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Biomedical subjects

L T Ho

Publications and source records attributed to L T Ho.

At least 91 records · Page 5Linked to original sources
PubMed1994

Neurotoxicity in conscious rats following intraventricular SNAP, a nitric oxide donor.

A solution containing S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO.-releasing compound, was microinjected in doses of 0.25-2 mumol into a lateral ventricle of conscious rats. SNAP produced dose-dependent convulsions similar to those associated with limbic stimulation, such as tonic extension of the hindlimbs and tail, and dystonia of the forepaws. At 2 mumol, SNAP evoked hyperventilation (arterial hypocapnia), arterial hyperglycemia and caused necrotic lesions of periventricular gray (e.g. lateral septal nucleus) and white matter structures. In the caudate nucleus and lateral septal nucleus ipsilateral to injection, SNAP elicited a bipolar metabolic pattern of low glucose metabolism proximal to the ventricle with higher values occurring more distally. In control studies, we proved that the residue of SNAP decomposition, N-acetylpenicillamine disulfide injected intraventricularly (2 mumol), was without physiological, behavioral, or histological effects. Ventricular pretreatment with methylene blue (2 nmol), a putative inhibitor of guanylate cyclase and superoxide generator, suppressed several of the behavioral manifestations of 1 mumol SNAP, such as the forepaw dystonia, squinting, and facial clonus, but was ineffective on the physiological and histological variables affected by the 2 mumol SNAP dose. Another NO. donor, sodium nitroprusside (2 mumol), produced fewer behavioral and cytotoxic effects over a 55-min observation period, but caused more intense and widely distributed metabolic stimulation, especially in commissural and projection white matter tracts. The results are the basis for a conscious rat model using intraventricular injection of nitrocompounds to examine the physiological, behavioral, metabolic and cytotoxic properties of NO. in the brain.

Acid-Base Equilibrium↗
PubMed1994

FR139317, a specific ETA-receptor antagonist, inhibits cerebral activation by intraventricular endothelin-1 in conscious rats.

A comprehensive series of time-related behavioral, physiological and cerebral metabolic studies was conducted using conscious Sprague-Dawley rats to discern the anti-endothelin (ET) properties of the specific ETA receptor antagonist, FR139317. Endothelin-1 (9 pmol given by injection into one lateral ventricle, i.c.v.) produced convulsions, acute arterial hypertension, arterial hyperglycemia, and hyperventilation. Brain structures close to the i.c.v. site of injection, such as the caudate nucleus, lateral septal nucleus, corpus callosum and hippocampal CA3 medial lamellae, as well as 14 other individual structures, displayed moderate-to-intense levels of metabolic activation after endothelin. Data were assessed quantitatively by means of the autoradiographic [14C]deoxyglucose technique combined with image analysis. Neural circuits in the efferent projection paths of the stimulated forebrain structures, such as the midbrain oculomotor complex, amygdaloid nuclei, substantia nigra pars reticulata and caudal subicular subregions of the hippocampal formation, were stimulated focally by endothelin. Specific medullary nuclei and cerebellar cortical subregions displayed high rates of glucose metabolism following endothelin injection at the time of maximum behavioral and physiological stimulation. I.c.v. treatment with > or = 14 nmol FR139317 before endothelin significantly inhibited the effects produced by the peptide. At the highest dose of FR139317 (28 nmol), there was only mild behavioral stimulation following endothelin injection, and hypermetabolic responses in the brain were abolished except in two specific areas of the cerebellar cortex (approx 40% increases in metabolic activity in the copula pyramis and paramedian lobule). The results indicate that the cerebral stimulatory effects of i.c.v. endothelin are mediated by the A type of endothelin receptor. By itself, i.c.v. FR139317 had no effects on the parameters assessed. Further evaluation of FR139317 is warranted as a possible therapeutic agent for neuropathologies suspected of deriving from central neural or vascular stimulation by endothelin, such as aneurysmal vasospasm, ischemia, excitotoxicity, and peptide-mediated epilepsies.

