Baricity of bupivacaine on maternal hemodynamics after spinal anesthesia for cesarean section: a randomized controlled trial

Background: After spinal anesthesia, patients undergoing cesarean section are more likely to develop hemodynamic changes. The baricity of local anesthetic has an important role on spinal blockade effects. The aim of this study was to compare the isobar and hyperbaric bupivacaine 0.5% plus fentanyl on maternal hemodynamics after spinal anesthesia for C/S

Methods: In this double-blind study, 84 healthy pregnant women undergoing C/S using bupivacaine 0.5% isobar [study group, n=42] or hyperbaric [control group, n=42] for spinal anesthesia were scheduled. The study was conducted from 21 April 2014 to 21 November 2014 at Al-Zahra Hospital, Tabriz, Iran. Parameters such as maternal hemodynamics, block characteristics, side effects, and neonatal Apgar scores were recorded. Data were analyzed using the SPSS software by performing chi-square test, Fisher's exact test, one-way ANOVA, Mann-Whitney U-test, and student's t test

Results: The incidence of hypotension in the isobar group was lower than the hyperbaric group, although it was not statistically significant [40.47% vs. 61.9%, P=0.08]. The duration of hypotension was shorter in the study group [1.6 +/- 7.8 min vs. 7.4 +/- 12.5 min, P=0.004]. The dose of ephedrine was lower in the study group [2.4 +/- 6.6 mg vs. 5.3 +/- 10.7 mg, P=0.006]. The main maternal side effect is sustained hypotension that was seen in 0 patients of the isobar and 7 [16.66%] of hyperbaric groups [P=0.006]. None of the neonates had Apgar score

Conclusion: Isobaric bupivacaine is associated with more hemodynamic stability and shorter sensory and motor blockade in mothers under spinal anesthesia for C/S

Optimization of carbon and nitrogen sources for extracellular polymeric substances production by chryseobacterium indologenes MUT.2

Background: Bacterial Extracellular Polymeric Substances [EPS] are environmental friendly and versatile polymeric materials that are used in a wide range of industries such as: food, textile, cosmetics, and pharmaceuticals. To make the production process of the EPS cost-effective, improvements in the production yield is required which could be implemented through application of processes such as optimized culture conditions, and development of the strains with higher yield [e.g. through genetic manipulation], or using low-cost substrates

Objectives: In this work, the effects of carbon and nitrogen sources were studied in order to improve the EPS production by the submerged cultivation of Chryseobacterium indologenes MUT.2

Materials and Methods: The mesophilic microorganism Chryseobacterium indologenes MUT.2, was grown and maintained in the Luria Bertani agar. The initial basal medium contained: glucose [20 g.L-1], yeast extracts [5 g.L[-1]], K[2]HPO[4] [6 g.L[-1]], NaH[2]PO[4] [7 g.L[-1]], NH[4]CL [0.7 g.L[-1]], and MgSO[4] [0.5 g.L[-1]]. For evaluating the carbon and nitrogen sources' effect on the fermentation performance, cultures were prepared in 500 mL flasks filled with 300 mL of the medium. The single-factor experiments based on statistics was employed to evaluate and optimize the carbon and nitrogen sources for EPS production in the liquid culture medium of Chryseobacterium indologenes MUT.2

Results: The preferred carbon-sources, sucrose and glucose, commonly gave the highest EPS production of 8.32 and 6.37 g.L[-1], respectively, and the maximum EPS production of 8.87 g.L[-1] was achieved when glutamic acid [5 g.L[-1]] was employed as the nitrogen source

Conclusions: In this work, the culture medium for production of EPS by Chryseobacterium indologenes MUT.2 was optimized. Compared to the basal culture medium in shake-flasks and stirred tank bioreactor, the use of optimized culture medium has resulted in a 53% and 73% increase in the EPS production, respectively

Radiosynthesis and evaluation of ytterbium-175 labeled bleomycin as therepeutic agent

