D-D4FC (?-D-2′,3′-didehydro-2′,3′-dideoxy-5-fluorocytidine),a new anti-HIV drug,is on its PhaseⅡ clinical trials in America,France and Germany. Our lab has synthesized D-D4FC successfully using N-deoxyribosyltransferase from Lactobacillus helveticto catalyzing the ribose transfer from D4T (?-D-2′,3′-unsaturated thymidine) to 5-FC (5-fluorocytidine).The yield of D-D4FC reached 25%.We discovered the reaction could also be done by using intact cells.The yield could increase to 50% in 12.5 hours and more convenient to industrial continuous process.In this paper,the conditions including pH,buffer,substrates concentration,cells amount,reaction time and a possible catalytic mechanism were studied and discussed.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Drug Chronotherapy ; Female ; Humans ; Leukopenia ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Neutropenia ; chemically induced ; Remission Induction ; Taxoids ; administration & dosage ; adverse effects

Adenoma, Pleomorphic ; surgery ; Adult ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; surgery

Endoscopes ; Endoscopy ; Epistaxis ; diagnosis ; etiology ; therapy ; Humans ; Nose

Coloboma ; Humans ; Infant, Newborn ; Male ; Optic Nerve ; abnormalities

OBJECTIVETo study the effects of low concentration dopamine(DA) on hydrogen peroxide-induced apoptosis in cultured rat cardiomyocytes as well as the possible molecular mechanisms.

METHODSCultured neonatal rat cardiomyocytes were randomly divided into the following groups: control group (control), hydrogen peroxide group (H2O2), pretreated with low concentration dopamine ( DA + H2O2), dopamine receptor l(DR1) antagonist group (DR1 + DA + H2O2), dopamine receptor 2(DR2) antagonist group (DR2 + DA + H2O2). The cell apoptosis was then assessed by MTT and flow cytometry. The cellular ultrastructure changes were observed by transmission electron micro- scope. The activity of lactate dehydrogenase(LDH )and superoxide dismutase (SOD) in cell medium was analyzed by colorimetry. The protein expressions of Cytochrone c, Caspase 3 and Caspase 9 were obtained by Western blot.

RESULTSCompared with hydrogen peroxide group, low concentration dopamine(10 µmol/L) decreased the apoptosis rate and the expression of protein of apoptosis related protein, enhanced SOD activity, decreased LDH activity. DR1 antagonist SCH-23390 treatment inhibited dopamine induced cardiac protective effect. DR2 antagonist haloperido treatment had no changes compared with dopamine group.

CONCLUSIONAbove findings indicate that low concentration dopanine inhibits apoptosis induced by hydrogen peroxide in neonatal rat cardiomyocytes, which is partly associated with the activation of DR1.

Animals ; Apoptosis ; Benzazepines ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cells, Cultured ; Dopamine ; pharmacology ; Hydrogen Peroxide ; L-Lactate Dehydrogenase ; metabolism ; Myocytes, Cardiac ; drug effects ; Rats ; Rats, Wistar ; Receptors, Dopamine D1 ; metabolism ; Superoxide Dismutase ; metabolism

This study aims to establish a method to determine the serum acetaminophen concentration based on diazo reaction, and apply it in the gastric emptying evaluation. Theoretically, acetaminophen could take hydrolysis reaction in hydrochloric acid solution to produce p-aminophenol, which could then take diazo reaction resulting in a product with special absorption peak at 312 nm. Then the serum acetaminophen concentration and recovery rate were calculated according to the standard curve drawn with absorbance at 312 nm. ICR mice were given a dose of acetaminophen (500 mg x kg(-1)) by gavage and the serum acetaminophen was dynamically measured through the diazo reaction. Besides, ICR mice were subcutaneously injected with the long-acting GLP-1 analog GW002 before the gavage of acetaminophen, and serum acetaminophen concentration was measured as above to study how GW002 could influence the gastric emptying. The data showed acetaminophen ranging from 0 to 160 μg x mL(-1) could take diazo reaction with excellent linear relationship, and the regression equation was y = 0.0181 x +0.0104, R2 = 0.9997. The serum acetaminophen was also measured with good linear relationship (y = 0.0045 x + 0.0462, R = 0.9982) and the recovery rate was 97.4%-116.7%. The serum concentration of acetaminophen reached peak at about 0.5 h after gavage, and then gradually decreased. GW002 could significantly lower the serum acetaminophen concentration and make the area under the concentration-time curve (AUC) decrease by 28.4%. In conclusion, a method for the determination of serum acetaminophen based on the diazo reaction was established with good accuracy and could be used in the evaluation of gastric emptying.
Acetaminophen ; blood ; pharmacokinetics ; Aminophenols ; Animals ; Gastric Emptying ; Mice ; Mice, Inbred ICR

