Antioxidant and antimicrobial properties of dihydroquercetin esters

Abstract Flavonoids display various beneficial biological properties, such as antioxidant activity and low cytotoxicity, which make them useful ingredients in foods, pharmaceuticals, and functional cosmetics. In particular, dihydroquercetin (DHQ) is found in various forms, and its derivatives exhibit interesting biological properties. Herein, we report the synthesis of acetylated and butyrylated dihydroquercetin derivatives and their antimicrobial and antioxidant properties. The DHQ derivatives were identified using 1H and 13C NMR spectroscopies and high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry. The chemical stabilities of the acetylated dihydroquercetin derivatives were found to depend on the number of acetate groups, with 3,3',4',4,7-pentaacetyldihydroquercetin found to be the most stable acetylated dihydroquercetin. Furthermore, 7,3',4'-triacetyl- dihydroquercetin exhibited potent antioxidant activity, with an IC50 of 56.67 ± 4.79 µg/mL in the 1,1-diphenyl-2-picrylhydrazyl assay, with DHQ exhibiting a value of 32.41 ± 3.35 µg/mL. The reactive-oxygen-species-scavenging activity of 7,3',4'-triacetyldihydroquercetin was highest among the esters in the ferric reducing ability of plasma assay, but lower than that of DHQ. Overall, both DHQ and 7,3',4'-triacetyldihydroquercetin exhibited antimicrobial behavior against S. aureus and P. acnes using the paper disc assay. DHQ displayed a higher antimicrobial activity, with minimum inhibitory concentrations of 625 µg/mL (P. acnes), 2,500 µg/mL (S. aureus), and 5,000 µg/mL (E. coli). DHQ and acetylated dihydroquercetins are potentially useful as complex antioxidant and antimicrobial materials

Cytotoxic evaluation and LC-MS/MS analysis of aerial parts of Eryngium kotschyi Boiss. grown in Turkey

Abstract Increasing biological activity and phytochemical investigations on Eryngium species showed its potential as pharmaceutical approach. Eryngium kotschyi Boiss. is one of the species of Eryngium genus and is endemic to Turkey. It is known that this plant is traditionally used in the South-western part of Turkey for the treatment of various diseases. This study focuses on cytotoxic activities of methanol extract and ethyl acetate, n-butanol and water sub-extracts from E. kotschyi in A549, COLO 205 and MDA-MB-231 cell lines by Sulforhodamin B assay and qualitative and quantitative determination of phytochemical constituents in active extract by LC-MS/MS. From the result of the study, it was seen that E. kotschyi ethyl acetate (EKE) sub-extract showed the strongest cytotoxic effect with the low IC50 values (50.00; 31.96 and 22.26 µg/mL in A549; COLO 205 and MDA-MB-231 cells at 48 h, respectively). Preliminary examination of the mass spectrums revealed the presence of 15 phytochemical compounds in active sub-extract and 7 of them was quantified. According to quantitative analyses the main compounds of EKE sub-extract were rosmarinic acid (485.603 µg/mgextract), chlorogenic acid (62.355 µg/mgextract) and caffeic acid (59.266 µg/mgextract). Moreover, this preliminary study on inhibitory activity of EKE sub-extract suggests further toxicologic investigations and detailed investigation on cytotoxic effect of various combinations of determined compounds

Acrocarpus fraxinifolius Wight and Arn. Bark; phenolics, toxicity studies, antioxidant and anti-inflammatory activities

The purpose of the survey was to determine acute & chronic toxicity; in vivo antioxidant and anti-inflammatory actions of the different extracts of A. fraxinifolius Wight and Arn bark; along with estimation of the phenolic, flavonoidal contents and investigation of phenolic metabolites that may attribute to the activities. LD50 of the total ethanol extract (TEE) was 7.1 g/kg b. wt, the radical scavenging activity of DPPH showed 60.31% inhibition, FRAP ability and ABTS+ activity showed 55.024 and 67.217 µmol Trolox/100 g dry weight, respectively. TEE followed by ethyl acetate extract (EAE) at 100 mg/kg b.w exhibited the highest in vivo antioxidant activity (94.51% and 91.08% potency, respectively) compared with Vit E (100%). The TEE & EAE exhibited the highest anti-inflammatory activity (3.81±0.08 & 3.79±.0.04) respectively in comparison with indomethacin 3.83±0.01 measured as edema diameter after 4 hours of extract administration. The total phenolic and total flavonoid contents in the total ethanol extract (TEE) estimated as gallic acid and catechin equivalents were 61.06± 0.08 µg eq GA/g, 40.33± 0.20 µg CE/g extract respectively. EAE revealed five phenolic acids and eight flavonoid compounds isolated for the first time from the plant

