Biomedical subjects
Publications and source records attributed to M T Lin.
The level of somatostatin in the hypothalamus was higher in satiated rats than in hungry rats. Elevating hypothalamic somatostatin levels by administering somatostatin into the hypothalamus produced a decrease in food intake, whereas lowering hypothalamic somatostatin levels by administering cysteamine into the peritoneal cavity produced an increase in food intake in rats.
(1) The changes in rectal temperature produced by an injection of a bacterial endotoxin piromen (10-40 ng in 1.0 microliter) on somatostatin-14 (SS-14; 0.1-0.3 microgram in 1.0 microliter) into the preoptic anterior hypothalamic area were assessed and compared in control rats, in rats with hypothalamic SS depletion, and in rats with hypothalamic SS receptor blockade. (2) Intrahypothalamic injection of either piromen or SS-14 produced a dose-related rise in rectal temperature in intact, control rats. The fever induced by intrahypothalamic injection of piromen or SS-14, as well as that induced by intraperitoneal injection of piromen, was antagonized by pretreatment of the hypothalamus with a SS-14 receptor antagonist (0.1 ng in 1.0 microliter) in rats. (3) On the other hand, intraperitoneal administration of cysteamine (30-100 mg/kg), in addition to producing a dose-related fall in rectal temperature, also caused a dose-related fall in hypothalamic SS-levels in rats. Furthermore, the fever induced by intrahypothalamic injection of piromen, but not SS-14, was antagonized by depletion of hypothalamic SS levels with an intraperitoneal dose of cysteamine (30 mg/kg). (4) The results indicate that a somatostatinergic pathway in the hypothalamus may mediate endotoxin-induced fever in the rat.
The changes in both the thermoregulatory responses and brain somatostatin (SS) levels produced by ambient temperature (Ta) changes were assessed in rats after they had been equilibrated to each of the Ta for a period of about 90 min. Cold exposure, in addition to elevating hypothalamic SS-levels, led to increased metabolism and cutaneous vasoconstriction at Ta = 8 degrees C. In contrast, heat exposure, in addition to lowering hypothalamic SS-levels, resulted in decreased metabolism and cutaneous vasodilation at Ta = 30 degrees C. Rats were chronically implanted with a hypothalamic cannula to allow intrahypothalamic injection of SS on the conscious rats. Direct administration of SS (0.1-0.3 micrograms) into the preoptic anterior hypothalamic area caused a dose-related rise in colon temperature at three Ta tested. The SS-induced hyperthermia was produced by increased metabolism at Ta = 8 degrees C, whereas at Ta = 30 degrees C, it was caused by cutaneous vasoconstriction. At Ta = 22 degrees C, the hyperthermia was caused by increased metabolism and cutaneous vasoconstriction. Systemic administration of cysteamine, in addition to lowering hypothalamic SS-levels, produced a dose-related fall in colon temperature at Ta of 8 degrees C and 22 degrees C. The hypothermia induced by cysteamine was produced by decreased metabolism at Ta = 8 degrees C, whereas at Ta = 22 degrees C, it was caused by both decreased metabolism and cutaneous vasodilation. The data indicate that the hypothalamic SS-levels mediate normal body temperature responses in rats.
The effects of intravenous administration of adrenoceptor agonists and antagonists on relative cerebral blood flow, cerebral perfusion pressure, intracranial pressure, mean arterial blood pressure and heart rate were assessed in rats under urethane anesthesia. Administration of phenylephrine (a preferential alpha 1-adrenoceptor agonist), adrenaline (a mixed alpha/beta-adrenoceptor agonist), noradrenaline (a mixed alpha/beta-adrenoceptor agonist) raised mean arterial pressure, cerebral perfusion pressure, cerebral blood flow and intracranial pressure, but lowered heart rate. On the other hand, administration of isoproterenol (a beta-adrenoceptor agonist), phentolamine (an alpha-adrenoceptor antagonist) or propranolol (a beta-adrenoceptor antagonist) lowered mean arterial pressure, cerebral perfusion pressure or cerebral blood flow. In addition, phentolamine raised both intracranial pressure and heart rate, whereas propranolol lowered both intracranial pressure and heart rate. However, isoproterenol produced a decrease in heart rate, without affecting intracranial pressure. There was no significant difference between the groups of animals for PCO2, PO2 or pH throughout the studies. The results suggest that adrenoceptor agonists or antagonists act through breakthrough of autoregulation, with acute hypertension or hypotension, to enhance or to reduce cerebral blood flow in rats.
