Biomedical subjects

S W Kuo

Publications and source records attributed to S W Kuo.

At least 19 recordsLinked to original sources

PubMed2003

The effect of surgical stress on insulin sensitivity, glucose effectiveness and acute insulin response to glucose load.

Hyperglycemia after stress is a very common clinical phenomenon. It is generally hypothesized that the underlying cause is a neuroendocrine-mediated deterioration in glucose metabolism. However, the detailed roles of insulin sensitivity, glucose effectiveness and acute insulin response to glucose load in response to stress have not been well established. Hernioplasty was used as a minor stress model for studying stress-induced hyperglycemia. Eleven healthy young men were enrolled voluntarily in this study. Their mean age was 22.0 +/- 0.9 yr and BMI 23.3 +/- 0.6 kg/m2. Frequently sampled i.v. glucose tolerance tests were performed one day before and one day after the surgery. Insulin sensitivity (SI), glucose effectiveness (EG) and area under acute insulin response (AIR) were calculated from "minimal model" algorithms. We also measured fasting concentrations of human GH, ACTH and F on the days of the test. Compared to the pre-operation data, levels of ACTH and F did not change significantly after the surgery. Only GH levels were marginally significant. On the other hand, the SI (0.75 +/- 0.1, 0.52 +/- 0.9 x 10(-5) min(-1)/pmol, p = 0.04), EG (0.023 +/- 0.03, 0.016 +/- 0.003 min(-1), p = 0.01) and AIR (6738.5 +/- 1111.6, 5130.0 +/- 1047.2 pmol, p = 0.005) were all significantly decreased after surgery. The percentages of decrease were 16.3 +/- 15.5, 32.1 +/- 10.3 and 17.8 +/- 10.3%, respectively. Finally, only the changes of EG positively correlate with the changes of ACTH before and after surgery. No significant changes were noted among other stress hormones and the changes of SI, EG and AIR. In conclusion, hernioplasty results in reduced SI, EG and AIR. Among them, although not statistically significant, the EG showed the most distinct decrease after the surgery, which has not been found in previous literature.

Adolescent↗

PubMed2000

Recombinant adeno-associated virus vector expressing glial cell line-derived neurotrophic factor reduces ischemia-induced damage.

To explore the potential of using the recombinant adeno-associated viral (rAAV) vector, expressing glial cell line-derived neurotrophic factor (GDNF) as the gene therapy for stroke, we injected rAAV vectors expressing GDNF (rAAV-GDNF) into the cortex of rats which had been experiencing transient bilateral common carotid artery ligation and right middle cerebral artery ligation for 90 min. GDNF levels in cortical tissues of rAAV-GDNF-injected animals were significantly higher than in the control animals injected with rAAV-expressing lacZ (rAAV-lacZ), indicating that rAAV can deliver and express the GDNF gene in cortical tissues. Triphenyltetrazolium chloride tissue stain analysis revealed that the rAAV-delivered GDNF gene could rescue the brain tissues from ischemia-induced injury. Cortical tissues which received rAAV-GDNF injections had both significantly smaller total volumes of infarction and smaller areas of infarction on each brain slice than those which were injected with rAAV-lacZ. An in situ labeling analysis demonstrated significantly less apoptotic cells in cortical tissues rescued by rAAV-GDNF, indicating prevention of apoptosis as the mechanism of cortical cell protection. Moreover, immunohistochemistry staining of Neu-N indicated that the rescued brain tissues contained the same number of Neu-N-positive neuronal cells as contralateral undamaged brain tissues. This provides strong evidence that cortical neuronal cells can be rescued by GDNF gene therapy. Indeed, these findings show that the rAAV is a potential delivery vector of GDNF gene for the therapy of stroke.

Adenoviridae↗

PubMed2000

B-cell depletion fails to abrogate the induction of oral tolerance of specific Th1 immune responses in mice.