Effect of lecithin on oxidative stress in an experimental model of rats colitis induced by acetic acid / Efeito da lecitina sobre o estresse oxidativo no modelo experimental de colite induzida por ácido acético em ratos

Ulcerative colitis (UC) is an inflammatory disease that affects the bowels. Reactive oxygen species (ROS) are involved in the progress of UC. Objective: Evaluate the antioxidant effect of lecithin in an experimental model of acute UC induced by administration of acetic acid (AA) in rats. Methods: Lecithin (0.5 mL/kg/day) administered orally 2 days before and after induction of colitis with 4% AA in a volume of 4 mL. Twenty-five male Wistar rats were divided in 5 groups: control (CO); control + lecithin (CO + LE); colitis (CL); colitis + lecithin (CL + LE); lecithin + colitis (LE + CL). Anal sphincter pressure, LPO (TBARS), and antioxidant activity of enzymes superoxide dismutase (SOD) and catalase (CAT) were measured, and a histological analysis with H&E was performed. Results and discussion: Anal sphincter pressure was significantly smaller in the CO group, lecithin treatment increased it in pre- and post-treated groups. LPO and SOD activity were increased in the CO group and decreased in the lecithin-treated groups. CAT activity was increased in CO group and decreased in lecithin groups. The histological analysis showed damage to the bowels with destruction of crypts, edema, and inflammatory infiltrate. Use of lecithin preserved the crypts and decreased the edema. Conclusion: Ulcerative colitis increased lipid peroxidation, and the use of lecithin was effective reducing damage to the bowels in the model of experimental colitis.

A retocolite ulcerativa (RCUI) é uma doença intestinal inflamatória. Espécies reativas de oxigênio (ERO) estão envolvidas no progresso da RCUI. Objetivo: Avaliar o efeito antioxidante de lecitina em modelo experimental de RCUI induzida pela administração de ácido acético (AA) em ratos. Métodos: A Lecitina (0,5 mL/kg/dia) foi administrada por via oral 2 dias antes e após a indução de colite com AA. Vinte e cinco ratos Wistar machos foram divididos em 5 grupos: controle (CO); controle + lecitina (CO + LE); colite (CL); colite + lecitina (CL + LE); lecitina + colite (LE + CL). Foram avaliadas: pressão do esfíncter anal, lipoperoxidação (LPO), atividade antioxidante das enzimas superóxido dismutase (SOD) e catalase (CAT), e foi realizada uma análise histológica com H&E. Resultados e discussão: A pressão do esfíncter anal foi significativamente menor no grupo CL, o tratamento com lecitina aumentou a pressão nos grupos pré e pós tratados. A LPO e atividade da SOD aumentaram no grupo CL e diminuíram nos grupos tratados com lecitina. A atividade da CAT foi aumentada no grupo CL e diminuiu nos grupos com lecitina. A análise histológica mostrou danos ao intestino com destruição das criptas, edema e infiltrado inflamatório. O uso de lecitina proporcionou uma preservação das criptas e diminuição do edema. Conclusão: A RCUI aumenta a LPO, a utilização de lecitina foi eficaz na redução dos danos ao intestino induzido por AA no modelo de colite experimental.

Efficacy and Safety of Montelukast Plus Fexofenadine Fixed Dose Combination in Allergic Rhinitis : Results of Post-Marketing Study In India.