Bleomycins are DNA-binding biomolecules, which can be used as targeted therapy carriers when labeled with particle-emitters such as Yb-175. In this work the development of Yb-175 bleomycin [[175]Yb-BLM] has been reported. Yb-175 chloride was obtained by thermal neutron irradiation [3 × 10[13] n.cm[-2].s[-1]] of natural Yb2O3 samples at various neutron fluxes and irradiation times. The radionuclide dissolved in acidic media [120mCi/mg] was used in the bleomycin [5 mg] labeling in buffer solution and warming at 60[degree sign]C for 48 h. Radiochemical purity was determined by ITLC as well as specific activity calculation followed by stability studies. Biodistribution studies of free Yb-175 and [175]Yb-BLM were performed in wild-type mice up to 8 days. At optimized conditions radiochemical purity of 97 +/- 0.88% and specific activity of 1360 MBq/mM was obtained. Biodistribution studies of free Yb-175 demonstrated liver and bone uptake while in case of [175]Yb-BLM the target tissues were lung, liver and spleen.[175]Yb-BLM complex was prepared at the optimized conditions and suitable characteristics. The accumulation of the radiolabeled compound in lungs, liver and spleen demonstrates a similar pattern to the other radiolabeled bleomycins. Further studies are to be performed for application of this labeled compound in tumor-bearing models

Preparation and quality control of [177]Lu-chitosan for radiosynovectomy

Rheumatoid arthritis [RA] is the most common autoimmune disease, leading to the destruction of the joints and causing pain, disability, and immobility in the patients. Radiosynovectomy [RSV] has been applied as an effective treatment for the patients with resistant synovitis after failure of long-term pharmacotherapy and intra-articular steroid injection for more than 50 years. Several radiopharmaceuticals have been developed for RSV so far, but still development of new radiophamaceuticals is of crucial interest. In this research, the [177]Lu-chitosan complex [[177]Lu-CHITO] was introduced as a new agent for RSV. [177]Lu was produced by irradiation of a natural Lu2O3 target at a thermal neutron flux of approximately 4 x 10[13] n/cm[2]s. [177]Lu-CHITO was prepared in the diluted acetic acid solution. The radiochemical yield was checked by ITLC method. The biodistribution of the complex was investigated by intra-articular injection to rabbits' and rats' knee joints. The leakage of injected dose from the injection site in the rabbit organs was investigated using SPECT imaging up to 48 hours. [177]Lu was prepared with a specific activity of 2.6-3 GBq.mg[-1] and radionuclide purity of 99.98%. [177]Lu-CHITO was prepared successfully with high radiochemical purity [95%] and specific activity of 888 TBq/mmol. Both the biodistribution data in rats and SPECT imaging of the rabbit showed that there was no significant leakage of the injected activity even after 192 h. Considering all of the excellent features of the complex, this radiopharmaceutical can be used for effective management of synovial inflammation

Treatment efficacy of 153Sm-EDTMP for painful bone metastasis

Involvement of the skeleton can cause an excruciating pain in two-thirds of terminal patients with a history of malignancy. Due to several limitations of other therapies, such as analgesics, bisphosphonates, chemotherapy, hormonal therapy and external beam radiotherapy; bone-seeking radiopharmaceuticals have an important role in palliation of pain from bone metastases. Although these kinds of therapies have many advantages including the ability to treat multiple sites of tumoral involvement simultaneously, no significant confliction with other treatments, ease of administration and the potential to be used repetitively; in Iran using of this modality is not widely practiced. In this study we evaluated the clinical usefulness of Sm-153 lexidronamfor pain management of bone metastases. 28 patients [14 males and 14 females] aged 38-77 years with a history of painful bone metastases caused by different cancers, not responding to conventional treatments were included in the study. All patients had a recent whole body bone scan indicating multiple bone metastases. 1 mCi/Kg Sm-153 lexidronam was injected intravenously to the patients. Whole body scintigraphy was done 3 or 18 hours post injection. Pain relief and quality of life have been evaluated by analog pain scale and Karnofsky index every week, respectively. Also, all patients were evaluated for hematological toxicity every two weeks. Active follow ups were performed. 43% of patients showed the presence of the flare phenomenon during the first three days after Sm injection with a mean duration of 2.2 days. The pain relief began between 2 and 16 days post injection and the duration of pain palliation was in the range of 4 to 32 weeks [mean +/- SD=15.22 +/- 7.8].64.3% of patients showed complete relief of pain and 21.4% achieved partial response to therapy. [Over all response to therapy was 85.7%]. The lowest amount of peripheral blood cells was detected in the fourth week for RBCs and in the 6th week for WBCs and PLTs. No one experienced hematological toxicity induced problems. Sm-153 lexidronam is an effective treatment for painful bone metastases. The complication rate is low and the quality of life of the patients after treatment would be significantly improved

