OBJECTIVETo study the protective effect of memantine on the regulation of N-methyl-D-aspartate (NMDA) receptor in dichlorvos-poisoned rat brain, and to understand the mechanism of its role in organophosphate poisoning.

METHODSSD rats were administrated dichlorvos (25 mg/kg, ip) then three groups were treated with memantine at doses of 5, 15 and 45 mg/kg respectively. The activity of acetylcholinesterase (AChE) and binding capacity of NMDA receptor with [(3)H]MK-801 were determined 16 h after dichlorvos injection.

RESULTSThe time of onset of toxic symptoms in 15, 45 mg memantine treated groups [(18.40 +/- 1.14) and (21.40 +/- 1.52) min respectively] was higher than that in dichlorvos alone group [(16.75 +/- 1.62) min]; the intensity of muscle fasciculation (1.60 +/- 1.14 and 0.80 +/- 0.84, respectively) was less than that in control group (2.85 +/- 0.37); the total score of poisoning symptoms (8.80 +/- 1.79 and 9.00 +/- 2.24 respectively) was also less than that in dichlorvos group (14.60 +/- 1.70). The AChE activities both in blood and brain of memantine treated groups were not significantly different from those in dichlorvos alone group. The affinity (Kd value) and density (Bmax value) of brain NMDA receptor in dichlorvos exposed rats [(75.55 +/- 7.87) nmol/L, (0.46 +/- 0.06) pmol/mg pro respectively] were higher and lower respectively than those in control group [(37.37 +/- 4.17) nmol/L, (0.62 +/- 0.04) pmol/mg pro respectively]. Lower level of memantine (5 and 25 mg/kg) could antagonize the dichlorvos-evoked down-regulation of [(3)H]MK-801 binding to NMDA receptor in rat brain [Bmax value: (0.55 +/- 0.07) and (0.64 +/- 0.07) pmol/mg pro; Kd value: (38.68 +/- 4.54) and (32.58 +/- 3.90) nmol/L respectively] while higher dose of memantine (45 mg/kg), the Bmax (0.45 +/- 0.06) pmol/mg pro and Kd (22.88 +/- 4.42) nmol/L of NMDA receptor were significantly decreased (P < 0.01).

CONCLUSIONMemantine in certain dose range could protect against the down-regulation of NMDA receptor in rat brain, and alleviate organophosphorus poisoning symptoms to some extent. The recovery of AChE activity inhibition wasn't involved in the treatment with memantine on dichlorvos poisoning, therefore, atropine and a proper AChE reactivator (an oxime) should be used clinically.

Acetylcholinesterase ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Dichlorvos ; toxicity ; Dopamine Agents ; pharmacology ; Insecticides ; toxicity ; Male ; Memantine ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; metabolism

OBJECTIVETo study the tolerance of rats induced by 28 day pretreatment with low dosage of dimthoate and the toxic effects challenged by higher dosage of dimethoate, and to investigate the change of M receptor and the mechanism of tolerance formation.

METHODSSD rats were given 25 mg/kg dimethoate daily(sc) while control group was given saline daily instead for 28 days. The activity of whole blood acetylcholinesterase (AChE) was examined. On the 29th day three groups of administrated rats were challenged by saline solution, 50 mg/kg and 100 mg/kg dimethoate, respectively. The density and mRNA level of brain M(1), M(2) receptor were determined. Lymphocytes of peripheral blood were isolated, and basal, inducible M(3) gene expression were measured by RT-PCR.

RESULTSDuring pretreatment, blood AChE activity decreased continually, it reached the lowest on the 13th day. And it decreased more after exposed to higher dosage of dimethoate. Brain AChE activity in the pretreated groups was lower than that in control group and decreased with the increase in challenging dosage. The density of M(1) receptor in negative control, pretreated, and 50, 100 mg/kg challenging groups were 979.15, 856.54, 539.46, 539.14 fmol/mg pro respectively. The change in relative levels of mRNA of M(1) receptor (2.59, 2.47, 2.20, 1.81) were consistent with the density of receptor but the level declined continually as the challenging dosage increased. The density of M(2) receptor were 507.38, 611.11, 548.42, 337.47 fmol/mg pro respectively, which were not obviously affected by pretreatment but decreased as the challenging dosage increased. The change in levels of M(2) receptor mRNA was not obvious. The basal gene expression of M(3) receptor mRNA was not different among all experimental groups while the inducible gene expression decreased with the increase in challenging dosage.