Background:Allergic rhinitis is one of the most common conditions in clinical practice. Motelukast and second generation antihistamine fexofenadine are routinely used in the management of allergic rhinitis. Individually both drugs have been found to be effective in allergic rhinitis. Fixed dose combination of montelukast 10 mg plus fexofenadine 120 mg is available in India is also used in the treatment of allergic rhinitis. Objective: To evaluate the efficacy and safety of montelukast and fexofenadine fixed dose combination in the management of patients with allergic rhinitis. Material and methods: Post marketing observational study was conducted in 809 patients from all over India. All the patients were treated with montelukast 10 mg plus fexofenadine 120 mg fixed dose combination once daily for 14 days. The primary outcome criteria was the change in total symptom score (Sum of total nasal symptom score and total ocular symptom score) at the end of study compared to baseline. The secondary outcome criteria included change in total nasal symptom score (nasal congestion, rhinorrhea, nasal itching, and sneezing) and total ocular symptom score (Itching/burning eyes, tearing/ watering eyes and eye redness) at the end of study compared to baseline and physician’s and patient’s global assessment for efficacy and tolerability. The patients were evaluated at baseline, day 7 and day 14 for efficacy evaluation while the safety parameters were assessed at screening and day 14. Results: The fixed dose combination of fexofenadine plus montelukast was significantly effective in reducing total symptom score, total nasal symptom score and total ocular symptom score (p<0.0001 for all parameters). The global assessment of efficacy evaluation by both patient and investigators demonstrated “excellent to good” efficacy in >95% of patients. Most of the study population reported “good” tolerability with the fixed drug combination. No adverse events were reported in the study. Conclusion: The fixed dose combination of fexofenadine plus montelukast was found to be efficacious and well tolerated in allergic rhinitis in Indian adult patients.

Estudio de bioequivalencia de montelukast en tabletas masticables de 5 mg / Bioequivalence study of montelukast 5 mg chewable tablets

Introducción. La importancia de los medicamentos genéricos radica en la posibilidad de la disminución de los costos en el sistema nacional de salud, sin sacrificar la calidad del servicio ni la eficacia y la seguridad de los tratamientos. Es importante resaltar que los estudios de bioequivalencia pretenden demostrar que los perfiles farmacocinéticos del producto de prueba y del producto de referencia son similares e intercambiables. El montelukast sódico está indicado para la profilaxis y el tratamiento crónico del asma, en adultos y pacientes pediátricos de 12 meses de edad o más. En general, es bien tolerado y las reacciones adversas son un poco más frecuentes en los pacientes tratados con el fármaco que en los tratados con placebo. Objetivos. Comparar la biodisponibilidad de Amisped®, montelukast en tabletas masticables de 5 mg fabricadas por Sanofi-Aventis con la de Singulair®, montelukast en tabletas masticables de 5 mg elaboradas por Merck Sharp & Dohme. Materiales y métodos. Se comparó la magnitud y la velocidad de la absorción de montelukast en 18 voluntarios sanos, empleando un diseño cruzado completo al azar. El bioanálisis de las muestras se hizo por cromatografía líquida de alta resolución. Resultados. Los resultados para el genérico y el innovador, respectivamente, fueron: Tmax (horas) 2,17±0,73 y 2,28±0,88; Cmax (ng/ml) 607,42±122,92 y 627,69±134,17; AUC0-t (ng*h/ml) 3.316,39±861,57 y 3.545,40±1.070,07; AUC0-∞ (ng*h/ml) 3.450,92±904,89 y 3.722,03±1120,60; Ke (1/h) 0,25±0,05 y 0,23±0,04 en el intervalo de confianza de 0,99-1,00 para lnCmax y 0,94-1,06 para lnAUC0-∞. Conclusiones. La formulación ensayada de Amisped® de Sanofi-Aventis es bioequivalente a la formulación de referencia Singulair® de Merck Sharp& Dohme.

Introduction. The importance of generic drugs is the possibility of reduced costs in the national health system without sacrificing quality of service and the efficacy and safety of treatments. However, bioequivalence studies must show that the pharmacokinetic profiles of the test product and reference product are similar and interchangeable. Montelukast sodium is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 12 months of age or older. It is generally well tolerated, although adverse reactions are more frequent in patients treated with the drug than in those treated with placebo. Objectives. To compare the bioavailability of Amisped® (5 mg montelukast chewable tablets) manufactured by Sanofi-Aventis and 5 mg chewable tablet montelukast (Singulair®) developed by Merck. Materials and methods. The magnitude and rate of absorption of montelukast was compared in 18 healthy volunteers using a randomized complete crossover design. The bioassay was performed by high performance liquid chromatography. Results. Results are indicated for the generic and innovator, respectively: Tmax (h) 2.17±0.73, 2.28±0.88; Cmax (ng/mL) 607.4±122.9, 627.7±134.2; AUC0-t (ng*h/ml) 3,316±861, 3,545±1,070; AUC0-∞ (ng*h/ml) 3,450±904, 3,722±1121; Ke (1/h) 0.25±0.05, 0.23±0.04 in the confidence range of 0.99-1.00 for lnCmax and 0.94-1.06 for lnAUC0-∞. Conclusions. The formula tested in Amisped® from Sanofi-Aventis is bioequivalent to the reference formulation of Merck Singulair®.

