Implication of inclusion complexation of glimepiride in cyclodextrin-polymer systems on its dissolution, stability and therapeutic efficacy

The effect of complexation of glimepiride, a poorly water-soluble antidiabetic drug, with β-cyclodextrin and its derivatives (HP-β-CyD and SBE-β-CyD) in presence of different concentrations of water-soluble polymers (HPMC, PVP, PEG 4000 and PEG 6000) on the dissolution rate of the drug has been investigated. The results revealed that the dissolution rate of the drug from these ternary systems is highly dependent on polymer type and concentration. The dissolution rate of the drug from ternary systems containing PEG 4000 or PEG 6000 seems to be generally higher than from systems containing HPMC or PVP. An optimum increase in the dissolution rate of the drug was observed at a polymer concentration of 5% for PEG 4000 or PEG 6000 and at 20% concentration of HPMC or PVP. The dissolution rate of the drug from the ternary system glimepiride–HP-β-CyD–5% PEG 4000 was high compared to the other systems. Tablets containing the drug or its equivalent amount of this ternary system were prepared and subjected to accelerated stability testing at 40 °C/75% R.H. to investigate the effect of storage on the chemical stability as well as therapeutic efficacy of the tablets. The results revealed stability of the tablets and consistent therapeutic efficacy on storage.     

Antioxidant and hepatoprotective effects of Orthosiphon stamineus Benth. standardized extract

Orthosiphon stamineus (OS), Benth. (Lamiaceae) is widely used in Malaysia for treatments of various kidney and liver ailments. In the experiment, DPPH* radicals scavenging, Fe(3+)-induced lipid peroxidation inhibiting activities and trolox equivalent antioxidant capacity (TEAC) of methanol/water extract of Orthosiphon stamineus (SEOS) were determined. The results indicated that SEOS exhibited antioxidant, lipid peroxidation inhibition and free radical scavenging activities. The hepatoprotective activity of the SEOS was studied using CCl(4)-induced liver toxicity in rats. The activity was assessed by monitoring liver function tests through the measurement of alanine transaminase (ALT) and aspartate transaminase (AST). Furthermore, hepatic tissues were also subjected to histopathological studies. Pretreatment of SEOS (125, 250, 500 and 1000 mg/kg p.o.) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of serum ALT and AST activities. The results of the present study indicated that the hepatoprotective effect of Orthosiphon stamineus might be ascribable to its antioxidant and free radical scavenging property.     

Hypothermic effect in rats of NAJA nigricollis venom: role of acetylcholine.

O. H. Osman, A. O. A. Elkhawad and M. Ismail. Hypothermic effect in rats of Naja nigricollis venom: role of acetylcholine. Toxicon15, 75–80, 1977.—Naja nigricollis venom produced a hypothermic effect when it was injected intraperitoneally into rats, while N. naja, N. nivea and N. melanoleuca venoms were ineffective. Similarly, when injected into the preoptic area and paraventricular nucleus of the hypothalamus, N. nigricollis venom produced a greater fall in body temperature. This hypothermic response was not modified by pretreatment with bromolysergic acid diethylamide, p-chlorophenylalanine, haloperidol, phentolamine, pimozide, or α-methyl-p-tyrosine. However, it was significantly antagonized by either central or peripheral hyoscine pretreatment. It is suggested that N. nigricollis venom may act by causing the release of acetylcholine in the hypothalamus which then mediates the hypothermia.     

Is routine measurement of international normalized ratio necessary as part of the investigation of patients with cardiac-type chest pain?

Dear editor, Chest pain is a frequent complaint of patients presenting to the emergency department(ED),and many of them are referred to the cardiology service f...     

Forming-Free Tunable Analog Switching in WOx/TaOx Heterojunction for Emulating Electronic Synapses

In this work, the sputtered deposited WO_x/TaO_x switching layer has been studied for resistive random-access memory (RRAM) devices. Gradual SET and RESET behaviors with reliable device-to-device variability were obtained with DC voltage sweep cycling without an electroforming process. The memristor shows uniform switching characteristics, low switching voltages, and a high R_ON/R_OFF ratio (~10²). The transition from short-term plasticity (STP) to long-term potentiation (LTP) can be observed by increasing the pulse amplitude and number. Spike-rate-dependent plasticity (SRDP) and paired-pulse facilitation (PPF) learning processes were successfully emulated by sequential pulse trains. By reducing the pulse interval, the synaptic weight change increases due to the residual oxygen vacancy near the conductive filaments (CFs). This work explores mimicking the biological synaptic behavior and further development for next-generation neuromorphic applications.     

