Abstract Traditionally dates is consumed as a rich source of iron supplement and the current research discuss the synthesis of silver nanoparticles (AgNPs) using methanolic seed extract of Rothan date and its application over in vitro anti-arthritic, anti-inflammatory and antiproliferative activity against lung cancer cell line (A549). FTIR result of synthesised AgNPs reveals the presence of functional group OH as capping agent. XRD pattern confirms the crystalline nature of the AgNPs with peaks at 38º, 44º, 64º and 81º, indexed by (111), (200), (220) and (222) in the 2θ range of 10-90, indicating the face centered cubic (fcc) structure of metallic Ag. HR- TEM results confirm the morphology of AgNPs as almost spherical with high surface areas and average size of 42 ± 9nm. EDX spectra confirmed that Ag is only the major element present and the Dynamic light scattering (DLS) assisted that the Z-average size was 203nm and 1.0 of PdI value. Zeta potential showed − 26.5mv with a single peak. The results of the biological activities of AgNPs exhibited dose dependent activity with 68.44% for arthritic, antiinflammatory with 63.32% inhibition and anti-proliferative activity illustrated IC50 value of 59.66 μg/mL expressing the potential of AgNPs to combat cancer.

Abstract Diabetic Neuropathy (DN) is one of the prevailing micro vascular complications of diabetes which can be characterized by neuropathic pain. Streptozotocin (STZ) induced diabetes in the rat has been increasingly used as a model of painful diabetic neuropathy. STZ injection leads to neurotoxicity of peripheral nerves that leads to development of Peripheral Diabetic Neuropathy in rat model. The present study was aimed at exploring the protective role of Tinospora cordifolia extract in STZ induced neurotoxicity and evaluating mechanisms responsible for attenuating neuropathic pain. Neuropathic pain markers like hyperalgesia, allodynia and motor deficits were assessed before STZ injection and after the treatment with 250 mg/kg and 500 mg/kg dose of Tinospora cordifolia. Oxidative stress markers, NGF expression in sciatic nerve were observed after seven weeks treatment. Our results demonstrated that seven weeks treatment with Tinospora cordifolia leaf extract significantly relieved thermal hyperalgesia and allodynia by increasing the antioxidant enzyme levels, decreasing the lipid peroxidation and by increasing the Nerve growth factor (NGF) expression in diabetic rat sciatic nerves. Our findings highlighted the beneficial effects of oral administration of Tinospora cordifolia extract in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and by inducing NGF m RNA in sciatic nerves.

Abstract Moringa stenopetala (Baker f.) Cufod., is an endemic species growing in the south of Ethiopia. M. stenopetala is often consumed as food and used in traditional medicine and it has also been traditionally used for relieving of pain in Ethiopia. This study aimed to investigate the antinociceptive effect and mechanisms of action of M. stenopetala leaves methanol extract in mice. The per-oral doses of 50, 100, and 200 mg/kg of M. stenopetala extract were tested for antinociceptive action by using hot-plate, tail-immersion, and writhing tests. The possible mechanisms of in the antinociceptive action were investigated by pre-treatment with 5 mg/kg naloxone (non-selective opioid antagonist), 1 mg/kg ketanserin (5-HT2A/2C receptor antagonist), and 1 mg/kg yohimbine (α2 adrenoceptor antagonist). The methanol extract of M. stenopetala showed antinociceptive effect in all tests. The significant involvement of 5-HT2A/2C receptors and α2 adrenoceptors in antinociception induced by M. stenopetala extract in the hot-plate and tail-immersion tests, as well as significant contribution of opioid receptors and α2 adrenoceptors in writhing test, were identified. In conclusion, these findings demonstrate that the methanol extract of M. stenopetala has potential in pain management. Thisstudywillcontributetonewtherapeuticapproachesandprovideguidancefornewdrug development studies.

Abstract The effect of hypothermia treatment on white blood cell (WBC), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) values as an indicator of inflammation was evaluated in newborns with hypoxic ischemic encephalopathy (HIE). The study was performed that the before-therapeutic hypothermia (TH) and after-TH WBC, lymphocytes, neutrophils, monocytes and NLR, LMR and PLR values of the complete blood cell count were retrospectively evaluated. The results of the patient group were compared with the results of healthy newborns. A total of 78 patients who underwent TH were evaluated in our study. Mean values before and after TH were NLR3.8/2.7, LMR 5.6/8.6, and PLR 60.3/67.1 respectively. A statistical significance was present for NLR values before and after TH in those with seizure in our study (4.15±2.95/3.01±2.54) but no statistical significance was found for LMR or PLR. In neonates with HIE, effect of TH on complete blood cell count and inflammatory mechanisms (mediated neutrophil and lymphocyte) may be minimal.

