Delta-aminolevulinic acid dehydratase enzyme activity in blood, brain, and liver of lead-dosed ducks

USGS Publications Warehouse

Dieter, M.P.; Finley, M.T.

1979-01-01

Mallard ducks were dosed with a single shotgun pellet (ca. 200 mg lead). After 1 month there was about 1 ppm lead in blood, 2.5 in liver, and 0.5 in brain. Lead-induced inhibition of delta-aminolevulinic acid dehydratase enzyme in blood and cerebellum was much greater than in cerebral hemisphere or liver and was strongly correlated with the lead concentration in these tissues. The cerebellar portion of the brain was more sensitive to delta-aminolevulinic acid dehydratase enzyme inhibition by lead than were the other tissues examined. There was also a greater increase in the glial cell marker enzyme, butyrylcholinesterase, in cerebellum than in cerebral hemisphere, suggesting that nonregenerating neuronal cells were destroyed by lead and replaced by glial cells in that portion of the brain. Even partial loss of cerebellar tissue is severely debilitating in waterfowl, because functions critical to survival such as visual, auditory, motor, and reflex responses are integrated at this brain center.

Enhanced 5-aminolevulinic acid-gold nanoparticle conjugate-based photodynamic therapy using pulse laser

NASA Astrophysics Data System (ADS)

Xu, Hao; Yao, Cuiping; Wang, Jing; Chang, Zhennan; Zhang, Zhenxi

2016-02-01

The low bioavailability is a crucial limitation for the application of 5-aminolevulinic acid (ALA) in theranostics. In this research, 5-aminolevulinic acid and gold nanoparticle conjugates (ALA-GNPs) were synthesized to improve the bioavailability of ALA and to investigate the impact of ALA photodynamic therapy (ALA-PDT) in Hela cells. A 532 nm pulse laser and light-emitting diode (central wavelengths 502 nm) were jointly used as light sources in PDT research. The results show a 532 nm pulse laser can control ALA release from ALA-GNPs by adjusting the pulse laser dose. This laser control release may be attributed to the heat generation from GNPs under pulse laser irradiation, which indicates accurately adjusting the pulse laser dose to control the drug release in the cell interior can be considered as a new cellular surgery modality. Furthermore, the PDT results in Hela cells indicate the enhancement of ALA release by pulse laser before PDT can promote the efficacy of cell eradication in the light-emitting diode PDT (LED-PDT). This laser mediated drug release system can provide a new online therapy approach in PDT and it can be utilized in the optical monitor technologies based individual theranostics.

Ameliorative Effect of Chronic Supplementation of Protocatechuic Acid Alone and in Combination with Ascorbic Acid in Aniline Hydrochloride Induced Spleen Toxicity in Rats.

PubMed

Khairnar, Upasana; Upaganlawar, Aman; Upasani, Chandrashekhar

2016-01-01

Background. Present study was designed to evaluate the protective effects of protocatechuic acid alone and in combination with ascorbic acid in aniline hydrochloride induced spleen toxicity in rats. Materials and Methods. Male Wistar rats of either sex (200-250 g) were used and divided into different groups. Spleen toxicity was induced by aniline hydrochloride (100 ppm) in drinking water for a period of 28 days. Treatment group received protocatechuic acid (40 mg/kg/day, p.o.), ascorbic acid (40 mg/kg/day, p.o.), and combination of protocatechuic acid (20 mg/kg/day, p.o.) and ascorbic acid (20 mg/kg/day, p.o.) followed by aniline hydrochloride. At the end of treatment period serum and tissue parameters were evaluated. Result. Rats supplemented with aniline hydrochloride showed a significant alteration in body weight, spleen weight, feed consumption, water intake, hematological parameters (haemoglobin content, red blood cells, white blood cells, and total iron content), tissue parameters (lipid peroxidation, reduced glutathione, and nitric oxide content), and membrane bound phosphatase (ATPase) compared to control group. Histopathology of aniline hydrochloride induced spleen showed significant damage compared to control rats. Treatment with protocatechuic acid along with ascorbic acid showed better protection as compared to protocatechuic acid or ascorbic acid alone in aniline hydrochloride induced spleen toxicity. Conclusion. Treatment with protocatechuic acid and ascorbic acid in combination showed significant protection in aniline hydrochloride induced splenic toxicity in rats.

Effectiveness of 5-aminolevulinic acid photodynamic therapy in the treatment of hidradenitis suppurativa: a report of 5 cases.

PubMed

Andino Navarrete, R; Hasson Nisis, A; Parra Cares, J

2014-01-01

Hidradenitis suppurativa has been described as a chronic, recurrent, and disabling inflammatory disease involving the entire hair follicle. Several treatments, including photodynamic therapy, have been used, but the results have been inconsistent and recurrence is high. In this prospective study, we evaluated disease severity, quality of life, and treatment tolerance in 5 patients with moderate to severe hidradenitis suppurativa treated with photodynamic therapy using 5-aminolevulinic acid and a 635-nm light source. Treatment effectiveness was evaluated using the Sartorius severity score, the Dermatology Life Quality Index, and a visual analog scale for pain and disease activity. Significant improvements were observed with all 3 instruments and the effects remained visible at 8 weeks. Our results suggest that photodynamic therapy with 5-aminolevulinic acid and a light wavelength of 635 nm could reduce disease severity and improve quality of life in patients with difficult-to-treat hidradenitis suppurativa. Copyright © 2013 Elsevier España, S.L. y AEDV. All rights reserved.

Modulation of δ-Aminolevulinic Acid Dehydratase Activity by the Sorbitol-Induced Osmotic Stress in Maize Leaf Segments.

PubMed

Jain, M; Tiwary, S; Gadre, R

2018-01-01

Osmotic stress induced with 1 M sorbitol inhibited δ-aminolevulinic acid dehydratase (ALAD) and aminolevulinic acid (ALA) synthesizing activities in etiolated maize leaf segments during greening; the ALAD activity was inhibited to a greater extent than the ALA synthesis. When the leaves were exposed to light, the ALAD activity increased for the first 8 h, followed by a decrease observed at 16 and 24 h in both sorbitol-treated and untreated leaf tissues. The maximum inhibition of the enzyme activity was observed in the leaf segments incubated with sorbitol for 4 to 8 h. Glutamate increased the ALAD activity in the in vitro enzymatic preparations obtained from the sorbitol-treated leaf segments; sorbitol inhibited the ALAD activity in the preparations from both sorbitol-treated and untreated leaves. It was suggested that sorbitol-induced osmotic stress inhibits the enzyme activity by affecting the ALAD induction during greening and regulating the ALAD steady-state level of ALAD in leaf cells. The protective effect of glutamate on ALAD in the preparations from the sorbitol-treated leaves might be due to its stimulatory effect on the enzyme.

Selective accumulation of PpIX and photodynamic effect after aminolevulinic acid treatment of human adenomyosis xenografts in nude mice.

PubMed

Suzuki-Kakisaka, Haruka; Murakami, Takashi; Hirano, Toru; Terada, Yukihiro; Yaegashi, Nobuo; Okamura, Kunihiro

2008-10-01

To evaluate the effect of photodynamic therapy with aminolevulinic acid (ALA) on human adenomyosis xenografts in a mouse model. Human adenomyosis tissues were implanted SC into nude mice. We measured 5-aminolevulinic acid pharmacokinetics in these mice by analyzing tissue sections 1 to 6 hours after intraperitoneal administration. Twenty-four hours after photodynamic therapy, we evaluated tissue morphologic features. Department of obstetrics and gynecology at a university hospital in Japan. Immunodeficient mice. Tissue grafts were taken from women with adenomyosis attending a university hospital. Photodynamic treatment. Peak fluorescence after intraperitoneal ALA administration and tissue histological changes 24 hours after photodynamic therapy. Peak fluorescence was observed 3 hours after intraperitoneal administration. Histological studies revealed decreased numbers of epithelial and stromal cells in adenomyosis models after therapy. Photodynamic therapy with ALA caused extensive cell death in human adenomyosis tissues implanted into nude mice. Photodynamic treatment using ALA is a potential treatment for patients with adenomyosis uteri.

Inhibitory Effect of Gabaculine on 5-Aminolevulinate Dehydratase Activity in Radish Seedlings 1

PubMed Central

Tchuinmogne, Simo J.; Huault, Claude; Aoues, Abdelkader; Balangé, Alain P.

1989-01-01

We have compared the activity of 5-aminolevulinate dehydratase (5-ALAD) with the amount of protein detected by specific antibodies in rocket immunoelectrophoresis. Parallel kinetic evolutions of enzymic activity and amount of antigen were observed in radish (Raphanus sativus L.) cotyledons, both in complete darkness or under standard far red light involving phytochrome. However, the treatment of seedlings with gabaculine leads to an important decrease in enzymic activity, while the specific protein content is maintained. This inhibition is not overcome by the addition of glutamic acid, but by 5-aminolevulinic acid which points to a specific control of 5-ALAD activity by its substrate. As there is no discrepancy between the enzymic activity and the amount of antigen during the time course development of seedlings, this could confirm a coordinate cellular control between 5-aminolevulinic acid formation and 5-ALAD protein synthesis, both being amplified by the action of phytochrome. PMID:16666925

Photodynamic therapy with 5-aminolevulinic acid: basic principles and applications

NASA Astrophysics Data System (ADS)

Pottier, Roy H.; Kennedy, James C.

1996-01-01

Numerous photosensitizing pigments that absorb visible light and are selectively retained in neoplastic tissue are being investigated as potential photochemotherapeutic agents. While much emphasis is being placed on the synthesis of new, far-red absorbing photosensitizers, an alternative approach has been to stimulate the human body to produce its own natural photosensitizer, namely protoporphyrin IX (PpIX). Exogenous 5-aminolevulinic acid (ALA) is rapidly bioconverted into PP by mitochondria, the process being particularly efficient in tumor cells. Since PpIX has a natural and rapid clearing mechanism (via the capture of iron in the process of being converted into heme), ALA-PDT does not suffer from lingering skin phototoxicity. ALA may be introduced orally, intravenously, or topically, and ALA-PDT has been shown to be effective in the treatment of both malignant and non-malignant lesions.

Intraoperative Detection of Superficial Liver Tumors by Fluorescence Imaging Using Indocyanine Green and 5-aminolevulinic Acid.

PubMed

Kaibori, Masaki; Matsui, Kosuke; Ishizaki, Morihiko; Iida, Hiroya; Okumura, Tadayoshi; Sakaguchi, Tatsuma; Inoue, Kentaro; Ikeura, Tsukasa; Asano, Hiroaki; Kon, Masanori

2016-04-01

Indocyanine green (ICG) and the porphyrin precursor 5-aminolevulinic acid (5-ALA) have been approved as fluorescence imaging agents in the clinical setting. This study evaluated the usefulness of fluorescence imaging with both ICG and 5-ALA for intraoperative identification of latent small liver tumors. There were 48 patients who had main tumors within 5 mm of the liver surface. 5-ALA hydrochloride was orally administered to patients 3 h before surgery. ICG had been intravenously injected within 14 days prior to surgery. Intraoperatively, after visual inspection, manual palpation and ultrasonography fluorescence images of the liver surface were obtained with ICG and 5-ALA prior to resection. With ICG, the sensitivity, specificity and accuracy for detecting the preoperatively identified main tumors were 96%, 50% and 94%, respectively. Twelve latent small tumors were newly detected on the liver surface using ICG, five of which proved to be carcinomas. With 5-ALA, the sensitivity, specificity and accuracy for detecting the main tumors were 57%, 100% and 58%, respectively. Five latent small tumors were newly detected using 5-ALA; all were carcinomas. Overall, five new tumors were detected by both ICG and 5-ALA fluorescence imaging; two were hepatocellular carcinomas (HCCs) and three were metastases of colorectal cancer. The sensitivity and specificity of ICG fluorescence imaging for main tumor detection were relatively high and low, respectively, but the opposite was true of 5-ALA imaging. Fluorescence imaging using 5-ALA may provide greater specificity in the detection of surface-invisible malignant liver tumors than using ICG fluorescence imaging alone. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization: current clinical status

NASA Astrophysics Data System (ADS)

Marcus, Stuart L.; Golub, Allyn L.; Shulman, D. Geoffrey

1995-03-01

Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization (ALA PDT) via endogenous protoporphyrin IX (PpIX) synthesis has been reported as efficacious, using topical formulations, in the treatment of a variety of dermatologic diseases including superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses. Application of ALA PDT to the detection and treatment of both malignant and non-malignant diseases of internal organs has recently been reported. Local internal application of ALA has been used for the detection, via PpIX fluorescence, of pathological conditions of the human urinary bladder and for selective endometrial ablation in animal model systems. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer and of colorectal cancer. This paper reviews the current clinical status of ALA PDT.

