An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of donepezil in human plasma. Donepezil and donepezil-D4 were extracted from human plasma by liquid-liquid extraction using a mixture of hexane and ethyl acetate (70:30 v/v). The extracted samples were analyzed using a Thermo Hypersil Gold C18 column with 5% acetic acid in 20 mM ammonium acetate buffer (pH 3.3) and 100% acetonitrile as a mobile phase with the 60:40 (v:v) isocratic method, at a flow rate of 0.3 mL/min. The injection volume was 3 µL, and the total run time was 3 min. Inter- and intra-batch accuracies ranged from 98.0% to 110.0%, and the precision was below 8%. The developed method was successfully applied to the quantification of donepezil in human plasma. The mean (standard deviation) maximum concentration and the median (range) time to maximum concentration were 8.6 (2.0) ng/mL and 2.0 h (1.0~5.0 h), respectively, in healthy Koreans after oral administration of 5 mg donepezil.
Acetic Acid ; Administration, Oral ; Ammonium Compounds ; Humans ; Liquid-Liquid Extraction ; Mass Spectrometry ; Methods ; Plasma

Acetic Acid ; administration & dosage ; therapeutic use ; Adult ; Aged ; Cysts ; drug therapy ; Female ; Humans ; Liver Diseases ; drug therapy ; Male ; Middle Aged

BACKGROUND/OBJECTIVES: Constipation is a condition that can result from intestinal deformation. Because humans have an upright posture, the effects of gravity can cause this shape deformation. Oligosaccharides are common prebiotics and their effects on bowel health are well known. However, studies of the physiological functionality of a product that contains both lactulose and galactooligosaccharides are insufficient. We investigated the constipation reduction effect of a dual-type oligosaccharide, Dual-Oligo, in loperamide-treated rats. MATERIALS/METHODS: Dual-Oligo consists of galactooligosaccharides (15.80%) and lactulose (51.67%). Animals were randomly divided into four groups, the normal group (normal), control group (control), low concentration of Dual-Oligo (LDO) group, and high concentration of Dual-Oligo (HDO) group. After 7 days of oral administration, fecal pellet amount, fecal weight, water content of fecal were measured. Blood chemistry, short-chain fatty acid (SCFA), gastrointestinal transit ratio and length and intestinal mucosa were analyzed. RESULTS: Dual-Oligo increased the fecal weight, and water content of feces in rats with loperamide-induced constipation. Gastrointestinal transit ratio and length and area of intestinal mucosa significantly increased after treatment with Dual-Oligo in loperamide-induced rats. A high concentration of Dual-Oligo tended to produce more acetic acid than that observed for the control group, and Dual-Oligo affected the production of total SCFA. Bifidobacteria concentration of cecal contents in the high-concentration oligosaccharide (HDO) and low-concentration oligosaccharide (LDO) groups was similar to the result of the normal group. CONCLUSIONS: These results showed that Dual-Oligo is a functional material that is derived from a natural food product and is effective in ameliorating constipation.
Acetic Acid ; Administration, Oral ; Alcian Blue ; Animals ; Chemistry ; Constipation* ; Feces ; Gastrointestinal Transit ; Gravitation ; Humans ; Intestinal Mucosa ; Lactulose ; Loperamide ; Oligosaccharides* ; Posture ; Prebiotics ; Rats* ; Water

