To investigate the earlier cellular alterations(Glucose-6-Pase activity and morphologic features) caused by a hepatotoxin, thioacetamide (TAA), a single dose of the agent (200mg per kg of body weight) was given intraperitoneally to mice, which were sacrificed at intervals of 4, 8 or 16 hours after corresponding treatments. For histochemical study of glucose-6-phosphatase (G6Pase) activity, unfixed frozen sections were incubation of the Wachstein and Meisel medium and stained. The smallest pieces of liver tissue were fixed in glutaraldehyde and osmic acid, and stained by the routine electron-microscopic techniques. Some pieces of liver were fixed in 10% formalin, embedded in paraffin, and stained with hematoxylin and eosin. There was a rapid and progressive loss of G6Pase activity, in an orderly time sequence, in the experimental group. There were also morphologic changes: loss of cytoplasmic basophilia, cell infiltration and necrosis in the centrilobular and intermediate zones, and an increase of sER, small vesicles and ribosomes in the cytoplasm of hepatocytes, the marked changes of nuclei and nucleoli, and a slight increase of lipid droplets in the cytoplasm at 16 hours after intoxication. The correlation between these cellular alterations was discussed in view of mechanisms in the hepatotoxic action.
Acetamides/adverse effects* ; Animal ; Glucose-6-Phosphatase/metabolism* ; Liver/drug effects* ; Liver/enzymology ; Liver/ultrastructure ; Male ; Mice ; Thioacetamide/adverse effects* ; MH - ; Substances: ; Acetamides ; Thioacetamide ; Glucose-6-Phosphatase

To investigate the earlier cellular alterations(Glucose-6-Pase activity and morphologic features) caused by a hepatotoxin, thioacetamide (TAA), a single dose of the agent (200mg per kg of body weight) was given intraperitoneally to mice, which were sacrificed at intervals of 4, 8 or 16 hours after corresponding treatments. For histochemical study of glucose-6-phosphatase (G6Pase) activity, unfixed frozen sections were incubation of the Wachstein and Meisel medium and stained. The smallest pieces of liver tissue were fixed in glutaraldehyde and osmic acid, and stained by the routine electron-microscopic techniques. Some pieces of liver were fixed in 10% formalin, embedded in paraffin, and stained with hematoxylin and eosin. There was a rapid and progressive loss of G6Pase activity, in an orderly time sequence, in the experimental group. There were also morphologic changes: loss of cytoplasmic basophilia, cell infiltration and necrosis in the centrilobular and intermediate zones, and an increase of sER, small vesicles and ribosomes in the cytoplasm of hepatocytes, the marked changes of nuclei and nucleoli, and a slight increase of lipid droplets in the cytoplasm at 16 hours after intoxication. The correlation between these cellular alterations was discussed in view of mechanisms in the hepatotoxic action.
Acetamides/adverse effects* ; Animal ; Glucose-6-Phosphatase/metabolism* ; Liver/drug effects* ; Liver/enzymology ; Liver/ultrastructure ; Male ; Mice ; Thioacetamide/adverse effects* ; MH - ; Substances: ; Acetamides ; Thioacetamide ; Glucose-6-Phosphatase

Acetamides ; adverse effects ; therapeutic use ; Anti-Infective Agents ; Female ; Humans ; Infant, Newborn ; Linezolid ; Male ; Oxazolidinones ; adverse effects ; therapeutic use ; Sepsis ; drug therapy

This study was purposed to evaluate the efficacy and safety of linezolid, vancomycin and teicoplanin for the treatment of patients infected by Gram-positive bacteria in the Department of Hematology by retrospective analysis. The patients with fever in our department from January to December in 2011 were selected for blood culture with Gram-positive bacteria and treated with linezolid, vancomycin or teicoplanin alone.Various parameters were recorded before and after treatment, such as fever time, respiratory symptoms, physical signs, radiographic changes, blood and biochemical routine, and adverse reactions. The efficacy and safety of linezolid, vancomycin and teicoplanin were compared according to the fever abating time, bacterial clearance rate, clinical efficiencies and adverse events. The patients were divided into linezolid group (15 patients), vancomycin group (17 patients) and teicoplanin group (20 patients). The results showed that the mean time of fever abating in linezolid group was (4.43 ± 3.15)d, bacterial clearance rate and clinical efficiency in linezolid group were 55.56% and 86.67%, respectively. The above three data in vancomycin group were (6.83 ± 4.67)d, 54.54% and 76.47% respectively, and were (5.57 ± 4.16)d, 41.67% and 80.00% in teicoplanin group respectively. There was no statistically significant difference between three groups (P > 0.05). There were one case of diarrhea and two cases of thrombocytopenia in the linezolid group, and one case of nausea and two cases of creatinine increase in the vancomycin group. There were three cases of thrombocytopenia in the teicoplanin group. The thrombocytopenia in five cases and the hemogram drop in patients with leukemia after treatment were overlapped, their drug treatment did not stop, but their thrombocytopoiesis recovered to normal-level, thus the drug treatment were considered as no relation with thrombocytopenia. It is concluded that the treatment efficacy between linezolid, vancomycin and teicoplanin for Gram-positive bacterial infections is not statistically different, but linezolid maybe have advantage over vancomycin and teicoplanin in fever abating time, bacterial clearance rate and clinical efficiency.
Acetamides ; adverse effects ; therapeutic use ; Adult ; Aged ; Female ; Gram-Positive Bacterial Infections ; diagnosis ; drug therapy ; Humans ; Linezolid ; Male ; Middle Aged ; Oxazolidinones ; adverse effects ; therapeutic use ; Retrospective Studies ; Teicoplanin ; adverse effects ; therapeutic use ; Vancomycin ; adverse effects ; therapeutic use

