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Biomedical subjects

N Mei

Publications and source records attributed to N Mei.

At least 19 recordsLinked to original sources

Effects of alverine citrate on cat intestinal mechanoreceptor responses to chemical and mechanical stimuli.

BACKGROUND: Alverine citrate is commonly used in the treatment of painful affections of the colon. AIM: To determine whether alverine citrate acts on the vagal sensory endings. METHODS: Unitary recordings were performed at the level of the vagal fibres in the nodose ganglion of anaesthetized cats using extracellular glass microelectrodes, and the patterns of response to chemical and mechanical stimuli applied to identified vagal intestinal mechanoreceptors were studied. RESULTS: The intestinal mechanoreceptors located at the endings of type C vagal fibres responded mainly to mechanical stimuli (distension and contraction), but also responded to chemical substances (cholecystokinin and substance P). The most conspicuous effect of alverine (2 mg/kg) was that it significantly inhibited the pattern of vagal activity produced in response to either cholecystokinin (5-10 microg/kg), substance P (5-10 microg/kg) or phenylbiguanide (5-10 microg/kg), a 5-HT3 receptor agonist. On the other hand, the unitary vagal response to the mechanical distension was slightly enhanced by alverine, as was any spontaneous activity present. CONCLUSIONS: Based on the present data, alverine citrate can be said to decrease the sensitivity of the intestinal mechanoreceptors, which is consistent with its previously established anti-spasmodic effects.

Animals↗

Influence of donor age on the cytotoxicity and mutagenicity of ethylnitrosourea in cultured human T-lymphocytes.

The effects of age on the cytotoxicity and mutagenicity of N-ethyl-N-nitrosourea (ENU) in human peripheral blood T-lymphocytes were investigated using colony-forming assay in vitro. ENU was shown to induce a dose-dependent increase in cell killing and in mutation frequencies (MF). No significant correlation between age and ENU-induced 6-thioguanine-resistant (TGr) MF at the hypoxanthine phosphoribosyl transferase (HPRT) locus of the X-chromosome was found after treatment with the same concentration of ENU (1 mM or 2 mM). There were also no significant differences among different donor age groups and the sensitivity parameters for exposure to ENU. As X-rays, the cytotoxic and mutagenic effects of ENU in cultured human T-lymphocytes appear not to be associated with age. These results suggest that the repair of mutagen-induced DNA lesions does not decline with age. Such knowledge has implications for risk assessment and protection against environmental mutagens.

Adolescent↗

Comparison of the frequency of T-cell receptor mutants and thioguanine resistance induced by X-rays and ethylnitrosourea in cultured human blood T-lymphocytes.

We have investigated two assays for measuring the induction of mutations using human T-lymphocytes isolated from leukocyte residue buffy coats obtained from normal donors. Variant cell frequency of T-cells defective in the T-cell receptor (TCR) gene expression was measured using a 2-color flow cytometry, and 6-thioguanine-resistant (TGr) cells were determined using a cloning technique at the HPRT gene after treatment with 250 kVp X-rays or ethylnitrosourea (ENU). The frequencies of TCR mutant cells as well as those of TGr cells increased with increasing doses of X-rays or concentrations of ENU studied. For TCR mutants, the induced mutation frequencies at D37 (giving 37% survival) were 31.7 x 10(-4) and 11.0 x 10(-4) for X-rays and ENU, respectively. For TGr T-cells, the induced mutation frequencies at D37 for the same mutagens were 14.4 x 10(-6) and 75.5 x 10(-6), respectively. Over the dose range studied the relationship appears to be linear between the mutation induction of TCR and that of TGr for X-rays or ENU. However, X-rays may induce more TCR mutants against less induction TGr T-cells, and ENU may cause a reverse result. The sensitivity of the assay of each biological endpoint in human blood T-lymphocytes may be different.

Adult↗

Involvement of the vagus nerve, substance P and cholecystokinin in the regulation of intestinal blood flow.

Intestinal blood flow was recorded in anesthetized rats and cats using laser-Doppler flowmetry (LDF). This new technique provides continuous and accurate measurements of the intestinal blood flow, without affecting the blood circulation. Electrical stimulation (1 ms, 5-30 V, 5-50 Hz) applied either afferent or efferent vagal fibres elicited changes in the intestinal blood flow consisting mainly of increases. Similar results were obtained upon applying chemical stimulation to intestinal sensory endings using cholecystokinin (CCK) or substrance P (SP; 10-20 micrograms/kg intravenously given). Bilateral vagotomy and atropine treatment markedly reduced or suppressed these vascular effects. In addition experiments in which the activation of gastrointestinal afferents were activated by applying electrical stimulation to the abdominal vagal nerves yielded similar results. Finally, these effects were reduced after selectively severing vagal afferents. It is concluded that intestinal blood changes may be triggered by activation of the sensory endings from the digestive organs through the vagal nerves.

