Tuncer Degim

Oral montelukast treatment of preschool-aged children with acute asthma.

BACKGROUND Increased amounts of cysteinyl leukotrienes have been demonstrated in urine samples from asthmatic patients, particularly during exacerbations of asthma. Although the use of leukotriene receptor antagonists has been recommended in the treatment of chronic asthma, no guidelines are available regarding their use in the treatment of acute asthma. OBJECTIVE To investigate the safety and effectiveness of a 4-mg tablet of oral montelukast in addition to short-acting beta2-agonist bronchodilator as the initial treatment in mild to moderate asthma exacerbations in children between 2 and 5 years old. METHODS Fifty-one patients who were experiencing mild to moderate asthma exacerbation were included in a randomized, double-blind, placebo-controlled, parallel-group study. Each patient received either a 4-mg tablet of montelukast or placebo in addition to inhaled salbutamol and were followed up for 4 hours. The pulmonary index score, respiratory rate, and pulse were determined at baseline and throughout 4 hours after administration. RESULTS Compared with placebo, the pulmonary index scores and respiratory rates were significantly lower in the montelukast group starting at 90 minutes (P = .01). This difference persisted at 120, 180, and 240 minutes of the study (P = .008, P = .02, and P = .048, respectively). At the end of the first hour of treatment, oral steroid need was 20.8% and 38.5% in patients randomized to the montelukast and placebo groups, respectively (P = .22). Hospitalization rates were not different between the 2 treatment groups. CONCLUSION A single 4-mg tablet of montelukast had the potential to provide additive clinical benefit in mild to moderate acute asthma in preschool-aged children when administered concomitantly with short-acting beta2-agonist bronchodilators as the initial treatment.

Rectal and vaginal administration of insulin–chitosan formulations: An experimental study in rabbits

Insulin is a polypeptide drug and it is degraded by gastrointestinal enzymes, therefore, it cannot be used via oral route readily. There are only parenteral forms available in the market. The aim of this study was to investigate the effect of rectal and vaginal administration of various insulin gel formulations on the blood glucose level as alternative routes in rabbits. Chitosan gel (CH-gel) was used as a carrier; the penetration enhancing effect of sodium taurocholate and dimethyl-β-cyclodextrin (DM-βCD) was also investigated. CH-gel provided longer insulin release. The maximum decreasing effect on blood glucose level was observed with insulin–CH-gel containing 5% DM-βCD. In conclusion, our results indicate that insulin may penetrate well through the rectal and vaginal mucosae from the CH-gel. DM-βCD was also found to be a useful agent to enhance the penetration of insulin through rectal and vaginal membranes.

SIMULTANEOUS DETERMINATION OF ACETAMINOPHEN, ACETYLSALICYLIC ACID AND ASCORBIC ACID IN TABLET FORM USING HPLC

The purpose of the present study was to develop a simple and accurate HPLC method to measure the amount of each agent in a multidrug pharmaceutical formulation. Three drugs, acetaminophen, acetylsalicylic acid and ascorbic acid, were analyzed simultaneously. A commercial pharmaceutical effervescent tablet was examined and the amount of each of these agents successfully determined. The present method appears to be more convenient than the current procedures described in American and British Pharmacopoeias in which each drug is assayed separately.

A sustained release dosage form of acyclovir for buccal application: An experimental study in dogs

Acyclovir is an antiviral agent and it has been particularly used for the treatment of herpes simplex infections. The treatment of infection in the oral cavity is often difficult, because of insufficient drug concentration in saliva when acyclovir is administered via the oral route in conventional tablet form for systemic uptake. Therefore, it was aimed to prepare a tablet for buccal administration and to investigate its effectiveness by performing in vitro and in vivo experiments. The solubility (1.559–4.584) and octanol/water partition coefficients ( − 2.176 to − 1.625) of the acyclovir were investigated at different pH conditions. A series of tablet formulations were prepared for buccal application and their dissolution properties were determined in artificial saliva medium. The effect of tablet ingredients on the release rate and mucoadhesion force was investigated. The dissolution properties of commercially available acyclovir tablets were also determined in the artificial gastric juice. Franz type diffusion cells were used to determine acyclovir penetration through buccal mucosa from prepared buccal tablets. Selected buccal tablets, commercial tablets and intravenous acyclovir solutions were administered to mongrel dogs and drug levels in the blood determined by HPLC. A pharmacokinetic model for buccal application was also developed and blood concentrations were calculated theoretically and compared with the experimental results. Prepared buccal tablets were found to be effective for the treatment of viral infections locally within the oral cavity and also for systemic treatment.

