and, consequently, there is a switch between prooxidant and inhibitory effect at some critical ratio of EDTA/iron.

Olivary projections from the mesodiencephalic structures in the cat studied by means of axonal transport of horseradish peroxidase and tritiated amino acids.

By means of horseradish peroxidase (HRP) and autoradiographic methods, olivary projections from mesodiencephalic structures were studied in the cat. Following HRP injections in various parts of the inferior olive, many cells were labeled ipsilaterally in the nucleus of Darkschewitsch, the nucleus accessorius medialis of Bechterew, the nucleus of the fields of Forel, and the subnucleus dorsomedialis and ventrolateralis of the parvocellular red nucleus. Some labeled cells also occurred ipsilaterally in the suprarubral reticular formation and a few labeled cells in the interstitial nucleus of Cajal. After injection of tritiated amino acids in different parts of the mesodiencephalic region mentioned above, labeled fibers were found in different parts of the inferior olive, presenting a high degree of the topographic correlation within the mesodiencephalo-olivary projection, which was exclusively ipsilateral. That is, the nucleus of Darkschewitsch was found to project to the rostral half of the medial accessory olive and the dorsomedial cell column. There was mediolateral topographic relation in this projection. The nucleus accessorius medialis of Bechterew was found to project to the ventral lamella and the lateral part of the dorsal lamella as well as to small rostromedial part of the caudal half of the medial accessory olive. The subnucleus dorsomedialis and ventrolateralis of the parvocellular red nucleus projected to the rostral and caudal halves, respectively, of the medial part of the dorsal lamella. The subnucleus ventrolateralis of the parvocellular red nucleus also sent fibers to the lateral part of the ventrolateral outgrowth. The nucleus of the fields of Forel, suprarubral reticular formation, and interstitial nucleus of Cajal appeared to project to the caudal half of the medial accessory olive, the medial part of the ventrolateral outgrowth, the rostral part of the dorsal cap, and the caudal part of the dorsal accessory olive.

Patterns of transmitter labelling and connectivity of the cat's nucleus of Darkschewitsch: a wheat germ agglutinin-horseradish peroxidase and immunocytochemical study at light and electron microscopical levels.

Immunocytochemical studies using antibodies raised against a number of probable synaptic transmitters of the mesodiencephalic area, and fibre-tracing studies using wheat germ agglutinin-horseradish peroxidase (WGA-HRP), have been performed in adult cats. Glutamate and aspartate immunoreactivity produced a strong labelling of many cell bodies and terminals in the nucleus of Darkschewitsch (ND). gamma-Aminobutyrate (GABA) immunoreactivity in the ND appeared as a moderate label in some small neurones, and as a strong label in a few glial-like cells, in addition to being present in high levels to produce strong labelling in many GABA-immunopositive terminals that possessed pleomorphic vesicles. Some choline acetyltransferase-positive terminals and dendrites and a few substance P-positive fine fibres possessing varicosities also were observed in the ND. Following WGA-HRP injection in the ND, dense terminal labelling was seen ipsilaterally in the rostral half of the medial accessory olive, suggesting that there may be a certain degree of mediolateral and dorsoventral topographic correspondance within the ND-olive projection. In the same cases, many cell bodies containing HRP reaction product also were found 1) ipsilaterally in the motor cortex, anterior pretectal nucleus, and a restricted area of the caudal part of the substantia nigra pars reticulata; 2) contralaterally in the anterior and posterior interposed cerebellar nuclei as well as in a portion of the lateral cerebellar nucleus; and 3) bilaterally in the zona incerta, the posterior pretectal nucleus, the pedunculopontine tegmental nuclei, the spinal trigeminal nucleus, the dorsal column nuclei, and the spinal cord. Details of the interrelationships and functional considerations amongst the ND, adjacent nuclei, and longitudinal zones of the cerebellum are discussed.

Projections from substantia nigra and zona incerta to the cat's nucleus of Darkschewitsch.