Esterification of pseudoephedrine hydrochloride by citric acid in a solid dose pharmaceutical preparation.

PubMed

Goel, Alok; Zhao, Zhicheng; Sørensen, Dan; Zhou, Jay; Zhang, Fa

2016-09-10

Esterification of pseudoephedrine hydrochloride (PSE) by citric acid was observed in a solid dose pharmaceutical preparation at room temperature and accelerated stability condition (40°C/75% relative humidity). The esterification of PSE with citric acid was confirmed by a solid-state binary reaction in the presence of minor level of water at elevated temperature to generate three isomeric esters. The structures of the pseudoephedrine citric acid esters were elucidated using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy (NMR). Occurrence of esterification in solid state, instead of amidation which is generally more favorable than esterification, is likely due to remaining HCl salt form of solid pseudoephedrine hydrochloride to protect its amino group from amidation with citric acid. In contrast, the esterification was not observed from solution reaction between PSE and citric acid. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmaceutical Approval Update.

PubMed

Kaufman, Michele B

2017-11-01

Aminolevulinic acid hydrochloride (Gleolan) for the visualization of malignant tissue during surgery; delafloxacin (Baxdela) for certain acute bacterial skin infections; and glecaprevir/pibrentasvir (Mavyret) for chronic HCV infection.

Fluorescence diagnosis of tumor cells in hemangioblastoma cysts with 5-aminolevulinic acid.

PubMed

Utsuki, Satoshi; Oka, Hidehiro; Sato, Kimitoshi; Shimizu, Satoru; Suzuki, Sachio; Fujii, Kiyotaka

2010-01-01

Peritumoral hemangioblastoma cysts are usually composed of fibrous tissue without tumor cells. The authors describe the first case in which fluorescence with 5-aminolevulinic acid (5-ALA) was used to diagnose a hemangioblastoma tumor in a peritumoral cyst wall. A 27-year-old woman with a homogeneous, enhanced nodular lesion in the right hemisphere of the cerebellum underwent surgical treatment. After the nodular lesion was removed, the cyst region was observed with the aid of a semiconductor laser with a peak wavelength of 405 +/- 1 nm, which was powered using a fiberoptic cable. The cyst region was visualized with strong fluorescence, which disappeared after tissue removal. The fluorescent cyst consisted of tumor cells. The authors conclude that fluorescence diagnosis performed using 5-ALA can inform the choice of removing hemangioblastoma cysts.

Oxygen-dependent delayed fluorescence measured in skin after topical application of 5-aminolevulinic acid.

PubMed

Harms, Floor A; de Boon, Wadim M I; Balestra, Gianmarco M; Bodmer, Sander I A; Johannes, Tanja; Stolker, Robert J; Mik, Egbert G

2011-10-01

Mitochondrial oxygen tension can be measured in vivo by means of oxygen-dependent quenching of delayed fluorescence of protoporphyrin IX (PpIX). Here we demonstrate that delayed fluorescence is readily observed from skin in rat and man after topical application of the PpIX precursor 5-aminolevulinic acid (ALA). Delayed fluorescence lifetimes respond to changes in inspired oxygen fraction and blood supply. The signals contain lifetime distributions and the fitting of rectangular distributions to the data appears more adequate than mono-exponential fitting. The use of topically applied ALA for delayed fluorescence lifetime measurements might pave the way for clinical use of this technique. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Self-association of analgesics in aqueous solution: micellar properties of dextropropoxyphene hydrochloride and methadone hydrochloride.

PubMed

Attwood, D; Tolley, J A

1980-08-01

The solution properties of several analgesics including dextropropoxyphene hydrochloride, methadone hydrochloride, dextromoramide acid tartrate and dipipanone hydrochloride have been examined using light scattering, conductivity, vapour pressure osmometry and surface tension techniques. A micellar pattern of association was established for dextropropoxyphene hydrochloride and methadone hydrochloride and critical micelle concentrations and aggregation numbers are reported. The hydrophobic contribution to the free energy of micellization of dextropropoxyphene was determined from measurement of the critical micelle concentration in the presence of added electrolyte.

Methyl - aminolevulinic acid photodynamic therapy and topical tretinoin in a patient with vulvar extramammary Paget's disease.

PubMed

Magnano, Michela; Loi, Camilla; Bardazzi, Federico; Burtica, Elena Cleopatra; Patrizi, Annalisa

2013-01-01

Extramammary Paget's disease is a rare neoplasm of apocrine gland-bearing areas of the skin. The most common site of presentation is the vulva. Surgery is the most frequently reported therapy so far; however, it is invasive and it is complicated by a high rate of recurrence. For this reason, several less-invasive treatments have been recently proposed, including photodynamic therapy. We describe in this article the case of an 84-year-old patient with a noninvasive vulvar extramammary Paget's disease successfully treated with methyl-aminolevulinic acid photodynamic therapy associated with topical tretinoin. © 2013 Wiley Periodicals, Inc.

[Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant gliomas--a new treatment modality].

PubMed

Cortnum, Søren; Laursen, Rene

2013-02-25

5-aminolevulinic acid (ALA) is a precursor of haemoglobin which leads to the synthesis of porphyrins in malignant gliomas which then appears with red fluorescence under blue light. In the literature we see that there is class Ib evidence that 5-ALA guided surgery significantly increases the radicalism of surgery and gives rise to a marked improvement in 6-month progression-free survival and that there is now class II evidence confirming the value of maximal cytoreductive surgery. Furthermore, existing class II evidence indicates that there is a synergistic effect between aggressive cytoreductive surgery and radiochemotherapy.

Photodynamic diagnosis following intravesical instillation of aminolevulinic acid (ALA): first clinical experiences in urology

NASA Astrophysics Data System (ADS)

Baumgartner, Reinhold; Kriegmair, M.; Stepp, Herbert G.; Lumper, W.; Heil, Peter; Riesenberg, Rainer; Stocker, Susanne; Hofstetter, Alfons G.

1993-06-01

Delta Aminolevulinic acid (ALA), a precursor of Protoporphyrin IX (PP IX) in hem biosynthesis has been topically applied in urinary bladders in order to study its potential as fluorescent tumor marker. Preclinical experiments have been performed on chemically induced tumors in rats, revealing a ratio of PP IX-fluorescence intensity up to 20:1 in tumors as compared to healthy urothelium. Synthesis of PP IX has been stimulated in 56 patients by intravesical instillation of a pH-neutral ALA-solution. After an incubation time of two to four hours strong red fluorescence was endoscopically observed even in tiny superficial tumors. Brightness and contrast allows visualization of early stage urothelial diseases with naked eyes and without the necessity suppressing background fluorescence or violet excitation light.

Randomized Vehicle-Controlled Study of Short Drug Incubation Aminolevulinic Acid Photodynamic Therapy for Actinic Keratoses of the Face or Scalp.

PubMed

Pariser, David M; Houlihan, Anna; Ferdon, Mary Beth; Berg, James E

2016-03-01

Aminolevulinic acid photodynamic therapy (ALA-PDT) can be effective and well tolerated when applied over a broad area and for short drug incubation times. To evaluate the effect of short-incubation time and application method on the safety and efficacy of ALA-PDT versus vehicle (VEH-PDT) in the treatment of actinic keratoses (AKs) of the face or scalp. Aminolevulinic acid or VEH was applied to face or scalp as a broad area application for 1, 2, or 3 hours or as a spot application for 2 hours before blue light activation. An identical treatment was repeated at Week 8 if any AK lesions remained. Median AK clearance rate for ALA-treated subjects ranged from 68% to 79% at Week 12, compared with 7% of the VEH-treated group (p < .0001). Complete clearance rate for ALA-treated subjects ranged from 17% (8/46) to 30% (14/47) at Week 12, compared with 2% (1/46) of the VEH-treated group (p = .0041). The safety profile seen in this study is consistent with previously reported side effects of the therapy. Short-incubation ALA-PDT was found to be superior to VEH-PDT for AK lesion clearance. A second treatment improves efficacy.

Delineating Normal from Diseased Brain by Aminolevulinic Acid-Induced Fluorescence

NASA Astrophysics Data System (ADS)

Stepp, Herbert; Stummer, Walter

5-Aminolevulinic acid (5-ALA) as a precursor of protoporphyrin IX (PpIX) has been established as an orally applied drug to guide surgical resection of malignant brain tumors by exciting the red fluorescence of PpIX. The accumulation of PpIX in glioblastoma multiforme (GBM) is highly selective and provides excellent contrast to normal brain when using surgical microscopes with appropriately filtered light sources and cameras. The positive predictive value of fluorescent tissue is very high, enabling safe gross total resection of GBM and other brain tumors and improving prognosis of patients. Compared to other intraoperative techniques that have been developed with the aim of increasing the rate of safe gross total resections of malignant gliomas, PpIX fluorescence is considerably simpler, more cost effective, and comparably reliable. We present the basics of 5-ALA-based fluorescence-guided resection, and discuss the clinical results obtained for GBM and the experience with the fluorescence staining of other primary brain tumors and metastases as well as the results for spinal cord tumors. The phototoxicity of PpIX, increasingly used for photodynamic therapy of brain tumors, is mentioned briefly in this chapter.

Nematicidal Effects of 5-Aminolevulinic Acid on Plant-Parasitic Nematodes

PubMed Central

Cheng, Feixue; Wang, Jian; Song, Zhiqiang; Cheng, Ju’e; Zhang, Deyong

2017-01-01

Plant-parasitic nematodes are important agricultural pests and often cause serious crop losses. Novel, environmental friendly nematicides are urgently needed because of the harmful effects of some existing nematicides on human health. 5-Aminolevulinic acid (ALA) was reported as a potential biodegradable herbicide, insecticide, or plant-growth promoting agent. Lack of information on ALA against plant-parasitic nematodes prompted this investigation to determine the effects of ALA on Meloidogyne incognita, Heterodera glycines, Pratylenchus coffeae, and Bursaphelenchus xylophilus. A series of in vitro assays and one greenhouse trial were conducted to examine the nematicidal effects of ALA. The results demonstrated that ALA exhibited a strong effect of suppression against the four nematodes tested. ALA also inhibited hatching of M. incognita and H. glycines. Results from the greenhouse experiment indicated that treatment of soil with 6.0 mM ALA significantly reduced the root-gall index (RGI) and egg mass number per root system compared with the uninoculated control (P ≤ 0.05). The metabolism assays indicated that ALA treatment significantly altered the nematode metabolism including the total protein production, malondialdehyde (MDA) content, and oxidase activities. This study suggested that ALA is a promising nematicide against plant-parasitic nematodes. PMID:29062152

Gateways to clinical trials.