Multiwalled Carbon Nanotube-Chitosan Scaffold: Cytotoxic, Apoptoti c, and Necrotic Effects on Chondrocyte Cell Lines

BACKGROUND Carbon nanotubes (CNTs) have been considered highly successful and proficient in terms of their mechanical, thermal and electrical functionalization and biocompatibility. In regards to their significant extent in bone regeneration, it has been determined that CNTs hold the capability to endure clinical applications through bone tissue engineering and orthopedic procedures. In the present study, we report on a composite preparation, involving the use of CNT-chitosan as scaffold for bone repair and regeneration. Through the use of water-soluble tetrazolium salt (WST-1) and double staining methods, the cytotoxic, necrotic, and apoptotic effects of chitosan-multiwalled carbon nanotube nanocomposites on the chondrocyte ATTC cell line have been exhibited. METHODS The chitosan-multiwalled carbon nanotube scaffolds were prepared. Chondrocytes differentiation tool (ATCC) cell line was prepared. WST-1 assay for cytotoxicity studies were performed by using chondrocytes cells in 12.5-200 μL concentration range. The samples of membranes (chitosan- multiwalled carbon nanotube scaffold) were measured at 2 mg/mL and further prepared amongst chitosan- multiwalled carbon nanotube scaffolds which were placed into separate wells. While in the process of incubation, in the four-hour time range, the plates were immediately read in an Elisa microplate Reader. To predict the number of apoptotic and necrotic cells in culture, the technique of double staining with Hoechst dye was performed with PI on the basis of scoring cell nuclei. The mechanical properties such as tensile strength and elongation at break values of the chitosan only and chitosan/CNT scaffolds were evaluated on Texture Analyzer. RESULTS Based on the results of the WST-1 assay procedure, the amount of cell viability was not significantly affected by nanocomposite concentrations and the lowest mortality rate of cells was obtained at a concentration of 12.5 μg/mL, whereas the highest mortality rate was obtained at a rate of 200 μg/mL. In addition, the effects of chitosan-CNT nanocomposites were not found to cytotoxic on chondrocyte cells. The double staining method has been able to determine the apoptotic and necrotic effects of chitosan MWCNT nanocomposites. The apoptotic and necrotic effects of the combined compounds had varied within the concentrations. In a similar manner to the outcome of the control groups, apoptosis was obtained at a percentage of 2.67%. Under a fluorescent inverted microscope, the apoptotic cell nuclei were stained with a stronger blue fluorescence in comparison to non-apoptotic cells, which may have had an effect. We also compared the strain-stress curve measurements results. The results indicated that the mechanical properties of scaffold were not different. Elongation at break values increased by addition of CNT. CONCLUSION CNTs as a biomaterial hold the potential to be used for applications in future regenerative medicine. By using the components of chondrocytes (ATTC) cell lines, the cytotoxicity evaluations were made for the chitosan-multiwalled carbon nanotube scaffold. The chitosan-MWCNT nanocomposites do not seem to induce drastic cytotoxicity to the chondrocyte cells.

The use of the corpus cavernosum for the administration of phenobarbital: an experimental study in dogs

Status epilepticus (SE) is classically defined as a generalized tonic-clonic seizure lasting longer than 30 min. Prolonged seizure activity can be resulted in irreversible cerebral injury. In addition, the existence evidence suggests that the longer the duration of the seizure activity is less likely to be controlled. The intravenous (IV) access is frequently difficult during SE, especially in infants and neonates. On the other hand, it has been demonstrated that high volumes of fluid can be injected into the corpora cavernosa. In this study, phenobarbital (PB) was administered to dogs using both IV and intracavernous (IC) routes with a dose of 20 mg/kg. The time period required to establish the IC route was less than 5 s. The levels of PB in the blood were measured and all results were compared. There was no statistically significant difference between the IV and IC administration with regard of the blood PB levels. Within 48 h of the experiment, none of animals demonstrated any evidence of infection or disability. Our findings suggest that the IC route may be an alternative route for the administration of PB when venous access is not immediately available or if it is not possible to achieve.

Intracavernous application of diazepam: an alternative route of the seizure treatment--an experimental study in rabbits.

Backround : There is a general need to terminate seizures as soon as possible using anticonvulsant drugs via an intravenous (i.v.) route, but it is often difficult to achieve a secure i.v. line during the seizure, especially in children. However, it has been demonstrated that high volumes of fluid can be injected into the corpora cavernosa. The purpose of this study was to evaluate the absorption properties of diazepam (DZ) after intracavernous (i.c.) administration and whether therapeutically significant plasma concentrations can be obtained or not.

