Osteonecrosis of the femoral head (ONFH) can cause femoral head depression and cortical discontinuity. Treatment for ONFH remains challenging. We performed botulinum toxin type A injection to psoas major muscle in five patients with radiological femoral head collapse (Association Research Circulation Osseus classification stage III) who were non-responsive after two years of conservative treatment (tramadol 200 mg/day, mefenamic acid 1,000 mg/day). At two weeks after the procedure, their mean hip pain was decreased from 88 ± 0.4/100 mm to 22 ± 0.4/100 mm based on visual analogue scale (VAS). The pain was maintained at a minimum of 20/100 mm and a maximum of 30/100 mm in VAS for at least six weeks after the procedure. These values were mean ± SD. These patients were followed-up for 6 months. There was no exacerbation of pain from repeated (three times) botulinum toxin type A injection to the psoas major muscle.
Botulinum Toxins* ; Botulinum Toxins, Type A* ; Classification ; Depression ; Femur Head Necrosis ; Head* ; Hip ; Humans ; Mefenamic Acid ; Osteonecrosis* ; Psoas Muscles*

PURPOSE: Mefenamic acid (MEF) as a non-steroidal anti-inflammatory drug is used as a medication for relieving of pain and inflammation. Radiation-induced inflammation process is involved in DNA damage and cell death. In this study, the radioprotective effect of MEF was investigated against genotoxicity induced by ionizing radiation in human blood lymphocytes. MATERIALS AND METHODS: Peripheral blood samples were collected from human volunteers and incubated with MEF at different concentrations (5, 10, 50, or 100 microM) for two hours. The whole blood was exposed to ionizing radiation at a dose 1.5 Gy. Lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis blocked binucleated lymphocyte. RESULTS: A significant decreasing in the frequency of micronuclei was observed in human lymphocytes irradiated with MEF as compared to irradiated lymphocytes without MEF. The maximum decreasing in frequency of micronuclei was observed at 100 microM of MEF (38% decrease), providing maximal protection against ionizing radiation. CONCLUSION: The radioprotective effect of MEF is probably related to anti-inflammatory property of MEF on human lymphocytes.
Cell Death ; Cytokinesis ; DNA Damage ; Healthy Volunteers ; Humans* ; Inflammation ; Lymphocytes* ; Mefenamic Acid* ; Micronucleus Tests ; Radiation, Ionizing ; Radiation-Protective Agents

A 26-year-old male undergoing thoracotomy and bleeding control received a preoperative thoracic epidural for postoperative analgesia. On the fifth postoperative day, paralysis of both lower limbs occurred and urgent magnetic resonance imaging showed massive anterior epidural hematoma. During laminectomy and decompression, platelet dysfunction was diagnosed and preoperative non-steroidal anti-inflammatory drugs medications were supposed to the cause of platelet dysfunction. After infusion of ten units of platelet concentrate, coagulopathy was improved. We should be more careful to drugs with antiplatelet effect when using regional analgesia.
Adult ; Analgesia ; Analgesia, Epidural* ; Blood Platelets ; Decompression ; Hematoma* ; Hemorrhage ; Humans ; Ketorolac* ; Laminectomy ; Lower Extremity ; Magnetic Resonance Imaging ; Male ; Mefenamic Acid* ; Paralysis ; Thoracotomy

mefenamic acid, aspirin and celecoxib, COX-2 inhibitor, were inoculated to HN 22 cell line, the following results were obtained through tumor cell viability by wortmannin, growth curve of tumor cell line, apoptotic index, PGE2 synthesis, total RNA extraction, RT-PCR analysis and TEM features.1. When wortmannin and celecoxib were given together, the survival rate of tumor cells was lowest about 47 percent. So wortmannin had an effect on the decrease of survival rate of tumor cells.2. In growth curve, the slowest growth was observed in celecoxib inoculated group.3. The synthesis of PGE2 was decreased in all group and the obvious suppression and highest apoptotic index was observed in celecoxib inoculated group.4. Suppression of expression of COX-2 mRNA was evident in celecoxib inoculated group. But that of COX-1,2 mRNA was observed in mefenamic acid inoculated group and aspirin inoculated group.5. In celecoxib inoculated group, mRNA expression of AKT1 was decreased and that of PTEN &d expression of caspase 3 and 9 was evidently increased.Depending on above results, when celecoxib was inoculated to oral squamous cell carcinoma cell line, an increase of mRNA expression of caspase 3,9 and PTEN is related to a decrease of mRNA expression of AKT1. Wortmannin had an effect on the decrease of survival rate of tumor cells. Celecoxib might induce apoptosis of tumor cell by suppression of AKT1 pathway and COX-2 inhibition. This results suggested that COX-2 inhibitor might be significantly effective in chemoprevention of oral squamous cell carcinoma.]]>
Androstadienes ; Apoptosis ; Aspirin ; Carcinoma, Squamous Cell ; Caspase 3 ; Cell Line ; Cell Line, Tumor ; Cell Survival ; Chemoprevention ; Dinoprostone ; Mefenamic Acid ; Pyrazoles ; RNA ; RNA, Messenger ; Sulfonamides ; Survival Rate ; Celecoxib