PubMed

Bayes, M; Rabasseda, X; Prous, J R

2003-05-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 2F5, 2G12, abetimus sodium, ABI-007, adalimumab, adefovir dipivoxil, AE-941, alefacept, altropane, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminopterin, anakinra, aprinocarsen sodium, atazanavir, atlizumab, atomoxetine hydrochloride; B7-1 vaccine, bevacizumab, biricodar dicitrate, BMS-188667, brasofensine sulfate, bryostatin 1; cantuzumab mertansine, CHS-828, cinacalcet hydrochloride, cipamfylline, creatine, CVT-3146; darbepoetin alfa, DITPA, drotrecogin alfa (activated), duloxetine hydrochloride; edatrexate, efalizumab, ENMD-0997, epoetin, erlosamide, esomeprazole magnesium, etiprednol dicloacetate, etoricoxib, everolimus, ezetimibe; fampridine, fenretinide, FTY-720; IGF-I/IGFBP-3, IL-1 cytokine trap, ilodecakin, interferon beta, ISIS-104838, ISIS-2503, ISIS-5132, ivabradine hydrochloride; lafutidine, lanthanum carbonate, l-Arginine hydrochloride, LEA29Y, lerdelimumab, levetiracetam, levobupivacaine hydrochloride, levosimendan, lopinavir; melagatran, mibefradil hydrochloride, miglustat, morphine-6-glucuronide; nesiritide; omalizumab, omapatrilat; p24-VLP, parecoxib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pitavastatin calcium, plevitrexed, prasterone, pregabalin, PRO-2000, prucalopride; rapacuronium bromide, rebimastat, RGA-0853, rubitecan, ruboxistaurin mesilate hydrate, RWJ-67657; S-16020-2, sarizotan, SLV-306, stiripentol; TA-CIN, tenecteplase, teriparatide, tezacitabine, tipifarnib, trabectedin, troglitazone; valdecoxib, vardenafil; Z-338, ziconotide.

Structure of the Mitochondrial Aminolevulinic Acid Synthase, a Key Heme Biosynthetic Enzyme.

PubMed

Brown, Breann L; Kardon, Julia R; Sauer, Robert T; Baker, Tania A

2018-04-03

5-Aminolevulinic acid synthase (ALAS) catalyzes the first step in heme biosynthesis. We present the crystal structure of a eukaryotic ALAS from Saccharomyces cerevisiae. In this homodimeric structure, one ALAS subunit contains covalently bound cofactor, pyridoxal 5'-phosphate (PLP), whereas the second is PLP free. Comparison between the subunits reveals PLP-coupled reordering of the active site and of additional regions to achieve the active conformation of the enzyme. The eukaryotic C-terminal extension, a region altered in multiple human disease alleles, wraps around the dimer and contacts active-site-proximal residues. Mutational analysis demonstrates that this C-terminal region that engages the active site is important for ALAS activity. Our discovery of structural elements that change conformation upon PLP binding and of direct contact between the C-terminal extension and the active site thus provides a structural basis for investigation of disruptions in the first step of heme biosynthesis and resulting human disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Biocompatible 5-Aminolevulinic Acid/Au Nanoparticle-Loaded Ethosomal Vesicles for In Vitro Transdermal Synergistic Photodynamic/Photothermal Therapy of Hypertrophic Scars

NASA Astrophysics Data System (ADS)

Zhang, Zheng; Chen, Yunsheng; Ding, Jiayue; Zhang, Chunlei; Zhang, Amin; He, Dannong; Zhang, Yixin

2017-12-01

Biocompatible 5-aminolevulinic acid/Au nanoparticle-loaded ethosomal vesicle (A/A-ES) is prepared via ultrasonication for synergistic transdermal photodynamic/photothermal therapy (PDT/PTT) of hypertrophic scar (HS). Utilizing ultrasonication, Au nanoparticles (AuNPs) are synthesized and simultaneously loaded in ethosomal vesicles (ES) without any toxic agents, and 5-aminolevulinic acid (ALA) is also loaded in ES with 20% of the entrapment efficiency (EE). The prepared A/A-ES displays strong absorbance in 600-650 nm due to the plasmonic coupling effect between neighboring AuNPs in the same A/A-ES, which can simultaneously stimulate A/A-ES to produce heat and enhance quantum yields of reactive oxygen species (ROS) by using 632 nm laser. In vitro transdermal penetrability study demonstrates that A/A-ES acts as a highly efficient drug carrier to enhance both ALA and AuNPs penetration into HS tissue . Taking human hypertrophic scar fibroblasts (HSF) as therapeutic targets, synergistic PDT/PTT of HS indicates that A/A-ES could enhance quantum yields of ROS by photothermal effect and localized surface plasmon resonance (LSPR) of AuNPs, resulting in a high level of apoptosis or necrosis. In a word, the prepared A/A-ES shows a better synergistic PDT/PTT efficiency for HSF than the individual PDT and PTT, encouraging perspective for treatment of HS.

Physiological and Metabolic Effects of 5-Aminolevulinic Acid for Mitigating Salinity Stress in Creeping Bentgrass

PubMed Central

Yang, Zhimin; Chang, Zuoliang; Sun, Lihong; Yu, Jingjin; Huang, Bingru

2014-01-01

The objectives of this study were to determine whether foliar application of a chlorophyll precursor, 5-aminolevulinic acid (ALA), could mitigate salinity stress damages in perennial grass species by regulating photosynthetic activities, ion content, antioxidant metabolism, or metabolite accumulation. A salinity-sensitive perennial grass species, creeping bentgrass (Agrostis stolonifera), was irrigated daily with 200 mM NaCl for 28 d, which were foliar sprayed with water or ALA (0.5 mg L−1) weekly during the experiment in growth chamber. Foliar application of ALA was effective in mitigating physiological damage resulting from salinity stress, as manifested by increased turf quality, shoot growth rate, leaf relative water content, chlorophyll content, net photosynthetic rate, stomatal conductance and transpiration rate. Foliar application of ALA also alleviated membrane damages, as shown by lower membrane electrolyte leakage and lipid peroxidation, which was associated with increases in the activities of antioxidant enzymes. Leaf content of Na+ was reduced and the ratio of K+/Na+ was increased with ALA application under salinity stress. The positive effects of ALA for salinity tolerance were also associated with the accumulation of organic acids (α-ketoglutaric acid, succinic acid, and malic acid), amino acids (alanine, 5-oxoproline, aspartic acid, and γ -aminobutyric acid), and sugars (glucose, fructose, galactose, lyxose, allose, xylose, sucrose, and maltose). ALA-mitigation of physiological damages by salinity could be due to suppression of Na+ accumulation and enhanced physiological and metabolic activities related to photosynthesis, respiration, osmotic regulation, and antioxidant defense. PMID:25551443

delta. -aminolevulinic acid dehydratase deficiency can cause. delta. -aminolevulinate auxotrophy in Escherichia coli

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Neill, G.P.; Michelsen, U.; Soll, D.

Ethylmethane sulfonate-induced mutants of several Escherichia coli strains that required {delta}-aminolevulinic acid (ALA) for growth were isolated by penicillin enrichment or by selection for respiratory-defective strains resistant to the aminoglycoside antibiotic kanamycin. Three classes of mutants were obtained. Two-thirds of the strains were mutants in hemA. Representative of a third of the mutations was the hem-201 mutation. This mutation was mapped to min 8.6 to 8.7. Complementation of the auxotrophic phenotype by wild-type DNA from the corresponding phage 8F10 allowed the isolation of the gene. DNA sequence analysis revealed that the hem-201 gene encoded ALA dehydratase and was similar tomore » a known hemB gene of E. coli. Complementation studies of hem-201 and hemB1 mutant strains with various hem-201 gene subfragments showed that hem-201 and the previously reported hemB1 mutation are in the same gene and that no other gene is required to complement the hem-201 mutant. ALA-forming activity from glutamate could not be detected by in vitro or in vivo assays. Extracts of hem-201 cells had drastically reduce ALA dehydratase levels, while cells transformed with the plasmid-encoded wild-type gene possessed highly elevated enzyme levels. The ALA requirement for growth, the lack of any ALA-forming enzymatic activity, and greatly reduced ALA dehydratase activity of the hem-201 strain suggest that a diffusible product of an enzyme in the heme biosynthetic pathway after ALA formation is involved in positive regulation of ALA biosynthesis. Analysis of another class of ALA-requiring mutants showed that the auxotrophy of the hem-205 mutant could be relieved by either methionine or cysteine and that the mutation maps in the cysG gene, which encodes uroporphyrinogen III methylase. The properties of these nonleaky ALA-requiring strains suggest that ALA is involved more extensively in E. coli intermediary metabolism than has been appreciated to date.« less

Urothelial conversion of 5-aminolevulinic acid to protoporphyrin IX following oral or intravesical administration

NASA Astrophysics Data System (ADS)

Moore, Ronald B.; Miller, Gerald G.; Brown, Kevin; Bhatnagar, Rakesh; Tulip, John; McPhee, Malcolm S.

1995-03-01

Preferential conversion of 5-aminolevulinic acid (5-ALA) to protoporphyrin-IX (Pp-IX) occurs in malignant tissue, with accumulation to diagnostic and therapeutic levels. Recent studies have suggested selective conversion in epithelial tissue following oral or intravenous administration. Topical application avoids systemic photosensitization. However, the glycosaminoglycan (GAG) layer lining the urinary bladder is believed to be a protective barrier generally limiting mucosal absorption. Our objective was to evaluate uptake and conversion of 5-ALA following intravesical or oral administration. Using a rat model, Pp-IX content within epithelial and muscularis layers was quantitated by fluorescence confocal microscopy. Following intravesical administration, Pp-IX accumulated predominantly in the urothelium; whereas following oral administration, Pp-IX accumulated in both the urothelium and muscularis. Intravesical 5-ALA administration is feasible and may afford selective photosensitization of the urothelium for treatment of carcinoma in situ.

Photodynamic diagnosis (PDD) of bladder cancer with intravesical 5-aminolevulinic-acid-induced fluorescence

NASA Astrophysics Data System (ADS)

Grimbergen, Matthijs C. M.; Jonges, T. G. N.; Lock, M. Tycho W.; van Swol, Christiaan F. P.; Boon, Tom A.; van Moorselaar, R. Jeroen A.

2001-05-01

Flat urothelial lesions as well as small papillary tumors are easily missed during transurethral resection (TUR). PDD is based on the detection of protoporphyrin-IX induced fluorescence after topical administration of 5- aminolevulinic acid (ALA). We report on our initial clinical results of 130 procedures in 98 patients. Two hours prior to TUR 1.5 g ALA dissolved in 50 ml 1.4% NaHCO3 solution was installed intravesically. For fluorescence excitation a blue light source (375-440 nm, Karl Storz) was used. In total 478 biopsies (2-9 per patient) were taken from fluorescent and nonfluorescent areas. Normal nonfluorescent bladder urothelium was blue, whereas cancer epithelium developed a brilliant red fluorescence. During white light cystoscopy, 143 bladder tumors were found. Sixty-three additional tumors were detected because of their positive fluorescence. The overall sensitivity of fluorescence cystoscopy (98%) was greater than that of white light cystoscopy (69%). Their specificities were 51% and 80% respectively.

An experimental and theoretical investigation of loperamide hydrochloride-glutaric acid cocrystals.