Effect of maxillary and mandibular extrusion arches on dentoskeletal changes in adults with anterior open bite: a quantitative analysis

ObjectiveTo quantify dentoskeletal changes accompanying the use of extrusion arches during the treatment of anterior open bite (AOB) in adults.Materials and MethodsA total of 23 adult patients with an AOB of −3.05 mm ± 1.27 mm were treated with upper and lower extrusion arches after the alignment phase. Lateral cephalograms were taken before placement of the extrusion arch, immediately after closure of the open bite (T2), and at the end of orthodontic treatment (T3). Data were statistically analyzed using repeated-measures analysis of variance and the Bonferroni post hoc test for pairwise comparisons (α = 0.05).ResultsSuccessful closure of AOB, with an overall change in overbite of 4.73 ± 1.93 mm, was achieved in an average of 3.8 months and remained stable at T3. Upper and lower incisors were significantly extruded by 2.05 mm ± 0.72 mm and 2.54 mm ± 1.63 mm, respectively, and significantly retroclined by 6.36° ± 1.63° and 8.45° ± 3.83°, respectively, with a resultant increase in the interincisal angle of 12.80° ± 2.09°. Statistically significant intrusion and mesial tipping (P < .001) of the maxillary and mandibular first molars were observed at T2. Dentoskeletal changes remained stable at T3, except for a significant reduction of the mesial tipping of the maxillary and mandibular first molars.ConclusionsThe combined use of maxillary and mandibular extrusion arches resulted in significant favorable dentoskeletal changes that led to the successful closure of AOB during a short duration of treatment.     

Natural history of periodontal disease in adults: findings from the Tecumseh Periodontal Disease Study, 1959-87

The purpose of this epidemiological study was to estimate the degree of change in periodontal attachment level in a sample of adults examined in 1959 and 1987 in Tecumseh, Michigan. Out of 526 individuals between the ages of five and 60 years in 1959, a sample of 325 resided within an 80-km-radius area in 1987. Of those, 167 were re-examined. Loss of periodontal attachment (LPA) was determined with a Michigan #0 probe on four tooth sites (disto-buccal, mid-buccal, mesio-buccal, mid-lingual) for all teeth present. Of the individuals contacted, 28 had lost all their teeth during the 28 years. Of the 167 adults examined, two refused periodontal probing. Out of the 165 adults with LPA measurements in 1987, only 22 (13.3%) had an average increased loss of 2 mm or more per person between 1959 and 1987; five adults (3.0%) had an average LPA increase of 3 mm or more, and only two adults (1.2%) had an average LPA increase of 4 mm or more. The attachment level in 59.3% of all the tooth sites examined in 1959 in the 165 individuals either did not change or changed within +/- 1.0 mm. On the basis of bivariate analyses, the individuals with high LPA increase (greater than or equal to 2 mm) had the following characteristics significantly different from those with low LPA increase: They were older, smoked, had tooth mobility at baseline, higher gingivitis, plaque, calculus, and tooth mobility scores at follow-up, lower education level, and irregular dental attendance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Small‐Angle X‐Ray Scattering Measurements on Amphiphilic Polymer Conetworks Swollen in Orthogonal Solvents

Amphiphilic polymer conetworks (APCNs), which combine two different polymer nanophases, have a broad range of applications that involve their unique potential to separately swell one of these nanophases in a selective solvent. Little is known about the structural changes of such APCNs upon swelling in dependence on the topology. Here, conetworks composed of poly(2‐ethylhexyl acrylate) crosslinked by poly(2‐methyl‐2‐oxazoline) (PMOx) are investigated with small‐angle X‐ray scattering in dry and swollen state using the orthogonal solvents water and toluene. The data clearly show that the structural changes induced by swelling are strongly dependent on the topology of the APCNs. While water leads to fusion of PMOx phases resulting in larger structures than found in the dry APCN, toluene is only swelling the hydrophobic phases without structural changes.