Antigen presentation by resting B cells has been shown to induce peripheral tolerance to intravenous (i.v.) administered soluble protein antigens. We further examined the role of resting B cells in the induction of oral tolerance. Mice were treated continuously from birth with rabbit antimouse IgM serum for 5 weeks. Immunohistological studies revealed that anti-IgM treatment depleted B cell-aggregated follicles in intestinal Peyer's patches. At 4-weeks-old, B cell-depleted mice were fed 25 mg ovalbumin or given 10% chicken egg white to drink for 5 days. Anti-IgM treatment was stopped 2 days after the last feed. Ten weeks later, the mice were immunized with 100 microg ovalbumin emulsified with complete Frund's adjuvant. Their T helper 1 (Th1) cell-regulated systemic delayed-type hypersensitivity, IgG2a antibody responses and spleen cell production of interferon-r and interleukin-2 were suppressed by prior ovalbumin or egg white feeding during anti-IgM treatment. Active suppression of Th1 immune responses was also demonstrated following adoptive transfer of egg white-fed donor spleen cells collected during anti-IgM treatment to naïve recipients. Although enormous small resting B cells are aggregated in the mantle zones of follicles of intestinal Peyer's patches, they are not the antigen-presenting cells seen in the induction of oral tolerance.

Administration, Oral↗

PubMed2000

Resting B cells are not antigen-presenting cells in the induction of oral tolerance of specific Th2 immune responses in mice.

BACKGROUND: It has been shown that antigen presentation by resting B cells can induce tolerance to intravenously administered protein antigens, but the role of resting B cells in the induction of oral tolerance is unclear. METHODS: Mice continuously treated since birth with rabbit anti-mouse IgM serum for 5 weeks were depleted of B cells. When 4 weeks old, B cell-depleted mice drank 10% chicken egg white (EW) for 5 days. Ten weeks later, they were immunized with 10 microgram of ovalbumin in alum and their T helper 2 (Th2) immune responses were tested. RESULTS: Th2 cell-mediated IgE and IgG1 antibody responses and spleen cell production of IL-4 and IL-5 were suppressed by prior EW feeding during anti-IgM treatment. When anti-IgM-treated spleen cells collected 1 week after EW ingestion were transferred to naïve recipients, active suppression of Th2 immune responses was also demonstrated. CONCLUSIONS: Although resting small B cells aggregate in the mantle zone of follicles of intestinal Peyer's patches, the present data suggest that they are not antigen-presenting cells in the induction of oral tolerance of Th2 immune responses to oral antigens.

Administration, Oral↗

PubMed1999

Relaxant effects of quercetin methyl ether derivatives in isolated guinea pig trachea and their structure-activity relationships.

In the present study, we attempted to compare quercetin methyl ethers and to look for the structure-activity relationships, which may be helpful for synthesizing more active compounds for the treatment of asthma. Four present and two previously studied quercetin methyl ethers concentration-dependently relaxed histamine (30 microM), carbachol (0.2 microM) and KCl (30 mM) induced precontraction. According to their IC25 values to histamine-induced precontraction, the potency order was quercetin 3,3',4,'5,7-pentamethyl ether (QPME), quercetin 3-methyl ether > quercetin, quercetin 3,4',7-trimethyl ether (ayanin) > quercetin 4'-methyl ether (tamarixetin), quercetin 3,3',4',7,-tetramethyl ether (QTME). Therefore, the methylation at 3, at 5, and at both 3 and 7 positions of the A or/and C ring of quercetin nucleus may increase their tracheal relaxant activity. However, the methylation at the 3' and at the 4' position of the B ring of quercetin nucleus may decrease their tracheal relaxant activity.

Animals↗

PubMed1999

Effects of lovastatin and gemfibrozil in subjects with high ratios of total cholesterol to high-density lipoprotein cholesterol.