Animals↗
PubMed1994

The influence of sulindac on experimental streptozotocin-induced diabetic neuropathy.

We studied the influence of sulindac, a nonsteroidal anti-inflammatory agent on experimental streptozotocin-induced diabetic neuropathy. Untreated diabetic rats were compared with nondiabetic rats, diabetic rats treated with low dose insulin and diabetic rats given sulindac (6.0 mg/kg by gavage 5 of 7 days weekly). Neuropathy was assessed by following serial in vivo motor and sensory caudal conduction, resistance to ischemic conduction failure, and in vitro conduction in sural myelinated and unmyelinated sensory fibers. The impact of low dose insulin and sulindac treatment on the microenvironment of the L4 dorsal root ganglion and sciatic endoneurium was assessed by measuring local perfusion and oxygen tension after 16 weeks of diabetes. Sulindac normalized conduction velocity in caudal sensory fibers, sural myelinated fibers and sural unmyelinated fibers, and reduced the number of diabetic cataracts. Sulindac also normalized a deficit in dorsal root ganglion blood flow and a reduction in sciatic endoneurial oxygen tension in diabetic rats. Low dose insulin improved neuropathy as well but the pattern of benefits was less robust than that of sulindac. Sulindac may be a candidate for a clinical trial in human diabetic polyneuropathy.

Animals↗
PubMed1994

Sumatriptan blocks neurogenic inflammation in the peripheral nerve trunk.

We tested the action of intraperitoneal sumatriptan, a 5-HT1D receptor agonist that aborts migraine headaches, using a model of neurogenic inflammation induced by capsaicin applied to the rat sciatic epineurium. Sumatriptan prevented the development of capsaicin-induced hyperemia without inducing pretreatment vasoconstriction or altering AV shunt flow. The findings indicate that sumatriptan prevents "neurogenic" vasodilation by a mechanism other than vasoconstriction or changes in AV shunt flow.

Animals↗
PubMed1994

Discordant secretions of ACTH and cortisol: an observation indicating multifactoral regulation of adrenal function.

To test the long-standing concept that secretion of adrenal glucocorticoids is solely dependent upon plasma level of adrenocorticotropic hormone (ACTH), we collected sequential blood samples from normal subjects and patients with pituitary-adrenal axis disorders at 30-min intervals for 24 hours and analyzed for both the plasma ACTH and cortisol profiles. In a majority of time points, the changes of cortisol levels coincided with those of ACTH. However, in all individuals tested so far, on more than 24 per cent of occasions, plasma cortisol rose together with a declining or fell with an elevating plasma ACTH level, that indicates a secretory discordance between these two hormones. These discordant patterns cannot be explained simply by the ACTH-stimulatory and cortisol-feedback inhibitory mechanisms. Since a generalized quantitative relationship between the overall profiles of plasma ACTH and cortisol did exist and the mutually regulatory pathways between pituitary and adrenal functions were mostly observable, there were no other known reasons explaining why these frequent and unsynchronized secretory activities should happen. Our observation reveals that cortisol secretion is probably under some other minor but normal influences in addition to the major regulatory action of ACTH.

Adolescent↗
PubMed1994

Effect of caffeine on the levels of brain serotonin and catecholamine in the genetically obese mice.

BACKGROUND: Most obesities are known low in sympathetic activity, and brain neurotransmitters may play roles in the defective exhibitions of obesity. Caffeine, a stimulant, which can prompt lipolysis, has been applied on the therapy of obesity. Although the interactive combinations between caffeine and certain neurotransmitters has been appreciated recently, but its regulatory mechanisms are still obscure. This study investigated the effect of caffeine on the body fat deposition, and its interactions with brain serotonin and catecholamine in the genetically obese (ob/ob) mice. METHODS: At 12-week of age, obese mice and their lean counterparts (+/?) were administered with caffeine (4 mg/d) in water for 4 weeks. The brain neurotransmitters levels and body fat content were measured. RESULTS: The obese mice without caffeine treatment had lower brain norepinephrine and epinephrine levels than the lean controls. And there had no difference between obese and lean mice in brain levels of serotonin, tryptophan, and 5-hydroxyindoleacetic acid. Caffeine treatment showed no effect on the food intake, but decreased the body fat content significantly in obese mice. Mice with caffeine treatment showed increase of the levels of brain neurotransmitters in both phenotypes; this effect was more predominant in obese mice. CONCLUSIONS: This study indicated that the effect of caffeine to decrease body fat deposition in the obese mice might be associated with the recovered increases of sympathetic activity.

