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T Unno

Publications and source records attributed to T Unno.

At least 55 records · Page 3Linked to original sources
PubMed1996

Modulation of peristalsis by neurotensin in isolated guinea-pig intestinal segments.

Neurotensin (1-100 nM) produced an inhibitory effect and an excitatory effect on the peristaltic activity elicited by intraluminal distension using the Trendelenburg method or the intraluminal perfusion method in isolated segments of guinea-pig small intestine. The relative contribution of these effects to the overall effect varied from one region to another of the small intestine. In the Trendelenburg preparation, the excitatory effect was found to be accompanied by a decrease in the threshold intraluminal pressure required to trigger a peristaltic reflex. A substantial difference between the jejunum and the ileum was noted in that neurotensin-induced stimulation of peristaltic activity was observed in a smaller number of the segments in the jejunum than in the ileum. A nonpeptide neurotensin receptor antagonist, SR 48692, 2-[(1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl) pyrazol-3-yl)carbonylamino]tricyclo(3.3.1.1.(3.7))decan++ +-2-carboxylic acid (90 nM), abolished both the inhibitory and excitatory effects. Apamin (10 nM) abolished the inhibitory effect. From these results, neurotensin appears to exert both excitatory and inhibitory actions, via its receptors sensitive to SR 48692, on peristaltic activity in guinea-pig small intestine. The excitatory action varies with an increasing gradient toward the terminal end of the small intestine, and the inhibitory action involves apamin-sensitive mechanism.

Animals↗
PubMed1996

Carbachol-induced [Ca2+]i oscillations in single smooth muscle cells of guinea-pig ileum.

1. Changes in cytosolic Ca2+ concentration ([Ca2+]i) produced by carbachol (CCh) were measured in single smooth muscle cells of guinea-pig ileum using a Ca(2+)-sensitive fluorescent dye, fura-2, to clarify the underlying mechanisms of muscarinic [Ca2+]i oscillations. 2. Half of the cells, when exposed to 0.2 microM CCh, exhibited repeated changes in [Ca2+]i giving a serrated appearance. The oscillatory changes in [Ca2+]i were very similar to those evoked by increasing extracellular K(+) concentration ([K+]o) to 30 mM, which were abolished by removal of extracellular Ca2+, nifedipine and La3+, but remained unchanged after depletion of internal Ca2+ stores with cyclopiazonic acid, thapsigargin and ryanodine. 3. Every individual [Ca2+]i oscillation was just like a [Ca2+]i increase generated spontaneously in about 8% of cells or triggered by an action potential evoked by a current pulse in current-clamped cells. 4. In the remaining half of the cells exposed to 0.2 microM CCh, slower [Ca2+]i oscillations were elicited and every individual [Ca2+]i oscillation was always preceded by the fast brief increase in [Ca2+]i. 5. [Ca2+]i oscillations elicited by 2 microM CCh were temporally and functionally distinct from those induced by high [K+]o. They were more or less regular in the periodicity and pattern, comprised pacemaker potential-like [Ca2+]i increases or sinusoidal types of [Ca2+]i increases, and could be elicited even in 100 mM K+(o). 6. Removal of extracellular Ca2+ or application of nifedipine, methoxyverapamil (D600), diltiazem or La3+ during CCh (2 micro M)-induced [Ca2+]i oscillations caused them to disappear. In cells i which internal Ca2+ stores were depleted, 2 microM CCh did not evoke [Ca2+]i oscillations but occasionally induced single or repeated generation of the increase in [Ca2+]i with a serrated appearance. 7. The results indicate that CCh can induce two types of [Ca2+]i oscillation in guinea-pig ileal smooth muscle cells; one arises from Ca2+ influx associated with action potential discharges and the other from periodic release of Ca2+ from internal stores. The latter [Ca2+]i oscillation requires extracellular Ca2+ to sustain it.

Animals↗
PubMed1996

Some evidence against the involvement of arachidonic acid in muscarinic suppression of voltage-gated calcium channel current in guinea-pig ileal smooth muscle cells.