The effects of depleting the tissue catecholamines with alpha-methyl-p-tyrosine (AMPT, an inhibitor of catecholamine synthesis) on the splenic NK cell cytotoxic activity were assessed both in vivo and in vitro. Treatment with i.p. doses of AMPT (3-500 mg/kg) produced a dose-related suppression in the splenic NK cytotoxic activity in many mouse strains. For an i.p. dose of 300 mg/kg of AMPT, the splenic NK cell activity began to fall 1 h after AMPT injection. The splenic NK cell activity reached its maximal level at 3 h, accompanied by a severe depletion of norepinephrine contents in the spleen. Both the NK activity and the splenic norepinephrine content returned to their control levels at 24 h. Direct addition of AMPT (up to 2500 micrograms/ml) to the cultured mouse spleen cells in vitro resulted in no NK suppression. However, when the serum obtained from the AMPT-treated mice was added to the cultured mouse spleen cells of the AMPT-untreated mice, the splenic NK cytotoxic activity was greatly suppressed. In addition, natural killing by spleen cells from AMPT-untreated mice was not reduced by the addition of spleen cells from AMPT-treated mice. No evidence of AMPT-induced cellular suppressors of natural killing could be detected. It was also found that both the splenic NK cell activity and the effector-target cell conjugation activity were suppressed by treatment with AMPT. These observations indicate that depleting the tissue catecholamines with AMPT results in the release of certain humoral factors which can suppress both the effector-target cell conjugation activity and the splenic NK cell activity in mice.
Both thyrotropin-releasing hormone (TRH) levels in the hypothalamus and thermoregulatory responses were assessed in rats after they had been equilibrated to each of three ambient temperatures (Ta: 8, 22 and 30 degrees C) tested. Cold exposure, in addition to elevating TRH levels in the hypothalamus, led to increased metabolism and cutaneous vasoconstriction in rats at Ta = 8 degrees C. In contrast, heat exposure resulted in decreased metabolism and cutaneous vasodilatation in rats accompanied by no change in hypothalamic TRH levels at Ta = 30 degrees C. In addition, rats were chronically implanted with a cerebroventricular cannula to allow administration of the pyrogenic substance polyriboinosinic acid-polyribocytidylic acis (Poly I:C) into the brain at Ta = 22 degrees C. Intracerebroventricular administration of Poly I:C, in addition to elevating hypothalamic TRH levels, produced a fever with a latency of onset of about 30 min. The fever induced by Poly I:C was brought about by increased metabolism and cutaneous vasoconstriction in rats. The results suggest that either cold stress or Poly I:C injection elevates TRH levels in rat hypothalamus and thus induces thermogenic reactions.
The antiangiogenic activity of several steroid eye drops was evaluated in a PGE-induced corneal neovascularization. Pred-Forte (1% prednisolone acetate) and Maxidex (0.1% dexamethasone) were very effective in preventing neovascularization. Medroxyprogesterone acetate at 0.1% in Tears Naturale was moderately effective and fluorometholone was less effective in blocking neovascularization. Cortisone alone was not very effective; however, the addition of heparin greatly enhanced its inhibitory effect. PGE1 induced corneal neovascularization and increased the leukocytes infiltration. The application of Maxidex right after the implantation of PGE1 pellet not only inhibited the leukocytes infiltration, but also blocked the neovascularization. These results suggested that the leukocytes infiltration might be one of the factors contributing to the development of neovascularization. The effect of steroid eye drops on the growth of preformed capillaries was also evaluated. The result demonstrated that Pred-Forte also suppressed the growth of well-developed capillaries.
The influence of cold stress, heat stress, or various agents on the development of brain edema were assessed in rats following a cryogenic brain lesion. Brain edema was induced by local cold injury to the cortex. Cerebral edema was assessed 0.5, 3.0 or 24 h after a cryogenic brain lesion by measuring the water content of two hemispheres. Pretreatment of animals with sodium pentobarbital (15 or 30 mg/kg, i.p.) or lidocaine (15 mg/kg, i.p.) did not influence the development of brain edema. In addition, pretreatment with an external heat stress (heat exposure of 32 degrees C for 6 h) exaggerated significantly the development of brain edema in the rat following a cryogenic brain lesion. On the other hand, pretreatment of animals with either external cold stress (cold exposure of 8 degrees C for 6 h), glycerol (10% 10 ml, i.p.), mannitol (15% 10 ml, i.p.), gamma-hydroxybutyric acid (300 mg/kg, i.p.), metiamide (5 mg/kg, i.p.), dexamethasone (4 mg/kg, i.p.), aminophylline (100 mg/kg, i.p.), or ketamine (30 mg/kg, i.p.) inhibited significantly the brain edema formation.