Preparation and quality control of scandium-46 bleomycin as a possible therapeutic agent

Due to interesting therapeutic properties of [46]Sc and antineoblastic antibiotic, bleomycin [BLM], 46Scbleomycin [[46]Sc-BLM] was developed as a possible therapeutic compound. In this work, Sc-46 chloride was obtained by thermal neutron flux [4 × 10[13] n.cm[-2].s[-1]] of natural metallic scandium sample followed by dissolution in acidic media as a substitute for [47]Sc in radiolabeling studies which was further used for labeling of bleomycin [BLM] followed by stability studies as well as biodistribution in wild-type rats. Sc-46 was obtained in high radiochemical purity [ITLC, >99%, two systems] as well as acceptable specific activity. At optimized conditions a radiochemical purity of 98% was obtained for [46]Sc-BLM shown by ITLC [Specific activity, 740 GBq/mmole]. The accumulation of the radiolabeled compound in lungs, liver and spleen demonstrates a similar pattern to the other radiolabeled bleomycins. Sc-BLM is a possible therapeutic agent in human malignancies and the efficacy of the compound should be tested in various tumor-bearing models

Production, quality control and pharmacokinetic studies of [177]lu-edtmp for human bone pain palliation therapy trials

Developing new bone pain palliation agents is a mandate in handling end-stage cancer patients around the world. Possibly, Lu-177 ethylenediaminetetramethylene phosphonic acid [[177]Lu-EDTMP] is a therapeutic agent which can be widely used in bone palliation therapy. In this study, [177]Lu-EDTMP complex was prepared successfully using synthesized EDTMP ligand and [177]LuCl[3]. Lu-177 chloride was obtained by thermal neutron irradiation [4 _ 10[13] n.cm[-2]s[-1]] of natural Lu[2]O[3] samples. Radiochemical purity of [177]Lu-EDTMP was determined by ITLC [more than 99%]. Stability studies of the final preparations in the presence of human serum were performed. The biodistribution of [177]Lu-EDTMP and [177]LuCl[3] in wild-type rats was studied by SPECT imaging. A comparative accumulation study for [177]Lu-EDTMP and [177]LuCl[3] was performed for vital organs up to 7 days. The complex was obtained in high radiochemical purity [more than 99%]. The complex was stable in vitro in presence of human serum as well as final formulation. Significant bone uptake [> 70%] was observed for the radiopharmaceutical. Due to better physical properties of Lu-177 compared to Sm-153 and acceptable biodistribution results of the compound, [177]Lu-EDTMP seemed to be an interesting new candidate for clinical trials for bone pain palliation therapy

Production of holmium-166 DOTMP: a promising agent for bone marrow ablation in hematologic malignancies