1. To see if arachidonic acid (AA) plays a role in the sustained suppression of voltage-gated calcium channel currents produced by muscarinic receptor stimulation by carbachol (CCh), the effects of AA on membrane currents were examined in whole-cell voltage-clamped smooth muscle cells of the guinea-pig ileum. 2. In cells bathed in Ba2+ PSS and dialysed with Cs(+)-based low EGTA (0.05 mM) pipette solution, and in which Ba2+ current (IBa) flowing through voltage-gated calcium channels was evoked repeatedly by stepping to 0 mV from the holding potential of -60 mV, AA (1-30 microM), applied extracellularly, gradually suppressed IBa in a concentration-dependent manner. The IBa suppression was observed even with 20 mM EGTA in the pipette. 3. AA (3 microM) and CCh (10 microM) shifted the voltage-dependent inactivation curve of IBa in the negative potential direction, but the effect of AA differed from that of CCh in that an accompanying appreciable decrease in the slope was observed. 4. The sustained suppression of IBa induced by CCh (10 microM) remained almost unaltered after pretreatment with 4-bromophenacyl bromide (10 microM), an inhibitor of phospholipase A2, or a combination of indomethacin (10 microM), an inhibitor of the cyclo-oxygenase pathway, and nordihydroguaiaretic acid (10 microM), an inhibitor of the lipoxygenase pathway. 5. In cells bathed in Ca2+ PSS and dialysed with K(+)-based pCa 6.5 pipette solution, voltage-dependent Ca2+ current (ICa) and K+ current (IK) were recorded simultaneously. AA (3 microM) suppressed IK as well as ICa, whereas CCh (10 microM) suppressed ICa but not IK. 6. We conclude from these results that AA or its metabolite is unlikely to be involved in the sustained suppression of voltage-gated calcium channel current induced by muscarinic receptor stimulation in guinea-pig ileal smooth muscle cells.

Animals↗
PubMed1996

Modulation of carbachol-induced [Ca2+]i oscillations by Ca2+ influx in single intestinal smooth muscle cells.

1. Oscillations of cytosolic Ca2+ concentration ([Ca2+]i) evoked by carbachol (CCh; 2 microM), a muscarinic agonist, were detected as oscillatory changes of muscarinic receptor-coupled cationic current (Icat) in guinea-pig ileal smooth muscle cells by the whole cell patch-clamp technique. 2. Reduction of extracellular Ca2+ from 2 mM to 0.2 or 0.05 mM, during CCh-induced Icat oscillations, caused them to disappear or to decrease markedly in frequency. A return to 2 mM Ca2+ concentration restored the initial Icat oscillations. 3. Application of nifedipine (1-3 microM) or D600 (2-5 microM) to block the voltage-gated Ca2+ channel (VGCC) decreased the frequency of the ongoing Icat oscillations in the cells held at -20 mV, but it was without effect in cells held at -60 mV. 4. Displacement of the holding potential of -20 mV to -60 mV to deactivate VGCC produced a decrease, an increase or no noticeable change in the frequency of the Icat oscillations in different cells. Displacement to 20 mV to inactivate VGCC invariably produced a decrease in the frequency. In nifedipine-treated cells, the Icat oscillations varied in frequency voltage-dependently in a reverse and linear way within the range -80 to 40 mV. 5. Application of thapsigargin (1 or 2 microM), an inhibitor of Ca(2+)-ATPase in the membrane of internal Ca2+ stores, caused CCh-induced Icat oscillations to disappear with a progressing phase during which their amplitude, but not frequency, declined. 6. The results suggest that membrane Ca2+ entry has a crucial role to play in regulation of the frequency of CCh-induced [Ca2+]i oscillations in addition to persistence of their generation, and that the effect is brought about by a potential mechanism independent of Ca2+ store replenishment. They also provide evidence that two types of Ca2+ permeant channels, VGCC and an as yet unidentified channel, are involved in the Ca2+ entry responsible for modulation of [Ca2+]i oscillations.