Scrub typhus (tsutsugamushi disease) is an acute infectious disease caused by Rickettsia tsutsugamushi transmitted through the bite of larvae of certain trombiculid mites. Geographical distribution in Asian-Pacific region is much of the roughly triangular area bounded by Japan, Pakistan and Australia. It is an endemic illness in the Pescadores Islands, but has scarcely been reported in central Taiwan. An eleven-year-old boy was admitted to Changhua Christian Hospital with the chief complaints of fever, lethargy and skin rash for seven days. On physical examination, he was found to have painless eschar, conjunctivitis, meningoencephalitis, pneumonitis, ascites, jaundice, hepatomegaly, liver function impairment and thrombocytopenia. His Proteus OX-K agglutinin titer increased from 1:160 in the acute sera to 1:640 in the convalescent sera. A greater than four-fold rise (greater than 1:640) in antibody titers to Karp, Gilliam, Kato strains of R. tsutsugamushi between acute and convalescent sera were demonstrated by immunofluorescent antibody. The patient was treated with minocycline and chloramphenicol and was completely recovered.
1. The effects of microinjection of 5-hydroxytryptamine (5-HT) or its antagonists methysergide (a 5-HT1 receptor antagonist), cyproheptadine (a mixed 5-HT1/5-HT2 receptor antagonist), or ketanserin (a 5-HT2 receptor antagonist) into the preoptic anterior hypothalamus on thermoregulatory responses were assessed in conscious rabbits at different ambient temperatures (Ta). 2. Intrahypothalamic injection of 5-HT caused dose-dependent hypothermia in rabbits when the Ta was 2 degrees C and 22 degrees C. At 2 degrees C the hypothermia was due to decreased metabolism, whereas at 22 degrees C the hypothermia was due to increased peripheral blood flow and increased respiratory evaporative heat loss. 3. In contrast, administration of either cyproheptadine, methysergide or ketanserin into the 5-HT-sensitive sites in the preoptic anterior hypothalamus caused dose-dependent hyperthermia in rabbits when the Ta was 2 degrees C, 22 degrees C and 32 degrees C. At 2 degrees C the hyperthermia was due to increased metabolism, whereas at 32 degrees C the hyperthermia was due to decreased peripheral blood flow and decreased respiratory evaporative heat loss. At 22 degrees C, the hyperthermia was due to increased metabolism and decreased peripheral blood flow. 4. For a given intrahypothalamic dose (e.g. 15-20 micrograms), either methysergide, cyproheptadine or ketanserin produced the same degree of rectal temperature elevation (e.g. about 1.4 degrees C) in rabbits. Thus, there did not appear to be any association between hypothalamic 5-HT receptor types and thermoregulation. 5. However, the present results suggest that hypothalamic 5-HT receptors mediate thermoregulatory responses in the rabbit.(ABSTRACT TRUNCATED AT 250 WORDS)
In two children with chronic idiopathic thrombocytopenic purpura (ITP) a transient remission of thrombocytopenia was observed after intercurrent measles infection. Both cases were girls who had a long history of thrombocytopenia. During acute measles infection, the delayed hypersensitivity response was suppressed. Total T lymphocytes, T-cell subsets, especially OKT4 cells, the lymphoproliferative response, and interleukin-2 (IL-2) and gamma-interferon production were decreased accompanying normalization of the OKT4/OKT8 ratio. However, OKT4 cells remained at a reasonably low level and the lymphoproliferative response stimulated with pokeweed mitogen was still in the lower normal range. Direct immunofluorescent study demonstrated that the measles antigen was present in the mononuclear cells, especially OKT4 cells. The levels of platelet-associated IgG antibody (PAIgG) and IgG circulating immune complex (CIC) were undetectable. One month later, the OKT4/OKT8 ratio lymphoproliferative response significantly increased, IL-2 and gamma-interferon production increased, and PAIgG and IgG CIC reappeared with the relapse of thrombocytopenia. There was also a significant increase in in vitro IgG production due to the presence of patient OKT8 cells and/or OKT4 cells. However, there was no enhancement in the presence of patient B cells. This suggests that the presence of specific OKT4 helper T cells and a defect in the suppressor function of suppressor OKT8 cells contribute to an overproduction of IgG and the appearance of PAIgG accompanied by thrombocytopenia. The transient remission associated with measles infection is probably related to the effect of the virus on the helper T cells, resulting in a decrease in specific OKT4 helper T cells and normalization of the OKT4/OKT8 ratio, suppression of IL-2 and gamma-interferon production, and platelet-associated IgG production.