In the present study, we aimed to analyze the antinociceptive, immunomodulatory and antipyretic activities of nymphayol were investigated in wistar rats and mice. Antinociceptive effect was evaluated by acetic acid induced writhing, formalin induced paw licking and hot-plate tests. Immunomodulatory activity was assessed by neutrophil adhesion test, humoral response to sheep red blood cells, delayed-type hypersensitivity, phagocytic activity and cyclophosphamide induced myelosuppression. Antipyretic activity was evaluated by yeast induced hyperthermia in rats. Nymphayol produced significant (p<0.05) antinociceptive activity in acetic acid induced writhing response and late phase of the formalin induced paw licking response. Pre-treatment with nymphayol (50 mg/kg, oral) evoked a significant increase in neutrophil adhesion to nylon fibres. The augmentation of humoral immune response to sheep red blood cells by nymphayol (50 mg/kg) was evidenced by increase in antibody titres in rats. Oral administration of nymphayol (50 mg/kg) to rats potentiated the delayed-type hypersensitivity reaction induced by sheep red blood cells. Treatment with nymphayol showed a significant (p<0.05) reduction in pyrexia in rats. The results suggest that nymphayol possesses potent anti-nociceptive, immunomodulatory and antipyretic activities.
Acetic Acid ; Administration, Oral ; Animals ; Cyclophosphamide ; Erythrocytes ; Fever ; Flowers* ; Formaldehyde ; Hypersensitivity ; Hyperthermia, Induced ; Immunity, Humoral ; Mice ; Neutrophils ; Nylons ; Nymphaea* ; Rats ; Rats, Wistar ; Sheep ; Yeasts

BACKGROUND: Cervical cancer is still the second most frequent cancer among Indonesian women, thus screening program is still critically important to prevent it. Visual inspection with acetic acid (VIA) was introduced as a method which is most suitable with Indonesia's condition compared with the other screening methods. The Female Cancer Program from Jakarta Regional collaborated with Leiden University in 2007 to 2011 has done cervical cancer screening using VIA method, involving 25,406 women spreading across several primary health centers in Jakarta. By using these data, we found out the prevalence, age distribution, and risk factor of VIA positive in Jakarta as a basis to predict the budget and logistics for the next cervical cancer screening and to do an advocating to the Jakarta's government. METHODS: A secondary data analysis was conducted from several areas in Jakarta from 2007 to 2011. VIA test was used as the screening method, and performed by doctors and midwives with technical supervision by gynecologists. RESULTS: From 25,406 women, there were 1,192 cases (4.7%) of VIA test positive. The risk factors that can significantly influence the result of VIA positive were number of marriage, parity, smoking habits, and the use of hormonal contraception with OR 1.51, 1.85, 1.95, and 0.68, respectively. CONCLUSIONS: Prevalence of VIA test-positive is 4.7% in Jakarta population. The findings of precancerous lesions and cervical cancers are not only between thirty and fifty years old, but also below the thirty years old and after fifty years old. We suggest that VIA test should be performed to all reproductive age and elder women who are not screened yet.
Acetic Acid ; Age Distribution* ; Budgets ; Contraception ; Female ; Humans ; Marriage ; Mass Screening ; Methods ; Midwifery ; Organization and Administration ; Parity ; Prevalence* ; Risk Factors* ; Smoke ; Smoking ; Statistics as Topic ; Uterine Cervical Neoplasms

Acetic Acid ; administration & dosage ; therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Cysts ; therapy ; Female ; Humans ; Liver Diseases ; therapy ; Male ; Middle Aged