Adipose Tissue↗
PubMed1994

Linear growth response to recombinant human growth hormone in children with growth hormone deficiency.

BACKGROUND: This study was to evaluate the efficacy, safety and immunogenicity of recombinant human growth hormone (rhGH) in treatment of children with growth hormone deficiency (GHD). METHODS: We selected 15 children with GHD for a 12-month clinical trial and separated them into three groups with each 5 patients receiving one of the 3 tested rhGH (Saizen by Serono, Aubonne, Switzerland; Genotropin by KabiVitrum, Stockholm, Sweden and Humatrope by Eli Lilly, Indianapolis, USA). RESULTS: In Saizen group, 3 boys and 2 girls with a mean chronological age (CA) of 10.6 +/- 1.7 yrs and bone age (BA) of 6.7 +/- 1.2 yrs, at dose of 0.2 IU/kg sc tiw, gained an average BA of 2.1 +/- 1.3 yrs. The mean height velocity (HV) increased from 3.7 +/- 1.2 to 11.1 +/- 3.3 cm/yr. The height standard deviation score (SDS) increased from -4.2 +/- 3.1 to -3.1 +/- 2.9. In Genotropin group, 2 boys and 3 girls with a mean CA of 9.2 +/- 2.3 yrs and BA of 5.6 +/- 2.1 yrs, at dose of 0.1 IU/kg sc qd, gained an average BA of 0.8 +/- 0.2 yr. The mean HV increased from 3.4 +/- 0.7 to 11.3 +/- 2.0 cm/yr. The height SDS increased from -4.0 +/- 0.5 to -2.7 +/- 0.7. In Humatrope group, 4 boys and 1 girl with a mean CA of 10.3 +/- 3.5 yrs and BA of 5.8 +/- 2.9 yrs, at dose of 0.1 IU/kg sc qd, gained at average BA of 0.8 +/- 0.7 yr. The mean HV increased from 4.0 +/- 1.3 to 9.4 +/- 1.9 cm2yr, and the height SDS increased from -2.9 +/- 0.7 to -2.2 +/- 1.0. Very low titers of anti-rhGH antibodies were noted only in two patients, one in Saizen group (titer = 1:10) and the other in Genotropin group (titer = 1:6). Their HV was not affected (Saizen: 13.3 cm/yr, Genotropin: 11.2 cm/yr). One patient evolved subclinical hypothyroidism whereas no side effect at all was noted in the rest of patients. CONCLUSIONS: Three tested GH (Saizen, Genotropin, Humatrope) produced by recombinant DNA technology appear to make no significant difference in this clinical trial, and rhGH therapy is an effective and safe treatment for prepubertal GHD children.

Adolescent↗
PubMed1993

The lung contents of endothelin are altered by thyroid hormone status in rat.

Endothelin-1 (ET-1) is a 21-residue peptide isolated from the conditioned medium of cultured porcine endothelial cells and is widely distributed throughout the body, with relatively high levels in the kidney and lung. Animal studies have revealed that the lung appears to have the largest capacity for ET-1 removal from the blood stream. In this study we have examined the possible influence of thyroid status on immunoreactive endothelin (IR-ET) levels in the plasma and lung of the male rats. 3 weeks after the surgical removal of the thyroid gland from male rats, the IR-ET levels in the lung were reduced by 39%. Similarly, IR-ET levels were decreased 46% in the lung of rats rendered hypothyroid by treatment with 0.1% (w/w) PTU in the drinking water for 30 days, and replacement with daily L-thyroxine (T4) injections (5 micrograms/100 g) prevented this decrease. However, thyrotoxicosis induced by daily L-T4 injections (10 micrograms/100 g) also caused a decrease of the lung IR-ET levels by 49%. Nevertheless, the plasma IR-ET levels are similar in each group. Fast protein liquid chromatography study verified the presence of ET-1 immunoreactivity in both rat plasma and lung tissue extracts. This study demonstrates that euthyroid status is required for the maintenance of physiological concentrations of IR-ET in the lung of male rats.