Therapeutic radiopharmaceuticals are radiolabeled molecules to deliver sufficient doses of ionizing radiation to specific disease sites such as bone metastases, brain and liver tumors and bone marrows malignancies including multiple myeloma. Among some therapeutic radiopharmaceuticals, 166Ho-1, 4, 7, 10-tetraazacyclo dodecane-1,4,7,10 tetraethylene phosphonic acid [166Ho-DOTMP] is used for delivering high doses to bone marrow. In this research production, quality control, pharmacokinetics and biodistribution studies of 166Ho-DOTMP with respect to its radiochemical and in vivo biological characteristics have been presented. Holmium-166 was produced by irradiation of holmium oxide [Ho2O3, purity>99.8%] at a thermal neutron flux. 166Ho-DOTMP complex was obtained in very high yields [radiochemical purity>99%] under the reaction conditions employed. Radiochemical purity and the stability of the 166Ho-DOTMP complex in human serum were assayed. Wild type rats were used for biodistribution and imaging studies of this agent. 166Ho produced by irradiation of holmium-165 oxide demonstrated high radionuclide purity. 166Ho-DOTMP was obtained in very high yield [radiochemical purity>99%] and the complex exhibited excellent in vitro stability at pH-7 when stored at room temperature and human serum. Biodistribution studies in rats showed favorable selective skeletal uptake with rapid clearance from blood along with insignificant accumulation of activity in other non-target organs. The scintigraphic image recorded in rat at 3 h after the injection of the 166Ho-DOTMP radiopharmaceutical revealed that 166Ho-DOTMP rapidly accumulated in skeleton especially in the thigh bones. Biodistribution, stability, imaging and pharmacokinetics studies of 166Ho-DOTMP radiopharmaceutical in this research showed favorable features such as; rapid and selective skeletal uptake, fast clearance from blood and almost no uptake in any other major organs. Our research demonstrated that 166Ho-DOTMP has promising features suggesting good potential for efficient use of this radiopharmaceutical for bone marrow ablation in different hematologic malignancies including multiple myeloma

Production, quality control and biological evaluation of [153] Sm-TTHMP as a possible bone palliation agent

Various bone palliative therapeutic agents have been developed and widely used for bone metastasis such as [153]Sm-EDTMP. In this study, production, quality control and biodistribution studies of a newly developed therapeutic compound have been presented followed by imaging studies in wild-type rodents. [153]Sm-TTHMP was prepared starting from [153]Sm-SmCl[3], prepared by neutron activation of an enriched [152]Sm sample [purity >98%], and in-house synthesized TTHMP in 1h at 25[degree sign] C followed by stability tests, partition coefficient determination and biodistribution studies of in wild-type rodents using scarification and SPECT imaging. The radiolabled Sm complex was prepared in high radiochemical purity [>99%, ITLC] and specific activity of 278 GBq/mmol and demonstrated significant ability at 4, 25 and 37 [degree sign] C [in presence of human serum]. Initial biodistribution data showed significant bone accumulation of the tracer in 48h. [153]Sm-TTHMP can be a potential candidate for bone pain palliation therapy in skeletal metastases, although further biological studies in other mammals is still needed

Development of sm-153 chitosan for radiosynovectomy

Developing new radiosynovectomy agents is of great importance due to the aging of human populations around the world and increasing the incidence of inflammatory diseases. In this work, Sm-153 chitosan agent was developed for the first time in our country and preparation and quality control of the compound is described. Sm-153 chloride was obtained by thermal neutron flux [4-5 x 10[13] n.cm [-2]. S[-1] of natural Sm[2]O[3] sample, dissolved in acidic media. [153] Sm-samarium chloride [370 MBq] was used in preparation of [153] Sm-chitosan complex followed by quality control using MeOH: H[2]O: acetic acid [4: 4: 2] as mobile phase. The complex stability and viscosity were checked in the final solution up to 2 days. The complex solution and [153]Sm[3+] [80 micro Ci/100 micro l] were injected intra-articularly into male rat knee joint followed by scarification studies 6d post injection. Sm-153 chitosan was prepared successfully with high radiochemical purity [>99%, ITLC] at room temperature after 10-30 min followed by autoclave sterilization. The complex was stable at room temperature and 37 [degree sign] C up to 2 days. No significant leackage of dose from injection site and its distribution in organs were observed up to 6 days for [153] Sm-chitosan. Approximately, more than 90% of injected dose remained in injection site after 6d. The complex is a dedicated agent for radiosynovectomy. The experience from this study would lead to the development of more sophisticated radiosynovectomy radiopharmaceuticals for human use in the country