Abstract The aqueous solubility of cefixime trihydrate (a water insoluble drug) using different hydrotropic agents was determined and solid dispersions of cefixime trihydrate were prepared by hydrotropic solubilization technique. The drugs content were determined. The aqueous solubility of v was increased many fold in presence of sodium acetate trihydrate as hydrotropic agent. This hydrotropic agent was used to prepare solid dispersion of cefixime trihydrate. Cefixime trihydrate and sodium acetate trihydrate were accurately weighed and taken in a 200 mL beaker. Distilled water 10-15 mL was taken to dissolve hydrotropic agent using heat (48-50 °C). The drug was then added to it and magnetically stirred till whole mass get viscous. The solid dispersions of cefixime trihydrate were characterized by XRD, DSC and IR studies. DSC thermogram, XRD and Infra-Red spectra were studied. Solid dispersions, thus prepared, showed faster release of the drug as compared to pure drug and physical mixture.

Abstract To investigate structure-property relationship of polymer-based curcumin solid dispersion (SD), three acrylic polymers were used to formulate curcumin SD by solvent evaporation method. Curcumin Eudragit EPO SD (cur@EPO), curcumin Eudragit RS PO SD (cur@RSPO) and curcumin Eudragit RL PO SD (cur@RLPO) showed deep red, golden orange and reddish orange color, respectively. Cur@RSPO entrapped 15.42 wt% of curcumin followed by cur@RL PO and cur@EPO. FTIR spectra indicated that in cur@EPO, curcumin may transfer hydrogen to the dimethylaminoethyl methacrylate group and thus change its color to red. In contrast, curcumin may form hydrogen bonding with Eudragit RS PO and Eudragit RL. Curcumin exists in amorphous state in three SDs as proved by differential scanning calorimetry and X-Ray diffraction measurement. In vitro digestion presented that lower pH value in simulated gastric fluid (SGF) stimulates the curcumin release from cur@EPO while permeability influences the release profile in other two SDs. When in simulated intestinal fluid (SIF), first order release model governs the release behaviors of all three SDs which showed sustained release pattern. Our results are helpful to elucidate how structure of polymer may impact on the major properties of curcumin contained SD and will be promising to broaden its therapeutic applications.

Abstract Vascular ulcers (VU) constitute a major cause of pain and disability, and significantly compromise quality of life. VU have a natural tendency to become chronic and in many cases exhibit anunsatisfactoryresponse to many of the standard therapeutic options.The case of a 73 year-old Caucasian female with severe pain and poorly-controlled pain (Visual Analogic Scale-VAS- of 8-9) due to three lower leg long-standing VUs is reported and discussed herein. The patient was treated with topical instillations of undiluted sevoflurane as per institutional off-label protocol (starting doses of 1mL/cm2 twice a day, and up-titrated according to response to a maximum of 7 mL twice daily). The VAS score dropped to 0-1 shortly after initiation of therapy and remained stable throughout treatment up until the closure of the observations. Subsequently, opioid therapy was gradually tapered down and ultimately abandoned.Sevoflurane application resulted on adequate and sustained pain management of refractory VU, with no significant side effects. On account of its beneficial effectivity and safety profiles, topical sevoflurane emerges as an add-on alternative for the long-term management of VU, and potentially other painful conditions.