Animals↗
PubMed1993

Vasa nervorum constriction from substance P and calcitonin gene-related peptide antagonists: sensitivity to phentolamine and nimodipine.

Previous work has suggested that vasa nervorum are 'tonically' vasodilated by substance P (SP) and calcitonin gene-related peptide (CGRP) arising from perivascular afferent nerve fibers. Local application of specific receptor antagonists of SP or CGRP results in constriction of vasa nervorum. In this work, we examined the responsiveness of vasa nervorum to epineurial spantide and spantide II (SP antagonists) and hCGRP (8-37) (CGRP antagonist) using serial hydrogen clearance curves in the rat sciatic nerve. Vasoconstriction from spantide and hCGRP (8-37) was dose-dependent, and was slightly greater with spantide than hCGRP (8-37). Spantide II induced vasoconstriction comparable to that of spantide. The vasoconstrictive effects of both spantide and hCGRP (8-37) were eliminated by concurrent systemic treatment with with either phentolamine or nimodipine. The findings support the hypothesis that SP or CGRP blockade interrupts 'tonic' peptide vasodilatation and permits vasoconstriction, perhaps by unopposed adrenergic action mediated through calcium channels. The findings however do not exclude a unique direct vasoconstrictive action of the peptide antagonists.

Animals↗
PubMed1993

Diabetes mellitus prevents capsaicin from inducing hyperaemia in the rat sciatic nerve.

Loss of neurogenic inflammation in response to tissue injury may be an important complication of diabetes mellitus. We studied local neurogenic inflammation in the peripheral nerve trunk of Sprague-Dawley rats 4 months following the induction of diabetes by streptozotocin injection. To assess neurogenic inflammation, the epineurial plexus of the sciatic nerve was exposed to topical capsaicin, an agent that releases vasoactive neuropeptides from perivascular afferent terminals. Under normal circumstances, local vasodilation results in endoneurial hyperaemia or a 'flare'. We evaluated the influence of capsaicin in diabetic sciatic nerve by making serial measurements of endoneurial blood flow using microelectrodes sensitive to hydrogen clearance. After 4 months of hyperglycaemia (glucose > 16.0 mmol/l), diabetic animals had slowing of unmyelinated and myelinated sural sensory conduction velocity compared to citrate buffer injected controls. Baseline sciatic endoneurial blood flow was unaltered by diabetes, and was comparable to controls. There was an expected hyperaemic response of endoneurial blood flow to capsaicin in control rat sciatic endoneurium but no consistent 'flare' response in diabetic rats. Our findings indicate that there is loss of capsaicin-related neurogenic inflammation in the vasa nervorum of experimental diabetes. It is possible that a similar deficit following nerve injury could impair the milieu for axonal regeneration in diabetes.

Animals↗
PubMed1993

Insulin-like growth factor-I receptor increases in aortic endothelial cells from diabetic rats.

