Effect of Dipyridamole Injected for Myocardial Perfusion Imaging on Blood Glucose Concentration; A Preliminary Study

Introduction: Dipyridamole inhibits adenosine reuptake and increases cyclic Adenosine Monophosphate (cAMP) levels in platelets, erythrocytes and endothelial cells, all of which influence blood glucose. Acute hyperglycaemia reduces endothelium-dependent vasodilation and suppresses coronary microcirculation; which, in theory, can alter the outcome of a radionuclide scan. Aim: The present study was conducted with the aim to investigate the changes in blood glucose level of patients receiving dipyridamole for cardiac scan. Materials and Methods: A total of 293 patients (85 men and 208 women, age: 60.59±10.43 years) were included in the study. Fasting Blood Glucose (FBG) was measured before and 8 min after dipyridamole (0.568 mg/kg) injection during myocardial perfusion imaging. The data in different groups were analysed by paired t-test. R esults: There was not a significant difference between first (106.89 ± 19.21mg/dL) and second (107.98 ± 17.57 mg/dL) FBG measurements (p= 0.293). However, when the patients were grouped based on the quartiles of first measurement, there was an increase in FBG following dipyridamole injection in the first quartile (mean difference: 7.15±21.27 mg/dL, p<0.01); in contrast, FBG levels showed a significant decrease after dipyridamole administration in the 4th quartile (mean difference: -9.53±18.20 mg/dL, p<0.001). The differences in 2nd and 3rd quartiles were negligible. The patients were divided into normal, ischemic and fixed lesions based on the outcome of scans, then the possible correlation of dipyridamole-induced FBG alteration and scan results were investigated. There were no significant difference between the FBG values before and after dipyridamole injection and the final outcome of scan. C onclusion: The effects of dipyridamole on blood glucose highly depend on the initial blood glucose level

A new approach in compatibilization of the poly(lactic acid)/thermoplastic starch (PLA/TPS) blends

tIn this study, a new compatibilizer was synthesized to improve the compatibility of the poly(lacticacid)/thermoplastic starch blends. The compatibilizer was based on maleic anhydride grafted poly-ethylene glycol grafted starch (mPEG-g-St), and was characterized using Fourier transform infraredspectroscopy (FTIR), dynamic mechanical thermal analysis (DMTA) and back titration techniques. Theresults indicated successful accomplishment of the designed reactions and formation of a starch coredstructure with many connections to m-PEG chains. To assess the performance of synthesized compati-bilizer, several PLA/TPS blends were prepared using an internal mixer. Consequently, their morphology,dynamic-mechanical behavior, crystallization and mechanical properties were studied. The compatibi-lizer enhanced interfacial adhesion, possibly due to interaction between free end carboxylic acid groupsof compatibilizer and active groups of TPS and PLA phases. In addition, biodegradability of the sampleswas evaluated by various methods consisting of weight loss, FTIR-ATR analysis and morphology. Theresults revealed no considerable effect of compatibilizer on biodegradability of samples

Assessment of the maximum uptake time of 99mTc-DMSA in renal scintigraphy in rat

Introduction: The optimal imaging time of a radionuclide scintigraphy is the time at which the organ of interest has the maximum uptake of the injected radionuclide. This study was performed to investigate the maximum uptake time of 99mTc-DMSA in rat renal scan. Methods: Renal scintigraphy was performed with 3 mCi of 99mTc-DMSA. Planar images were acquired every 20 minutes for 8 hours post-injection using a small-animal SPECT. Results: Activity and the count rate per pixel (CRPP) of the kidneys peaked 1 h post-injection, plateaued for about 1 h, and declined time-dependently. Kidney to background ratio (KBR) reached to 61.7% at 1 h after injection and remained almost constant afterwards. Conclusion: The kidneys had maximum emission and CRPP between 1 to 2 h after 99mTc-DMSA injection, whereas there was no significant difference between the KBRs after 1 h. Our results showed that image acquisition of 1-2 h post-injection is recommended for renal scintigraphy with DMSA in rat

A comparative study on the physicochemical and biological stability of IgG1 and monoclonal antibodies during spray drying process