Insulin resistance is associated with hypertriglyceridemia, low serum high-density lipoprotein cholesterol (HDL-C) concentrations and high serum total cholesterol (TC) to HDL-C ratios. Several reports have demonstrated that either lovastatin or gemfibrozil may favorably lower serum lipid concentrations. However, their effects on insulin sensitivity are unknown. The primary aim of this study was to compare the effects of lovastatin and gemfibrozil on insulin sensitivity and serum leptin concentrations in subjects with high TC/HDL-C ratios. We enrolled 25 nondiabetic patients, similar in terms of age and weight with TC/HDL-C ratios greater than 5. Thirteen subjects were treated with lovastatin 20 mg per day, and 12 received gemfibrozil 300 mg twice per day. Plasma lipids, glucose, and leptin were measured, and a 75-g oral glucose tolerance test (OGTT) and a modified insulin suppression test were performed before and after 3 months of treatment. The study showed the mean plasma TC, low-density lipoprotein cholesterol (LDL-C) concentrations, and TC/HDL-C ratio were significantly reduced in the lovastatin-treated group, but no obvious effects on plasma triglyceride (TG) and HDL-C were noted. In the gemfibrozil group, plasma TG and HDL-C were markedly lowered, but no significantly different effects in other plasma lipids were found. Gemfibrozil did not affect steady-state plasma glucose (SSPG) concentrations, whereas lovastatin significantly increased SSPG concentrations. Neither drug affected the serum leptin concentration during the OGTT. We conclude that lovastatin significantly lowers plasma TC and LDL-C ratio, and TC/HDL-C concentrations and adversely affects insulin sensitivity, while gemfibrozil markedly reduces plasma TG concentrations without altering insulin sensitivity in subjects with high TC/HDL-C ratios.

Adult↗

PubMed1998

Urinary compound W in pregnant women is a potential marker for fetal thyroid function.

OBJECTIVE: Previously we reported 3,3'-diiodothyronine sulfate-like material (compound W) in maternal serum, and studies suggest that compound W is derived from thyroid hormones of fetal origin. In this study we characterized gestational changes of urinary compound W concentrations to correlate with changes in serum concentrations. STUDY DESIGN: Urinary samples were collected from 94 women at various gestational ages ranging from 3 to 40 weeks. Urinary compound W was first identified biochemically. The concentrations of compound W (adjusted for creatinine levels) were assessed by a 3,3'-diiodothyronine sulfate radioimmunoassay in ethanol extracts of urine samples. RESULTS: Compound W increased to 88 +/- 1.4 pmol (of 3,3'-diiodothyronine sulfate equivalent)/mmol creatinine in urinary samples obtained from 26 women in the first trimester of pregnancy compared with 40 +/- 6.9 pmol/mmol creatinine in 10 nonpregnant women. Excretion of compound W increased further during the second and third trimesters: 171 +/- 17 (n = 18) and 434 +/- 26 (n = 50) respectively. In contrast, urinary 3,3',5-triiodothyronine sulfate concentrations measured by radioimmunoassay were similar during pregnancy to values in nonpregnant women. CONCLUSIONS: Urinary compound W concentrations increase with the progression of normal pregnancy and correlate with the increase in serum levels. Random spot urine compound W concentrations, adjusted for creatinine levels, may be used in place of serum levels in conditions in which obtaining serum samples may be technically difficult, especially during population screening.

Biomarkers↗

PubMed1997

Increased urinary thyroxine sulfate excretion in thyroxine therapy.