Production and quality control of [166]Ho-chitosan for therapeutic applications

In this research, [[166]Ho]Holmium chitosan complex production is described in details, followed by determination of complex radiochemical purity, stability and biodistribution [after intra-articular injection] in wild-type male rats. Finally a Ho-166 based chitosan kit for ultimate radiosynovectomy as well as radiotherapy applications was developed. [166]Ho-chitosan complex was prepared using chitosan concentrations and [166]HoCl[3] followed by intra-articular injection and biodistribution studies in wild-type rats including and excluding injected knee. The [[166]Ho]Holmium chitosan complex was prepared with high radiochemical yield [>95%] in the optimized condition [35mg/3ml of chitosan in%1 AcOH, pH. 3, >98%, ITLC] was injected to wild-type rats followed by the biodistribution studies of the compound among the tissues excluding the injected knee data. Intra-articular injection of [[166]Ho]holmium chitosan complex to male wild-type rats and investigation of leakage of activity in the body showed that most of injected dose has remained in injection site 144 h after injection. Successful development and formulation of [166]Ho-chitosan kit is described. This kit has the potential for use in clinical setting namely for radiosynovectomy and cancer radiochemotherapy

Production, quality control and biological evaluation of [153]Sm-EDTMP in wild-type rodents

Nowadays various bone pain palliative therapeutic agents have been developed for bone metastases. Among those, [153]Sm-ethylenediamine tetramethylene phosphonic acid [[153]Sm-EDTMP] is the major therapeutic agent which is widely used in the world. In this study, production, quality control and biodistribution studies of this therapeutic radiopharmaceutical have been presented and followed by imaging studies in a wild-type rabbit for the first time in order to make preparations for this agent to be officially approved in the country. [153]Sm-EDTMP was produced using [153]Sm-SmCl[3], prepared by neutron activation of an enriched [152]Sm sample [purity >98%], and in-house synthesized EDTMP in 4h at 100°C. The analytical data for the structure determination and purity of the ligand was obtained and shown to be identical to an authentic sample from a European vendor. The Radiochemical purity of [153]Sm-EDTMP was checked by RTLC and ITLC. The biodistribution of [153]Sm-EDTMP in wild-type rodents was checked and SPECT imaging as well as following sacrificing the animal. The radiolabeled Sm complex was prepared in high radiochemical purity [>99%, RTLC] followed by initial biodistribution data with the significant bone accumulation [>70%] of the tracer in 48h which is comparable with the reported methods. The produced [153]Sm-EDTMP properties suggest good potential for efficient use of this radiopharmaceutical for bone pain palliation and as substitute for other agents, such as [89]SrCl[2] and [32]P, currently used in the country

Production of recombinant human granulocyte-colony stimulating factor by Pichia pastoris

Human granulocyte-colony stimulating factor [hGCSF] cDNA was expressed in the methylotrophic yeast Pichia pastoris under the control of the alcohol oxidase [AOX1] promoter. An expression vector for hG-CSF secretion was constructed using pPIC9 vector. Higher levels of hG-CSF was obtained using a P. pastoris Mut+ [methanol utilization fast] phenotype. The effects of environmental factors such as, temperature and pH on the P. pastoris cell growth and hGCSF production during fermentation were investigated. Cell growth and hG-CSF production were found to be optimal at 28C and pH 6.0. A fed-batch fermentation process was also developed to obtain high cell density and higher levels of protein expression. Using a high cell density cultivation method, cell dry weight and hGCSF concentration reached 100 g/l and 35 mg/l, respectively