Objective Using mouse autoimmune premature ovary failure (POF) model to seek theoretical evidence for a possible clinical therapy of autoimmune POF with glucocorticoid (GC) or an-drogen. Methods After autoimmune POF was induced in 60 mice by Pzp3, the mice were randomly as-signed into 3 groups (n=20) : Two groups were treated with GC or androgen and the control group was treated with distilled water. We observed the changes in the sexual cycles of the mice, the serum level of AzpAb, infiltration of cells positively expressing CD45 in the ovary, and pathological alterations of the ovary. Results The sexual cycle of each therapy group was significantly different from that of the control group. The mean serum level of AzpAb of each therapy group was significantly lower than that of the con-trol group, and the mean serum level of AzpAb in the GC group was significantly higher than that of the androgen group. The percentage of growing follicles in the ovary of each therapy group was significantly higher than that of the control group. Ovaries infiltrated by cells positively expressing CD45 of each thera-py group were significantly fewer than those of the control group. Conclusion GC or androgen in mice with autoimmune POF could obviously ameliorate the pathogenetic conditions of the disorder, and both treatments have similar therapeutic efficacy.

Objective To explore the effect of endoscopic sinus surgery combined with postoperative nasal irrigation on the symptoms improvement and prognosis for patients with allergic fungal sinusitis.Methods The clinical data of 145 patients with allergic fungal sinusitis who had received treatment in our hospital from January 2010 and January 2014 were reviewed.According to different treatment methods,they were divided into two groups,65 cases in the control group was treated with conventional surgical treatment,80 cases in the obeservation group was treated with endoscopic sinus surgery combined with postoperative treatment.The therapeutic conditions of two groups were compared. Results The symptom scores of patients with polyps,edema,rhinorrhea in two groups were decreased compared with those before treatment, and the obeservation group decreased more significantly (P <0.05,P <0.01).After the operation,patients with nasal mucociliary transport rate of two groups were higher compared with postoperative 6 months and 9 months,and the obeservation group improved more significantly (P <0.05).In addition,two groups of postoperative SNOT-20 scores (physiological problems,limitations and affective outcomes)treatment were lower than those before,and the obeservation group decreased significantly than that of the control group (P <0.05,P <0.01).Con-clusion Endoscopic sinus surgery combined with postoperative nasal irrigation can effectively alleviate the symptoms and improve the prog-nosis in the treatment of allergic fungal sinusitis.

Objective To study the roles of the contact heat evoked potential (CHEP) in evaluating the small nerve fibers of cranial and spinal in elderly diabetic patients,and to analyze the feature of the small fibers in order to provide scientific foundations for early diagnosis of diabetic neuropathy (DN).Methods Totally 50 diabetic patients and 40 healthy subjects were included in this study.The diabetic patients were divided into the normal nerve conduction group (n=17) and the abnormal nerve conduction group (n=33).CHEP was determined and thermal stimuli was given to the area of eyelid,forearm and peroneal.Sensory and motor nerve conduction velocity in the upper and lower limbs were tested in all diabetic patients.Results Compared with the healthy group,the N wave latencies were prolonged and the N-P amplitudes were reduced in the area of eyelid,forearm and peroneal in diabetic patients (all P＜0.01).Compared with the healthy group,the logarithm of N-P amplitudes were reduced in areas of forearm and peroneal [(1.70±0.10) vs.(1.60±0.14),(1.65±0.078) vs.(1.54±0.15),both P＜0.05] and N wave latencies were prolonged in eyelid area [(343.1±18.2) ms vs.(385.4±26.5) ms,P＜0.05] in normal nerve conduction group.Compared to group with normal nerve conduction velocity,the logarithm of N-P amplitudes was reduced in peroneal area [(1.54±0.15) vs.(1.44±0.15),P＜0.05] in abnormal nerve conduction group.Conclusions CHEP can detect the early impairment of the small fibers in elderly diabetic patients.The early smallfiber impairments in diabetic neuropathy may be axon-oriented in spinal nerves and myelin-oriented in cranial nerves.