Montelukast Induced Hypertriglyceridemia.

Montelukast a LT4 receptor antagonist is a prophylactic agent used in chronic asthma, to improve asthma control and reduce the frequency of asthma exacerbation. Advantage of Montelukast is, it is well tolerated in both adult and children upto 6 years of age. Suspected adverse effect reported to U.K, CSM follow the launch of Montelukast are anaphylaxis, angioedema, urticaria, chest pain, vertigo, athralgia, fever. Further suspected side effects are nightmare, palpitation, and sweating and Churg Strauss syndrome. Hypertriglyceridemia associated with this agent is rarely found in any published medical report or literature. This is a case of a male patient who was suffering from chronic asthma since childhood, developed allergic rhinitis since November´10. He developed hypertriglyceridemia and associated lipid profile abnormality after taking Montelukast and was also receiving salbutamol inhalation since childhood. His lipid profile before Montelukast administration was normal. Routine investigation done 4 months following drug intake shows serum triglyceride to be 732mg/dl.Montelukast was immediately withdrawn, but salbutamol was continued The triglyceride level reaches near the base line 4 months following drug withdrawal. This case highlights a rare case of Montelukast induced hypertriglyceridemia. Physician should be vigilant of the fact that Montelukast can induce hypertriglyceridemia following therapy with it.

The effect of montelukast in a model of gouty arthritis induced by sodium monourate crystals / Efecto de montelukast en un modelo de artritis gotosa inducido por cristales de monourato de sodio

Non-steroidal anti-inflammatory drugs (NSAIDS) are the first line of therapy in acute gouty arthritis. NSAIDs inhibit the cyclooxygenase pathway, but not the lipooxygenase activity and can have many adverse effects and thus have a limited effect on the control of inflammation in this disease. In this work we studied the effect of montelukast on the cellular inflammatory infiltrate in a model of murine arthritis induced by sodium monourate crystals (SMU), using a subcutaneous air cavity (air pouch) in BALB/c mice. Seven groups of BALB/c mice (n = 4) were distributed into five experimental groups and two inflammatory control groups, a positive and a negative one. Previous to SMU exposure, the experimental groups received montelukast (1 and 0.01 mg/Kg/w) and/or indomethacine (2.5 mg/Kg/w), followed by administration of SMU in the air pouch. The total and differential counts of inflammatory cells were analyzed after 2, 6, 12 and 24 hours. Montelukast, significantly reduced the total number of cells (p<0.05), with a predominant impact on polymorphonuclear over mononuclear cells, especially after 12 hours of the medication. The montelukast/indometacine combination showed an additive effect. Our data show that montelukast has an anti-inflammatory effect in the model of gouty arthritis. Consequently, anti-leukotrienes could represent a new and effective therapy, either isolated or combined with conventional therapy of gouty arthritis.

En artritis gotosa aguda las drogas antiinflamatorias no esteroideas son la primera línea terapéutica. Este tratamiento no es satisfactorio porque inhibe la ciclooxigenasa sin modificar la actividad de la lipooxigenasa, y puede acompañarse de numerosos efectos adversos. Investigamos el efecto de montelukast sobre el infiltrado celular inflamatorio en un modelo de artritis múrida inducida por cristales de monourato de sodio (MUS) en el modelo experimental de la bolsa de aire (air pouch). Siete grupos de ratones BALB/c (n = 4) fueron distribuidos en cinco grupos experimentales y dos grupos controles inflamatorios: positivo y negativo. Los grupos experimentales recibieron, montelukast (1 y 0,01 mg/Kg/p) y/o indometacina (2,5 mg/Kg/p) por vía oral, previo a la administración de MUS en la bolsa del aire. El conteo absoluto y diferencial de las células inflamatorias fue analizado después de 2, 6, 12 y 24 horas de tratamiento. El tratamiento con montelukast redujo significativamente el número total de células presentes en el infiltrado inflamatorio (p < 0,05), con un efecto mayor sobre polimorfonucleares que sobre las células mononucleares, y con un máximo efecto a las 12 horas después de la administración del medicamento. La combinación montelukast/indometacina mostró un efecto aditivo. Los resultados demuestran que montelukast tiene un efecto antiinflamatorio en el modelo de la artritis gotosa. Por lo tanto, los anti-leucotrienos podrían representar una nueva y eficaz terapia, aislada o en combinación con la terapéutica convencional, para la artritis gotosa.

