Background: In Vietnam, there are a number of studies on the application of ATRA in treating acute promyelocytic leukemia (AML \u2013 M3) but they have still faced with certain difficulties. Objectives: (1). Study PML/RAR alpha fusion gene on the patients diagnosed with AML \u2013 M3. (2). Study the index of hematology of the PML/RAR alpha positive group. Subject and Method: 21 patients with acute promyelocytic leukemia (M3) were studied. All patients were examined with morphology, coagulation and cytogenetic tests and RNA were extracted from leukemic cells and PCR for PML/RAR alpha fusion transcript. Result and conclusion: PML/RAR alpha positive in 67% including 4 patients which were not discovered t(15; 17) by cytogenetic technique. Rates of three subtype (bcr1, bcr2 and bcr3) of PML/RAR alpha were 7 patients (50%), 3 patients (21,5%) and 4 patients (28,5%), respectively. WBC and bone marrow cells of PML/RAR alpha positive group were 5.08+/-3.87 and 155.82+/-106.21. D \u2013 Dimer level was 1954.89+/-1575.28; 93% of patients in the PML/RAR alpha positive group had DIC.
Acute promyelocytic leukemia ; M3 ; PML/RAR alpha

Cardiovascular disease, with high morbidity and mortality, has been threatening the health of human beings. Therefore, expecting to find a more effective therapeutic method, a plenty of researchers devote themselves to the study of the cardiovascular disease all the time. Since discovered on the heart, M3 receptor of muscarinic acetylcholine receptor (mAchR, M receptor) became a new starting point of the research of the cardiovascular disease. With more and more investigation, many people found that M3 receptor could protect the heart from kinds of cardiovascular disease, which may make it a new hopeful therapeutic point. So, expecting to give support to the reference and encouragement for the study of disease related to M3 receptor in future, this review expounds M3 receptor on the heart from the main following aspects: the effect on the heart, the influence on the cardiovascular disease and the mechanism of M3 receptor involved.
Cardiovascular Diseases ; prevention & control ; Heart ; physiology ; physiopathology ; Humans ; Receptor, Muscarinic M3 ; physiology

OBJECTIVE[corrected] To characterize the insulinotropic action of hippocampal cholinergic neurostimulating peptide (HCNP) and analyze the role of type 3 muscarinic receptor (M(3)R) pathway in the action of HCNP.

METHODSINS-1 cells were incubated in routine RPMI 1640 medium (control group), RPMI 1640 supplemented with 50 pg/ml synthetic HCNP (HCNP group), or HCNP-containing medium with the addition of PMA 18 h prior to insulin release assay. The insulin levels in the medium was measured using radioimmunoassay following stimulation with different concentrations of glucose. Real-time quantitative PCR was used for detecting the gene expression of HCNP-pp, choline acetyltransferase (ChAT) and M(3)R in HCNP group and control group.

RESULTSAfter stimulation with different concentrations of glucose (5.6 and 16.7 mmol/L), HCNP group showed significantly higher insulin levels than the control and HCNP+ PMA groups. Compared with those in the control group, the mRNA levels of HCNP-pp, ChAT, and M(3)R were all lowered in HCNP group.

CONCLUSIONHCNP can promote insulin release in INS-1 cells by increasing ChAT activity and activating M(3)R, and this effect is inhibited by PMA.

Animals ; Cell Line ; Insulin ; secretion ; Neuropeptides ; pharmacology ; Rats ; Receptor, Muscarinic M3 ; metabolism

OBJECTIVETo investigate the effect of diabetic autonomic neuropathy on the seminal vesicle and search for the theoretical evidence for the prevention and treatment of diabetic infertility by observing changes in the contents of the nerve growth factor (NGF) and muscarinic M3 receptor in the seminal vesicle of diabetic rats.

METHODSDiabetic models were established in 10 of the 15 male adult SD rats by intraperitoneal injection of streptozotocin (STZ), and the other 5 were included in a normal control group. Eight weeks after modeling, seminal vesicles were collected from the rats for HE and immunohistochemical staining.

RESULTSCompared with the normal controls, the diabetic models showed a decreased number of smooth muscle cells, thinner cytoplasm of glandular epithelial cells and disordered structure in the seminal vesicle. The intensity of NGF-positive staining was significantly enhanced, but that of M3 markedly reduced in the diabetic group. There were statistically significant differences in the mean integrated optical density (IA) of muscarinic M3 receptors and NGF between the control and diabetic groups (0.0187 +/- 0.0024 vs 0.0100 +/- 0.0015 and 0.0209 +/- 0.0085 vs 0.0412 +/- 0.0117, P<0.01).