Background: The main concern in formulation of antibodies is the intrinsic instability of these labile compounds. To evaluate the physicochemical stability of antibody in dry powder formulations, physical stability of IgG1 and a monoclonal antibody (trastuzumab) during the spray drying process was studied in a parallel study and the efficacy of some sugar based excipients in protection of antibodies was studied. Results: The SDS-PAGE analysis showed no fragmentation of antibodies after spray drying in all formulations. The secondary structure of antibodies contained 40.13 to 70.19% of β structure in dry state. Also, CD spectroscopy showed the similar secondary structure for trastuzumab after reconstitution in water. ELISA analysis and cell culture studies were conducted in order to evaluate bioactivity of monoclonal antibody. Formulations containing combination of excipients provided maximum tendency of trastuzumab to attach to the ELISA antigen (86.46% ± 2.3) and maximum bioactivity when incubated with SKBr3 cell line (the cell viability was decreased to 65.99%± 4.6). Incubation of formulations with L929 cell line proved the biocompatibility of the excipients and non-toxic composition of formulations. Conclusion: The IgG1 and trastuzumab demonstrated similar behavior in spray drying process. The combination of excipients containing trahalose, hydroxypropyl beta cyclodextrin and beta cyclodextrin with proper ratio improved the physical and chemical stability of both IgG1 and monoclonal antibody

The role of serotonin in memory: interactions with neurotransmitters and downstream signaling

Abstract Serotonin, or 5-hydroxytryptamine (5-HT), is found to be involved in many physiological or pathophysiological processes including cognitive function. Seven distinct receptors (5-HT1–7), each with several subpopulations, have been identified for serotonin, which are different in terms of localization and downstream signaling. Because of the development of selective agonists and antagonists for these receptors as well as transgenic animal models of cognitive disorders, our understanding of the role of serotonergic transmission in learning and memory has improved in recent years. A large body of evidence indicates the interplay between serotonergic transmission and other neurotransmitters including acetylcholine, dopamine, γ-aminobutyric acid (GABA) and glutamate, in the neurobiological control of learning and memory. In addition,there has been an alteration in the density of serotonergic receptors in aging and Alzheimer’s disease, and serotonin modulators are found to alter the process of amyloidogenesis and exert cognitive-enhancing properties. Here, we discuss the serotonin-induced modulation of various systems involved in mnesic function including cholinergic, dopaminergic, GABAergic, glutamatergic transmissions as well as amyloidogenesis and intracellular pathways

Indomethacin-Enhanced Anticancer Effect of Arsenic Trioxide in A549 Cell Line: Involvement of Apoptosis and Phospho-ERK and p38 MAPK Pathways

Background. Focusing on novel drug combinations that target different pathways especially apoptosis and MAPK could be a rationaleforcombinationtherapyinsuccessfultreatmentoflungcancer.Concurrentuseofcyclooxygenase(COX)inhibitorswith arsenictrioxide(ATO)mightbeapossibletreatmentoption.Methods.CytotoxicityofATO,dexamethasone(Dex),celecoxib(Cel), andIndomethacin(Indo)individuallyorincombinationwasdeterminedat24,48,and72hrsinA549lungcancercells.TheCOX-2 gene and protein expression, MAPK pathway proteins, and caspase-3 activity were studied for the most cytotoxic combinations. Results. The IC 50s of ATO and Indo were 68.

Comparison of 99mTc-DMSA renal scintigraphy with biochemical and histopathological findings in animal models of acute kidney injury

Biochemical and histological assays are currently used for the diagnosis and characterization of kidney injury. The purpose of this study was to compare technetium- 99m-labeled dimercaptosuccinic acid (99mTc- DMSA) renal scintigraphy, as a non-invasive method, with common biochemical and histopathological methods in two animal models of acute kidney injury. Nephrotoxicity was induced either by gentamicin (100 mg/kg/day for one week) or unilateral ureteral ligation (UUO). Renal scintigraphy was performed 1 h after intravenous injection of 99mTc-DMSA (3 mCi). Furthermore, plasma levels of blood urea nitrogen (BUN), creatinine, sodium, and potassium were determined using an autoanalyzer. At the end of experiments, kidneys were excised for the measurement of activity uptake (mCi/gr) using a dose calibrator as well as histopathological examinations with hematoxylin and eosin (H&E) staining. There was a significant decrease in 99mTc-DMSA uptake in both gentamicin (P value = 0.049) and UUO (P value = 0.034) groups, and it was more significant in the former. The levels of BUN and creatinine increased in both gentamicin and UUO groups, while the levels of sodium and potassium remained unchanged. Furthermore, a strong correlation was found between DMSA uptake and histopathological findings. Scintigraphy with 99mTc-DMSA is capable of detection of kidney injury in both gentamicin and UUO groups. Moreover, a significant correlation was found between scintigraphy parameters and histopathological findings. This suggests 99mTc-DMSA as a non-invasive method for the evaluation of kidney injury induced by drugs or anatomical disorders

Brain Single Photon Emission Computed Tomography With Tc-99m MIBI or Tc-99m ECD in Comparison to MRI in Multiple Sclerosis