Although increased thyroxine sulfate (T4S) levels have recently been detected in fetal serum and amniotic fluid, changes in patients in a high thyroxine (T4) state remain unclarified. This study was conducted to determine the changes in T4S in thyroid hormone regulation in women receiving suppressive T4 therapy. With a highly sensitive and specific radioimmunoassay, we measured the serum and urinary concentrations of T4S in 16 premenopausal women with benign nodular goiter before and after three months administration of T4 (3.2 micrograms/kg/day). Serum levels of other thyroid hormones were also measured. Significant increases in mean serum T4 levels post-treatment (11.1 vs. 6.6 micrograms/dL pre-treatment; P < 0.01) were found, although only low T4S levels were detectable in serum both pre- and post-T4 treatment. The mean urinary or creatinine corrected urinary T4S values post-treatment were significantly increased (20 ng/dL or 396 ng/g creatinine vs. 12 ng/dL or 174 ng/g creatinine pre-treatment, P < 0.01). There was a significant correlation between increased creatinine-corrected urine T4S and increased serum free T4. Our results indicate that the sulfation of T4 may be related to the regulation of thyroid hormone metabolism in T4-treated subjects with relative hyperthyroxinemia.

Adult↗

PubMed1996

Reversal of the temperature-shift-induced growth restriction of a temperature-sensitive simian virus 40 T-antigen-transformed human fibroblast cell line by treatment with retinoic acid.

We previously established a human fibroblast cell line, HFL 6-2, that contains a temperature sensitive simian virus 40 (SV40) T antigen, permitting cell growth at 35 degrees C but restricting growth at 39 degrees C. p21 (Waf1/Cip1) was significantly induced by temperature shifts in HFL 6-2 cells. Here we show that all-trans-retinoic acid (RA) treatment prevented the growth restriction of HFL 6-2 cells at 39 degrees C. In the presence of RA, HFL 6-2 cells proliferated into sizeable colonies even at 39 degrees C. [3H]Thymidine incorporation and flow cytometry analysis revealed that cells exposed to RA maintained DNA synthesis at 39 degrees C. Prevention of growth restriction by RA was correlated with a lack of induction of p21 at the transcription level. These observations suggest that RA may prevent the senescence process by repressing p21 gene expression, and perturb the growth regulation of somatic cells.

Antigens, Polyomavirus Transforming↗

PubMed1996

Increased urinary excretion of sulfated 3,3',5-triiodothyronine in patients with nodular goiters receiving suppressive thyroxine therapy.

Increased serum 3,3',5-triiodothyronine sulfate (T3S) levels have been detected in various pathophysiologic states. However, little is known about T3S concentrations in other biological fluids. By employing a highly sensitive, specific, and reproducible radioimmunoassay (RIA), we measured T3S in the serum and urine of 20 premenopausal women with benign nodular goiters before and after administration of thyroxine for 6 months (T4; 3.2 micrograms/kg/day). Serum T3 concentrations did not change significantly after treatment (2.0 vs. 1.7 nmol/L; p > 0.05). However, the mean serum T4 and free T4 concentrations were significantly higher after treatment (138 vs. 88 nmol/L and 28 vs. 17 pmol/L; p < 0.01, respectively). Serum thyroid stimulating hormone (TSH) levels were significantly reduced after T4 treatment (0.13 vs. 0.66 mU/L, p < 0.01) and the serum levels of T3S were significantly increased after treatment (82 vs. 45 pmol/L; p < 0.01). A good correlation was observed between increased serum T3S and T4 concentrations (r = 0.66; p < 0.001). The sulfoconjugate of T3 was significantly increased in creatinine-corrected urine after treatment (606 vs. 253 pmol/umol Cr.; p < 0.01). There was a significant correlation between increased creatinine-corrected urine T3S and increased serum free T4 (r = 0.65; p < 0.001). In summary, significant increases in serum and urine T3S levels were noted in T4-treated patients with subnormal serum TSH and borderline elevated T4. We thus conclude that the sulfation pathway may play a role in the homeostasis of thyroid hormone metabolism in T4-treated subjects with relative hyperthyroxinemia. In addition, the creatinine-corrected urine concentrations of T3S may serve as an index for the evaluation of T4-treated patients with elevated levels of T4.

Adult↗

PubMed1996

Maturation of hepatic desulfation activity in developing rats.