The goal of the present experiments was to examine the relationships of the nucleus of Darkschewitsch (ND) with the substantia nigra pars reticulata (SNr), the zona incerta (ZI), and the oculomotor nuclei by using wheat germ agglutinin-horseradish peroxidase (WGA-HRP) as a retrograde and anterograde neuronal tracer injected into various sites of the cat's brain. To eliminate the possibility that fibres of passage from the motor cortex passing through the SNr and ZI were responsible for the ND label, WGA-HRP also was injected into the SNr or the ZI after a large area of the frontal cortex, including the motor area, was destroyed. Retrograde axonal transport demonstrated that many cells of the rostromedial part of the ZI project to the ND, with the ipsilateral projections being dominant. Some cells of the caudomedial part of the SNr project to the ND, again, with the ipsilateral projection being dominant. A few small cells in the ND project bilaterally to the oculomotor nucleus. Anterograde tracer demonstrated that the SNr-ND terminal fields are less dense than the ZI-ND terminal fields. A few fine terminal fibres were observed bilaterally in the oculomotor, trochlear, and abducens nuclei. Electron microscopic examination demonstrated that these fine, labelled terminals contain pleomorphic vesicles and have symmetrical synaptic contacts with dendrites. These results indicate that the ND, a structure that is known to be important for the control of axial muscles (i.e., eye, head, and body muscles), is the target of projections from restricted areas of the SNr and ZI: areas that, during saccadic eye movement, may lead to disinhibition of the ND-oculomotor projection. Accordingly, the ND may function to inhibit the activity of extraocular muscles during saccades.

Effects of endurance exercise on three-dimensional trabecular bone microarchitecture in young growing rats.

Appropriate endurance exercise is capable of increasing bone mass and strength in both animals and humans. We examined the skeletal changes induced by treadmill running exercise in young growing rats with a particular emphasis on three-dimensional trabecular bone microarchitecture. Fourteen male Wistar rats were divided into sedentary (CON; n = 7) and exercised (RUN; n = 7) groups at the age of 4 weeks. The rats in the RUN group performed the treadmill running exercise of 30 m/min for 60 min, 5 times a week. After 10 weeks of exercise, bone mineral density (BMD), cortical geometry, diaphyseal breaking force, and trabecular bone microarchitecture in the femur were measured. Three-dimensional trabecular bone microarchitecture was evaluated at the distal femoral metaphysis using microcomputed tomography. The running exercise significantly increased BMD, bone volume, bone volume fraction, trabecular thickness, and trabecular number, whereas trabecular bone pattern factor, the parameter associated with decreased trabecular connectivity, was significantly lower in the RUN group than the CON group. On the other hand, no significant difference in the degree of anisotropy and structure model index was observed between the two groups. At the femoral diaphysis, running exercise significantly increased cortical bone area, width, and maximum load without affecting bending stress, implying that the material properties of bone had not changed in the exercised rats. These results suggest that the increase in bone strength induced by endurance exercise is mediated by changes in trabecular bone microarchitecture as well as density and cortical geometry.

Passive hemagglutination and hemolysis tests for the detection of anti-DNA antibody.

Passive hemagglutination (PHA) and hemolysis (PHL) tests using chromium chloride-treated sheep red blood cells were developed to detect and measure the anti-DNA antibodies. Sonication of native DNA was found to prevent the incidence of non-specific agglutination. Sheep red cells were coated with double-stranded DNA (dsDNA) which had been sonicated and treated with nuclease S1 to digest the single-stranded regions in the DNA. The specificities for dsDNA-coated cells were checked by inhibition studies in PHA test and plaque assay. In clinical studies fairly close correlations were found between the antibodies to DNA and the activity of the disease in patients with systemic lupus erythematosus (SLE). Complement-fixing antibodies were detected in most of SLE patients with active lupus nephritis, but rarely in those in remission. Anticomplementary activity seemed to be negligible in PHL test. These tests are simple and may be useful to the diagnosis and the management of SLE.

Controlled study of circadian rhythm of blood pressure in patients with aldosterone-producing adenoma compared with those with essential hypertension.

OBJECTIVE: The circadian rhythm of blood pressure in patients with aldosterone-producing adenoma (APA) is not well understood. We evaluated the circadian blood pressure rhythm in such patients by comparison with that in patients with essential hypertension (EHT). The latter are characterized by a nocturnal blood pressure decline, the so called 'dipping' blood pressure pattern. DESIGN AND METHODS: A total of 12 patients with APA and 36 patients with EHT who were matched by age and sex, and who had no severe organic disorders, were hospitalized to control their diet (low sodium) and activities. Ambulatory blood pressure monitoring was conducted for 24 h. The 24-h blood pressure was divided into waking blood pressure (0600-2130 h) and sleeping blood pressure (2200-0530 h). RESULTS: The two groups showed no significant differences in age, sex, serum creatinine, plasma glucose, daily urinary sodium excretion, and left ventricular mass index. Although the 24-h mean blood pressure was higher in APA (112 +/- 8 mmHg) than EHT (102 +/- 12 mmHg), the dipping mean blood pressure ratio (%), which was calculated from the sleeping and waking blood pressures, did not differ significantly between the two groups (93.2 +/- 5.4 versus 92.8 +/- 5.9). CONCLUSION: The dipping ratio of blood pressure in patients with APA resembled that of patients with EHT. Variables that would influence the circadian rhythm of blood pressure were controlled during study. The results suggest that a circadian blood pressure in patients with APA is of the dipping type, characterized by a nocturnal blood pressure decline, when a low sodium diet is ingested.