Comparison between Ringer's lactate and balanced salt solution on postoperative outcomes after phacoemulsfication: A randomized clinical trial.

Aim: To compare the effects of balanced salt solution (BSS) and Ringer's lactate (RL) on corneal thickness, endothelial morphology, and postoperative anterior chamber inflammation in eyes undergoing phacoemulsification. Setting: Iladevi cataract and IOL research center, Ahmedabad, India. Materials and Methods: This prospective randomized study comprised 90 consecutive patients with age-related cataract who were randomly assigned to either Group 1 (n = 45) with BSS or Group 2 (n = 45) with RL. Observations made included measurement of central corneal thickness (CCT), presence of anterior chamber flare and cells, endothelial cell loss, and change in coefficient of variation (CV). Data was analyzed using Mann Whitney test and test of proportion. Results: Mean increase in CCT on postoperative Day 1 was 58microm and 97microm in Groups 1 and 2 respectively ( P = 0.01). Increase in CCT at one month was 10microm and 11microm in Groups 1 and 2 respectively ( P = 0.99); increase in CCT at three months was 3microm and 6microm in Groups 1 and 2 respectively ( P = 0.86). Number of eyes with flare grades in a range of 0 to 3 was statistically higher in Group 2 on postoperative Day 1 ( P = 0.004, 0.016, < 0.001, 0.047 for Grade 0, 1, 2 and 3 respectively). Number of eyes with cells of Grade 3 on first postoperative day was significantly higher in Group 2 as compared to Group 1 ( P = 0.004). Three months postoperatively, endothelial cell loss was 5.5% and 7.8% in Groups 1 and 2 ( P = 0.21) and change in CV was 3 and 5.4 in Groups 1 and 2 ( P = 0.20) respectively. Conclusion: BSS offers a significant advantage over RL in terms of increase in corneal thickness and postoperative inflammation on the first postoperative day in patients undergoing phacoemulsification.

Efficacy of montelukast and loratadine as treatment for allergic rhinitis in children.

The objective of this study was to compare the effectiveness of montelukast combined with loratadine once daily to loratadine alone for a 2-week treatment course of allergic rhinitis in a randomized, double-blind placebo controlled trial which enrolled 115 children, 6- 15-years-old. The patients were randomly assigned to receive montelukast and loratadine (treatment group) or placebo and loratadine (control group). The primary outcome was the mean percent change of the total daytime nasal symptom scores (PDTS) and secondary outcomes were the mean percent changes of the nighttime nasal, daytime eye and composite symptom scores (PNTS, PES, PCS), as well as the nasal secretion, turbinate swelling and nasal congestion scores (PNSS, PTSS, PNCS). There were no significant differences in the PDTS of the 2 groups. The change in the night time nasal congestion score (PNTS-congestion) was higher in the treatment group, but not statistically significant (p = 0.077). Only the mean percent change in decreased turbinate swelling was significantly greater in the montelukast and loratadine group than the loratadine alone group (-22 +/- 7 vs. -1 +/- 5, p < 0.05).

Correlation between intradialytic hypotension in patients undergoing routine hemodialysis and use of acetate compared in bicarbonate dialysate.