The antinociceptive role of spinal serotonin (5-HT) neurons descending from 5-HT cells near the ventrolateral surface of the medulla oblongata was investigated by stimulating these cells in normal rats, in rats with generalized or selective chemical ablation of 5-HT nerves, and in rats with postsynaptic blockade of 5-HT receptors. Electrical stimulation of the lateral medulla elicited analgesia in normal rats; the increase in pain threshold was proportional to the intensity and to the frequency of stimulation. In addition, microinjection of kainic acid or L-glutamate at the same sites also produced analgesia. However, generalized destruction of CNS 5-HT nerves produced by intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) or selective destruction of spinal 5-HT nerves produced by intraspinal injection of 5,7-DHT reduced the magnitude of the antinociceptive responses to electrical stimulation. Postsynaptic blockade of CNS 5-HT receptors produced by intraventricular injection of cyproheptadine also reduced the stimulation-produced analgesia. The specificity of the lesions for 5-HT nerves is demonstrated by the lack of effect on the levels of noradrenaline in the same brain regions. The results indicate that the activity of 5-HT nerve cells adjacent to the ventrolateral surface of the medulla oblongata and projecting to the spinal cord serves to elevate pain threshold.
The effects of intracerebral administration of interferon (IFN) or its inducer polyriboinosinic acid-polyribocytidylic acid (poly I:C) on thermoregulatory responses were assessed in conscious rabbits. Administration of IFN (10(2)-10(6) IU) or poly I:C (0.012-12 micrograms) into the preoptic anterior hypothalamus or the third cerebral ventricle caused a dose-dependent fever in rabbits at three ambient temperatures (Ta) tested. In the cold (Ta = 8 degrees C), the fever was due to increased metabolism, whereas in the heat (Ta = 32 degrees C) the fever was due to a reduction in respiratory evaporative heat loss and ear skin blood flow. At the moderate environmental temperature (Ta = 22 degrees C), the fever was due to increased metabolism and cutaneous vasoconstriction. Compared with the febrile responses induced by cerebroventricular route injection of IFN or poly I:C, the hypothalamic route of injection required a much lower dose of IFN or poly I:C to produce a similar fever. Furthermore, the fever induced by intrahypothalamic injection of IFN or poly I:C was reduced by pretreatment of animals with a systemic dose of indomethacin (an inhibitor of all prostaglandins formation) or cycloheximide (an inhibitor of protein synthesis). The data indicate that IFN or its inducer may act through the endogenous release of a prostaglandin or a protein factor of an unknown chemical nature in the preoptic anterior hypothalamic region to induce fever in rabbits. The fever induced by IFN or its inducer is brought about by a decrease in heat loss and/or an increase in heat production in rabbits.
In the presented studies, both the spontaneous motor activity and the locomotor responses to amphetamine challenge were assessed in normotensive rats and in hypertensive rats. As compared to their appropriate controls, both experimentally (either renal or deoxycorticosterone salt) hypertensive rats and spontaneously hypertensive rats maintained a higher level of spontaneous motor activity. In addition, intraperitoneal administration of amphetamine produced stimulation of forward locomotion, and head and body rearing (as shown by an increase in gross movements) and increased grooming and sniffing (as shown by an increase in fine movements). It was also found that either experimentally or spontaneously hypertensive rats displayed a greater degree of locomotor stimulant responses to amphetamine administration as compared to their appropriate controls. The results indicate that the mechanisms underlying the pathogenesis of hypertension may be related to the development of locomotor hyperactivity in rats.