The present study was carried out to further characterize the maturation of desulfation activity in developing rats. High levels of 3,3',5-triiodothyronine sulfate (T3S) were found in rat fetal serum whereas 3,3',5-triiodothyronine (T3) levels were low. The ratio of T3S/T3. was dramatically reversed in the rat maternal circulation. Maternal rats had higher desulfation activity than did near-term fetuses. Desulfation of T3S to T3 by microsomes of fetal and maternal livers were studied by incubating microsomes with T3S as a substrate. Desulfated T3 was measured by radioimmunoassay. The Km and Vmax values for desulfation of T3S to T3 by hepatic microsomes in different age groups were compared. Little desulfation activity was found in hepatic microsomal preparations from fetal rats compared with newborn rats. There was a trend of increasing desulfation activity in rats after birth until 1 month of age, although this was not significant. A surge of desulfating activity was observed between the 1- and 2-month old groups. The K(m) values for T3S desulfation activity were similar in all age groups. The Vmax values for the T3S to T3 desulfation activity progressively increased after birth until 2 months of age. The Vmax of the latter group, however, was comparable to that of the maternal group. These results suggest that the maturation of desulfation activity in the microsomal preparations from rat livers is completed by 2 months of age and is mainly due to increased enzyme capacity. Sulfation-desulfation of T3 may play a role in the thyroid hormone regulation of developing mammals.

Age Factors↗

PubMed1995

Human papillomavirus 11 E5a delays the growth restriction induced by temperature shift in temperature-sensitive simian virus 40 T antigen-immortalized keratinocytes.

The transfection with human papillomavirus type 11 E5a oncoprotein can cause longer and more active proliferation in the human keratinocytes previously transfected stably with temperature sensitive SV40 T antigen at 39 degrees C. Also, after the E5a transfection in parental temperature sensitive SV40 T antigen gene transfected cells, we observe a delay in the accumulation of p21 gene at 39 degrees C. Moreover, T antigen degradation did not occur at 39 degrees C in the E5a transfected cells as it did in the parental cells. We draw from these observations that E5a may transiently stabilize temperature sensitive T antigen and/or repress p21 synthesis.

Antigens, Polyomavirus Transforming↗

PubMed1995

Differential regulation of cyclin A, cyclin B and p21 concentrations in a growth-restricted human fibroblast cell line.

When the culture temperature was shifted from 35 degrees C to 39 degrees C, human fibroblasts immortalized by the temperature-sensitive simian virus 40 T antigen became larger and acquired the morphological characteristics of senescent fibroblasts. After culture at 39 degrees C for 48 h, most cells had ceased to proliferate. A rapid depletion of cells with S-phase DNA content was observed after the temperature shift. To elucidate the mechanism governing this rapid arrest of proliferation, we studied the expression of genes involved in the regulation of cell cycle progression. Cyclin A, cyclin B and p34cdc2 concentrations were not changed during growth restriction, whereas p21 was rapidly induced in these growth-restricted cells. Transient expression of exogenous p21 in cells cultured at 35 degrees C led to growth restriction and morphological changes characteristic of senescence. Furthermore, we studied the reversibility of growth restriction induced by the temperature increase. The results showed that senescent morphology and growth arrest were not reversible. In these cells the p21 concentration remained high and p34cdc2 remained undetectable. This indicates that p21 accumulation might be responsible for the maintenance of senescence. Our findings provide information on the use of growth restriction of immortalized fibroblasts induced by a temperature shift as a model system to study senescence.

CDC2 Protein Kinase↗

PubMed1995

Differential induction and regulation of c-jun, junB, junD and c-fos by human papillomavirus type 11 E5a oncoprotein.

The E5a gene of human papillomavirus type 11 (HPV-11) is a transforming oncogene. In this study, we investigated the mechanism of E5a induced transformation. Our results show that the expression of c-jun and junB, but not junD, was activated by HPV-11 E5a in NIH 3T3 cells and human epidermal keratinocytes. However, the expression of c-fos was activated by E5a in NIH 3T3 cells, but not in keratinocytes. We further investigated the mechanism of c-jun and junB induction by E5a. The amount of c-jun and junB RNAs correlated with the amount of E5a RNA in the heavy metal inducible system. E5a constitutively activated the expression of c-jun and junB at the initiation of transcription level. In addition, analyses of the effect of serum on c-jun expression in E5a transformed human epidermal keratinocytes show that EGF might have a stimulatory effect on c-jun gene expression in E5a expressing keratinocytes.