Abstract The use of plants in disease treatment is cost effective and relatively safe. This study was designed to investigate anti-hyperlipidemic and anti-diabetic activity of ethanolic leaf extract of Catharanthus roseus alone and in combination therapy in hyperlipidemic & diabetic mice. Eight groups comprising five mice each were used. Group A was hyperlipidemic control, group B, C, D received atorvastatin (20 mg/kg), leaf extract (200 mg/kg) and leaf extract in combination with atorvastatin (200 mg/kg and 20 mg/kg) orally for 15 days. Group E was diabetic control. Group F, G, H received sitagliptin (40 mg/kg), leaf extract (200 mg/kg) and extract in combination with sitagliptin (200 mg/kg and 40 mg/kg) orally for 7 days. Blood cholesterol levels were measured at 1st, 5th, 10th and 15th day and fasting blood sugar levels were measured at 2, 12, 24, 72 and 168 hours during treatment. One-way ANOVA with tukey- kramer multiple comparison test was used. The chemical characterization of ethanolic extract of Catharanthus roseus leaves showed presence of alkaloids, saponins, tannins and flavonoids. Ethanolic extract of Catharanthus roseus has significant anti-hyperlipidemic & anti-diabetic effects (p<0.05, p<0.01) when compared with control but had not cause significantly increase in anti-hyperlipidemic effects of atorvastatin. While significantly increased the antidiabetic effect of sitagliptin (p<0.05).

Abstract To assess the performance indicators for pharmaceutical services (PS) in primary health care (PHC), the level of satisfaction with pharmacy services among users and managers / pharmacists’ impressions in relation to the findings were evaluated. The study used mixed methods, including a retrospective and descriptive study of the performance indicators for PS in PHC, an observational study on the level of satisfaction and a qualitative study of users’ perception of pharmacy services at Health Units. Managers and pharmacists’ impressions of the study results were also collected. Only 44.4% of pharmacies had a full-time pharmacist. From the establishments visited, 5.3% did not have an air-conditioned environment, and only 33.3% of the items essential to the Good Practices of Storage of Medicines and Supplies criteria were fulfilled. Although 77.9% of the prescribed medicines were dispensed, it did not reach the 80% standard. The satisfaction level of users was 3.2±0.6, indicating dissatisfaction with pharmacies’ services. By means of an evaluation of each item within the questionnaire, it was possible to observe that variables related to pharmaceutical care presented low scores in relation to other domains, thus evidencing the fragility of the pharmaceutical- patient relationship in users’ perception. Managers and pharmacists suggested that these results were related to the inadequate physical infrastructure of pharmacies, work overload, lack of recognition and undervaluation of pharmacists, lack of interaction within the PHC team, high turnover of pharmacists, and lack of PS prioritization by the administration. PS in PHC has structural and organizational weaknesses that require changes. In general, users are dissatisfied with pharmacies’ services, especially with pharmaceutical care.

Abstract Risperidone is an atypical antipsychotic drug widely prescribed all over the world due to its clinical advantages. The currently available long acting marketed depot formulation of risperidone is a microsphere based preparation using poly-[lactide-co-glycolide] (PLGA) as drug release barrier. It is however, a cold chain product due to thermal instability of PLGA at room temperature. After beginning the depot injection therapy it is administered every two weeks but associated with another drawback of about 3 weeks lag time due to which its tablets are also administered for three weeks so as to attain and maintain therapeutic drug concentration in the body. The present work attempts to develop a long acting depot delivery system of risperidone for once a month administration based on the combination of sucrose acetate isobutyrate and polycaprolactone dissolved in benzyl benzoate to provide an effective drug release barrier for one month without any lag time and which can be stored at room temperature precluding the requirement of cold supply chain. The developed depot formulation showed a sustained in vitro drug release profile with 88.95% cumulative drug release in 30 days with little burst release. The in vivo pharmacokinetic studies of the developed formulation conducted on rats showed attainment of mean peak plasma drug concentration of 459.7 ng/mL in 3 days with a mean residence time of 31.2 days, terminal half-life of 20.6 days, terminal elimination rate constant of 0.0336 per day, and a good in vitro- in vivo correlation.

Abstract We were carried out to investigate the efficacy of Rape (Rapeseed, Brassica napus L.) flower on BPH (benign prostatic hyperplasia) in rats. We found that the extract from Rape flower prevented hyperplasia in testosterone-induced BPH model, the relevant animal model of human BPH. Extract reduced the weight of prostate and induced significantly cell apoptosis in prostate in BPH model. In addition, the extract controlled expression of TGF-β1 in prostate gland and promoted urinary output in dose-dependence in BPH model. Our data provide that Rape flower may be useful for treatment of BPH.