Mefenamic acid and COX-2 selective inhibitor, Celecoxib in HN4 cell line. And then the cell line was evaluated with MTT assay and growth curve, the production of PGE2, total RNA extraction and RT-PCR analysis, and TEM The results were obtained as follows: 1. After administration of medication, in the result of MTT assay, Celecoxib inoculated group inhibit the cell growth rather than Mefenamic acid inoculated group. 2. The growth curve of cell line showed as time passes by there was a dramatic cell growth in the control group, and gradual growth inhibition was found in medication inoculated group and, in Celecoxib inoculated group there was more inhibition of cell growth. 3. After the administration of medication, Celecoxib tend to inhibit the synthesis of PGE2 more than Mefenamic acid. Mefenamic acid inhibit the synthesis of PGE2 more as the concentration gets high, but Celecoxib inhibited the synthesis of PGE2 even in low concentration. 4. After the administration of medication, the revelation of COX mRNA in cell line, there was a 50% decrease in COX-1, 60% decrease in COX-2 as in 50 micrometer Mefenamic acid, and in Celecoxib 50 micrometer there was not much difference in COX-1 and 90% decrease in COX-2 was found. 5. HN4 cell line showed broken nucleus and tangled cytoskeleton bundles in cytoplasm which meant apoptotic features after the treatment of Celecoxib in TEM view. Depending on the above results, we estimate that the inhibition of the expression of COX-2 cause the growth suppression of the oral squamous cell carcinoma, and it get achieved through pathway of reduced PGE2 production and increased apoptosis. In addition to, because COX-2 selective inhibitor specifically act to COX-2, it is considered that COX-2 selective inhibitor has the adequate potential as chemopreventive agent for oral squamous cell carcinoma.]]>
Apoptosis ; Carcinoma, Squamous Cell ; Cell Line ; Cytoplasm ; Cytoskeleton ; Dinoprostone ; Mefenamic Acid ; Mouth Neoplasms ; Pyrazoles ; RNA ; RNA, Messenger ; Sulfonamides ; Celecoxib

It has been focused on the importance of the host inflammatory response in periodontal pathogenesis and progression, treatment has been introduced to control the host response and the method, which diminishes production and activity of MMP by doxycycline, has been used in periodontal field. MMP is a proteolytic enzyme which plays a major role in tissue destruction and MMP-1 is secreted in the periodontally healthy tissue, while MMP-8, 9, 13, etc in the inflammatory state. Among these, MMP-13 has been discovered lately and reported to degrade primarily type II collagen. Periodontal ligament (PDL) cell plays a role in destruction of periodontal tissue. This study was to evaluate the effect of doxycycline and mefenamic acid, non-steroidal antiinflammatory drug on MMP-13 mRNA expression in the rat PDL cell. Doxycycline concentration of 1~100 microgram/ml was added rat PDL cell and cell activity was measured by MTT assay at day 1 and 3. MMP-13 gene expression was evaluated by RT-PCR after PDL cells were pre-treated for 1 hour with doxycycline (50 microgram/ml) alone or with mefenamic acid (10(-6)M), then added IL-1beta(1.0 ng/ml) and incubated for 16 -18 hours. The results are as follows: 1. Cell activity decreased significantly at 24 and 72 hours in 100 microgram/ml (p<0.05). 2. Level of MMP-13 mRNA was in 202% increase by IL-1beta and in pre-treating doxycycline group, expression of IL-1beta induced MMP-13 mRNA was inhibited by 31% than IL-1beta treated only. 3. Mefenamic acid did not inhibit on the expression of IL-1beta induced MMP-13 mRNA, while mefenamic acid in combination with doxycycline inhibited the expression by 41% compared to only IL-1beta stimulation. These results suggest that doxycycline synergistically inhibit the expression of IL-1beta induced MMP-13 mRNA in combination with mefenamic acid.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; Collagen Type II ; Doxycycline* ; Gene Expression ; Mefenamic Acid* ; Periodontal Ligament* ; Rats* ; RNA, Messenger*