Animals↗
PubMed1996

Measurement of nitric oxide in human nasal airway.

The nasal output of nitric oxide (NO) is known to be high, but there have been varying reports of the exact level. We attempted to establish a quantitative measurement of nasal NO, and looked for a possible relationship with nasal resistance, at rest and during exercise. Nasal airway ventilation was performed by using an air pump at a constant flow rate, whilst the soft palate was elevated voluntarily. In a preliminary study, the flow rate for sampling was changed and concentrations of NO were measured. After determination of flow rate, rhinomanometry for nasal resistance and measurement of nasal NO by chemiluminescence were carried out before and after moderate exercise. The concentration of NO ([NO]) exhibited a hyperbolic relationship with flow rate of ventilation (V'E), indicating [NO] x V'E = net nitric oxide output (V'NO) = constant. Hence, nasal NO was expressed quantitatively as V'NO (nL.min-1). For 1 L.min-1 of ventilation, [NO] varied between 2 and 500 parts per billion (ppb) (mean = 323 ppb). The average nasal V'NO in 12 healthy male subjects was 323 +/- 91 nL.min-1 (mean +/- SD). After exercise on a treadmill (10 degrees, 5 km.h-1) for 4 min, nasal V'NO decreased to 229 +/- 63 nL.min-1. At rest, expiratory and inspiratory nasal resistance was 0.27 +/- 0.04 and 0.27 +/- 0.06 Pa.s.cm-3, respectively. After exercise, expiratory and inspiratory nasal resistance decreased to 0.17 +/- 0.04 and 0.16 +/- 0.04 Pa.s.cm-3, respectively. These data indicate that nasal NO can be measured quantitatively as V'NO and might be involved in the control of nasal resistance.

Adult↗
PubMed1996

Analysis of (-)-epigallocatechin gallate in human serum obtained after ingesting green tea.

A method for analyzing the EGCg concentration in human serum was developed by using high-performance liquid chromatography with electrochemical detection. EGCg was detected in human serum after the ingestion of 5 g of green tea powder (matsu-cha) dissolved in 200 ml of hot water. The concentration of EGCg in the serum reached the highest level about 2 h after ingesting the green tea, and then decreased.

Antimutagenic Agents↗
PubMed1996

Pharmacological characterization of adrenoceptors mediating contractile and relaxant responses to noradrenaline in the longitudinal muscle of guinea-pig ileum.

Mechanical responses to noradrenaline (NA) were recorded in longitudinal muscle strips from the terminal and intermediate regions (3-10 cm and 30-40 cm from the ileo-caecal junction, respectively) of the guinea-pig ileum. NA(0.16-1,600 microM) produced a concentration-dependent contraction in the terminal ileum with the EC50 value of 11.9 +/- 4.3 microM (n = 5). In the intermediate ileum, NA produced relaxation at concentrations ranging from 0.016 microM to 1.6 microM. Responses to NA at 16 microM varied among preparations: no noticeable change in tension, a moderate relaxation and a small contraction. At higher concentrations, NA produced contractile responses and their peak tension increased in a concentration-dependent manner. The contractile effect of NA in the terminal ileum remained unaltered after treatment with propranolol (1.4 microM) or yohimbine (1.1 microM), or a combination of these drugs. In the intermediate ileum, the relaxant effect of NA was markedly reduced or abolished by propranolol (1.4 microM). Yohimbine (1.1 microM) had little effect on NA-induced relaxation. The contractile effect of NA in both the terminal ileum and intermediate ileum was inhibited by prazosin (1.1 microM), so that the contractions were converted to relaxation or markedly reduced. Propranolol abolished the relaxant response induced by NA at 0.16 microM, but did not inhibit those induced by NA at 1.6 microM. Methoxamine (0.16-1,600 microM) produced a concentration-dependent contraction in both the terminal ileum and the intermediate ileum. The EC50 was 93.5 +/- 28.5 microM (n = 8) in the terminal ileum and 83.3 +/- 27.7 microM (n = 10) in the intermediate ileum. There was no significant difference between the values. The results showed that NA is capable of producing contraction or relaxation in the longitudinal muscle layer of the terminal and intermediate regions of the guinea-pig ileum. The contraction, which is mediated by alpha 1-adrenoceptors, predominates in the terminal ileum, but relaxation, which is mediated by beta-adrenoceptors and uncharacterized adrenoceptors, predominates in the intermediate ileum.