3T3 Cells↗

PubMed1995

Establishment of the sulfated 3,3'-diiodothyronine radioimmunoassay and its application in pregnant women.

Sulfation of iodothyronines is a major alternate pathway of thyroid hormone metabolism during fetal development. Sulfated 3,3'-diiodothyronine (T2S) is a low end metabolite of this pathway. Its clinical implications in the prenatal evaluation of fetal thyroid disorders are now being intensively investigated. A highly sensitive and reproducible radioimmunoassay (RIA) for T2S has been established in our laboratory. The detection threshold of the RIA approximated 5 pg T2S. The dose-response curve of T2S was essentially linear between 5-200 pg. An essentially parallel correlation of the dose-response curves for inhibition of binding of radiolabeled T2S and T2S antiserum was found between serial dilutions of serum extracts and the standards. The average intra- and inter-assay coefficients of variation were 7% and 15%, respectively. By applying the T2S RIA, we found that serum titers of T2S in pregnant women increased proportionately to the gestational age (first trimester vs. second trimester vs. third trimester: 30.1 +/- 1.4 vs. 41.6 +/- 1.9 vs. 98.0 +/- 3.9 ng/dL; p < 0.001 each). A high concentration of T2S was detected in cord and maternal serum at birth as compared to the results for non-pregnant women (165.1 +/- 10.3 vs. 113.7 +/- 5.6 vs. 7.5 +/- 0.9 ng/dL). The T2S levels decreased remarkably in maternal circulation 10 days after partuition. Four pregnant women who had two blood samplings four or more weeks apart during the third trimester showed invariable increases of serum T2S titers at later sampling times. Additionally, in the case of a pregnant woman who received two doses of T4 injections (200 micrograms/wk) intraamniotically for a previous Cretin birth, the maternal serum levels of T2S increased promptly from 47 ng/dL [corrected] to 96 ng/dL. Our findings imply that the established T2S RIA is clinically applicable, provide further evidence that the coincident increase of serum T2S titers in pregnant women may reflect ontogenesis of fetal thyroid hormone maturation, and provide a clue to the fetal thyroid status in the prenatal stage. However, more knowledge is still needed regarding the transfer and transformation of sulfated iodothyronine(s) from the fetal compartment to maternal circulation.

Analysis of Variance↗

PubMed1994

Effect of thyroxine administration on serum thyrotropin receptor antibody and thyroglobulin levels in patients with Graves' hyperthyroidism during antithyroid drug therapy.

Graves' hyperthyroidism is due primarily to overproduction of antibodies to thyrotropin receptors (TR-ab), which stimulate the thyroid gland and cause hyperthyroidism. Antibody production during antithyroid drug therapy is an important determinant of the course of the disease. We therefore observed the changes of serum TR-ab, thyroglobulin (Tg) and thyroid hormone levels in response to administration of L-thyroxine (T4) in Graves' hyperthyroid patients during antithyroid drug therapy. Serum levels of TR-ab, Tg and other thyroid hormones were measured by radioimmunoassay (RIA) during either methimazole treatment alone or in combination with thyroxine in 60 Graves' hyperthyroid patients. The patients initially were treated with 30 mg of methimozole daily for 3 months, which was then reduced to 15 mg daily for the following 3 months. All patients were euthyroid 6 months after the start of antithyroid therapy and the TR-ab level decreased from 61 +/- 11% (+/- SD) to 28 +/- 7% (p < 0.01). Patients then were divided into three groups: group A (N = 25), whose TR-ab level was 10% or more (the cut-off value for positivity), received 0.1 mg of T4 and 10 mg of methimazole daily for 6 months; group B (N = 15), whose TR-ab level also was 10% or more and was age- and thyroid function-matched with group A, received only 10 mg of methimazole daily for 6 months; group C (N = 20), with a TR-ab level of less than 10%, received 10 mg of methimazole alone daily for 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Sympathoadrenal reactions during asphyxia in hypoglycemia and hyperglycemia of cats.