AIM: To determine the incidence of intradialytic hypertension (IDH) during hemodialysis (HD) in end-stage renal disease (ESRD) patients using acetate dialysate compared to those using bicarbonate dialysate. METHODS: This study was a double-blind cross-over randomized clinical trial. The effect of acetate and bicarbonate dialysate on blood pressure was analyzed in two consecutive HD sessions. The selected subjects were 41 stable ESRD patients scheduled for dialysis 2 times/week/from the HD unit of Dr.Soetom Hospital Surabaya, aged between 21-65 years old, with a hemoglobin level > or = 7 g/dL, serum albumin > or = 3 mg/dL and interdialytic weight gain < 4 Kg, and an average Qb 150-250 ml/minute. The dialysate sodium level was 138 mEq/L/ The study subjects were divided into tow groups: 21 patients in the group who received Acetate on the first session and Bicarbonate on the next (AB) and 20 patients in the group receiving Bicarbonate first (BA). Comparison of IDH during use of each dialysate was analyzed by Chi-Square and Mc Nemar Chi-Square test. RESULTS: No characteristic differences were found in both groups: HD duration (for AB) was 28.83 +/- 13.89 vs. 34.95 +/- 24.80 months (for BA) (p = 0.333); Age (for AB) was 47.61 +/- 9.49 vs. 47.75 +/- 11.80 years (for BA) (p = 0.969); Hemoglobin (Hb) level (for AB) 8.19 +/- 0.84 vs. 7.94 +/- 0.41 mg/dL (for BA) (p = 0.238); serum Albumin (for AB) was 3.79 +/- 0.26 vs. 3.82 +/- 0.30 g/dl (for BA) (p = 0.652). The number of patients with IDH during acetate dialysate with IDH during bicarbonate dialysate was 1 (2.4%). Overall, there were 11 patients with Diabetic Kidney Disease (26.8%). Six out of them (54.5%) had IDH during acetate dialysate and only and 1 patient (9.1%) had IDH during acetate and bicarbonate. CONCLUSION: The incidence of IDH in hemodialysis using acetate is significantly greater than that when bicarbonate is used (p = 0.000).

Intraocular irrigating solutions. A clinical study of BSS Plus and dextrose bicarbonate fortified BSS as an infusate during pars plana vitrectomy.

PURPOSE: To compare the effect of Balanced Salt Solution Plus (BSS Plus, Alcon Laboratories, Fort Worth, Texas, USA) and fortified regular BSS on the cornea and lens, when used for continuous irrigation in pars plana vitrectomy (PPV) surgery. METHODS: Prospective, investigator masked, randomised study. Forty patients were randomly assigned to undergo PPV using BSS Plus (n=20) or fortified BSS (n=20) [regular BSS, fortified with 10.5 cc. of dextrose in water (D5W) and 13.1 cc. of 8.4% sodium bicarbonate]. Intraoperative features of the corneal epithelium, postoperative changes in the corneal endothelial cell denstiy (ECD) at 3 months, and clarity of the lens during surgery and postoperatively were evaluated. RESULTS: Intraoperative epithelial changes were similar in both groups with 7 (35%) of the cases having the epithelium removed in the BSS Plus group and 8 (40%) in the BSS fortified group (P=0.23). The mean differences in ECD (3 months versus preoperative) in the operated eyes when adjusted for changes in the control eye showed no difference with the type of BSS (P=0.98). Intraoperative lens changes were more significant (P=0.018) in the BSS fortified group. Postoperative lens status at 3 months was similar for both groups. Though there was a trend towards worse postoperative nuclear sclerosis change in the BSS fortified group, it was not significant (P=0.160). CONCLUSION: Standard BSS fortified with dextrose and bicarbonate is an efficacious infusion fluid during pars plana vitrectomy. Both solutions showed comparable effects on postoperative corneal endothelial cell density and corneal epithelial changes intraoperatively. BSS fortified has more lenticular changes intraoperatively than BSS Plus although no lens had to be removed in either group. The study implications are important since BSS fortified is significantly less expensive than BSS Plus.

Spinal Gabapentin and Antinociception: Mechanisms of Action

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.

Gabapentin and lamotrigine in Indian patients of partial epilepsy refractory to carbamazepine.

52 patients (25 males and 27 females) suffering from refrectory partial seizures, of not more than two years duration and on carbamazepine monotherapy were enrolled in this study. Patients were randomly put on gabapentin (19 males and 8 females) or lamotrigine (6 males and 19 females) as add on therapy. The efficacy of the drugs was assessed by the seizure frequency, pattern of seizures and seizure free interval. The safety was evaluated from the biochemical investigations and the adverse effects observed or reported by the patients during the course of the study. The average frequency of basal partial seizures was 6.26+3.86 and 5.04+2.47 which decreased significantly (p<. 001) after 12 weeks of add on therapy to 1.75+2.16. and 1.68+2.94 in the GBP and LTG group respectively. However, there was no significant difference between the two drugs after 12 weeks of add on therapy. The PCB (primary change in basal seizure frequency) values decreased to -72+34.92 and -76.22+29.68 in the GBP and LTG group respectively. The difference in these two groups was not significant. The responder rate was 77.7% and 92% respectively in GBP and LTG group respectively. GBP was found to be more effective in partial seizures with secondarily generalization while LTG was effective in all subtypes of partial seizures. The abnormal scalp EEG was recorded in 33.3% (9 of 27 patients) in GBP group and 40 %( 10 of 25 patients) in LTG group and it did not revert to normal in 33.3% and 40% of patients in either of groups (GBP/LTG). Minor side effects which were self limiting were noticed in 80% in groups I and 74% were groups II.