CONCLUSIONThe changes in the expressions of NGF and M3 receptors in the seminal vesicle of diabetic rats suggest that diabetes mellitus may induce autonomic neuropathy of the seminal vesicle.

Animals ; Diabetes Mellitus, Experimental ; metabolism ; Male ; Nerve Growth Factor ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Muscarinic M3 ; metabolism ; Seminal Vesicles ; metabolism

Our previous studies document the expression of adrenoceptors and purinoceptors in the rat prostate neuroendocrine cells (RPNECs). However, a direct investigation of the receptors for acetylcholine (ACh) is still lacking in the prostate neuroendocrine cells. RPNECs were freshly isolated from the ventral lobes of rat prostate by using collagenase. Effects of ACh and various muscarinic antagonists on the intracellular Ca2+ concentration ([Ca2+]c ) were investigated by using the fura-2 spectrofluorimetry. Single-cell RT-PCR analysis was applied to identify the transcripts for the muscarinic receptor subtypes. ACh (5 micrometer) induced a sharp transient increase in the [Ca2+]c of RPNECs, which was independent of the extracellular Ca2+. In the same RPNECs, high KCl (60 mM), phenylephrine (5micrometer), UTP (P2Y1/2 agonist, 50, micrometer), and alpha, beta-meATP (P2X1/3 agonist, 0.5micrometer) also increased the [Ca2+]c. The ACh-induced [Ca2+]c change (delta[Ca2+]c ) was blocked by atropine or by para-fluorohexahydrosiladifenidol (M3 antagonist, 0.3micrometer), but not by telenzepine (M1 antagonist, 1 micrometer) and himbacine (M2 and M4 antagonist, 1 mircoM). The single-cell RT-PCR demonstrated the selective expression of mRNAs for M3 in RPNECs. In summary, RPNECs express M3 muscarinic receptors that are linked to the release of Ca2+ from intracellular stores. The Ca2+ signals of RPNECs might mediate the parasympathetic regulation of prostate gland.
Acetylcholine/pharmacology ; Animals ; Calcium/*metabolism ; Calcium Signaling ; Male ; Neurosecretory Systems/*metabolism ; Prostate/*metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Muscarinic M3/*physiology ; Research Support, Non-U.S. Gov't

OBJECTIVETo observe the therapeutic effect of tiotropium bromide powder inhalation on stable bronchiectasis.

METHODSTwenty-two patients with stable bronchiectasis received inhalation of totropium bromide powder at the daily dose of 18 microg, and on days 1 and 28, the patients were examined for forced expiratory volume in one second (FEVl), predicted value [FEVl(%)], forced expiratory volume (FEV), and FEVl/FVC. The symptom score and BODE index were also recorded.

RESULTSAfter 1 month of inhalation therapy, the FEV1% of the patients showed a moderate increase but the increment was not statistically significant (t=-1.875, P>0.05); the symptom score and BODE index decreased significantly after the therapy (t=7.091, P<0.001; t=2.982, P<0.05).

CONCLUSIONLong-term inhalation of tiotropium bromide powder can improve the clinical symptoms and BODE index and enhance the exercise tolerance and quality of life of the patients with bronchiectasis.

Administration, Inhalation ; Adult ; Aged ; Bronchiectasis ; drug therapy ; Female ; Forced Expiratory Volume ; Humans ; Male ; Middle Aged ; Powders ; Receptor, Muscarinic M3 ; antagonists & inhibitors ; Scopolamine Derivatives ; administration & dosage ; Tiotropium Bromide

Animals ; Arecoline ; pharmacology ; Cholinergic Agonists ; pharmacology ; Female ; Guinea Pigs ; In Vitro Techniques ; Male ; Muscle Contraction ; drug effects ; Muscle, Smooth ; physiology ; Pyloric Antrum ; physiology ; Receptor, Muscarinic M3 ; metabolism