In 26 cats anesthetized with alpha-chloralose and urethane, cardiovascular changes during asphyxia in hypoglycemia and hyperglycemia were studied. Systemic hypoglycemia (serum glucose decrease from 148 to 31 mg/100 ml) was produced by i.v. injection of insulin 20 U/kg, followed by continuous I.V. infusion of 10 U/kg/hr. Systemic hyperglycemia (serum glucose increase from 187 to 657 mg/100 ml) was produced by I.V. infusion of 25% glucose at a rate of 1.5 gm/kg/hr. During hypo- or hyperglycemia, resting mean systemic arterial pressure (MSAP) and heart rate did not change significantly. Brain transection at various levels, i.e., midcollicular decerebration, ponto-medullary or medulla-spinal transection progressively decreased the resting MSAP, but not the heart rate. The most apparent reduction was at the medulla-spinal junction. After induction of systemic hypo- or hyperglycemia, plasma catecholamine concentrations increased significantly. Further increase occurred during asphyxia. Increases of MSAP and plasma catecholamine concentrations during asphyxia were attenuated after midcollicular decerebration and decreased further after subsequent ponto-medullary and medulla-spinal transections. Increases in plasma catecholamines during asphyxia were greater in hypoglycemic than those in hyperglycemic state. The increase in plasma catecholamine persisted in hypoglycemic animals during asphyxia after midcollicular decerebration and ponto-medullary transections. As the terminal stage of asphyxia approached spasmodic contractions of urinary bladder occurred. Bladder contractions were abolished after intracerebroventricular (lateral) injection of insulin (0.25 unit/kg). In conclusion, asphyxia produced very marked cardiovascular and plasma catecholamine responses during hypo- or hyperglycemia and more so during the former condition. These reactions depend mainly on the neural mechanisms of medullary structures. Neural structures rostral to the midcollicular level are not essential.

Animals↗

PubMed1993

Effects of insulin on the cardiovascular integrating mechanisms of brain stem in cats.

In 65 cats anesthetized with alpha-chloralose and urethane, the effects of insulin on cardiovascular responses to stimulation of various structures in the brain stem were studied. The threshold dose of insulin injected intravenously that produced systemic hypoglycemia was 5-10 U/kg. Subthreshold hypoglycemic doses of insulin were used intracerebroventricularly (0.25 U/kg) or intracerebrally (2 mU in 200 nl). Sixty minutes after intravenous insulin, when serum glucose concentrations decreased from 158 to 43 mg/100 ml, pressor responses to stimulation of the periaqueductal gray of midbrain (PAG), locus coeruleus (LC), dorsal medulla (DM), ventrolateral medulla (VLM), and parvocellular reticular nucleus (PVC) decreased significantly. Depressor and bradycardiac response to stimulation of paramedian reticular nucleus or dorsal motor nucleus of vagus (DMV) decreased significantly as well. Thirty minutes after intracerebroventricular insulin, pressor responses of PAG, DM, and the bradycardiac response of DMV decreased significantly. Thirty minutes after intracerebral insulin, pressor responses and renal nerve activities of LC (but not PAG), VLM, DM, and PVC decreased significantly. A similar but faster onset (5 min) of depression of cardiovascular responses on stimulating the LC, VLM, DM, and PVC was observed in another six acutely midcollicular-decerebrate cats recovered from halothane anesthesia. These findings suggest that insulin directly inhibits the vasomotor structures of the brain stem and decreases the pressor responses to stimulation.

Animals↗