OBJECTIVE: We wanted to determine whether combined radiofrequency ablation (RFA) and acetic acid-hypertonic saline solution (AHS) instillation can increase the extent of thermally mediated coagulation in in vivo rabbit liver tissue. We also wished to determine the optimal concentration of the solution in order to maximize its effect on extent of the RFA-induced coagulation. MAERIALS AND METHODS: Forty thermal ablation zones were produced in 40 rabbits by using a 17-gauge internally cooled electrode with a 1-cm active tip under ultrasound guidance. The rabbits were assigned to one of four groups: group A: RFA alone (n=10) ; group B: RFA with 50% AHS instillation (n=10) ; group C: RFA with 25% AHS instillation (n=10) ; group D: RFA with 15% AHS instillation (n=10). A range of acetic acid concentrations diluted in 36% NaCl to a total volume of 1 mL were instilled into the liver before RFA. The RF energy (30 W) was applied for three minutes. After RFA, in each group, the maximum diameters of the thermal ablation zones in the gross specimens were compared. Technical success and the complications that arose were evaluated by CT and on the basis of autopsy findings. RESULTS: All procedures are technically successful. There were six procedure-related complications (6/40; 15%) : two localized perihepatic hematomas and four chemical peritonitis. The incidence of chemical peritonitis was highest for group B with the 50% AHS solution instillation (30%). With instillation of 15% AHS solution, a marked decrease of tissue impedance (24.5+/-15.6 omega) and an increase of current (250 mA) occurred as compared to RFA alone. With instillation of the solutions before RFA (group B, C and D), this produced a greater mean diameter of coagulation necrosis than the diameters for rabbits not instilled with the solution (group A) (p < 0.05). However, there was no significant difference between group B, C, and D. CONCLUSION: Combined AHS instillation and RFA can increase the dimension of coagulation necrosis in the liver with a single application. A low concentration of AHS (15%) showed similar effects in increasing the extent of RF-induced coagulation, but there were less side effects as compared to the high concentration of AHS.
Acetic Acid/*administration & dosage ; Animals ; *Catheter Ablation ; Combined Modality Therapy ; Instillation, Drug ; Liver/*drug effects/pathology/*surgery ; Liver Neoplasms/drug therapy/surgery ; Necrosis ; Rabbits ; Saline Solution, Hypertonic/*administration & dosage

Gabapentin decreases the level of glutamate and elevates that of garmma-amino-butyric acid in the central nervous system. Gabapentin was shown to have antinociceptive effects in several facilitated pain models. Intrathecal gabapentin was also known to be effective in reducing mechanical allodynia in animals with neuropathic pain. In this study, we investigated to see whether intrathecal gabapentin produces antihyperalgesic effects on thermal and mechanical hyperalgesia in neuropathic rats and whether its effects are associated with motor impairment. To induce neuropathic pain in Sprague-Dawley rats, left L5 and L6 spinal nerves were ligated. After a week, lumbar catheterization into subarachnoid space was performed. Then, paw withdrawal times to thermal stimuli and vocalization thresholds to paw pressure were determined before and up to 2 hr after intrathecal injection of gabapentin. Also, motor functions including performance times on rota-rod were determined. Intrathecal gabapentin attenuated significantly thermal and mechanical hyperalgesia in neuropathic rats, but did not block thermal and mechanical nociception in sham-operated rats. Intrathecal gabapentin of antihyperalgesic doses inhibited motor coordination performance without evident ambulatory dysfunction. This study demonstrates that intrathecal gabapentin is effective against thermal and mechanical hyperalgesia, in spite of moderate impairment of motor coordination.
Acetic Acids/administration & dosage/*pharmacology ; *Amines ; Analgesics/administration & dosage/*pharmacology ; Animals ; *Cyclohexanecarboxylic Acids ; Dose-Response Relationship, Drug ; Injections, Spinal ; Ligation ; Male ; Rats ; Rats, Sprague-Dawley ; Spinal Nerves/*injuries ; Time Factors ; *gamma-Aminobutyric Acid