The relationship between M3 cholinergic receptor agonist (carbachol) hyperstimulation-induced pancreatic acinar cellular injury and trypsinogen activation or NF-kappaB activation in rats was studied in vitro. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, the active protease inhibitor (pefabloc), and NF-kappaB inhibitor (PDTC) in vitro. Intracellular trypsin activity was measured by using a fluorogenic substrate. The cellular injury was evaluated by measuring the leakage of LDH from pancreatic acinar cells. The results showed that as compared with control group, 10(-3) mol/L carbachol induced a significant increase of the intracellular trypsin activity and the leakage of LDH from pancreatic acinar cells. Pretreatment with 2 mmol/L pefabloc could significantly decrease the activity of trypsin and the leakage of LDH from pancreatic acinar cells (P < 0.01) following the treatment with a high concentration of carbachol (10(-3) mol/L) in vitro. The addition of 10(-2) mol/L PDTC didn't result in a significant decrease in the activity of trypsin and the leakage of LDH from pancreatic acinar cells treated with a high concentration of carbachol (10(-3) mol/L) in vitro (P > 0.05). It was concluded that intracellular trypsinogen activation is likely involved in pancreatic acinar cellular injury induced by carbachol hyperstimulation in vitro. NF-kappaB activation may not be involved in pancreatic acinar cellular injury induced by carbachol hyperstimulation in vitro.
Carbachol/*pharmacology ; Cholinergic Agonists/pharmacology ; NF-kappa B/*metabolism ; Pancreas/metabolism ; Pancreas/*pathology ; Rats, Wistar ; Receptor, Muscarinic M3/agonists ; Trypsinogen/*metabolism

OBJECTIVE: To observe the expression of Muscarinic receptor M1, M3, M5 subunits in rat flocculus following left unilateral labyrinthectomy (UL). METHOD: The RT-PCR was used to observe the expression of Muscarinic receptor M1, M3, M5 subunits post-unilateral labyrinthectomy and investigate its effect on vestibular compensation. RESULT: Muscarinic receptor M1, M3, M5 subunits were induced decrease in both side flocculus after unilateral labyrinthectomy. The expression was the least in the 1 d flocculus of following UL. The expression is rising from the 3-7 d flocculus of following UL. No difference was observed in the 7 d and sham operation flocculus following UL. No difference was observed in the ipsilateral and contralateral flocculus at any group. CONCLUSION Muscarinic receptor M1, M3, M5 subunits were induced decrease in the flocculus after unilateral labyrinthectomy. But the significance of the change of Muscarinic receptor M1, M3, M5 subunits in the vestibular compensation is still unknown.
Animals ; Cerebellum ; metabolism ; Functional Laterality ; Gene Expression ; Male ; Postoperative Period ; Rats ; Receptor, Muscarinic M1 ; metabolism ; Receptor, Muscarinic M3 ; metabolism ; Receptor, Muscarinic M5 ; metabolism ; Vestibule, Labyrinth ; metabolism ; surgery

OBJECTIVE: To investigate the expression of M3 subtype of muscarinic receptors (M3R) during the incised wound healing of the skin in mice and the characteristics of its time-dependent. METHODS: The change of M3R in skin incised wound was detected by immunohistochemical staining and Western blot. RESULTS: M3R-positive cells were detected in epidermis, hair follicle, sebaceous glands, sweat glands, dermomuscular layer in normal mouse skin. Expression of M3R was mainly detectable in polymorphonuclear cells (PMNs) in the wound specimens aged from 6h to 12h after injury. Afterwards, the M3R-positive cells were mostly mononuclear cells (MNCs) and fibroblastic cells (FBCs) at 1 d to 3d post-injury, whereas the M3R-positive cells were mostly FBCs aged from 5 d to 14d. Morphometrically, the ratio of the M3R-positive cells increased aged from 6h to 12h after injury, with a peak at 12h. The ratios kept a high relatively level aged from 1 d to 5 d, but significantly that lowered as compared with aged 12h after injury. The ratio reached the peak at 7 d again after injury, and then decreased gradually. The M3R protein also revealed a time-dependent tendency with double peaks at 12h and 7 d after injury as detected by Western blotting. CONCLUSION M3R is time-dependently expression in PMNs, MNCs and FBCs suggesting that it may play roles during the skin incised wound healing, and M3R may be used as a marker for wound age determination.
Animals ; Blotting, Western ; Fibroblasts/metabolism* ; Immunohistochemistry ; Male ; Mice ; Monocytes/metabolism* ; Neutrophils/metabolism* ; Receptor, Muscarinic M3/metabolism* ; Skin/metabolism* ; Time Factors ; Wound Healing ; Wounds and Injuries/metabolism*