Afferent Pathways↗

Individual variation and age dependency in the radiosensitivity of peripheral blood T-lymphocytes from normal donors.

To investigate individual variation and age dependency in normal cell radiosensitivity, we measured the in vitro radiosensitivity of cultured peripheral blood T-lymphocytes derived from 56 healthy male blood donors. Dose-survival tests using colony formation assay were done with exponential growing T-cells (day 3, PHA-stimulated cells). 6-Thioguanine (6-TG)-resistant mutation assays at the hypoxanthine phosphoribosyl transferase (HPRT) locus were done with G0 phase T-cells (day 0, unstimulated cells). The mean inactivation dose (MID) computed by integration of the fitted survival curves was 1.25 +/- 0.23 Gy (mean +/- SD). The X-ray dose required to kill 90% of the cells (D10) was 2.81 +/- 0.51 Gy. The MID ranged from 0.82 to 1.86 Gy with a coefficient of variation (CV) of 18%. The induced mutation frequencies (MF) per 10(6) cells at 2 Gy of X-rays ranged from 9.10 to 54.80 with a mean +/- SD value of 24.63 +/- 12.51 and a CV of 51%. It appears that the radiosensitivity of cell killing and mutagenicity varies among individuals. Although the spontaneous MF at the HPRT locus increases with age, the induced MF after exposure to 2 or 4 Gy of X-rays was not associated with age. Moreover, there were no significant correlations between age and MID values or the other dose-survival parameters. The findings indicate there is significant inter-individual variation in cellular radiosensitivity, but that in human T-lymphocytes aging does not affect the cytotoxic and mutagenic effects of X-irradiation.

Adolescent↗

Modification of radio-thermo-chemotherapy by AK-2123 and hydralazine in tumor bearing mice.

The effects of chemical modifiers of hypoxic radiosensitizer, a 3-nitrotriazole derivative AK-2123 (200 mg/kg) before treatment, and vasodilator of hydralazine (HDZ; 5.0 mg/kg) after treatment on tumor growth of SCCVII of mice were investigated in the radio-thermotherapy combined with mitomycin C (MMC; 2.0 mg/kg) or adriamycin (ADM; 3 mg/kg). The tumor treated by 10 Gy alone (tumor doubling time = 7.5 days), MMC alone (6.9 days), and hyperthermia (43 degrees C, 30 min; HT) alone (8.0 days) showed a slight growth delay (control: 5.6 days). Prolonged growth delay (23.2 days) was observed by MMC-radio-thermotherapy (MMC-10Gy/HT) than that (12.4 days) by 10 Gy/HT. The modification of MMC-radio-thermotherapy by HDZ administered between 10 Gy and HT (MMC-10 Gy/HDZ/HT) resulted in the significant prolongation of tumor growth delay (31.7 days). AK-2123 administration before this treatment, (MMC-AK-2123)-10 Gy/HDZ/HT), enhanced a further tumor growth delay (37.6 days) which is equal to that by 50 Gy alone and resulted in the highest dose modifying factor (DMF) of 5.2. While modification of ADM-radio-thermotherapy by AK-2123 and HDZ, (ADM-AK-2123)-10 Gy/HDZ/HT, gave the equal tumor growth delay to that by 30 Gy alone (DMF = 3.1). These high efficacies of radio-thermo-chemotherapy modified by AK-2123 and HDZ may be caused by tumor blood flow reduction.

Animals↗

Periodontal and gastric convergences within the hypothalamic ventromedial nucleus area--single unit study on anesthetized rats.

Unitary activities were recorded in the ventromedial nucleus of the hypothalamus (VHM) of anesthetized rats. Cells responding to periodontal stimulation (100-200 g disto-mesial traction applied to an upper incisive) were selected. The effects of gastric stimulation (2-5 ml distension) were then investigated. Out of the 40 cells activated (22 cells) or inhibited (18 cells) by periodontal stimulation, only seventeen were influenced by gastric stimulation. Eight of them responded in the same way and nine in the opposite way. Unlike the periodontal stimulation, which elicited specific spatio-temporal patterns, the gastric stimulation had only weak effects. These data nevertheless demonstrate that periodontal-gastric convergences exist in the VHM nucleus, which is consistent with the role previously ascribed to this area in alimentary behaviour.

Afferent Pathways↗

Current data and ideas on digestive sensitivity.

Remarkable advances have recently been made in the study of visceral sensitivity. Both electrophysiological and histological data emphasize the richness and the complexity of information elicited in the visceral area including the digestive tract. In addition these afferents are largely involved in physiological mechanisms which are not only restricted to the visceral area. The current knowledge of visceral sensitivity leads us to reconsider the classical ideas and concepts previously accepted in this field and raises questions to help gain a better comprehension of sensory physiology in general.