Endothelial cells are likely to play an important role in the development of diabetic vascular diseases, since they are exposed directly to the abnormal circulating metabolites of diabetes and may be easily damaged early in the natural course of vascular complications. In this study, aortic endothelial cells were cultured from diabetic BB rats. Their binding and internalization of insulin-like growth factor-I (IGF-I) were measured. IGF-I binding was higher in cells of diabetic rats than of control rats at both 37 degrees C (4.5% +/- 1.6% v 2.74% +/- 0.9% per mg protein, P < .05) and 4 degrees C (20.6% +/- 5.6% v 13.7% +/- 4.6% per mg protein, P < .01). Internalization of IGF-I also increased (1.62% +/- 0.2% v 0.74% +/- 0.15% of total count at 37 degrees C after 60 minutes, P < .05). Cross-linking studies showed that in cells from diabetic rats, the major band of 140 kd corresponding to the alpha-subunit of the IGF-I receptor increased in density by 50% compared with those from control rats. The IGF-I-stimulated tyrosine kinase activity (TKA) of partially purified receptor from cells of diabetic rats, measured using poly-glu-tyr as substrate, was normal. Since the biological effects of IGF-I are initiated by its binding to the IGF-I receptor, which is able to transduce mitogenic and metabolic signals, our results support the hypothesis that the IGF-I receptor is involved in the development of diabetic vascular complications.

Affinity Labels↗
PubMed1993

Tissue contents of endothelin vary according to thyroid hormone status in rat.

Endothelin-1 (ET-1) is a 21-residue peptide isolated from the conditioned medium of cultured porcine endothelial cells and is widely distributed throughout the body, with relatively high levels in the kidney and lung. In this study we examined the influence of thyroid hormone status on immunoreactive endothelin (ir-ET) levels in the plasma, lung, and kidney tissues of rats. Three weeks after surgical removal of the thyroid gland from male rats, the ir-ET levels in the lung and kidney were reduced by 39% and 42%, respectively. Similarly, ir-ET levels were decreased by 46% in the lung and 45% in the kidney of rats rendered hypothyroid by treatment with 0.1% (wt/wt) n-propylthiouracil (PTU) in the drinking water for 30 days. Replacement with daily L-thyroxine (T4) injections (5 micrograms/100 g) prevented this decrease. However, thyrotoxicosis induced by daily L-T4 injections (10 micrograms/100 g) also caused a decrease of the lung ir-ET levels by 49%, but had no significant effect on the renal ir-ET levels. However, the plasma ir-ET levels were similar in each group. Fast protein liquid chromatography study verified the presence of ir-ET-1 in the plasma and tissue extracts. This study demonstrates that thyroid hormone status affects tissue levels of ir-ET differently and that a euthyroid status is required for the maintenance of physiologic concentrations of ir-ET in the lung of male rats.

Animals↗
PubMed1993

Evidence that capsaicin hyperaemia of rat sciatic vasa nervorum is local, opiate-sensitive and involves mast cells.

1. In previous work, we identified a prolonged and intense hyperaemic response of rat sciatic endoneurial vasa nervorum produced by epineurial application of capsaicin. We postulated that this response, which was blocked by substance P (SP) or calcitonin gene-related peptide (CGRP) antagonists, was a result of local release of neuropeptides on the 'feeding' epineurial vascular plexus. 2. In the present study, we evaluated factors that might influence capsaicin-induced hyperaemia of the rat sciatic endoneurium as measured by hydrogen clearance: central afferent connections, the epineurial vascular plexus, the release of histamine and administration of opiates. 3. Interruption of central afferent connections by proximal nerve section or removal of the epineurial vascular plexus did not influence baseline endoneurial perfusion. Plexus removal, but not proximal section, prevented capsaicin hyperaemia. 4. The epineurial vascular plexus was desensitized to the effect of capsaicin by prior application of capsaicin. Capsaicin hyperaemia was also prevented by: topical treatment with Spantide II ((D-NicLys1,3-Pal3,D-Cl2Phe5,Asn6,D-Trp7,9,Nl e11) substance P) an SP antagonist, systemic pretreatment with a combination of H1 and H2 histamine receptor antagonists, systemic pretreatment with cromolyn sodium or systemic pretreatment with morphine. None of these pretreatments influenced baseline perfusion. When systemic morphine was given together with systemic naloxone, an opiate antagonist, capsaicin-induced hyperaemia was restored. 5. These findings indicate that the capsaicin hyperaemia of vasa nervorum is locally mediated, is independent of central afferent connections and is sensitive to a variety of interventions. It requires an intact epineurial plexus that 'feeds' endoneurial microvessels and the release of histamine by mast cells. Its inhibition by morphine suggests that there are local opiate receptors on epineurial perivascular peptidergic fibres.