Animals↗
PubMed1996

[A fundamental study of relationships between rhinomanometry and acoustic rhinometry].

A cylindrical model consisting of a single or plural acrylic plates with holes of various cross-sectional areas was ventilated by a Harvard pump. Pressure flow curves of the combinations were drawn and analyzed according to the percent expression method. The length of the cylinder through the same cross-sectional area did not influence the ventilatory resistance. Divergent flow toward the downstream part decreased the resistance, but convergent flow from the upstream part did not. Simultaneous setting of convergent flow from the upstream part and divergent flow to the downstream part decreased the resistance most effectively, as much as approximately 70% of the original resistance. Two separately positioned cross-sectional areas in a respiratory circuit increased the resistance about 1.4 times when the separation length was more than 3 cm, while the resistance remained between 1 and 1.4 times when the separation was shorter than 3 cm. The average values of the minimum areas measured by acoustic rhinometry were usually much larger than expected from the present study. One of the factors affecting this difference may be that the axis from the nostril to the choana is complicated enough to significantly modify the aerodynamics of the nasal cavity.

Acoustics↗
PubMed1996

[Retroperitoneal laparoscopic pelvic lymphadenectomy for patients with prostate cancer].

Between February 1994 and February 1995, we performed retroperitoneal laparoscopic pelvic lymphadenectomy on 7 patients with prostate cancer between 63 and 76 years old, consisting of 6 patients with clinical stage B2, and 1 patient with stage C. Retroperitoneal laparoscopic procedures were performed under general anesthesia. First, the prevesical space was separated by a balloon dissector to create the working space. Then, three trocars were inserted into the retroperitoneal space at the lower abdominal midline. Except for the first patient, only two surgeons were needed to dissect the obturator lymph nodes, under 5 mmHg CO2 insufflation. The mean operating time was 133 minutes for bilateral lymphadenectomy. The mean number of removed lymph nodes was 4.8 on the left side and 4.2 on the right side. The estimated blood loss ranged from 10 to 66 ml. As none of the patients showed node involvement on the microscopic examination of the frozen section, they immediately underwent total prostatectomy. Additionally removed lymph nodes were 0.8 on the left side and 1.5 on the right side. As for intraoperative complications, endotidal CO2 was elevated in the first patient, but the other patients had no complications. Retroperitoneal laparoscopic pelvic lymphadenectomy is a safe and useful procedure, and may facilitate a lymphadenectomy better than a peritoneal procedure.

Adenocarcinoma↗
PubMed1995

Inhibitory effect of muscarinic receptor activation on Ca2+ channel current in smooth muscle cells of guinea-pig ileum.