PURPOSE: For the management of patent ductus arteriosus(PDA) in premature infants, fluid restriction, correction of anemia, mechanical ventilation, diuretics, and surgery have been used, and the closure rate of PDA has improved significantly since the introduction of indomethacin and mefenamic acid as pharmacologic treatments of PDA. We studied to evaluate and compare the therapeutic effects of indomethacin and mefenamic acid in the management of premature infants with PDA. METHODS: 32 inborn premature infants who were hospitalized in NICU and diagnosed as PDA by cardiac sector were retrospectively studied and divided into two groups : An indomethacin treated group and a mefenamic acid treated group. Their gestational age, birth weight, blood urea nitrogen(BUN), creatinine(Cr), platelet count, urine output, fluid therapy, postnatal age, closure rate of PDA, and etc. were examined and conpared through the medical record review. RESULTS: The mean postnatal age on drug use was 4.6 days in intravenous indomethacin treated group(n=18), 9.0 days in oral mefenamic acid treated group(n=14), and the mean gestational age was 32.0 weeks and 32.3 weeks, respectively. After the use of each drugs, platelet count and urine output decreased, whereas blood urea nitrogen and creatinine increased. The closure rate of PDA was 94.4%(17/18) in the indomethacin treated group and 85.7%(12/14) in the mefenamic acid treated group(P=0.568). On the multivariate analysis except for the drugs, the most significant factor on PDA closure in preterm neonates was total amount of intake(P=0.000). CONCLUSION: We conclude that intravenous indomethacin is as effective as oral mefenamic acid in the therapy of preterm infants with PDA.
Anemia ; Birth Weight ; Blood Urea Nitrogen ; Creatinine ; Diuretics ; Ductus Arteriosus, Patent* ; Fluid Therapy ; Gestational Age ; Humans ; Indomethacin* ; Infant, Newborn ; Infant, Premature* ; Medical Records ; Mefenamic Acid* ; Multivariate Analysis ; Platelet Count ; Respiration, Artificial ; Retrospective Studies ; Urea

Vibrio vulnificus cytolysin caused platelet cytolysis and increased intracellular calcium concentration ((Ca2+))i) of rat platelets in a concentration-dependent manner. In the presence of V. vulnificus cytolysin (3 HU/ml), lactate dehydrogenase (LDH) activity was increased from 1.3+/-0.4% of control to 64.3+/-3.4% in platelet suspension buffer. In Ca2+-free platelet suspension buffer, however, V. vulnificus cytolysin did not induce (Ca2+)i increase and LDH release. Addition of EGTA (2 mM) to suspension buffer after the initial Ca2+ influx reversed (Ca2+)i to the control level. However, a Ca2+ channel blocker verapamil (20 muM) or mefenamic acid (20 muM) did not inhibit V. vulnificus cytolysin-induced (Ca2+)i increase and LDH release. Divalent cations such as Co2+, Cd2+ or Mn2+ (2 mM each) also did not alter V. vulnificus cytolysin-induced (Ca2+)i increase and LDH release. V. vulnificus cytolysin (3 HU/ml)-induced calcium influx was completely blocked by lanthanum (2 mM). Lanthanum (2 mM) also completely blocked V. vulnificus cytolysin (3 HU/ml)-induced LDH release. Osmotic protectants such as, raffinose, sucrose or PEG600 (50 mM each) did not inhibit the lytic activity of V. vulnificus cytolysin. In conclusion, lanthanum sensitive Ca2+ influx plays a significant role in Vibrio vulnificus cytolysin-induced platelet cytolysis and thrombocytopenia in V. vulnificus infection.
Animals ; Blood Platelets* ; Calcium ; Cations, Divalent ; Egtazic Acid ; Ethanol ; L-Lactate Dehydrogenase ; Lanthanum ; Mefenamic Acid ; Perforin* ; Raffinose ; Rats* ; Sucrose ; Thrombocytopenia ; Verapamil ; Vibrio vulnificus* ; Vibrio*