Animals↗

Intestinal effects of the products of lipid digestion on gastric electrical activity in the cat. Possible involvement of vagal intestinal receptors sensitive to lipids.

The relationship between the lipid content of the intestinal lumen and gastric motor activity was studied in anesthetized cats. For this purpose the electromyographic activity was recorded in the antrum whereas the small intestine (duodenum and first part of jejunum or ileum) was perfused with various solutions including calcium propionate, tributyrin, sodium caprylate, potassium oleate, mixtures containing linoleic acid, monolein, triolein, mixture of triglycerides, and glycerol. Long-chain lipids and glycerol both induced a decrease in the rate of basal antral activity. This effect was found to depend on the state of lipid hydrolysis (triglycerides, monoglycerides, and fatty acids) and was most marked with monolein, linoleic acid, and glycerol. With the middle-chain lipids used, these effects were only slight; short-chain lipids did not induce any visible changes in gastric activity. All these effects were prevented by cervical bivagotomy. It was concluded that the two types of lipid-sensitive vagal receptors, which we recently showed to exist in the small intestine, trigger an inhibitory enterogastric reflex that contributes to the regulation of gastric emptying.

Animals↗

Effects of periodontal stimulation on VHM neurones in anesthetized rats.

In anesthetized rats, mechanical stimulations, the direction and intensity of which could be modified, were applied to the superior incisive while single neurone activities were recorded within the VHM region by means of extracellular glass microelectrodes. The great sensitivity of periodontal receptors to the direction and the intensity of the stimulations was demonstrated at this level. This finding, which is reported here in detail for the first time, suggests that the periodontal afferents might be involved in physiological mechanisms including food intake regulation and osteomorphogenesis.

Action Potentials↗

[Intestinal sensitivity disorders and irritable bowel syndrome].

Long neglected in the past, the study of visceral sensitivity (interoception) has progressed in recent years because of advances in neurobiological techniques. Dealing with the structure or the function of single neurons, these techniques have profoundly increased our knowledge about the sensitive mechanisms in the digestive tract. According to recent data, the visceral sensitivity organs are richer and more complex than imagined previously. Microphysiological techniques have shown that intestinal sensitive terminations are capable of transmitting information concerning visceral activity and physicochemical modifications of intestinal contents directly to the central nervous system. This means that visceral sensitivity intervenes under physiological as well as pathological conditions. This notion is new and of great interest. As progress was being made concerning the morphologic and electrophysiologic aspects and contemporaneous studies were establishing the richness of visceral, and particularly, intestinal, sensitive receptors, basic science research in humans and animals have emphasized the diversity of the implication of the extrinsic nervous system in pain, regulation of digestive motility, homeostasis and alimentary behaviour. Our present knowledge on the nervous and neurohumoral mechanisms has shed new light on the determinisms in digestive tract pathology. This is especially true in the irritable bowel syndrome which can be considered as an extrinsic nervous system derangement. Due to abnormal sensitivity by modification of the threshold values of sensitivity to distension, and/or to stimulation by substances such as cholecystokinin, for example, motor disorders occur. Other factors, such as stress, can be responsible for revelation or exacerbation of neurohumoral disorders.

Colonic Diseases, Functional↗

[Morphologic and functional peculiarities of the visceral protoneuron reexamined in light of recent data].

The recent works showing the richness and complexity of the sensory innervation of viscera raise various questions which are of general interest for modern physiology. 1 - The primary afferent neurons are much more numerous and heterogeneous than it was usually expected. Moreover, another category of neurones, namely the sensory intrinsic neurons, must be taken in consideration. These neurones end either in the intrinsic plexuses of viscera or in the prevertebral ganglia. 2 - Another major question concerns the mechanisms responsible for the functional diversity of interoceptors including the chemoreceptors. Several hypothesis have been proposed involving the presence of membrane receptors, the release of neurotransmitters by chromaffin cells and the deformation of tissue. In any way, the functional characteristics of interoceptors do not result in morphological differentiation since free endings are mainly found in the visceral area. 3 - Does the functional properties of primary afferent neurons are related to their morphological (diameter of fibres, size of cell bodies) or their biochemical (type of neurotransmitters) characteristics? So far, it is not possible to answer this question. Nevertheless the available data suggest that a such relationship partly exists. 4 - The visceral afferents are largely implicated in various physiological mechanisms involving visceral motility, homeostasis and behaviour. Therefore, their role in pain appear relatively less important than previously expected. Conversely, the nervous mechanisms induced by the interoceptor activation play a major part in that they prepare and potentialize the effects produced by the other mechanisms.

Animals↗

Laryngeal afferents activated by phenyldiguanide and their response to cold air or helium-oxygen.