PubMed

Bruni, Giovanna; Maietta, Mariarosa; Maggi, Lauretta; Mustarelli, Piercarlo; Ferrara, Chiara; Berbenni, Vittorio; Freccero, Mauro; Scotti, Federico; Milanese, Chiara; Girella, Alessandro; Marini, Amedeo

2013-07-11

Cocrystallization is a powerful method to improve the physicochemical properties of drugs. Loperamide hydrochloride is a topical analgesic for the gastrointestinal tract showing low and pH-dependent solubility; for this reason, an enhancement of its solubility or dissolution rate, particularly at the pH of the intestinal tract, could improve its local efficacy. Here we prepared cocrystals of this active principle with glutaric acid and so obtained a new crystalline solid representing a viable alternative to improve the physicochemical properties and thus the pharmaceutical behavior of the drug. Differential scanning calorimetry, X-ray powder diffraction, Fourier infrared spectroscopy, solid-state NMR, and scanning electron microscopy coupled to the energy-dispersive X-ray spectrometry were used to investigate the new solid-phase formation. DFT calculations at B3LYP/6-31G(d) level of theory, in the gas phase, including frequencies computation, provided a rationale for the interaction between loperamide hydrochloride and glutaric acid. The cocrystals showed improved water solubility in comparison with loperamide HCl, and the pharmaceutical formulation proposed was able to release the drug more rapidly in comparison with three reference commercial products when tested at neutral pH values.

Gateways to clinical trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2006-10-01

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (-)-gossypol, 2-deoxyglucose, 3,4-DAP, 7-monohydroxyethylrutoside; Ad5CMV-p53, adalimumab, adefovir dipivoxil, ADH-1, alemtuzumab, aliskiren fumarate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, amrubicin hydrochloride, AN-152, anakinra, anecortave acetate, antiasthma herbal medicine intervention, AP-12009, AP-23573, apaziquone, aprinocarsen sodium, AR-C126532, AR-H065522, aripiprazole, armodafinil, arzoxifene hydrochloride, atazanavir sulfate, atilmotin, atomoxetine hydrochloride, atorvastatin, avanafil, azimilide hydrochloride; Bevacizumab, biphasic insulin aspart, BMS-214662, BN-83495, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, cetuximab, chrysin, ciclesonide, clevudine, clofarabine, clopidogrel, CNF-1010, CNTO-328, CP-751871, CX-717, Cypher; Dapoxetine hydrochloride, darifenacin hydrobromide, dasatinib, deferasirox, dextofisopam, dextromethorphan/quinidine sulfate, diclofenac, dronedarone hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Edaravone, efaproxiral sodium, emtricitabine, entecavir, eplerenone, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, ezetimibe, ezetimibe/simvastatin; Finrozole, fipamezole hydrochloride, fondaparinux sodium, fulvestrant; Gabapentin enacarbil, gaboxadol, gefitinib, gestodene, ghrelin (human); Human insulin, human papillomavirus vaccine; Imatinib mesylate, immunoglobulin intravenous (human), indiplon, insulin detemir, insulin glargine, insulin glulisine, intranasal insulin, istradefylline, i.v. gamma

Utilization of 5-aminolevulinic acid in the photodynamic therapy of tumors: biochemical and photobiological aspects

NASA Astrophysics Data System (ADS)

Pottier, Roy H.; Kennedy, James C.

1994-03-01

Inherent in both plants and animals is the natural porphyrin, Protoporphyrin IX (Pp). Although Pp does not appear to have any intrinsic biological activity, it is a potent natural photosensitizer. When activated with ultraviolet or visible light, this photosensitizer can induce significant photodynamic effects on tissues, cells, subcellular elements, and macromolecules via the production of singlet oxygen. The biosynthesis of endogenous Pp is under strict enzymatic control. It is possible to bypass a rate controlling step and induce large, transient concentrations of Pp by the addition of exogenous 5-aminolevulinic acid (ALA). ALA may be administered systemically or topically. Much larger amounts of Pp are produced in certain types of tumor tissue than in adjacent normal tissue. Topically applied ALA can be used to treat a variety of skin lesions, including actinic keratosis, basal cell carcinomas and psoriasis.

The application of 5-aminolevulinic acid in the treatment of precancerous lesions, skin cancer, and a new approach to the control of therapy

NASA Astrophysics Data System (ADS)

Kulas, Zbigniew; Bereś-Pawlik, Elżbieta; Bieniek, Andrzej; Matusiak, Łukasz

2009-02-01

The aim of our work was to determine a therapeutic effect of photodynamic therapy (PDT). Twenty five patients with the Bowen's disease, actinic keratosis and basal cell carcinoma (superficial, nodular) were examined. They were treated with photosensitizer - aminolevulinic acid (metabolized in protoporphyrin IX), and the new red light source built of high-power diodes. A new method, based on numerical analysis of fluorescence imaging of tissues, was proposed as a way for controlling therapy.

18F-Fluorocholine PET/CT, Brain MRI, and 5-Aminolevulinic Acid for the Assessment of Tumor Resection in High-Grade Glioma.

PubMed

García Vicente, Ana María; Jiménez Aragón, Fátima; Villena Martín, Maikal; Jiménez Londoño, German Andrés; Borrás Moreno, Jose María

2017-06-01

High-grade glioma is a very aggressive and infiltrative tumor in which complete resection is a chance for a better outcome. We present the case of a 57-year-old man with a brain lesion suggestive of high-grade glioma. Brain MRI and F-fluorocholine PET/CT were performed previously to plan the surgery. Surgery was microscope assisted after the administration of 5-aminolevulinic acid. Postsurgery brain MRI and PET were blind evaluated to the surgery results and reported as probably gross total resection.

Transport of 5-aminolevulinic acid by the dipeptide permease in Salmonella typhimurium.

PubMed

Elliott, T

1993-01-01

In a previous search for mutants of Salmonella typhimurium that are defective in heme synthesis, one class that is apparently defective in 5-aminolevulinic acid (ALA) uptake (alu) was found. Here, I describe the characterization of these mutations. The mutations all map to a single locus near 77.5 min on the genetic map, which is transcribed counterclockwise. Nutritional tests, genetic and physical mapping, and partial DNA sequence analysis revealed that alu mutants are defective in a periplasmic binding protein-dependent permease that also transports dipeptides, encoded by the dpp operon. The uptake of labeled ALA is defective in dpp mutants and is markedly increased in a strain that has elevated transcription of the dpp locus. Unlabeled L-leucyl-glycine competes with labeled ALA for uptake. In a strain carrying both a dpp-lac operon fusion and a functional copy of the dpp locus, the expression of beta-galactosidase is not induced by ALA, nor, in a hemL mutant, does expression of dpp change substantially during starvation for ALA. The dipeptide permease displays a relaxed substrate specificity that allows transport of the important nonpeptide nutrient ALA, whose structure is closely related to that of glycyl-glycine.

Treatment of actinic cheilitis by photodynamic therapy with 5-aminolevulinic acid and blue light activation.

PubMed

Zaiac, Martin; Clement, Annabelle

2011-11-01

Actinic cheilitis (AC), a common disorder of the lower lip, should be treated early to prevent progression to invasive squamous cell carcinoma. This study evaluated the safety and efficacy of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) activated by blue light for the treatment of AC. Fifteen patients with clinically evident or biopsy-proven AC received two treatments with ALA PDT with blue light activation. Treatments were spaced three to five weeks apart. Most patients achieved 65% to 75% clearance three to five weeks after the first treatment and all achieved more than 75% clearance one month after the second treatment. Three patients achieved complete clearance. Pain and burning during irradiation were absent or mild. All patients said they would repeat the procedure. ALA PDT with 417 nm blue light is a promising option for the treatment of AC of the lower lip.

Scanning Fiber Endoscope Improves Detection of 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence at the Boundary of Infiltrative Glioma.

PubMed

Belykh, Evgenii; Miller, Eric J; Hu, Danying; Martirosyan, Nikolay L; Woolf, Eric C; Scheck, Adrienne C; Byvaltsev, Vadim A; Nakaji, Peter; Nelson, Leonard Y; Seibel, Eric J; Preul, Mark C

2018-05-01

Fluorescence-guided surgery with protoporphyrin IX (PpIX) as a photodiagnostic marker is gaining acceptance for resection of malignant gliomas. Current wide-field imaging technologies do not have sufficient sensitivity to detect low PpIX concentrations. We evaluated a scanning fiber endoscope (SFE) for detection of PpIX fluorescence in gliomas and compared it to an operating microscope (OPMI) equipped with a fluorescence module and to a benchtop confocal laser scanning microscope (CLSM). 5-Aminolevulinic acid-induced PpIX fluorescence was assessed in GL261-Luc2 cells in vitro and in vivo after implantation in mouse brains, at an invading glioma growth stage, simulating residual tumor. Intraoperative fluorescence of high and low PpIX concentrations in normal brain and tumor regions with SFE, OPMI, CLSM, and histopathology were compared. SFE imaging of PpIX correlated to CLSM at the cellular level. PpIX accumulated in normal brain cells but significantly less than in glioma cells. SFE was more sensitive to accumulated PpIX in fluorescent brain areas than OPMI (P < 0.01) and dramatically increased imaging time (>6×) before tumor-to-background contrast was diminished because of photobleaching. SFE provides new endoscopic capabilities to view PpIX-fluorescing tumor regions at cellular resolution. SFE may allow accurate imaging of 5-aminolevulinic acid labeling of gliomas and other tumor types when current detection techniques have failed to provide reliable visualization. SFE was significantly more sensitive than OPMI to low PpIX concentrations, which is relevant to identifying the leading edge or metastasizing cells of malignant glioma or to treating low-grade gliomas. This new application has the potential to benefit surgical outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Regulation of ion homeostasis by aminolevulinic acid in salt-stressed wheat seedlings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Türk, Hülya, E-mail: hulyaa.turk@hotmail.com; East Anatolian High Technology Research and Application Center, Ataturk University, Erzurum; Genişel, Mucip, E-mail: m.genisel@hotmail.com

2016-04-18

Salinity is regarded as a worldwide agricultural threat, as it seriously limits plant development and productivity. Salt stress reduces water uptake in plants by disrupting the osmotic balance of soil solution. In addition, it creates a damaged metabolic process by causing ion imbalance in cells. In this study, we aim to examine the negative effects of 5-aminolevulinic acid (ALA) (20 mg/l) on the ion balance in wheat seedling leaves exposed to salt stress (150 mM). Sodium is known to be highly toxic for plant cells at high concentrations, and is significantly increased by salt stress. However, it can be reduced by combinedmore » application of ALA and salt, compared to salt application alone. On the other hand, while the K{sup +}/Na{sup +} ratio was reduced by salt stress, ALA application changed this ratio in favor of K{sup +}. Manganese, iron, and copper were also able to reduce stress. However, ALA pre-treatment resulted in mineral level increments. Conversely, the stress-induced rise in magnesium, potassium, calcium, phosphorus, zinc, and molybdenum were further improved by ALA application. These data clearly show that ALA has an important regulatory effect of ion balance in wheat leaves.« less

5-Aminolevulinic Acid Accumulation in a Cerebral Infarction Mimicking High-Grade Glioma.