Abstract Interferon-β-1a (INF-β-1a) has gained significant attention due to its emerging applications in the treatment of different human diseases. Therefore, many researchers have attempted to produce it in large quantities and also in a biologically active form using different expression systems. In the present study, we aimed to improve the expression level of INF-β-1a by Pichia pastoris using optimization of culture conditions. The codon-optimized INF-β- 1a gene was cloned into pPICZαA plasmid under the control of alcohol oxidase I (AOX1) promoter. The protein expression was induced using different concentrations of methanol at different pHs and temperatures. The biological activity of produced protein was evaluated by anti-proliferative assay. The ideal culture conditions for the expression of INF-β-1a by P. pastoris were found to be induction with 2% methanol at pH 7.0 culture medium at 30 C which yielded a concentration of 15.5 mg/L INF-β-1a in a shake flask. Our results indicate that differences in glycosylation pattern could result in different biological activities as INF- β-1a produced by P. pastoris could significantly more reduce the cell viability of HepG-2 cells, a hepatocellular carcinoma cell line, than a commercially available form of this protein produced by CHO.

Abstract The hepatoprotective potential of alcesefoliside (AF) from Astragalus monspessulanus was investigated. Iron sulphate/ascorbic acid (Fe2+/AA) lipid peroxidation was induced in rat liver microsomes and pre-incubated with AF and silybin (100, 10 and 1 µmol). Pronounced effects were observed in 100 µmol. In vivo experiments were carried out on rats, challenged orally with carbon tetrachloride (CCl4) alone and after pre-treatment and followed by curative treatment with AF (10 mg/kg). The activity of the serum and antioxidant enzymes, together with reduced glutathione (GSH) levels and malonedialdehyde (MDA) quantity were measured. Microsomal incubation with Fe2+/AA increased MDA production. The pre-incubation with AF reduced the formation of MDA, comparable to silybin. These findings were supported by the in vivo study where CCl4-induced liver damage was discerned by significant increase in serum enzymes and in MDA production as well as by GSH depletion and reduced antioxidant enzymes activity. The AF pre-treatment and consecutive curative treatment normalizes the activity of the serum and antioxidant enzymes alike, as well as the levels of GSH and MDA. Histological examination of AF-treated livers showed a decrease in the abnormal accumulation of lipids in hepatocytes as well as reduced alterative changes in their structure in a model of CCl4-induced toxicity.

Abstract The objective of this study was to evaluate drug interactions based on medical records of patients hospitalized in University Hospital Lauro Wanderley (UHLW) in João Pessoa-PB, Brazil. This was a quantitative, descriptive study with a cross-sectional design. This research was conducted in the medical clinic of the above hospital by analyzing pharmaceutical intervention in medical records. The investigated samples consisted of all medical profiles with drug interaction information of patients hospitalized from June 2016 to June 2017. Most of these drug interactions were determined and classified by Micromedex® Solutions database. This research was approved by the Ethics Committee in Institutional Human Research, protocol number 2.460.206. In total, 331 drug interactions were found in 131 medical profiles. Dipyrone, enoxaparin, sertraline, ondansetron, quetiapine, tramadol, bromopride, amitriptyline, and simvastatin were medications that showed highest interactions. According to Anatomical Therapy Classification (ATC), drugs that act on the central nervous system result in more interactions. The most prevalent interaction was between dipyrone and enoxaparin. Some limitations of this study are the lack of notifications and data on drug interactions.

Abstract There is no biodistribution or imaging data on 99mtechnetium (Tc)-hexamethyl propylamine oxime (HMPAO)-labeled platelets in the literature. The current study aimed to present updated information about the clinical procedures for preparation and use of labeled platelets. Following two-step centrifugation at 1500 and 2500 rpm, the platelets were extracted from whole blood into platelet-rich plasma (PRP) above the buffy coat and then from PRP into a platelet pellet at the bottom of the tube. The 99mTc-HMPAO-labeled platelets were inspected for purity, viability, release of 99mTc from platelets, and sterility. Also, microscopic examination and thin layer chromatography (TLC) were performed. Biodistribution was assessed following necropsy in BALB/c mice and through imaging of New Zealand rabbits. The separation ratio was estimated at 98%, and radiochemical purity was measured to be 80%. The labeling efficiency was above 30% in more than half of the assays (range: 17-43%). The release of 99mTc from platelets was 9% per hour at 37ºC. After 24 hours, stability was estimated at 54% in the human serum. The target organs of mice included the spleen and liver. In rabbits, the imaging results indicated liver as the target organ. Thyroid uptake was negligible up to 90 minutes. Based on the findings, extraction of platelets and labeling them with 99mTc-HMPAO is a feasible and safe approach in routine practice.