CONCLUSIONLow level dosage of dimethoate could induce animals to tolerate dimethoate toxicity. Reduction of M(1) receptor density which may be induced by the decrease in its gene expression may be the mechanism of tolerance. The change of M(3) receptor mRNA inducible expression in lymphocyte accorded with M(1) receptor mRNA expression in the brain.

Animals ; Brain ; metabolism ; Dimethoate ; toxicity ; Gene Expression ; drug effects ; Insecticides ; toxicity ; Lymphocytes ; metabolism ; Male ; Maximum Tolerated Dose ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Muscarinic ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors

OBJECTIVETo study the expression of muscarinic receptor M(3) gene in peripheral blood lymphocytes of workers exposed to organophosphorus pesticides (OPPs) and to explore its role in the adverse effects of OPPs.

METHODSThe lymphocytes of peripheral blood from 33 workers exposed to dimethoate and 15 control people were isolated and treated with saline and dimethoate respectively in vitro. RT-PCR technique was used to determine M(3) gene expression. Basal and inducible gene expression levels were measured.

RESULTSThere was no significant difference in basal gene expression level between exposed group and control group, while the inducible gene expression level was significantly higher in exposure group (1.92 +/- 1.07) than in control group (1.22 +/- 0.19) and basal level (1.49 +/- 0.45, P < 0.05). No differences in basal and inducible gene expression level were found between male and female people in both exposed and control group. The level of inducible M(3) gene expression increased with the increase in length of exposure time [< 5 a: (1.69 +/- 0.95), 5 - 25 a: (1.91 +/- 1.03), > 25 a: (2.09 +/- 1.25), the latter was significantly different from that of < 5 a (P < 0.05)].

CONCLUSIONAfter long-term exposure to OPPs, the basal M(3) receptor gene expression level in the exposed workers did not show any difference from the control group, but the inducible gene expression level (treated with dimethoate in vitro) was increased and related to the extent of exposure to dimethoate.

Dimethoate ; blood ; poisoning ; Female ; Gene Expression ; Humans ; Insecticides ; blood ; poisoning ; Lymphocytes ; cytology ; metabolism ; Male ; Occupational Exposure ; analysis ; RNA, Messenger ; genetics ; metabolism ; Receptor, Muscarinic M3 ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

The characteristics of purinoceptors in the membrane of rat trigeminal ganglion (TG) neurons were studied by using whole- cell patch clamp technique. The results showed that most of neurons examined (78.9%, 142/180) were responsive to ATP in a concentration-dependent manner; the others (21.1%, 38/180) were ATP insensitive. Of the ATP-sensitive cells, the majority (95.1%, 135/142) responded to ATP with an inward current, a few (2.1%, 3/142) with an outward current, and the rest (2.8%, 4/142) with biphasic current. Small sized cells (<30 mum) responded to ATP with a rapid desensitizing inward current and were highly sensitive to vanilloid; the medium sized cells (30~40 mum) responded to ATP with slow desensitizing inward current and were not sensitive to vanilloid; while the majority of large sized cells (>40 mum) did not respond to ATP and vanilloid. The waveform of ATP-activated inward currents was related to the cell diameter. The I-V curves for both small and medium sized cells manifested obvious inward rectification. Furthermore, we studied the kinetic features of ATP-activated currents and the effects of P2 purinoceptor agonists and antagonists on I(ATP). The findings suggest that ATP receptor-ion channels are expressed differently among different types of rat TG neurons.
Adenosine Triphosphate ; metabolism ; Animals ; Animals, Newborn ; Neurons ; metabolism ; physiology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Receptors, Purinergic P2X ; physiology ; Trigeminal Ganglion ; cytology ; metabolism ; physiology