PubMed

Behling, Felix; Hennersdorf, Florian; Bornemann, Antje; Tatagiba, Marcos; Skardelly, Marco

2016-08-01

5-Aminolevulinic acid (5-ALA) has become an integral part in the neurosurgical treatment of malignant glioma. Over time, several other tumor entities have been identified to metabolize 5-ALA and show a similar fluorescence pattern during surgical resection. This case report is the first description of 5-ALA accumulation in postischemic cerebral tissue. This evidence questions the assumption that 5-ALA accumulation in glioma is exclusively attributed to tumor infiltration. Instead, 5-ALA accumulation can also occur beyond the tumor borders and may be partially ascribed to inflammatory changes in the surrounding brain tissue. A 64-year old woman presented with episodes of apraxia and a ring-enhancing lesion in postcontrast T1-weighted magnetic resonance sequences suggestive of high grade glioma. Strong fluorescence was observed during 5-ALA-guided resection. However, although the frozen section was inconclusive, the final histopathologic examination revealed a stage II cerebral infarction. 5-ALA accumulation in postischemic cerebral tissue should be considered for intended supramarginal resections near eloquent brain regions. Therefore, sufficient preoperative imaging should regularly include magnetic resonance imaging spectroscopy and perfusion sequences to ascertain the proper diagnosis. Moreover, further research is warranted to determine the role of 5-ALA accumulation in postischemic and inflammatory brain tissue. Copyright © 2016 Elsevier Inc. All rights reserved.

Synergetic effects of 5-aminolevulinic acid and Ascophyllum nodosum seaweed extracts on Asparagus phenolics and stress related genes under saline irrigation.

PubMed

Al-Ghamdi, Abdullah A; Elansary, Hosam O

2018-06-09

Salinity is one of the major agricultural problems that may threat food security and limit the agricultural lands expansion worldwide. Exploring novel tools controlling saline conditions and increase valuable secondary metabolites in the horticultural crops might have outstanding results that serve humanity in the current century. The current study explores the effects of weekly seaweed extracts (7 mL   L -1 ) and/or 5-aminolevulinic acid (3, 5 and 10 ppm) sprays on Asparagus aethiopicus plants subjected to saline stress conditions (2000 and 4000 ppm) for 6 weeks in two consecutive seasons of 2016 and 2017. Under saline conditions, there were stimulatory synergetic effects of seaweed extracts (SWE) and 5-aminolevulinic acid (ALA) on branch length and number of treated plants. Similar increases were also found in fresh and the dry weight of treated plants compared to control. These morphological improvements associated with increased accumulation of specific phenols (robinin, rutin, apigein, chlorogenic acid and caffeic acid) as revealed by High-Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD). There were increases in the antioxidant activities of leaf extracts, chlorophyll content and sugars and proline accumulation. The transpiration and photosynthetic rates as well as the stomatal conductance were enhanced. The morphological and physiological improvements associated with increased expression of several genes responsible for water management (ANN1, ANN2 and PIP1), secondary metabolite production (P5CS1 and CHS) and antioxidants accumulation (APX1 and GPX3) in plants. Our findings indicate that SWE + ALA had stimulatory synergetic effects on the growth and secondary metabolites of A. aethiopicus subjected to saline conditions. Several mechanisms are involved in such effects including gas exchange control, sugar buildup, increasing non-enzymatic and enzymatic antioxidants control of reactive oxygen species accumulation as well as

Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminolevulinic acid.

PubMed

Hillemanns, P; Untch, M; Dannecker, C; Baumgartner, R; Stepp, H; Diebold, J; Weingandt, H; Pröve, F; Korell, M

2000-03-01

Photodynamic (PDT) therapy is a relatively new technique with unique properties that make it attractive for the local treatment of superficial epithelial disorders. The objective of this study was to investigate the clinical response of PDT with the photosensitizing agent 5-aminolevulinic acid (5-ALA) in patients with vulvar intraepithelial neoplasia (VIN) grades 1 to 3. Twenty-five patients with 111 lesions of VIN 1-3 were topically sensitized with 10 ml of a 20% solution of 5-ALA and treated with 57 cycles of laser light at 635 nm (100 J/cm(2)). Seventy (64%) of the 111 VIN lesions regressed after various PDT cycles. A complete response was achieved in 13 patients (52%) with 27 lesions. All patients with VIN 1 and mono- and bifocal VIN 2-3 showed complete clearance. However, a complete response could be achieved in only 4 (27%) of 15 women with multifocal VIN 2-3, whereas a partial response was noted in 9 of these patients with a total of 70 lesions, out of which 44 (63%) lesions disappeared. No response was seen in 2 patients with multifocal VIN 3. Histological assessment of the fluorescence-directed biopsies revealed that increased pigmentation and hyperkeratosis of the lesions were associated with low response rates. PDT using 5-ALA represents an alternative treatment modality for VIN which is easy to perform and has the advantage of minimal tissue destruction, low side effects and excellent cosmetic results. However, multifocal VIN disease with pigmented and hyperkeratinic lesions remains difficult to treat. Copyright 2000 Wiley-Liss, Inc.

Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend.

PubMed

Kenawy, El-Refaie; Bowlin, Gary L; Mansfield, Kevin; Layman, John; Simpson, David G; Sanders, Elliot H; Wnek, Gary E

2002-05-17

Electrospun fiber mats are explored as drug delivery vehicles using tetracycline hydrochloride as a model drug. The mats were made either from poly(lactic acid) (PLA), poly(ethylene-co-vinyl acetate) (PEVA), or from a 50:50 blend of the two. The fibers were electrospun from chloroform solutions containing a small amount of methanol to solubilize the drug. The release of the tetracycline hydrochloride from these new drug delivery systems was followed by UV-VIS spectroscopy. Release profiles from the electrospun mats were compared to a commercially available drug delivery system, Actisite (Alza Corporation, Palo Alto, CA), as well as to cast films of the various formulations.

The utility of 5-aminolevulinic acid-mediated photodynamic diagnosis in the detection of intraoperative bile leakage.

PubMed

Inoue, Yoshihiro; Imai, Yoshiro; Fujii, Kensuke; Hirokawa, Fumitoshi; Hayashi, Michihiro; Uchiyama, Kazuhisa

2017-06-01

The purpose of this retrospective study was to evaluate the utility of the new intraoperative bile leakage test as a preventive measure of postoperative bile leakage. 737 patients were retrospectively analyzed with respect to the management of intra- and post-operative bile leakage. Nine (8.3%) of 109 patients evaluated using conventional white light fluorescent imaging were recognized as having intra-operative bile leakage. However, performance of 5-aminolevulinic acid (5-ALA)-mediated PDD detected bile leakage intraoperatively not only in these 9 patients, but also in an additional 6 patients, such that 'red fluorescence' at the cut surface of the liver, was visualized in a total of 15 patients. The postoperative courses of most patients were uneventful, and postoperative bile leakages occurred in only one (0.9%) patient. 5-ALA fluorescence imaging may be needed to prevent postoperative bile leakage in patients at high risk for this surgical complication after hepatic resection. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of metal ions on biomass and 5-aminolevulinic acid production in Rhodopseudomonas palustris wastewater treatment.

PubMed

Liu, Shuli; Zhang, Guangming; Li, Jianzheng; Li, Xiangkun; Zhang, Jie

2016-01-01

This work investigated the effects of eight metal ions on Rhodopseudomonas palustris growth and 5-aminolevulinic acid (ALA) yield in wastewater treatment. Results show that metal ions (Mg(2+) of 15 mmol/L, Fe(2+) of 400 μmol/L, Co(2+) of 4 μmol/L, Ni(2+) of 8 μmol/L and Zn(2+) of 4 μmol/L) could effectively improve the chemical oxygen demand (COD) removal, Rp. palustris biomass and ALA yield. The highest ALA yield of 13.1 mg/g-biomass was achieved with Fe(2+) of 400 μmol/L. ALA yields were differentially increased under different metal ions in the following order: Fe(2+) group > Mg(2+) group > Co(2+) group = Ni(2+) group > Zn(2+) group = Mo(2+) group > control. Cu(2+) and Mn(2+) inhibited Rp. palustris growth and ALA production. Mechanism analysis revealed that metal ions changed ALA yields by influencing the activities of ALA synthetase and ALA dehydratase.

5-Aminolevulinic Acid-Protoporphyrin IX Fluorescence-Guided Surgery of High-Grade Gliomas: A Systematic Review.

PubMed

Guyotat, Jacques; Pallud, Johan; Armoiry, Xavier; Pavlov, Vladislav; Metellus, Philippe

2016-01-01

The current first-line treatment of malignant gliomas consists in surgical resection (if possible) as large as possible. The existing tools don't permit to identify the limits of tumor infiltration, which goes beyond the zone of contrast enhancement on MRI. The fluorescence-guided malignant gliomas surgery was started 15 years ago and had become a standard of care in many countries. The technique is based on fluorescent molecule revelation using the filters, positioned within the surgical microscope. The fluorophore, protoporphyrin IX (PpIX), is converted in tumoral cells from 5-aminolevulinic acid (5-ALA), given orally before surgery. Many studies have shown that the ratio of gross total resections was higher if the fluorescence technique was used. The fluorescence signal intensity is correlated to the cell density and the PpIX concentration. The current method has a very high specificity but still lower sensibility, particularly regarding the zones with poor tumoral infiltration. This book reviews the principles of the technique and the results (extent of resection and survival).

Optimization of Biomass and 5-Aminolevulinic Acid Production by Rhodobacter sphaeroides ATCC17023 via Response Surface Methodology.

PubMed

Liu, Shuli; Zhang, Guangming; Li, Jianzheng; Li, Xiangkun; Zhang, Jie

2016-06-01

Microbial 5-aminolevulinic acid (ALA) produced from wastewater is considered as potential renewable energy. However, many hurdles are needed to be overcome such as the regulation of key influencing factors on ALA yield. Biomass and ALA production by Rhodobacter sphaeroides was optimized using response surface methodology. The culturing medium was artificial volatile fatty acids wastewater. Three additives were optimized, namely succinate and glycine that are precursors of ALA biosynthesis, and D-glucose that is an inhibitor of ALA dehydratase. The optimal conditions were achieved by analyzing the response surface plots. Statistical analysis showed that succinate at 8.56 mmol/L, glycine at 5.06 mmol/L, and D-glucose at 7.82 mmol/L were the best conditions. Under these optimal conditions, the highest biomass production and ALA yield of 3.55 g/L and 5.49 mg/g-biomass were achieved. Subsequent verification experiments at optimal values had the maximum biomass production of 3.41 ± 0.002 g/L and ALA yield of 5.78 ± 0.08 mg/g-biomass.

Gross total resection rates in contemporary glioblastoma surgery: results of an institutional protocol combining 5-aminolevulinic acid intraoperative fluorescence imaging and brain mapping.

PubMed

Schucht, Philippe; Beck, Jürgen; Abu-Isa, Janine; Andereggen, Lukas; Murek, Michael; Seidel, Kathleen; Stieglitz, Lennard; Raabe, Andreas

2012-11-01

Complete resection of contrast-enhancing tumor has been recognized as an important prognostic factor in patients with glioblastoma and is a primary goal of surgery. Various intraoperative technologies have recently been introduced to improve glioma surgery. To evaluate the impact of using 5-aminolevulinic acid and intraoperative mapping and monitoring on the rate of complete resection of enhancing tumor (CRET), gross total resection (GTR), and new neurological deficits as part of an institutional protocol. One hundred three consecutive patients underwent resection of glioblastoma from August 2008 to November 2010. Eligibility for CRET was based on the initial magnetic resonance imaging assessed by 2 reviewers. The primary end point was the number of patients with CRET and GTR. Secondary end points were volume of residual contrast-enhancing tissue and new postoperative neurological deficits. Fifty-three patients were eligible for GTR/CRET (n = 43 newly diagnosed glioblastoma, n = 10 recurrent); 13 additional patients received surgery for GTR/CRET-ineligible glioblastoma. GTR was achieved in 96% of patients (n = 51, no residual enhancement >0.175 cm); CRET was achieved in 89% (n = 47, no residual enhancement). Postoperatively, 2 patients experienced worsening of preoperative hemianopia, 1 patient had a new mild hemiparesis, and another patient sustained sensory deficits. Using 5-aminolevulinic acid imaging and intraoperative mapping/monitoring together leads to a high rate of CRET and an increased rate of GTR compared with the literature without increasing the rate of permanent morbidity. The combination of safety and resection-enhancing intraoperative technologies was likely to be the major drivers for this high rate of CRET/GTR.