Rats with portacaval shunt, although showing no changes in their spontaneous pain threshold, did display an increased sensitivity of analgesic responses to morphine injection. In addition, these portacaval-shunted animals had a lower level of spontaneous motor activity and a reduced sensitivity of locomotor stimulant responses to amphetamine administration. However, these portacaval-shunted animals displayed same thermoregulatory responses to various ambient temperatures as those of normal unoperated or sham-operated animals. Biochemical examination revealed that these portacaval-shunted animals had a higher indoleamine synthesis in both the hypothalamus and the brain stem, but had a lower catecholamine synthesis in both the hypothalamus and the corpus striatum. The data suggest that alterations in antinociceptive and locomotor stimulant responses of the portacaval-shunted animals correlate with patterns of monoamine synthesis in different brain regions (patterns that differed from those observed in normal unoperated animals or in sham-operated animals).
The effects of changes in central serotoninergic transmission on clonidine analgesia were assessed in monkeys. The minimum electrical current required for producing jaw opening is referred to as the pain threshold. Pain was induced by electrical stimulation of tooth pulp afferents. In the first series of studies, intracerebroventricular administration of clonidine (5-30 micrograms) produced dose-dependent analgesia in monkeys. The clonidine-induced analgesia was abolished or attenuated by prior injection of the animals with p-chlorophenylalanine or 5,7-dihydroxytryptamine into the third cerebral ventricle. On the other hand, pretreatment of the animals by injecting 5-HT or its precursor 5-hydroxytryptophan into the cerebral ventricle potentiated the clonidine-induced analgesia in monkeys. In the second series of experiments, administration of clonidine (1-10 micrograms) into the diencephalic periventricular gray (of the anterior hypothalamic portion), the periaqueductal gray, or the dorsal raphe nuclei also produced dose-dependent analgesia in monkeys. The analgesia induced by clonidine injection into the diencephalic periventricular gray or the periaqueductal gray was effectively antagonized by pretreatment of the animals by injecting two 5-HT receptor antagonists (such as ketanserine and methysergide) into the diencephalic periventricular gray or the periaqueductal gray. The clonidine-induced analgesia in monkeys was not affected by pretreatment of the animals with injections of either ketanserine or methysergide into the dorsal raphe nuclei. The results suggest that the functional activity of central 5-HT neurons correlate well with the analgesic sensitivity of clonidine microinjected centrally. In addition, the analgesia induced by clonidine microinjected into the diencephalic periventricular gray or the periaqueductal gray was mediated by the 5-HT receptors at the site of injection.
The effects of analgesic, thermoregulatory and endocrine functions of administering morphine sulphate (0.3 mg) into the lateral cerebral ventricle via an Ommaya catheter were assessed in eight patients with cancer pain. Satisfactory control of intractable pain was obtained in these patients, without any change in other sensory modalities. The delay in the onset of pain relief and the duration of analgesia ranged, respectively, from 20 to 40 min and from 12 to 16 h after drug injection. In addition, intraventricular administration of morphine caused a reduction in rectal temperature in these patients at an ambient temperature of 24 degrees C. The hypothermia in response to the injection of morphine was due to cutaneous vasodilation and sweating. There was no change in metabolism or in respiratory evaporative heat loss after morphine injection. Further, 10 to 20 min after intraventricular administration of morphine, the blood levels of prolactin, growth hormone and glucose were elevated in these patients. The changes in temperature and endocrine levels lasted for 1-3 h. In addition to the pain relief, these side-effects of morphine treatment were short-lasting and disappeared as the morphine treatment continued. The results indicate that activation of opiate receptors in the brain produced pain relief, hypothermia (due to cutaneous vasodilation and sweating), and increased blood levels of prolactin, growth hormone and glucose in patients with cancer pain.
To explore the mode of the locomotor stimulant action of thyrotropin-releasing hormone (TRH), rats with or without administration of opiate or catecholaminergic receptor antagonists were infused with TRH through previously implanted hypothalamic cannula. Administration of TRH, but not the normal saline or TSH, into the ventromedial hypothalamus caused an enhancement in both the gross movements (including stimulation of forward locomotion, head and body rearing) and fine movements (including increased grooming and head swaying). The locomotor stimulant action provoked by TRH was antagonized by pretreatment of ventromedial hypothalamus with either an alpha-adrenergic receptor antagonist (yohimbine), a dopaminergic receptor antagonist (haloperidol) or an opiate receptor antagonist (naloxone), but not with a beta-adrenergic receptor antagonist (propranolol). The results indicate that all the adrenergic, dopaminergic and opiate receptors in the ventromedial hypothalamus are involved in the TRH-induced hyperactivity in the rat.