Neuronal firing is crucial to the information processing in the nervous system. In order to make a further study of bifurcation scenarios, experiments were performed on neural pacemakers formed at the injured site of rat sciatic nerve subjected to chronic ligatures. We chose the conductance of voltage-dependent potassium ion channels as conditional parameter, and the extracellular calcium concentration as bifurcation parameter, to give a demonstration of how the firing pattern of neural pacemaker responses to dual parameter adjusting. Among 28 preparations observed, 21 were insensitive to dual parameter adjusting since no change of bifurcation scenario structure was detected. On the contrary, the residual 7 preparations showed dramatic bifurcation scenario shifting corresponding to different dual parameter configuration. Briefly, when concentration of 4-aminopyridine (4-AP), a voltage-dependent potassium ion channels blocker, was kept at different level and extracellular Ca2+ concentration was decreased gradually, different bifurcation scenarios of firing patterns were exhibited in an identical neural pacemaker. The two-parameter bifurcation scenarios of experimental neural pacemaker with different parameter configuration were also different. The results show that neural firing pattern is different when the parameter configuration is different, and the bifurcation scenario is a fundamental framework to identify the transitions between firing patterns.
4-Aminopyridine ; pharmacology ; Action Potentials ; physiology ; Animals ; Calcium ; metabolism ; Male ; Neurons ; physiology ; Periodicity ; Potassium Channels ; physiology ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; injuries ; physiopathology

Authors raised that staging based strategies and practice of integrative medicine (IM) by combining syndrome typing and disease identification, and choosing suitable measures in accordance with different persons and seasonal conditions after more than ten years' clinical practice and researches. Radical operation as prior (as evil eliminating) and strengthening vital qi in perioerative period are best strategy for promoting rapid rehabilitation of early stage prostate cancer patients. Strengthening body resistance to eliminate evil was used in treating advanced prostate cancer patients. For example, a comprehensive treatment program for hormone-dependent patients was combined with endocrinotherapy and Chinese herbs for synergisic efficacy-enhancing actions. In this way, these patients' quality of life (QOL) were improved and time to castration resistant prostate cancer (CRPC) was delayed, even some patients were clinically cured. There are lack of effective medicines and methods for CRPC patients. Greatly tonifying original qi is mainly used for improving their clinical symptoms and prolonging survivals. Practice has proved staging based strategies and practice of IM has favorable advantages in treating prostate cancer, especially showing prospect in prolonging survival and postponing progression of advanced prostate cancer patients. Besides, it also could provide beneficial considerations and inspiration for combination of syndrome typing and disease identification.
Disease Progression ; Humans ; Male ; Medicine, Chinese Traditional ; Neoplasm Staging ; Prostatic Neoplasms, Castration-Resistant ; diagnosis ; Quality of Life

OBJECTIVETo observe the morphological changes and the regenerating ability of the fungiform papillae and taste buds after 60Co radiation with clinical doses in rats.

METHODSThe heads, faces and necks of 30 SD rats were radiated with a large dose and one time of 60Co in the clinical radiation. The general living condition and the number and shape of the fungiform papillae and taste buds of the tongues were observed after the radiation in rats.

RESULTSIn the group of 60Co radiation, the animals had wilting, decreasing appetite, losing weight. The heads, faces and necks of animals appeared redness, peeling of hair, increasing of secretions in 5 days after the 60Co radiation. The changes reached the summit in 10 days and the general living condition of the animals recovered in 60 days. The fungiform papillae and taste buds of the animals appeared degeneration, atrophy and collapsing in 5 days after the 60Co radiation. The injuries reached the summit in 10-20 days and the fungiform papillae and taste buds regenerated partially, and the some atrophied fungiform papillae and taste buds were not regenerated in 60 days.

CONCLUSIONThe damage to fungiform papillae and taste buds of tongue following the 60Co radiation with the clinical doses was very serious. The damaged fungiform papillae and taste buds can regenerate partially, but not completely.

Animals ; Radiation Injuries, Experimental ; pathology ; Rats ; Rats, Sprague-Dawley ; Regeneration ; Taste Buds ; pathology ; radiation effects ; Tongue ; pathology ; radiation effects

OBJECTIVETo investigate the anatomic characteristics of splenic flexure, surgical techniques, and oncologic outcomes in 52 patients with non-obstructive splenic flexure colon cancer.

METHODSClinical data of 52 patients with non-obstructive splenic flexure colon cancer from March 2004 to March 2011 in the Department of General Surgery at the Henan Province Tumor Hospital were analyzed retrospectively.