Afferent Pathways↗
PubMed1993

Space-resolved fluoroimmunoassay for quantifying alpha-fetoprotein in serum.

A nickel-coated surface was used to adsorb a monolayer of anti-human alpha-fetoprotein antibody. After incubation with a patient's serum, the sample was stained with fluorescein isothiocyanate (FITC)-conjugated anti-human alpha-fetoprotein antibody. These slides were then read with a space-resolved fluorometer to determine the amount of FITC adsorbed onto the metal surface. We used an argon laser as the light source in the fluorometer. The parallel laser beam was tilted at about 45 degrees to the sample surface. The fluorescence from FITC was read with a perpendicular photon counter to reduce noise. The CV for these tests was approximately 10%. Comparison of these results (y) with those of a conventional radioimmunoassay (x) produced the regression equation y = 0.99x + 0.5, over the range 10-140 micrograms/L (n = 51).

Adsorption↗
PubMed1993

A primary cell-culture system for physiological studies of adrenocortical function.

We used guinea-pig adrenal tissue to develop a primary culture, enriched with zona fasciculata (ZF) cells. In a continuous culture up to 2 weeks, the cells maintained the characteristic of glucocortical function by producing cortisol as the final steroidogenic product and secreting it into culture medium. When culture medium, which was replaced at 24-hr intervals, was assayed for cortisol, the basal steroidogenic function peaked on day 5 and then declined. In response to 24-hr treatment with the bioactive adrenocorticotropic hormones (ACTH) on day 4, production of cortisol was stimulated and prolonged, and also cells were morphologically hypertrophic. This in vitro system provides a convenient laboratory method which can be used for studying adrenocortical function under a possibly physiological condition.

Adrenal Cortex↗
PubMed1993

[Alterations of zinc levels in patients with thyroid disorders].

It is known that patients with hyperthyroidism have a lower zinc content in their erythrocytes, and that this decrement returns to normal after treatment with anti-thyroid drugs. This study was designed to investigate the alteration of body zinc levels in thyroid disorder. Two groups of out-patients associated with hyperthyroidism or hypothyroidism, and a group of normal healthy controls were collected. Zinc contents in the blood, hair and 24-hour urine samples were determined by a flame atomic absorption spectrometer. The results showed that patients with hyperthyroidism had a lower erythrocyte zinc level and an increased urinary zinc excretion (p < 0.05). The hypothyroidism had a higher hair zinc content and a decrement in urinary zinc excretion (p < 0.05). Body zinc levels, excluding the plasma zinc, held a certain correlation to the plasma thyroid hormones levels. The urinary zinc levels showed a more parallel variation in the thyroid disorders (p < 0.05). This data indicates that the alteration of urinary zinc levels might be a useful index for thyroid disorder evaluation. Body zinc could also play a physiological role in the metabolic regulation(s) of a thyroid disorder.

Adult↗
PubMed1993

[The evaluation of blood perfusion of lower extremities in patients with NIDDM by 133Xe muscle clearance test: a preliminary report].

In this study, we collected twenty NIDDM patients with impaired sensation and clinically suspected angiopathy over both lower extremities. All the patients underwent testing by means of the ultrasonic Doppler technique and were separated into two groups, group 1 with impaired blood flow, and group 2 with no significant impairment of blood flow. Ten normal persons were also included in this study (group 3). The results of the 133Xe muscle clearance test showed that the Q value of group 1 was 0.85 +/- 0.24 [mean +/- SE, ml (100g tissue min-1)], 1.05 +/- 0.31 in group 2 and 1.78 +/- 0.23 in group 3 of normal controls. After statistical analysis, there were significant differences in groups 1 and 2 relative to group 3 (p < 0.05), respectively. This preliminary result indicates that the 133Xe muscle clearance test may be an effective and convenient method to evaluate angiopathy of lower extremities in patients with NIDDM.

Adult↗