Immediate acid-suppressing effects of ranitidine hydrochloride and rabeprazole sodium following initial administration and reintroduction: A randomized, cross-over study using wireless pH monitoring capsules.

PubMed

Ono, Shouko; Kato, Mototsugu; Ono, Yuji; Imai, Aki; Yoshida, Takeshi; Shimizu, Yuichi; Asaka, Masahiro

2009-04-01

Histamine 2 receptor antagonists and proton-pump inhibitors, drugs that are widely used for the treatment of acid-related diseases, have different clinical characteristics. The objective of this study was to compare the acid-suppressing effects of ranitidine hydrochloride and those of rabeprazole sodium at the first administration and re-administration after withdrawal. The study was designed as an open-label, randomized, two-way cross-over trial. Seven Helicobacter pylori-negative healthy volunteers were enrolled in this study. Ranitidine hydrochloride (300 mg/day) or rabeprazole sodium (20 mg/day) was administered from days 1 to 7 and from days 11 to 13. The percentage of time with gastric pH < 4 and the median gastric pH were evaluated for 15 consecutive days by a Bravo capsule fixed to the stomach. On day 1, there was no significant difference between the acid-suppressing effects of the two drugs (ranitidine vs rabeprazole: not significant). Although rabeprazole sodium maintained a potent and stable effect from days 2 to 7 (ranitidine vs rabeprazole: P < 0.05), the effect of ranitidine hydrochloride was attenuated after day 4. In addition, the effect of ranitidine hydrochloride at re-administration was attenuated (days 11, 12, and 13 vs pre-administration: not significant). In view of our observations, we expect symptoms associated with gastric acidity to be more adequately controlled with rabeprazole sodium in the short term when compared to ranitidine hydrochloride.

Use of 5-aminolevulinic acid in fluorescence-guided resection of meningioma with high risk of recurrence. Case report.

PubMed

Kajimoto, Yoshinaga; Kuroiwa, Toshihiko; Miyatake, Shin-Ichi; Ichioka, Tsugumichi; Miyashita, Minoru; Tanaka, Hidekazu; Tsuji, Motomu

2007-06-01

It has been established that fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is useful in glioma surgery. The authors report on a 65-year-old woman who had a huge atypical left-hemisphere meningioma, which extended into the skull and to the superior sagittal sinus and demonstrated fluorescence in response to administration of 5-ALA. After the tumor was removed, the operative field was observed under the fluorescent mode of a fluorescence surgical microscopy system. Several minute areas of residual tumor tissue were visualized as strong fluorescence behind the vein and sinus, in a part of the hypertrophic dura, and along the edge of the skull. These remnants were completely removed. The authors concluded that fluorescence-guided resection using 5-ALA is useful in cases of atypical meningiomas with a high risk of recurrence.

Spectrofluorimetric determination of 3-methylflavone-8-carboxylic acid, the main active metabolite of flavoxate hydrochloride in human urine.

PubMed

Zaazaa, Hala E; Mohamed, Afaf O; Hawwam, Maha A; Abdelkawy, Mohamed

2015-01-05

A simple, sensitive and selective spectrofluorimetric method has been developed for the determination of 3-methylflavone-8-carboxylic acid as the main active metabolite of flavoxate hydrochloride in human urine. The proposed method was based on the measurement of the native fluorescence of the metabolite in methanol at an emission wavelength 390 nm, upon excitation at 338 nm. Moreover, the urinary excretion pattern has been calculated using the proposed method. Taking the advantage that 3-methylflavone-8-carboxylic acid is also the alkaline degradate, the proposed method was applied to in vitro determination of flavoxate hydrochloride in tablets dosage form via the measurement of its corresponding degradate. The method was validated in accordance with the ICH requirements and statistically compared to the official method with no significant difference in performance. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of Oral Glucosamine Hydrochloride Administration on Plasma Free Amino Acid Concentrations in Dogs

PubMed Central

Azuma, Kazuo; Osaki, Tomohiro; Tsuka, Takeshi; Imagawa, Tomohiro; Okamoto, Yoshiharu; Takamori, Yoshimori; Minami, Saburo

2011-01-01

We examined the effects of oral glucosamine hydrochloride (GlcN), N-acetyl-d-glucosamine (GlcNAc) and d-glucose (Glc) administration on plasma total free amino acid (PFAA) concentrations in dogs. The PFAA concentrations increased in the control group and the GlcNAc group at one hour after feeding, and each amino acid concentration increased. On the other hand, in the GlcN group and the Glc group PFAA concentrations decreased at one hour after feeding. A significant decrease in amino acid concentration was observed for glutamate, glycine and alanine. Our results suggest the existence of differences in PFAA dynamics after oral administration of GlcN and GlcNAc in dogs. PMID:21673884

Mechanisms of 5-aminolevulinic acid uptake at the choroid plexus.

PubMed

Novotny, A; Xiang, J; Stummer, W; Teuscher, N S; Smith, D E; Keep, R F

2000-07-01

5-Aminolevulinic acid (5-ALA) is a precursor of porphyrins and heme that has been implicated in the neuropsychiatric symptoms associated with porphyrias. It is also being used clinically to delineate malignant gliomas. The blood-CSF barrier may be an important interface for 5-ALA transport between blood and brain as in vivo studies have indicated 5-ALA is taken up by the choroid plexuses whereas the normal blood-brain barrier appears to be relatively impermeable. This study examines the mechanisms of 5-[(3)H]ALA uptake into isolated rat lateral ventricle choroid plexuses. Results suggest that there are two uptake mechanisms. The first was a Na(+)-independent uptake system that was pH dependent (being stimulated at low pH). Uptake was inhibited by the dipeptide Gly-Gly and by cefadroxil, an alpha-amino-containing cephalosporin. These properties are the same as the proton-dependent peptide transporters PEPT1 and PEPT2, which have recently been shown to transport 5-ALA in frog oocyte expression experiments. Choroid plexus uptake was not inhibited by captopril, a PEPT1 inhibitor, suggesting PEPT2-mediated uptake. The presence of PEPT2 and absence of PEPT1 in the choroid plexus were confirmed by western blotting. The second potential mechanism was both Na(+) and HCO(3)(-) dependent and appears to be an organic anion transporter, although it is possible that removal of Na(+) and HCO(3)(-) may indirectly affect PEPT2 by affecting intracellular pH. The presence of PEPT2 and a putative Na(+)/HCO(3)(-)-dependent organic anion transporter is important not only for an understanding of 5-ALA movement between blood and brain but also because these transporters may affect the distribution of a number of drugs between blood and CSF.

Intake of Ethanol, Sodium Chloride, Sucrose, Citric Acid, and Quinine Hydrochloride Solutions by Mice: A Genetic Analysis

PubMed Central

Bachmanov, A. A.; Reed, D. R.; Tordoff, M. G.; Price, R. A.; Beauchamp, G. K.

2013-01-01

Mice of the 129/J (129) and C57BL/6ByJ (B6) strains and their reciprocal F1 and F2 hybrids were offered solutions of ethanol, sucrose, citric acid, quinine hydrochloride, and NaCI in two-bottle choice tests. Consistent with earlier work, the B6 mice drank more ethanol, sucrose, citric acid, and quinine hydrochloride solution and less NaCI solution than did 129 mice. Analyses of each generation’s means and distributions showed that intakes of ethanol, quinine, sucrose, and NaCI were influenced by a few genes. The mode of inheritance was additive in the case of ethanol and quinine, for sucrose the genotype of the 129 strain was recessive, and for NaCI it was dominant. Citric acid intake appeared to be influenced by many genes with small effects, with the 129 genotype dominant. Correlations of sucrose consumption with ethanol and citric acid consumption were found among mice of the F2 generation, and the genetically determined component of these correlations was stronger than the component related to environmental factors. The genetically determined correlation between sucrose and ethanol intakes is consistent with the hypothesis that the higher ethanol intake by B6 mice depends, in part, on higher hedonic attractiveness of its sweet taste component. PMID:8990535

Gateways to clinical trials.

PubMed

Bayes, M; Rabasseda, X; Prous, J R

2005-01-01

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate; ACP-103, Ad.Egr.TNF.11 D, adalimumab, AF-IL 12, AIDSVAX gp120 B/B, alefacept, alemtuzumab, a-Galactosylceramide, ALVAC vCP 1452, alvimopan hydrate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anidulafungin, antarelix, aprepitant, aripiprazole, arsenic sulfide, asoprisnil, atazanavir sulfate, atomoxetine hydrochloride; Bevacizumab, bimatoprost, BMS-184476, bortezomib, bosentan, botulinum toxin type B, BrachySil, brivudine; Caffeine, calcipotriol/betamethasone dipropionate, cannabidiol, capsaicin for injection, caspofungin acetate, CC-4047, cetuximab, CGP-36742, clofazimine, CpG-7909, Cypher; Darbepoetin alfa, dextromethorphan/quinidine sulfate, dimethylfumarate, dronabinol/cannabidiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, eletriptan, emtricitabine, enfuvirtide, eplerenone, esomeprazole magnesium, estradiol acetate, eszopiclone, etoricoxib, exenatide, ezetimibe, ezetimibe/simvastatin; Fampridine, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GPI-0100; hA 20, HTU-PA, human insulin, HuOKT 3 gamma 1(Ala 234-Ala 235), hyaluronic acid; Icatibant, imatinib mesylate, Indiplon, INKP-100, INKP-102, iodine (I131) tositumomab, istradefylline, IV gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, landiolol, lanthanum carbonate, lasofoxifene tartrate, LB-80380, lenalidomide, lidocaine/tetracaine, linezolid, liposomal doxorubicin, liposomal vincristine sulfate, lopinavir, lopinavir/ritonavir, lumiracoxib, lurtotecan; Maribavir, morphine glucuronide, MVA-5 T

Role of 5-aminolevulinic acid-conjugated gold nanoparticles for photodynamic therapy of cancer

NASA Astrophysics Data System (ADS)

Zhang, Zhenxi; Wang, Sijia; Xu, Hao; Wang, Bo; Yao, Cuiping

2015-05-01

There are three possible mechanisms for 5-aminolevulinic acid (5-ALA) conjugated gold nanoparticles (GNPs) through electrostatic bonding for photodynamic therapy (PDT) of cancer: GNPs delivery function, singlet oxygen generation (SOG) by GNPs irradiated by light, and surface resonance enhancement (SRE) of SOG. Figuring out the exact mechanism is important for further clinical treatment. 5-ALA-GNPs and human chronic myeloid leukemia K562 cells were used to study delivery function and SOG by GNPs. The SRE of SOG enabled by GNPs was explored by protoporphyrin IX (PpIX)-GNPs conjugate through electrostatic bonding. Cell experiments show that the GNPs can improve the efficiency of PDT, which is due to the vehicle effect of GNPs. PpIX-GNPs conjugate experiments demonstrated that SOG can be improved about 2.5 times over PpIX alone. The experiments and theoretical results show that the local field enhancement (LFE) via localized surface plasmon resonance (LSPR) of GNPs is the major role; the LFE was dependent on the irradiation wavelength and the GNP's size. The LFE increased with an increase of the GNP size (2R ≤50 nm). However, the LSPR function of the GNPs was not found in cell experiments. Our study shows that in 5-ALA-conjugated GNPs PDT, the delivery function of GNPs is the major role.