The Effect of Intrathecal Gabapentin on Mechanical and Thermal Hyperalgesia in Neuropathic Rats Induced by Spinal Nerve Ligation

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.

Effects of antileukotriene among asthmatic patients.

STUDY OBJECTIVE: To determine the effect of antileukotriene (montelukast) 10 mg once daily for the treatment of mild to moderate asthma. DESIGN: Open label, prospective. PATIENTS: Thirty asthmatic patients > or = 18 years of age with baseline FEV1 > 60 per cent and < or = 80 per cent of predicted values and evidence of reversible airway obstruction, as defined by an increase in FEV1 of > or = 20 per cent. INTERVENTIONS: Montelukast 10 mg once daily orally for 12 weeks, back up beta-2 agonist inhaler was available. MEASUREMENT AND RESULTS: Spirometry was performed during the screening period, and every month after starting antileukotriene. Subjects recorded asthma-related symptoms and use of supplement beta-2 agonists daily on diary cards. Over 12 weeks of treatment, the FEV1 increased 10 per cent, 14 per cent and 19 per cent respectively, compared to the baseline (p < 0.05). The physician and patients evaluation scores were quite good in the study. CONCLUSION: Oral montelukast once daily gave a favorable effect in management of mild to moderate asthmatic patients.

Acute effect of intracerebroventricular administration of zinc on the drinking behavior of rats induced by dehydration or central cholinergic and angiotensinergic stimulation

1. Zinc is a metal important for several biological functions including neuromodulation and neurotransmission in the central nervous system. 2. In the present paper we studied the acute effects of third ventricle injections (2 µl) of minute amounts of zinc acetate on the water intake of male, adult, Wistar rats (N = 7-14) under three conditions: water deprivation (14 h, overnight) and after third ventricle injections of carbachol (11 nmoles/rat in 2 µl) or angiotensin II (AII, 9.6 pmoles/rat in 2 µl). 3. Central injections of zinc acetate in different doses (0.3 and 3.0 nmoles/rat) induced a partial blockade of water intake of rats under all three conditions studied. Water intake after 120 min in control dehydrated rats (those receiving NaAc instead of Zn(Ac)2) was 7.89 + or - 0.47 ml while dehydrated animals receiving Zn(Ac)2 in the highest dose employed (3.0 nmoles/rat) animals receiving carbachol (2.41 + or - 0.84 ml). Angiotensin-treated animals exhibit a water intake of 3.85 + or - 0.48 ml after 45 min, a value reduced to 1.13 + or - 0.6 ml in those animals receiving angiotensin II plus zinc (3.0 nmoles/rat). 4. It is suggested that zinc alters the functional integrity of cholinergic and angiotensinergic systems in the central nervous system mediating water-intake behavior in rats

Antitumor effects of rhodium (II) complexes on mice bearing Ehrlich tumors

Rhodium (II) trifluoracetate (TFARh), rhodium (II) trifluoracetate adduct with sulfadiazine (TFARh.Sd) and rhodium (II) acetate adduct with sulfisoxazole (RhSx) were tested in mice for acute toxicity, antitumoral activity against Ehrlich ascites carcinoma and for viability of Ehrlich tumor cells in culture. At ip doses up to 60 µmg/kg (40-70 and 59 mg/kg, respectively), these coumpounds had no toxic effects up to 14 days. At ip doses of 10 µmol Kg-1 day-1 for 5 days, TFARh and TFARh.Sd significantly increased the survival rate of mice bearing Ehrlich ascites cells (probability of survival to the end of 34th day, controls = 0.23, TFARh = 0.85, TFARh.Sd = 0.74). No significant effect was observed for RhSx. In vitro, these rhodium complexes at 40 µM significantly increased the number of dead cells in cultured Ehrlich tumor cells