Acetamides ; adverse effects ; Adult ; Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Case-Control Studies ; Humans ; Liver ; drug effects ; metabolism ; pathology ; Liver Diseases ; epidemiology ; Middle Aged ; Occupational Exposure ; adverse effects ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of oseltamivir phosphate as treatment for naturally acquired influenza infection.

METHODSThis study was conducted as a double-blind, randomized, placebo-controlled, multicenter trial during the influenza epidemic season from January to April 2001 at 7 centers in China. A total of 478 adults without other medical history, aged 18 to 65 years, were enrolled into the study. All subjects demonstrated febrile respiratory illness of no more than 36 hours' duration with a temperature of 37.8 degrees C or more plus at least two of the following symptoms: coryza/nasal congestion, sore throat, cough, myalgia/muscles aches and pain, fatigue, headache or chills/sweats. Individuals were randomized into either the oseltamivir phosphate or placebo group with identical-looking capsules. Either oral oseltamivir phosphate, 75 mg twice daily, or placebo was administered to the subjects for 5 days.

RESULTSA total of 451 individuals were analyzed for efficacy as the intent-to-treat population (ITT) (216 oseltamivir and 235 placebo) and 273 individuals were identified as influenza-infected through laboratory test, who were then defined as the intent-to-treat infected population (ITTI) (134 oseltamivir and 139 placebo). Four hundred and fifty nine individuals were included in the safety analysis. In the ITTI population, the cumulative alleviation proportion of oseltamivir group was significantly higher than that of the placebo group (P = 0.0466)). The median duration of illness was 91.6 h [95% confidence interval (CI) = 80.2 - 101.3 h] in the oseltamivir group and 95 h (95% CI = 84.5 - 105.3 h) in the placebo group. The median area under the curve of decreased total score was significantly higher in the oseltamivir group than in the placebo group, 1382.9 and 1236.7 score-hours, respectively (P = 0.0196). For the ITT population, similar results were observed. Adverse events (AE) were similarly reported in both the oseltamivir group and the placebo group. The main adverse events following test drug were gastrointestinal symptoms, neurological symptoms and rashes.

CONCLUSIONOseltamivir was effective and well tolerated as treatment of early naturally acquired influenza.

Acetamides ; adverse effects ; therapeutic use ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; Double-Blind Method ; Enzyme Inhibitors ; therapeutic use ; Female ; Humans ; Influenza, Human ; drug therapy ; Male ; Middle Aged ; Neuraminidase ; antagonists & inhibitors ; Oseltamivir

The treatment of benzodiazepine withdrawal is difficult, and the search continues for substances that can reduce craving and the risk of relapse. Here, we report three cases of benzodiazepine addicts with histories of unsuccessful withdrawal attempts who experienced marked reductions in craving and improved relapse prognoses under add-on administration of agomelatine. These cases demonstrate a possible area of use for the antidepressant agomelatine in the treatment of benzodiazepine withdrawal and addiction. The extent to which this effect is due to the anti-craving effects of agomelatine, or its profile of receptor activation, should be further investigated in larger clinical and experimental studies.
Acetamides ; therapeutic use ; Adult ; Antidepressive Agents ; therapeutic use ; Behavior, Addictive ; Benzodiazepines ; adverse effects ; Female ; Follow-Up Studies ; Humans ; Hypnotics and Sedatives ; adverse effects ; Lorazepam ; adverse effects ; Male ; Middle Aged ; Substance Withdrawal Syndrome ; drug therapy ; Substance-Related Disorders ; drug therapy ; Time Factors ; Treatment Outcome

Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also contributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3 mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3 mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water (AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Furthermore, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3 mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3 mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.
Acetamides ; therapeutic use ; Animals ; Chemokine CXCL10 ; metabolism ; Chloroquine ; toxicity ; Chronic Disease ; Cyclopropanes ; adverse effects ; Dehydration ; complications ; Dinitrofluorobenzene ; adverse effects ; Disease Models, Animal ; Formaldehyde ; toxicity ; Freund's Adjuvant ; toxicity ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity ; drug effects ; Pain ; chemically induced ; Pruritus ; chemically induced ; pathology ; Pyrimidines ; therapeutic use ; Receptors, CXCR3 ; antagonists & inhibitors ; genetics ; metabolism ; Skin ; pathology ; Spinal Cord ; drug effects ; metabolism ; pathology ; Time Factors ; p-Methoxy-N-methylphenethylamine ; toxicity