Thermosetting gel for the delivery of 5-aminolevulinic acid esters to the cervix.

PubMed

Collaud, Sabine; Peng, Qian; Gurny, Robert; Lange, Norbert

2008-07-01

5-Aminolevulinic acid (5-ALA)-mediated photodynamic therapy has been proposed as an alternative, cervix-sparing treatment for cervical intraepithelial neoplasia (CIN). In this context, topical application of 5-ALA to the cervix is beneficial due to the small necessary dose and its minimal side effects. Therefore, lipophilic 5-ALA esters, such as hexylaminolevulinate (HAL), have led to improved local bioavailability and therapeutic efficacy. Hydrogels have shown to be more appropriate for the local delivery of these derivatives, but due to the limited long-term stability of such formulations at 25 degrees C, the development of an extemporaneously prepared hydrogel targeting CIN can be advantageous. Therefore, a poloxamer 407 thermosetting gel, which is liquid at room temperature and becomes a semi-solid when in contact with the female genital tract, has been evaluated in vitro and in vivo. Rheological evaluation has shown that a 17.0% poloxamer 407 hydrogel with a sol-gel transition at 24.8 +/- 0.6 degrees C was the best formulation for easy application and optimal residence time. Furthermore, similarly to other hydrogels previously tested, such a formulation shows a more complete HAL release in vitro than conventional cream vehicles, and tends to increase porphyrin accumulation in nude mice skin. Finally, in vitro release profiles were correlated to the in vivo results.

Association between Blood Lead Levels and Delta-Aminolevulinic Acid Dehydratase in Pregnant Women

PubMed Central

La-Llave-León, Osmel; Méndez-Hernández, Edna M.; Castellanos-Juárez, Francisco X.; Esquivel-Rodríguez, Eloísa; Vázquez-Alaniz, Fernando; Sandoval-Carrillo, Ada; García-Vargas, Gonzalo; Duarte-Sustaita, Jaime; Candelas-Rangel, Jorge L.; Salas-Pacheco, José M.

2017-01-01

Blood lead levels (BLLs) and delta-aminolevulinic acid dehydratase (ALAD) activity are considered biomarkers of lead exposure and lead toxicity, respectively. The present study was designed to investigate the association between BLLs and ALAD activity in pregnant women from Durango, Mexico. A total of 633 pregnant women aged 13–43 years participated in this study. Blood lead was measured by a graphite furnace atomic absorption spectrometer. ALAD activity was measured spectrophotometrically. Mean blood lead was 2.09 ± 2.34 µg/dL; and 26 women (4.1%) crossed the Centers for Disease Control (CDC) recommended level of 5 µg/dL. ALAD activity was significantly lower in women with levels of lead ≥5 µg/dL compared to those with BLLs < 5 µg/dL (p = 0.002). To reduce the influence of extreme values on the statistical analysis, BLLs were analyzed by quartiles. A significant negative correlation between blood lead and ALAD activity was observed in the fourth quartile of BLLs (r = −0.113; p < 0.01). Among women with blood lead concentrations ≥2.2 µg/dL ALAD activity was negatively correlated with BLLs (r = −0.413; p < 0.01). Multiple linear regression demonstrated that inhibition of ALAD in pregnant women may occur at levels of lead in blood above 2.2 µg/dL. PMID:28420209

Association between Blood Lead Levels and Delta-Aminolevulinic Acid Dehydratase in Pregnant Women.

PubMed

La-Llave-León, Osmel; Méndez-Hernández, Edna M; Castellanos-Juárez, Francisco X; Esquivel-Rodríguez, Eloísa; Vázquez-Alaniz, Fernando; Sandoval-Carrillo, Ada; García-Vargas, Gonzalo; Duarte-Sustaita, Jaime; Candelas-Rangel, Jorge L; Salas-Pacheco, José M

2017-04-18

Blood lead levels (BLLs) and delta-aminolevulinic acid dehydratase (ALAD) activity are considered biomarkers of lead exposure and lead toxicity, respectively. The present study was designed to investigate the association between BLLs and ALAD activity in pregnant women from Durango, Mexico. A total of 633 pregnant women aged 13-43 years participated in this study. Blood lead was measured by a graphite furnace atomic absorption spectrometer. ALAD activity was measured spectrophotometrically. Mean blood lead was 2.09 ± 2.34 µg/dL; and 26 women (4.1%) crossed the Centers for Disease Control (CDC) recommended level of 5 µg/dL. ALAD activity was significantly lower in women with levels of lead ≥5 µg/dL compared to those with BLLs < 5 µg/dL ( p = 0.002). To reduce the influence of extreme values on the statistical analysis, BLLs were analyzed by quartiles. A significant negative correlation between blood lead and ALAD activity was observed in the fourth quartile of BLLs (r = -0.113; p < 0.01). Among women with blood lead concentrations ≥2.2 µg/dL ALAD activity was negatively correlated with BLLs (r = -0.413; p < 0.01). Multiple linear regression demonstrated that inhibition of ALAD in pregnant women may occur at levels of lead in blood above 2.2 µg/dL.

Effect of 5-aminolevulinic acid on erythropoiesis: A preclinical in vitro characterization for the treatment of congenital sideroblastic anemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujiwara, Tohru; Department of Molecular Hematology/Oncology, Tohoku University Graduate School, Sendai; Okamoto, Koji

2014-11-07

Highlights: • Treatment with ALA induces erythroid differentiation of K562 cells. • Transportation of ALA into erythroid cells occurs predominantly via SLC36A1. • ALA restores defects in ALAS2 in human iPS cell-derived erythroblasts. • ALA may represent a novel therapeutic option for CSA caused by ALAS2 mutations. - Abstract: Congenital sideroblastic anemia (CSA) is a hereditary disorder characterized by microcytic anemia and bone marrow sideroblasts. The most common form of CSA is attributed to mutations in the X-linked gene 5-aminolevulinic acid synthase 2 (ALAS2). ALAS2 is a mitochondrial enzyme, which utilizes glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA), amore » crucial precursor in heme synthesis. Therefore, ALA supplementation could be an effective therapeutic strategy to restore heme synthesis in CSA caused by ALAS2 defects. In a preclinical study, we examined the effects of ALA in human erythroid cells, including K562 cells and human induced pluripotent stem cell-derived erythroid progenitor (HiDEP) cells. ALA treatment resulted in significant dose-dependent accumulation of heme in the K562 cell line. Concomitantly, the treatment substantially induced erythroid differentiation as assessed using benzidine staining. Quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis confirmed significant upregulation of heme-regulated genes, such as the globin genes [hemoglobin alpha (HBA) and hemoglobin gamma (HBG)] and the heme oxygenase 1 (HMOX1) gene, in K562 cells. Next, to investigate the mechanism by which ALA is transported into erythroid cells, quantitative RT-PCR analysis was performed on previously identified ALA transporters, including solute carrier family 15 (oligopeptide transporter), member (SLC15A) 1, SLC15A2, solute carrier family 36 (proton/amino acid symporter), member (SLC36A1), and solute carrier family 6 (neurotransmitter transporter), member 13 (SLC6A13). Our analysis revealed that SLC36A1 was

Photodynamic therapy of urethral condylomata acuminata using topically 5-aminolevulinic acid

NASA Astrophysics Data System (ADS)

Wang, Xiuli; Wang, Hongwei; Wang, Haishan; Xu, Shizheng; Liao, Kanghuang; Hillemanns, Peter

2005-07-01

Background Electrocoagulation and laser evaporation for urethral condylomata acuminata have high recurrence rates and can be associated with urethral malformations. Objective To investigate the effect of photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) on urethral condylomata acuminata and to examine the histological changes in lesions of condylomata acuminata after ALA-PDT. Methods One hundred and sixty-four urethral condylomata patients were given topical ALA followed by intraurethral PDT through a cylindrical fiber. Among the cases, 16 penile and vulval condylomatous lesions in 11 patients were treated with topical ALA-PDT at same time. After the treatment, biopsy specimens were collected from the 16 penile and vulval lesions. The histological changes were then evaluated by light microscope and electron microscope. Results The complete response rate for urethral condylomata by topical ALA-PDT was 95.12% and the recurrence rate was 5.13% after 6 to 24 months follow-up. Keratinocytes in middle and upper layers of the epidermis with marked vacuolation and some necrocytosis were detected one and three hours after PDT. Necrosis in all layers of the epidermis was noted five hours after PDT by microscopy. In electron microscopy of kerationcytes, distinct ultrastructural abnormalities of mitochondrion, endoplasmic reticulum and membrane damage were observed. Apoptotic bodies were detected three hours after PDT and a large number of the keratinocytes exhibited necrosis five hours after PDT by electron microscope. Conclusions Results suggests that topical ALA-PDT is a simple, effective, relatively safe, less recurrent and comparatively well tolerated treatment for urethral condylomata acuminata. The mechanisms might be that ALA-PDT could trigger apoptotic process and necrosis in the HPV infected keratinocytes. Key words:

[Determination of ephedrine hydrochloride, pseudoephedrine hydrochloride and methylephedrine hydrochloride in maxingshigan decoction by CE].

PubMed

Yu, Li-ping; Wang, Xiao-ke; Luo, Jia-bo

2011-04-01

To establish the method for determination of ephedrine hydrochloride, pseudoephedrine hydrochloride and methylephedrine hydrochloride in maxingshigan decoction by capillary electrophoresis. The separation was performed on a fused silica capillary of 60 cm x 55 microcrpm ID (52 cm of effective length). 60 mmol/L NaB4O7 + 10% (V/V) CH3OH (pH 9.0) was selected as the running buffer. The separation voltage was 12 kV. The samples was injected by gravity (10 s, 15 cm). The detection wavelength was 210 nm and berberine hydrochloride was the internal standard. The linear range of determination for ephedrine hydrochloride, pseudoephedrine hydrochloride and methylephedrine hydrochloride were 20.0-160.0 microg/mL (r = 0.9999), 7.5-60.0 microg/mL (r = 0.9991) and 2.0-10.0 microg/mL (r = 0.9993). The average recoveries were 98.0%, 97.0% and 97.8%, the precisions of the method were 2.31%, 2.21% and 2.00% (n=6), respectively. The method is convenient, rapid and accurate for the quality control of maxingshigan decoction.

Topical versus systemic 5-aminolevulinic acid administration for photodynamic therapy of the colon in B10.RBP mice

NASA Astrophysics Data System (ADS)

Gil, Maciej; Woszczynski, Marek; Regula, Jaroslaw; MacRobert, Alexander J.; Butruk, Eugeniusz; Bown, Stephen G.

1999-07-01

5-aminolevulinic acid (5-ALA) is an interesting photosensitizing substance for photodynamic therapy (PDT), successfully applied topically for urological malignancy. In gastroenterology it has proven efficacy for treatment of some GI neoplasms after systemic administration. This study was aimed at investigating the possibility of topical 5-ALA administration also for the PDT of gut cancer in a mice model. 5-ALA solution at different concentrations (5%, 1.5%, and 0.5%) was instilled in the colon of mice, which was later removed and examined by fluorescence microscopy. The results of fluorescence studies were compared with those obtained in a control group treated with 5-ALA given systematically. Satisfactory epithelial fluorescence levels and good selectivity between gut layers were obtained after intracolonic 5-ALA instillation. However, mean fluorescence intensity was higher after systemic drug applications. Our results suggest that 5-ALA may probably be used topically for the PDT of some gut neoplasms.

Colestipol hydrochloride prophylaxis of diarrhea during pelvic radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stryker, J.A.; Chung, C.K.; Layser, J.D.