1. The effect of muscarinic receptor stimulation on voltage-gated calcium channel currents was examined in whole-cell voltage-clamped smooth muscle cells of the guinea-pig ileum. 2. In cells voltage clamped at -60 mV and in which calcium channel currents (ICa) were elicited repeatedly by depolarizing pulses (25 ms duration, 0.25 Hz frequency) to 0 mV, carbachol (CCh, 10 microM) induced an inward current (ICCh) and were suppressed ICa, in a biphasic manner; an initial transient component was followed by a more sustained one. 3. A calcium channel current (IBa), when Ba2+ was used as a charge carrier, was also suppressed by CCh in a biphasic manner, as with ICa. The sustained phase of the IBa suppression was significantly smaller than that of the ICa suppression, suggesting that Ca2+ entry exerts a potentiating effect on the current suppression. 4. CCh had little or no effect on calcium channel currents (ICa and IBa) in cells dialysed with a pipette solution containing EGTA (20 mM). 5. Inclusion of GDP-beta-S (1 mM) in the pipette solution abolished ICCh and the suppression of IBa. With GTP-gamma-S (10 microM) in the pipette, the sustained phase of the IBa suppression remained almost unchanged even after removal of CCh. 6. Pretreatment with 2 micrograms ml-1 pertussis toxin (PTX), which abolished ICCh, did not change noticeably the initial transient and sustained phases of IBa suppression. 7. Neomycin (100 microM) or heparin (5 mg ml-1) in the pipette each abolished the initial transient component of ICCh as well as the initial transient phase of IBa suppression. 8. The biphasic effect of CCh on IBa was observed in the presence of either staurosporine (1 microM) or 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (100 microM). Phorbol 12-myristate 13-acetate and phorbol 12,13-dibutyrate (up to 10 microM) had no inhibitory effect on ICa and IBa. 9. The results suggest that stimulation of the muscarinic receptor causes a biphasic suppression of the voltage-gated calcium channel currents through a PTX-insensitive G protein in guinea-pig ileal smooth muscle cells. The initial transient phase may be brought about by the release of Ca2+ from internal storage sites, and the sustained phase by a Ca(2+)-dependent mechanism which is independent of the phosphatidylinositol pathway.

Animals↗
PubMed1995

Caffeine and carbachol act on common Ca2+ stores to release Ca2+ in guinea-pig ileal smooth muscle.

To characterize intracellular Ca2+ stores, the Ca(2+)-releasing effects of caffeine, carbachol and inositol 1,4,5-trisphosphate (IP3) were compared by measuring the drug-induced tension development in beta-escin-skinned longitudinal smooth muscle of guinea-pig ileum. Caffeine (20 mM), carbachol (10 or 100 microM) or IP3 (40 microM), applied after loading Ca2+ within intracellular stores, produced a transient rise in tension in a Ca(2+)-free solution. This change in tension occurred in response to release of Ca2+ from the stores. The effect of either caffeine or carbachol was markedly reduced or abolished after preceding application of the other drug. IP3 was without effect when applied subsequently to caffeine. The effects of carbachol and IP3 were abolished after combined treatment with ryanodine (30 microM) and caffeine (20 mM) which causes functional removal of caffeine-releasable Ca2+ stores, but not after combined treatment with ryanodine (30 microM) and carbachol (10 microM). The results suggest that caffeine, carbachol and IP3 all act on common Ca2+ stores to release Ca2+.

Animals↗
PubMed1995

Possible involvement of a small G-protein sensitive to exoenzyme C3 of Clostridium botulinum in the regulation of myofilament Ca2+ sensitivity in beta-escin skinned smooth muscle of guinea pig ileum.

The effects of exoenzyme C3 of Clostridium botulinum on Ca(2+)- and drug-induced tension developments were investigated in beta-escin skinned smooth muscle of guinea pig ileum to test the involvement of a small G-protein in the regulation of myofilament Ca2+ sensitivity. C3 is known to ADP-ribosylate the rho p21 family of small G-proteins. Treatment with C3 (0.35 microgram/ml, for 30 min) shifted the pCa-tension curve rightward along the Ca2+ concentration axis, indicating a decrease in Ca2+ sensitivity of the contractile elements. The inhibitory effect of C3 was not preserved after treatment with GDP beta S (1 mM), an antagonist of GTP for the binding to G-proteins. Stimulation of muscarinic receptors with carbachol (CCh, 100 microM) shifted the pCa-tension curve leftward, indicating Ca2+ sensitization of tension development. The Ca(2+)-sensitizing effect of CCh was not observed after C3 treatment. When GTP gamma S (10 microM), an activator of G-proteins, was applied at a plateau of tension development produced by a moderate concentration of Ca2+, further increase in tension was elicited and the effect of GTP gamma S was inhibited by C3 treatment. The results suggest the possible involvement of a rho p21-like small G-protein in the regulation of Ca2+ sensitivity of smooth muscle myofilaments.