Spinal gabapentin has been known to show the antinociceptive effect. Although several assumptions have been suggested, mechanisms of action of gabapentin have not been clearly established. The present study was undertaken to examine the action mechanisms of gabapentin at the spinal level. Male SD rats were prepared for intrathecal catheterization. The effect of gabapentin was assessed in the formalin test. After pretreatment with many classes of drugs, changes of effect of gabapentin were examined. General behaviors were also observed. Intrathecal gabapentin produced a suppression of the phase 2 flinching, but not phase 1 in the formalin test. The antinociceptive action of intrathecal gabapentin was reversed by intrathecal NMDA, AMPA, D-serine, CGS 15943, atropine, and naloxone. No antagonism was seen following administration of bicuculline, saclofen, prazosin, yohimbine, mecamylamine, L-leucine, dihydroergocristine, or thapsigargin. Taken together, intrathecal gabapentin attenuated only the facilitated state. At the spinal level, NMDA receptor, AMPA receptor, nonstrychnine site of NMDA receptor, adenosine receptor, muscarinic receptor, and opioid receptor may be involved in the antinociception of gabapentin, but GABA receptor, L-amino acid transporter, adrenergic receptor, nicotinic receptor, serotonin receptor, or calcium may not be involved.
Acetic Acids/administration & dosage ; Acetic Acids/metabolism ; Acetic Acids/pharmacology* ; Adrenergic Antagonists/metabolism ; Adrenergic alpha-Antagonists/metabolism ; Analgesics/administration & dosage ; Analgesics/metabolism ; Analgesics/pharmacology* ; Animals ; Atropine/metabolism ; Dihydroergocristine/metabolism ; Enzyme Inhibitors/metabolism ; Excitatory Amino Acid Agonists/metabolism ; GABA Antagonists/metabolism ; Injections, Spinal ; Leucine/metabolism ; Male ; Mecamylamine/metabolism ; Muscarinic Antagonists/metabolism ; N-Methylaspartate/metabolism ; Naloxone/metabolism ; Narcotic Antagonists/metabolism ; Nicotinic Antagonists/metabolism ; Pain Measurement ; Quinazolines/metabolism ; Rats ; Rats, Sprague-Dawley ; Serine/metabolism ; Spinal Cord/drug effects* ; Thapsigargin/metabolism ; Triazoles/metabolism ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism

Bi-yuan-ling granule (BLG) is a traditional Chinese medicine compound composed mainly of baicalin and chlorogenic acid. It has been demonstrated to be clinically effective for various inflammatory diseases such as acute rhinitis, chronic rhinitis, atrophic rhinitis and allergic rhinitis. However, the underlying mechanisms of BLG against these diseases are not fully understood. This study aimed to explore the anti-inflammatory and analgesic activities of BLG, and examine its protective effects on mouse acute lung injury (ALI). The hot plate test and acetic acid-induced writhing assay in Kunming mice were adopted to evaluate the pain-relieving effects of BLG. The anti-inflammatory activities of BLG were determined by examining the effects of BLG on xylene-caused ear swelling in Kunming mice, the cotton pellet-induced granuloma in rats, carrageenan-induced hind paw edema and lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The results showed that BLG at 15.5 mg/g could significantly relieve the pain by 82.5% (P<0.01) at 1 h after thermal stimulation and 91.2% (P<0.01) at 2 h after thermal stimulation. BLG at doses of 7.75 and 15.5 mg/g reduced the writhing count up to 33.3% (P<0.05) and 53.4% (P<0.01), respectively. Additionally, the xylene-induced edema in mice was markedly restrained by BLG at 7.75 mg/g (P<0.05) and 15.5 mg/g (P<0.01). BLG at 5.35 and 10.7 mg/g significantly reduced paw edema by 34.8% (P<0.05) and 37.9% (P<0.05) at 5 h after carrageenan injection. The granulomatous formation of the cotton pellet was profoundly suppressed by BLG at 2.68, 5.35 and 10.7 mg/g by 15.4%, 38.2% (P<0.01) and 58.9% (P<0.001), respectively. BLG also inhibited lung W/D ratio and the release of prostaglandin E2 (PGE2) in ALI mice. In addition, the median lethal dose (LD50), median effective dose (ED50) and half maximal inhibitory concentration (IC50) of BLG were found to be 42.7, 3.2 and 12.33 mg/g, respectively. All the findings suggest that BLG has significantly anti-inflammatory and analgesic effects and it may help reduce the damage of ALI.
Acetic Acid ; Acute Lung Injury ; chemically induced ; drug therapy ; pathology ; Analgesics ; pharmacology ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Carrageenan ; administration & dosage ; Chlorogenic Acid ; pharmacology ; Dinoprostone ; antagonists & inhibitors ; biosynthesis ; Disease Models, Animal ; Dosage Forms ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Ear ; pathology ; Edema ; chemically induced ; drug therapy ; pathology ; Flavonoids ; pharmacology ; Lipopolysaccharides ; administration & dosage ; Male ; Mice ; Mice, Inbred Strains ; Pain ; chemically induced ; drug therapy ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Xylenes ; administration & dosage