In anesthetized cats, sensory neurons in the superior laryngeal nerves (SLN) were identified with respect to their response to (1) phenyldiguanide (PDG) i.v., (2) mechanical stimulation and (3) lowering temperature in an isolated tracheolaryngeal segment. The activity originating from 107 SLN afferent units activated by PDG was recorded using glass microelectrodes advanced in the nodose ganglion. All tested afferent units increased their discharge rate during direct touching of the airway mucosa. None showed flow or pressure related activity during abrupt changes in constant laryngeal flow or transmural pressure in the isolated segment. Fifteen units were inhibited by cold air. Sixty-two units significantly increased their firing rate when the temperature approached 18 degrees C, reached a peak discharge near 15 degrees C, then their activity decreased or stopped. The response to cold air was compared to cold heliox (79% He-21% O2), which enhanced the respiratory heat loss by conduction. The peak firing rate was significantly higher with heliox (+356% compared to +246% with air), the temperature threshold higher (25 degrees C +/- 1.0 degree C) and the temperature range broader (25-11.5 degrees C). Present results show that a large proportion (58%) of afferent SLN fibres activated by PDG are likely non-proprioceptive units, which are stimulated by cooling the inspired gas. Thermosensitive units in the upper airways may act as sensors of the thermal flux through the airway wall more than as detectors of the absolute value of temperature in the airway lumen.

Action Potentials↗

Osmosensitive vagal receptors in the small intestine of the cat.

In anesthetized cats, the unitary activity of 66 sensory vagal neurones was recorded with extracellular glass microelectrodes implanted in the nodose ganglia. These neurones had non-medullated afferent fibres with conduction velocities between 0.8 and 1.2 m/s, as do most of the intestinal vagal fibres, and were silent or fired at low frequencies before any simulation. They were activated by perfusion of the small intestine (duodenum and first part of jejunum) with tap water and various solutions (glucose, NaCl and mannitol, in particular) having osmotic pressures ranged between 4 and 1100 mOsm. In general, hypotonic solutions and tap water induced the more marked responses, but differences were observed according to the solution used. Most of these neurones were also excited by other forms of stimulation including stroking of the mucosa and perfusion with warm (39-55 degrees C) and acid (HCl at pH 1) solutions. Therefore they must be considered to be polymodal receptors sensitive to osmotic pressure. The short latency of responses elicited by osmotic stimulations, the marked sensitivity to mucosal stroking and the disappearance of nervous activity after local anesthesia indicate that these receptors are located close to the epithelium. The role of these osmosensitive endings is discussed. Analysis of their general characteristics suggests that they may be involved in the inhibitory entero-gastric reflex modulating gastric emptying.

Action Potentials↗

Further data on the inhibitory enterogastric reflex triggered by intestinal osmotic changes in cats.

The relationship between osmotic pressure in the intestinal lumen and gastric motor activity was studied in anesthetized cats. For this purpose the EMG was recorded in the antrum while the small intestine (duodenum and the first part of jejunum) was perfused with various solutions: tap water (5 mOsm), NaCl, mannitol and glucose having an osmotic pressure of 70, 138, 275, 550 or 1100 mOsm. Hypotonic and hypertonic solutions both induced a decrease in the gastric activity, i.e. an increase in period of electrical control activity. This effect was found to depend both on the osmolarity value (the osmotic pressures furthest removed from the isotonic value produced the greatest effect) and on the substance used (glucose, mannitol and NaCl, in decreasing order of efficiency). The isotonic solution of glucose and, to a lesser extent, of mannitol was also active, unlike the isotonic solution of NaCl. All these gastric changes were prevented by cervical bivagotomy. It was concluded that the vagal osmosensitive receptors located in the small intestine trigger this inhibitory enterogastric reflex which probably constitutes an important part in the regulation of gastric emptying.

Action Potentials↗

[Role of the autonomous nervous system in the regulation of the transit, absorption and storage of nutriments].

The possible role of the autonomic nervous system (ANS) in nutrition must be reevaluated in view of recent experimental data. The ANS plays a major part in both initiating and maintaining peristalsis and in coordinating gastrointestinal motility. Intestinal absorption involves extra-epithelial mechanisms such as motility and vasomotricity of the digestive tract. In addition, the ANS (sympathetic fibres) might act directly on enterocytes, or indirectly via the intestinal plexuses through a glucose-dependent mechanism. The control of exocrine and endocrine secretions depends partly on the ANS. In particular the mucous mechanoreceptors, chemoreceptors and thermoreceptors located in the intestinal area supply the sensory information needed in that kind of regulation. The efferent fibres of the ANS intervene in the control of storage of carbohydrates in the liver and of lipids in brown adipose tissue. On the other hand, gastrointestinal afferents might be implicated in this mechanism through the hypothalamic ventro-median nucleus. Finally, these data are consistent with a modern conception suggesting that the ANS is largely involved in the regulation of visceral motility, homeostasis and alimentary behaviour.

Adipose Tissue, Brown↗