PURPOSE: Nonsteroidal anti-inflammatory drugs inhibit the synthesis of prostaglandin(PG) through inhibition of the enzyme, cyclooxygenase. Some of the arachidonic acid metabolites may influence the spread of electrocortical activity, and delay the pentylenetetrazol(PTZ)-induced seizures. The purpose of the present study was to evaluate systematically the effect of pretreatment with PG synthetase inhibitors on PTZ-induced seizures. METHODS: To evaluate the effects of pretreatment with PG synthetase inhibitors on seizures produced by 30mg/kg, 60mg/kg PTZ, free-moving Sprague-Dawley rats weighing 250-300gm with chronically-implanted supracortical electrodes were used. Electrocorticogram was recorded for 1hr prior to pretreatment administration of either saline (control) or PG synthetase inhibitor and 1hr after administration of PTZ. RESULTS: 1) A 30mg/kg dose of PTZ produced bursts of high voltage activity after a latency of 616+/-72sec. Although the animals showed spontaneous movements throughout the test period, they were motionless or myoclonus. The number of high voltage bursts during the first hr of the test period was 368+/-31.2) A 30mg/kg of PTZ produced high voltage bursts after a latency of 1118+/-35sec which was significantly greater for the ibuprofen-pretreated groups receiving 90mg/kg when compared to the saline-pretreated group. In addition, the number of high voltage bursts(173+/-17) which occurred during the first hr of the test period was significantly smaller than that recorded from the saline-pretreated group. 3) After pretreatment with a 450mg/kg dose of paracetamol, a 30mg/kg of PTZ produced bursts of electrocortical activity with onset latencies of 665+/-112sec which were not significantly different than those recorded from the saline-pretreated group. The number of high voltage bursts during the first hr of the test period was 141+/-30 which was significantly smaller than that recorded from the saline-pretreated group. 4) A 50mg/kg dose of mefenamic acid pretreatment caused 30mg/kg PTZ-induced high voltage bursts after latency of 227+/-47sec which was significantly shorter than that recorded from the saline-pretreated group. The number of high voltage bursts during the first hr of the test period was 522+/-42 which was significantly greater than that recorded from the saline-pretreated group.5) A 60mg/kg dose of PTZ produced bursts of high voltage activity after a latency of 79+/-14sec. An electrocortical seizure with concurrent convulsions appeared subsequently by 129+/-30sec. 6) A 60mg/kg of PTZ produced high voltage bursts after a latency of 217+/-38sec which was significantly greater for the ibuprofen-pretreated groups receiving 90mg/kg when compared to the saline-pretreated group. An electrocortical seizure with concurrent convulsions appeared subsequently by 287+/-30sec.7) After pretreatment with paracetamol(450mg/kg), a 60mg/kg of PTZ produced bursts of electrocortical activity with onset latencies of 143+/-36sec which were significantly different than those recorded from the saline-pretreated group. There was no convulsive or no electrocortical seizure.8) A 50mg/kg mefenamic acid pretreatment caused 60mg/kg PTZ-induced high voltage bursts after latency of 35+/-5sec which was significantly shorter than that recorded from the saline-pretreated group. An electrocortical seizure appeared subsequently by 58+/-10sec which was significantly different than that recorded from the saline-pretreated group. CONCLUSION: It is possible that the delay and/or block of convulsions induced by the higher doses of PTZ was the result of PG synthesis inhibition. However, the PG synthetase inhibitors had a more differential effect on general PTZ-induced excitation of the CNS evidenced by changes in electrocortical activity. The mechanism underlying this action could be either through inhibition of the activity of cyclooxygenase in tissues which play a role in the manifestation of seizure activity or through an action not related to their common action on cyclooxygenase.
Acetaminophen ; Animals ; Arachidonic Acid ; Electrodes ; Ibuprofen ; Ligases ; Mefenamic Acid ; Myoclonus ; Pentylenetetrazole ; Prostaglandin-Endoperoxide Synthases* ; Rats, Sprague-Dawley ; Seizures*

PURPOSE: Patent ductus arteriosus, derived left to right shunt flows, elevate the pulmonary artery pressure in infants and children and may alter right ventricular afterload thereby right ventricular function. Therefore, we examined the effects of patent ductus arteriosus on the right ventricular systolic time interval in premature infants by non-invasive Doppler echocardiography. METHODS: Tweleve premature infants with patent ductus arteriosus were studied by M-mode and Doppler echocardiography before and after treatment with mefenamic acid. Heart rate (HR), ratio of left atrium/aorta (LA/AO), right ventricular preejection period (RVPEP), right ventricular ejection time (RVET) and right ventricular systolic time interval (RVSTI : ratio of RVPEP/RVET), both corrected or uncorrected for heart rate were measured. RESULTS: After mefenamic acid treatment, in infants showing clinical response, right ventricular preejection period (RVPEP) and right ventricular systolic time intetrval (RVSTI), both corrected or uncorrected for heart rate, decreased significantly following ductal closure (RVPEP : 70.3msecc +/- 14.5 vs 54.3msec +/- 10.9, P<0.01, RVPEPc : 129.2msec +/- 13.5 vs 111.7msec +/- 8.4, P<0.01, RVSTI : 0.38 +/- 0.09 vs 0.28 +/- 0.05, P<0.05, RVSTIc : 0.31 +/- 0.04 vs 0.27 +/- 0.03, P<0.01). CONCLUSION: Premature infants with patent ductus arteriosus exhibit echocardiographic evidence of increased RVSTI as a result of increased right ventricular afterload. This results suggest that we have to make every effort to prevent the ductal reopening or early closure of ductus arteriosus in premature infants.
Child ; Ductus Arteriosus ; Ductus Arteriosus, Patent* ; Echocardiography ; Echocardiography, Doppler* ; Heart Rate ; Heart Ventricles* ; Humans ; Infant ; Infant, Newborn ; Infant, Premature* ; Mefenamic Acid ; Pulmonary Artery ; Systole ; Ventricular Function, Right