Animals↗
PubMed1995

A kinetic study of the endolymphatic sac epithelial cells.

The kinetics of S-phase (the period of DNA synthesis) cells in the endolymphatic sac (ES) was investigated by immunohistochemical methods. A monoclonal antibody against 5 bromo 2'-deoxyuridine (BrdUrd) was used. After administration of BrdUrd i.p., guinea pigs were sacrificed with acid formalin at designated survival times until 28 days, and the decalcified temporal bones were examined immunohistochemically. After survival for 30 min, scattered cells labelled with an anti-BrdUrd antibody were detected within the ES, whereas they were not found any other part of the inner ear. Labelled cells were observed more frequently in the rugose portion than in the other portion of the ES. At 3 days after BrdUrd labelling, increased numbers of labelled cells were detected. Labelled mitoses could be observed in the epithelium after long survival times. Our results show that the epithelial cells of the ES in adult animals turn over in the steady-state.

Animals↗
PubMed1994

Mechanical and current responses to neurotensin in the smooth muscle of guinea-pig intestine.

1. The effects of neurotensin (NT) on the mechanical activity of the smooth muscle and membrane currents of enzymatically-dispersed single smooth muscle cells of guinea-pig intestine were investigated by the isometric tension recording method and the whole-cell patch clamp technique, respectively. 2. NT (0.3-670 nM) produced an initial relaxation followed by a contraction in segment preparations of the jejunum and ileum. Atropine (0.2 microM) abolished the contraction. In 30% of ileal segments, NT produced a slowly-developed contraction in the presence of atropine. The atropine-resistant contraction was insensitive to tetrodotoxin (TTX, 0.2 microM). The relaxant effect of NT was unaffected by TTX (0.2 microM) and guanethidine (2 microM), but markedly reduced or abolished by apamin (67 nM). 3. In segment preparations of the colon and rectum, NT produced a biphasic response, similar to that in the small intestine, or a triphasic one (relaxation, contraction and relaxation). The contractile effect of NT was affected neither by atropine (0.2 microM) nor by TTX (0.2 microM). The first relaxation in response to NT was similar in pharmacological properties to that in the small intestine. 4. Responses to NT in longitudinal muscle strips were similar to those in segment preparations. The taenia caecum responded to NT with a contraction alone and the effect was unaffected by atropine (0.2 microM) and TTX (0.2 microM). 5. NT had little or no effect on the mechanical activity in the circular muscle of the small intestine. In the circular muscle of the large intestine, NT had a weak inhibitory effect on the spontaneous activity which was followed by a small rise in muscle tone. Apamin (67 nM) converted the biphasic response to a contraction. 6. In cells dialysed with a KCl-based solution under voltage clamp at 0 mV, NT (5 microM) produced a brief, outward current in a very small fraction of cells (4 out of 40 cells). When cells were dialysed with a CsCl-based solution under voltage clamp at -50 or -60 mV, no current response to NT (5 microM) was observed in all 37 cells, but NT increased inward Ca2+ currents evoked upon depolarization. 7. From these results, it appears that there is a regional difference in the mode of action of NT to contract and relax the smooth muscle of guinea-pig intestine, and NT acts on its receptors on the smooth muscle to enhance activation of voltage-dependent Ca2+ channels, which underlies the slow contraction in the longitudinal muscle of the intestine.

Adenosine Triphosphate↗
PubMed1994

S-phase cells in the guinea pig endolymphatic sac.