Effect of disopyramide on initiation of atrial fibrillation and relation to effective refractory period.

Electrophysiologic studies were performed before and after intravenous administration of disopyramide (2 mg/kg) to 40 patients with either documented or suspected atrial fibrillation (AF). In control studies, sustained AF (greater than 1 minute), nonsustained AF (1 to 60 seconds) and no AF were found in 14, 18 and 8 patients, respectively. After disopyramide, the ability to initiate AF was totally lost in 18 patients (group A), while 22 patients (group B) showed sustained AF (11 patients) or nonsustained AF (11 patients). The effective refractory period of the atrium was 232 +/- 41 ms in the control study and 266 +/- 49 ms after disopyramide. Atrial functional refractory periods before and after disopyramide were 282 +/- 43 and 317 +/- 48 ms, respectively. The differences and ratios of the refractory periods after and before disopyramide were higher in group A than in group B (p less than 0.001). The prolongation of atrial refractoriness after disopyramide was important to suppress the initiation of AF in group A. In some group B patients, on the other hand, the initiation of AF was promoted after disopyramide. Disopyramide may alter the atrial electrophysiologic substrate required for AF initiation.

Absence of antioxidant effects of nifedipine and diltiazem on myocardial membrane lipid peroxidation in contrast with those of nisoldipine and propranolol.

Both the production of active oxygen species and cellular damage due to concurrent lipid peroxidation are believed to be important factors in the pathogenesis of cardiovascular diseases and the ageing process. Since cardiovascular drugs are often administered over a long term, it might be advantageous if they reduced lipid peroxidation. There have been conflicting reports concerning the antiperoxidant effect of nifedipine. Therefore, we investigated whether nifedipine could inhibit lipid peroxidation in a nonenzymatic active oxygen-generating system, utilizing rat crude myocardial membranes, and compared its effect with those of propranolol, nisoldipine, and diltiazem. Nifedipine and diltiazem had no inhibitory effects on the lipid peroxidation of myocardial membranes. In contrast, nisoldipine and propranolol had a concentration-dependent antiperoxidant effect, with IC50 values of 28.2 and 50.1 microM, respectively. In addition, nisoldipine appeared to possess dual antiperoxidant mechanisms, involving both preventive and chain-breaking properties.

A projection linking motor cortex with the LM-suprageniculate nuclear complex through the periaqueductal gray area which surrounds the nucleus of Darkschewitsch in the cat.

Whereas a previous study by one of us (Hicks et al., 1986) suggested that periaqueductal gray (PAG) neurons projecting to the lateralis medialis-suprageniculate (LM-SG) complex might mediate transmission of affective-related nociceptive information, our present work suggests instead, a function in processes related to movement. Cells of the nucleus of Darkschewitsch (ND) are known to have reciprocal projections with the motor cortex (MX), in particular with the hand area of MX, and also to project to the rostral medial accessory olivary (MAO) nucleus (Onodera and Hicks, 1995a). That the ND might be related to saccadic oculomotor function, as well as to the control of hand movements through its connections via the olivo-cerebellar circuit, is indicated by the fact that ND receives a strong projection from the substantia nigra pars reticulata and zona incerta (SNR/ZI) and projects directly and/or indirectly to eye movement nuclei (Onodera and Hicks, 1995b). Thus, ND may function in permitting integration of eye-hand motor coordination. This study focussed on the area of PAG surrounding ND. WGA-HRP was injected into MX and many labelled terminals and large neurones were in ND, with lesser numbers being observed in the area of the PAG surrounding ND. After injections into ND and closely adjacent areas, labelled terminals were observed sparsely distributed with a restricted area of the LM-SG complex. After injections into LM-SG area, small neuronal somata were seen in the area of the PAG surrounding ND, but no labelled somata were detected in ND. Thus if the cells of this PAG area, like those of ND, have similar functions owing to their common reciprocal connections with MX, then the small neurones in PAG projecting to LM-SG may constitute an important link in the circuitry subserving visual processing and/or the regulation of orienting movements of the hand, head and eye.