Fenobarbital Uygulamasında Intravenöz ve Intraosseöz Yolların Karşılaştırılması

SuleymanDemirel Universitesi TIP FAKULTESI DERGISI: 1999 Aralik; 6(4) Fenobarbital Uygulamasinda Intravenoz ve Intraosseoz Yollarin Karsilastirilmasi Rusen Dundaroz, Turner Turkbay, Ali Sizlan, Tuncer Degim, Faysal Gok, Tahir Ozisik Ozet Status epileptikus klasik olarak 30 dakikadan uzun suren jenaralize tonik-klonik nobet olarak tarif edilir. Uzun suren nobet aktivitesi irreversibl serebral hasar ile sonuclanabilir. Ustelik, nobet aktivitesinin uzun surmesinin kontrol edilebilirligini azalttigi yonunde kanitlar vardir. Damar yolunun saglanmasi nobet esnasinda siklikla zordur. Ote yandan intraosseoz yol (IO) kullanima hazirdir. Bu ca¬lismada, 20 mg/kg dozunda fenobarbital IV ve IO yoldan tavsanlara uygulandi. Fenobarbital kan duzey¬leri olculdu ve sonuclar karsilastirildi. Fenobarbital plazma profilinin IO uygulamada terapotik seviyede oldugu goruldu. IO yolun fenobarbital verilmesinde IV yola alternatif olabilecegi sonucuna varildi. Anahtar Kelimeler: Fenobarbital, kemik iligi infuzyonu, intraosseoz infuzyon, intravaskuler giris, status epileptikus Abstract Comparison of Intravenous and Intraosseous Routes for The Administration of Phenobarbital Status epilepticus (SE) is classically defined as a generalized tonic-clonic seizure lasting longer than 30 min. Prolonged seizure activity can result in irreversible cerebral injury. In addition, evidence suggests that the longer the duration of the seizure, the less likely the activity is to be controlled. IV access, however, is frequently difficult to achieve during the seizure. On the other hand, intraosseous (IO) access is available. In this study, phenobarbital was administered to rabbits using both IV and IO lines at the dose of 20 mg/kg. The levels of phenobarbital in the blood were measured and the results were compared. The plasma profile of phenobarbital was found to be in the therapeutic level when it was administered by IO route. It was concluded that the IO line appeared to be an alternative route to IV access in the administration of phenobarbital. Key Words: Phenobarbital, bone marrow infusion, intraosseous infusion, intravascular access, status epilepticus

Administration of Anticonvulsant Drugs by the Intraperitoneal Route

SuleymanDemirel Universitesi TIP FAKULTESI DERGISI: 1999 Eylul; 6(3) Administration ofAnticonvulsant Drugs by the Intraperitoneal Route Rusen Dundaroz, Tuncer Degim, Ali Sizlan, Mehmet Yasar, Metin Denli, Ugur Tamer Abstract Status epilepticus or seizures cause serious brain damages and irreversible cerebral injury if it prolongs and it is essential to terminate seizure rapidly. Antiepileptic drugs can be introduced to the patients intravenously (IV), hut it is almost impossible to achieve IV access during the seizure. Intraperitoneal (IP) route can be accessible but, IP route of administration of antiepileptic drugs has not been used so far. Therefore the possibility of IP administration of anti epileptic drugs was investigated in this study. Antiepileptic drug (diazepam, phenytoin or phenobarbital) was introduced rabbits and dogs by IV and IP routes and blood samples were collected by the time during the period of 60 to 120 minutes. Blood samples vere analyzed and drug contents -were determined. The plasma profiles of antiepileptic drugs were obtained and compared. The plasma profiles of antiepileptic drugs were found to be low when they were administered by IP route. It was concluded that the IP administration of antiepileptic drugs could not be an alternative route to IV administration. Key Words: Convulsion, anticonvulsant drugs, Intraperitoneal route Antikonvulzon Ilaclarin Intraperitonal Yoldan Verilmeleri Ozet Epilepsi veya epilepsi nobeti ciddi beyin hasarlarina neden olabilir, ve eger fazla uzun surerse geri donussuz beyin harabiyetine neden olabilir, bu nedenle nobetin suratle durdurulmasi oldukca onemlidir. Antiepileptik ilaclar hastalara intravenoz(IV) yolla verilebilir ancak nobetler esnasinda hastaya IV ulasim hemen hemen imkansizdir ancak intraperitonal(IP)yol ile ilac verilmesi mumkundur.