S-phase (the period of DNA synthesis) cells in the endolymphatic sac (ES) were investigated by immunohistochemical methods. Monoclonal antibodies against 5-bromo-2'-deoxyuridine (BrdUrd) and proliferating cell nuclear antigen (PCNA) were used. After administration of BrdUrd i.p., guinea pigs were sacrificed with acid formalin and the decalcified temporal bones examined immunohistochemically. Scattered cells labelled with anti-BrdUrd or anti-PCNA antibodies were detected within the ES whereas labelled cells were not found in either the cochlea or the vestibule. From the morphological findings, these labelled cells within the ES epithelium were considered to be epithelial cells and the sub-epithelial stained cells looked like fibroblastic cells. Some labelled resident floating cells were found in the ES lumen. Our results reveal that the ES, where resident cells proliferate, is the sole site of the cell-renewing system in the inner ear of an adult animal.

Animals↗
PubMed1993

Development of vagal innervation to the muscle of the avian gizzard.

The development of the vagal innervation to the gizzard has been investigated in chick embryos and young chicks. The membrane potential, first measurable on the 15th day of incubation, was -54 +/- 0.5 mV and increased with development to -67 +/- 0.4 mV. The latter value was attained 5 days after hatching and persisted thereafter. Stimulation of intramural nerves elicited a cholinergic, excitatory junction potential (EJP) for the first time, only in a small fraction of cells, on the 20th day of incubation. Within 3 days after hatching, cholinergic transmission showed the same features as in older chicks. Stimulation of the vagus nerve elicited no membrane potential responses before hatching but as early as 4 days after hatching, non-adrenergic, inhibitory junction potentials (IJPs) were evoked. In the next 10 days or so, the IJP was replaced with a cholinergic EJP as seen in mature tissues. After atropine (0.1-1 microM) treatment, both vagal and intramural nerve stimulation evoked a non-adrenergic IJP in a small fraction of cells immediately after hatching. The fraction of cells exhibiting the IJP increased with growth and reached 100% 5 days after hatching. Hexamethonium (50 or 100 microM) abolished the vagally-evoked EJPs. The vagally-evoked IJPs remained unchanged after application of hexamethonium in the early days after hatching, but later they were abolished in about half of the cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

Clinical pathology reference ranges of laboratory animals. Working Group II, Nonclinical Safety Evaluation Subcommittee of the Japan Pharmaceutical Manufacturers Association.

We analyzed historical control data of clinical pathology testings provided by sixty-seven member companies of the Japan Pharmaceutical Manufacturers Association covering study populations of approximately 7,000 rats/sex, 5,000 dogs/sex, and 700 monkeys/sex. This paper assesses the relationship between conditions of sample collection, methods of measurement, etc. and potential factors contributing to variations in reference data, based on weighted means and standard deviations thereof derived from data for rats, dogs and monkeys for those parameters measured using methods most common to the participating facilities. Parameters included erythrocyte count (RBC), hematocrit (Ht), hemoglobin concentration(Hb), reticulocyte count (Rt), platelet count, total leukocyte count (WBC), differential leukocyte count (%WBC), coagulation time (activated partial thromboplastin time: APTT, prothrombin time: PT), and serum/plasma levels of GOT, GPT, ALP, LDH, glucose, cholesterol, triglycerides (TG), total protein, albumin, urea nitrogen (UN), creatinine, sodium (Na), potassium (K), calcium (Ca), chloride (Cl), inorganic phosphorus (Ip), and CPK. Analyses of the data revealed species differences in RBC, Ht, Rt, platelet count, WBC, %WBC, ALP, LDH, glucose, cholesterol, TG, total protein, UN, creatinine, Ca, Ip, and CPK. There were strain differences in rats in platelet count, WBC, GOT, ALP, UN, creatinine, and CPK. Sex differences were noted for Hb, Ht, WBC, ALP, glucose, cholesterol, TG, total protein, A/G ratio, UN, and Ip. Age differences were observed with RBC, Hb, Ht, Rt, %WBC, GOT, GPT, ALP, LDH, cholesterol, TG total protein, Ip, and CPK. APTT, PT, ALP, glucose, TG and UN were found to be subject to the influence of fasting/feeding. In rats, Ht, WBC, CPK and K showed differences by the site of bleeding. Observed values for LDH and CPK varied with specimen type, plasma or serum; serum assay values showed greater variation than plasma values.

Animals↗