Purpose: To evaluate whether or not brain single photon emission computed tomography (SPECT) with Tc-99m MIBI or Tc-99m ECD (ethyl cysteinate dimer) can detect any abnormality in patients with definite multiple sclerosis (MS). We then compared these values with the results of T1, T2, and fluid-attenuated inversion recovery in magnetic resonance imaging (MRI). Materials and Methods: A total of 16 patients with proved MS were enrolled in the study, and the MRI with and without gadolinium contrast and also brain SPECT with Tc-99m MIBI (8 cases) or Tc-99m ECD (8 other cases) were performed. Results: MRI studies was performed in 16 patients (13 women and 3 men, aged 16-38 years) and an average of 10.47, 3.7, 5.3, 1.7, and 0.9 lesions was found in respect in periventricular white matter, juxtacortical white matter, corpus callosum, cerebellar peduncles, and brainstem, whereas brain SPECT with Tc-99m MIBI or Tc-99m ECD detected no abnormality. In addition, 6 cases had some degree of contrast enhancement. Conclusions: It seems that brain SPECT with Tc-99m MIBI or Tc-99m ECD would not improve this insufficiency. The small sizes of some plaques, particularly in chronic atrophic form of lesions, and the possibility of deeper anatomic positions of plaques can explain to some extent why the MS lesions were impossible to delineate on brain scan, although additional studies are needed. Copyright © 2010 by Lippincott Williams & Wilkins

Antiepileptic Treatment Is Associated with Bone Loss: Difference in Drug Type and Region of Interest

effects of antiepileptic drugs (AEDs) on bone mineral density (BMD) are well addressed, but data on children, especially concerning new antiepileptic medications, are scarce. This study aimed to reveal the impact of these drugs on the BMD of ambulatory patients with epilepsy. Methods: BMD and detailed clinical information were obtained on 108 patients and 38 controls using dual-energy x-ray absorptiometry. The patients were categorized into 2 groups: enzyme-inducing AEDs (EIAEDs) and non-EIAEDs. Also, the patients were classified as being in either a monotherapy or a polytherapy group. All patients completed a 63-item questionnaire. In this study, the raw value of BMD, T score, and z score of the spine, neck of femur, total hip, and forearm were analyzed. Results: Patients receiving AEDs showed diminished lumbar BMD, compared with controls (P , 0.05), regardless of the type of AED (EIAEDs or non-EIAEDs). In addition, there was a significant decrease in femoral neck BMD in patients receiving EIAEDs (0.922 6 0.161, P , 0.05) but not in those treated with non-EIAEDs. Patients undergoing carbamazepine monotherapy (33 patients) showed diminished lumbar and femoral neck BMD, whereas those receiving valproate (22 patients) or undergoing polytherapy showed a BMD similar to that of controls in all studied regions of interest. There was no notable change in BMD in the Ward triangle, trochanter, or total hip in either the EIAED or the non-EIAED group. Conclusion: AED therapy, especially in patients on new-generation medication, is associated with low bone density. It is hoped that the presented data stressing several clinical and diagnostic points will stimulate a high index of suspicion to facilitate early diagnosis an

Formulation and Optimization of Oral Mucoadhesive Patches of Myrtus Communis by Box Behnken Design

Purpose: Recurrent aphthous stomatitis (RAS) is the most common painful ulcerative disease of oral mucosa happening in ~20% of people. Aimed to develop Myrtus communis L. (Myrtle) containing oral patches, we applied box-behnken design to evaluate the effect of polymers such as Polyvinyl pyrrolidone (PVP), Gelatin, Methylcellulose (MC) and Pectin. Methods: The patches properties such as tensile strength, folding endurance, swelling index, thickness, mucoadhesive strength and the pattern of myrtle release were evaluated as dependent variables. Then, the model was adjusted according to the best fitted equation with box behnken design. Results: The results indicated that preparation of myrtle patch with hydrophilic polymers showed the disintegration time up to 24h and more. Using of polyvinyl pyrrolidone as a water soluble polymer and a pore-former polymer led to faster release of soluble materials from the patch to 29 (min-1). Also it decreases swelling index by increasing the patch disintegration. Gelatin and Pectin, with rigid matrix and water interaction properties, decreased the swelling ratio. Pectin increased the tensile strength, but gelatin produced an opposite effect. Thinner Myrtle patch (about 28μm) was obtained by formulation of methyl cellulose with equal ratio with polyvinyl pyrrolidone or gelatin. Conclusion: Altogether, the analysis showed that the optimal formulation was achieved with of 35.04 mg of Gelatin, 7.22 mg of Pectin, 7.20 mg of polyvinyl pyrrolidone, 50.52 mg of methyl cellulose and 20 mg of Myrtle extract