RESULTSThere were 37 patients of regular type, 5 of mobile type, and 10 of adhesive type. All the patients received radical operation. Eighteen patients received pre-small intestine anastomosis, including 12 cases with regular type, 4 with mobile type, and 2 with adhesive type. The difference in pre-small intestine anastomosis among the three types was not statistically significant(P=0.062). In addition, 32 cases received retro-ileum anastomosis. There were no significant differences in operative time, intraoperative blood loss, number of lymph node dissection and positive lymph node, and postoperation complication rate among the three types. Follow up was available in all the cases. Five-year survival rates of cases with regular type, mobile type and adhesive type were 62.5%, 59.2% and 58.7% respectively(P>0.05).

CONCLUSIONSRadical resection can provide satisfactory survival for splenic flexure colon cancer patients. The anatomy of splenic flexure does not affect the type of anastomosis. Retro-ileum anastomosis is a simple and effective method for reconstruction after radical resection of the tumor.

Adult ; Aged ; Anastomosis, Surgical ; Colon, Transverse ; anatomy & histology ; pathology ; surgery ; Colonic Neoplasms ; pathology ; surgery ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo investigate long-term survival after multivisceral resection in patients with locally advanced right colon cancer.

METHODSThe clinical data and survival of 13 patients with locally advanced right colon cancer were retrospectively analyzed.

RESULTSThere were 8 males and 5 females with a mean age of 58.6 years. Location of the primary tumor included hepatic flexure(n=6), transverse colon(n=2), and ascending colon(n=5). Three patients had duodenal invasion alone, 9 had involvement of duodenum and other organs, and 1 had pancreas and stomach involvement. Right colectomy and pancreaticoduodenectomy and(or) resection of other organs were performed. The 1-, 3-, and 5-year survival rates were 69%, 54%, and 30%, respectively.

CONCLUSIONRight colectomy combined with multivisceral resection is a promising procedure for selected patients with locally advanced colon cancer.

Adult ; Aged ; Colonic Neoplasms ; surgery ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo study the relationship between the polymorphism of butyrylcholinesterase (BChE, EC 3.1.1.8) and paraoxonase (PonE, EC 3.1.8.1), and the individuals' genetic susceptibility to organophosphates pesticides (OPs) exposure.

METHODS75 OPs exposure workers were selected to determine their BChE-K, PON-192 and PON-55 genotypes using PCR-RFLP. The accumulative symptom scores and the whole blood acetylcholinesterase activity (mmol x h(-1) x ml(-1)) were used as health index. Firstly, the health condition related to single gene site of the three gene loci was analyzed to determine which kinds of genotype were susceptible. Then, used the multiple variance analysis was to see if there existed interactions among these three gene loci. Finally, established the multi-factor linear regression equation, in which considered some other factors that might influence the health situation such as age, gender and the exposure time. According to the equation, could get the accumulative symptom scores of each kind of subpopulation of different genotypes.

RESULTSThe mean AChE activities of the exposed workers with BChE-K genotype UU (61 cases), genotype UK (12 cases) and genotype KK (2 cases) were 105.0 +/- 23.0, 84.4 +/- 16.4, 79.0 +/- 9.9, respectively; The accumulative symptom scores were 3.7 +/- 3.8, 9.2 +/- 3.0, 12.5 +/- 0.7, respectively. The AChE activities of the exposed workers with PON-192 genotype BB (37 cases), genotype AB (27 cases) and genotype AA (11 cases) were 116.8 +/- 15.1, 91.2 +/- 15.6, 72.3 +/- 21.4, respectively; The accumulative symptom scores were 2.0 +/- 3.2, 6.7 +/- 3.3, 9.7 +/- 1.8, respectively. Similarly, the AChE activities of the exposed workers with PON-55 genotype LL (70 cases) and genotype LM (5 cases) were 102.4 +/- 23.0, 82.8 +/- 22.0; The accumulative symptom scores were 4.5 +/- 4.2, 9.2 +/- 3.6, respectively. Single variance analysis showed that the accumulative symptom scores of the individuals with abnormal homozygote of these three gene loci were the highest, which indicated that they were most susceptible to OPs. Multiple variance analysis showed there were no interactions among the three gene loci. Age, gender and exposure time had no statistical significance, while genotypes of the three gene loci had statistical significance to health situation.

CONCLUSIONGenotypes of BChE-K, PON-192 and PON-55 are related to susceptibility to OPs exposure.

Adult ; Aryldialkylphosphatase ; genetics ; Butyrylcholinesterase ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Occupational Exposure ; Organophosphorus Compounds ; adverse effects ; Pesticides ; adverse effects ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length