1983-02-01

Thirty-three patients were randomized prior to pelvic radiotherapy to receive the bile acid-sequestering resin colestipol hydrochloride, 5 grams qid, during the entire time of their therapy or diphenoxylate hydrochloride and atropine sulfate 2.5-20 mg per day (control) if they experienced diarrhea. The colestipol patients also took diphenoxylate if they had diarrhea. The patients in the colestipol group often experienced nausea, vomiting, and abdominal cramps and 8 were forced to discontinue the drug. There was no difference in the weekly stool frequency between the colestipol and the control patients but the colestipol patients who took at least 50% of the prescribedmore » dose required fewer diphenoxylate tablets than the controls. The data suggest that colestipol hydrochloride is not of value in preventing radiation-induced diarrhea because of the side effects associated with the drug, but the theory on which the use of bile acid-sequestering agents is based may be correct.« less

5-Aminolevulinic Acid-Squalene Nanoassemblies for Tumor Photodetection and Therapy: In Vitro Studies

NASA Astrophysics Data System (ADS)

Babič, Andrej; Herceg, V.; Bastien, E.; Lassalle, H.-P.; Bezdetnaya, L.; Lange, Norbert

2018-01-01

Protoporphyrin IX (PpIX) as natural photosensitizer derived from administration of 5-aminolevulinic acid (5-ALA) has found clinical use for photodiagnosis and photodynamic therapy of several cancers. However, broader use of 5-ALA in oncology is hampered by its charge and polarity that result in its reduced capacity for passing biological barriers and reaching the tumor tissue. Advanced drug delivery platforms are needed to improve the biodistribution of 5-ALA. Here, we report a new approach for the delivery of 5-ALA. Squalenoylation strategy was used to covalently conjugate 5-ALA to squalene, a natural precursor of cholesterol. 5-ALA-SQ nanoassemblies were formed by self-assembly in water. The nanoassemblies were monodisperse with average size of 70 nm, polydispersity index of 0.12, and ζ-potential of + 36 mV. They showed good stability over several weeks. The drug loading of 5-ALA was very high at 26%. In human prostate cancer cells PC3 and human glioblastoma cells U87MG, PpIX production was monitored in vitro upon the incubation with nanoassemblies. They were more efficient in generating PpIX-induced fluorescence in cancer cells compared to 5-ALA-Hex at 1.0 to 3.3 mM at short and long incubation times. Compared to 5-ALA, they showed superior fluorescence performance at 4 h which was diminished at 24 h. 5-ALA-SQ presents a novel nano-delivery platform with great potential for the systemic administration of 5-ALA.

Bi-functional prodrugs of 5-aminolevulinic acid and butyric acid increase erythropoiesis in anemic mice in an erythropoietin-independent manner.

PubMed

Rephaeli, Ada; Tarasenko, Nataly; Fibach, Eitan; Rozic, Gabriela; Lubin, Ido; Lipovetsky, Julia; Furman, Svetlana; Malik, Zvi; Nudelman, Abraham

2016-08-25

Anemia is a major cause of morbidity and mortality worldwide resulting from a wide variety of pathological conditions. In severe cases it is treated by blood transfusions or injection of erythroid stimulating agents, e.g., erythropoietin (Epo), which can be associated with serious adverse effects. Therefore, there is a need to develop new treatment modalities. We recently reported that treatment of erythroleukemic cells with the novel the bi-functional prodrugs of 5-aminolevulinic acid (ALA) and butyric acid (BA), AN233 and AN908, enhanced hemoglobin (Hb) synthesis to a substantially higher level than did ALA and BA individually or their mixture. Herein, we describe that these prodrugs when given orally to mice induced histone deacetylase inhibition in the kidneys, bone marrow and spleen, thus, indicating good penetrability to the tissues. In mice where anemia was chemically induced, treatment with the prodrugs increased the Hb, the number of red blood cells (RBCs) and the percentage of reticulocytes to normal levels. The prodrugs had no adverse effects even after repeated treatment at 100-200mg/kg for 50days. The lack of increased levels of Epo in the blood of mice that were treated with the prodrugs suggests that AN233 and AN908 affected the Hb and RBC levels in an Epo-independent manner. Taken together with our previous studies, we propose that the prodrugs increase globin expression by BA inhibition of histone deacetylase and elevation heme synthesis by ALA. These results support an Epo-independent approach for treating anemia with these prodrugs. Copyright © 2016 Elsevier B.V. All rights reserved.

A gas chromatography-mass spectrometry method for the determination of delta-aminolevulinic acid in plant leaves.

PubMed

Hijaz, Faraj; Killiny, Nabil

2016-05-20

Delta-aminolevulinic (δ-ALA) acid is an important intermediate for tetrapyrroles biosynthesis and it has recently received great attention in plant physiology and human toxicology. However, the colorimetric method which is the most common method for determination of δ-ALA is time consuming and is not specific. In this study, a method for determination of δ-ALA in plant tissues was developed based on the trimethylsilyl (TMS) derivative of the pyrrole formed from the reaction of δ-ALA with ethyl acetoacetate via Knorr condensation. The δ-ALA in the HCl extract was reacted with ethyl acetoacetate to form a pyrrole. Then, the pyrrole compound was extracted using ethyl acetate and the solvent was evaporated to dryness. The dried sample was derivatized to its TMS ester and analyzed using GC-MS. The concentration of δ-ALA in citrus leaves incubated with levulinic acid was also determined by the conventional colorimetric method. The linear range was 10-200ppm in the full scan mode and 0.1-20ppm in the selected ion monitoring (SIM). The limit of detection was 6ppm in the full scan and 0.05ppm in SIM mode, representing a four-fold increase in sensitivity compared to the colorimetric method. The GC-MS method developed in this study is simple, accurate, sensitive, and could also be used to measure δ-ALA in other biological samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Aminolevulinic acid-photodynamic therapy combined with topically applied vascular disrupting agent vadimezan leads to enhanced antitumor responses.

PubMed

Marrero, Allison; Becker, Theresa; Sunar, Ulas; Morgan, Janet; Bellnier, David

2011-01-01

The tumor vascular-disrupting agent (VDA) vadimezan (5,6-dimethylxanthenone-4-acetic acid, DMXAA) has been shown to potentiate the antitumor activity of photodynamic therapy (PDT) using systemically administered photosensitizers. Here, we characterized the response of subcutaneous syngeneic Colon26 murine colon adenocarcinoma tumors to PDT using the locally applied photosensitizer precursor aminolevulinic acid (ALA) in combination with a topical formulation of vadimezan. Diffuse correlation spectroscopy (DCS), a noninvasive method for monitoring blood flow, was utilized to determine tumor vascular response to treatment. In addition, correlative CD31-immunohistochemistry to visualize endothelial damage, ELISA to measure induction of tumor necrosis factor-alpha (TNF-α) and tumor weight measurements were also examined in separate animals. In our previous work, DCS revealed a selective decrease in tumor blood flow over time following topical vadimezan. ALA-PDT treatment also induced a decrease in tumor blood flow. The onset of blood flow reduction was rapid in tumors treated with both ALA-PDT and vadimezan. CD31-immunostaining of tumor sections confirmed vascular damage following topical application of vadimezan. Tumor weight measurements revealed enhanced tumor growth inhibition with combination treatment compared with ALA-PDT or vadimezan treatment alone. In conclusion, vadimezan as a topical agent enhances treatment efficacy when combined with ALA-PDT. This combination could be useful in clinical applications. © 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

Photodynamic Therapy (PDT) using intratumoral injection of the 5- aminolevulinic acid (5-ALA) for the treatment of eye cancer in cattle

NASA Astrophysics Data System (ADS)

Hage, Raduan; Mancilha, Geraldo; Zângaro, Renato A.; Munin, Egberto; Plapler, Hélio

2007-02-01

A six-year old Holstein cow with an eye cancer (ocular squamous cell carcinoma) involving the third eyelid and conjunctiva was submitted to photodynamic therapy using intratumoral 20% aminolevulinic acid (5-ALA - Aldrich Chemical Company, Milwaukee, USA) and a light emitting diode (LED - VET LED - MMOptics (R)) with wavelength between 600 and 700 nm, 2 cm diameter circular light beam, power of 150 mW, light dose of 50 J/cm2 as a source of irradiation. Fifteen days after the experimental procedure we observed about 50% tumor reduction and complete remission after 3 months. Relapse was not observed up to 12 months after the treatment. Although the study only includes one animal not allowing definite conclusions, it indicates that PDT represents a safe and technically feasible approach in the treatment of eye cancer in cattle.

Citric Acid Suppresses the Bitter Taste of Olopatadine Hydrochloride Orally Disintegrating Tablets.

PubMed

Sotoyama, Mai; Uchida, Shinya; Tanaka, Shimako; Hakamata, Akio; Odagiri, Keiichi; Inui, Naoki; Watanabe, Hiroshi; Namiki, Noriyuki

2017-01-01

Orally disintegrating tablets (ODTs) are formulated to disintegrate upon contact with saliva, allowing administration without water. Olopatadine hydrochloride, a second-generation antihistamine, is widely used for treating allergic rhinitis. However, it has a bitter taste; therefore, the development of taste-masked olopatadine ODTs is essential. Some studies have suggested that citric acid could suppress the bitterness of drugs. However, these experiments were performed using solutions, and the taste-masking effect of citric acid on ODTs has not been evaluated using human gustatory sensation tests. Thus, this study evaluated citric acid's taste-masking effect on olopatadine ODTs. Six types of olopatadine ODTs containing 0-10% citric acid were prepared and subjected to gustatory sensation tests that were scored using the visual analog scale. The bitterness and overall palatability of olopatadine ODTs during disintegration in the mouth and after spitting out were evaluated in 11 healthy volunteers (age: 22.8±2.2 years). The hardness of the ODTs was >50 N. Disintegration time and dissolution did not differ among the different ODTs. The results of the gustatory sensation tests suggest that citric acid could suppress the bitterness of olopatadine ODTs in a dose-dependent manner. Olopatadine ODTs with a high content of citric acid (5-10%) showed poorer overall palatability than that of those without citric acid despite the bitterness suppression. ODTs containing 2.5% citric acid, yogurt flavoring, and aspartame were the most suitable formulations since they showed low bitterness and good overall palatability. Thus, citric acid is an effective bitterness-masking option for ODTs.

A comparative study of two polymorphs of L-aspartic acid hydrochloride.

PubMed

Benali-Cherif, Rim; Takouachet, Radhwane; Bendeif, El-Eulmi; Benali-Cherif, Nourredine

2014-07-01

Two polymorphs of L-aspartic acid hydrochloride, C4H8NO4(+)·Cl(-), were obtained from the same aqueous solution. Their crystal structures have been determined from single-crystal data collected at 100 K. The crystal structures revealed three- and two-dimensional hydrogen-bonding networks for the triclinic and orthorhombic polymorphs, respectively. The cations and anions are connected to one another via N-H···Cl and O-H···Cl interactions and form alternating cation-anion layer-like structures. The two polymorphs share common structural features; however, the conformations of the L-aspartate cations and the crystal packings are different. Furthermore, the molecular packing of the orthorhombic polymorph contains more interesting interactions which seems to be a favourable factor for more efficient charge transfer within the crystal.

5-Aminolevulinic Acid-Induced Fluorescence in Cerebellar Primary Central Nervous System Lymphoma: A Case Report and Literature Review.

PubMed

Yamamoto, Junkoh; Kitagawa, Takehiro; Akiba, Daisuke; Nishizawa, Shigeru

2015-01-01

5-Aminolevulinic acid (5-ALA)-induced fluorescence-guided resection is a widely used procedure for patients with malignant gliomas. However, the clinical application of 5-ALA for surgery in primary central nervous system lymphoma (PCNSL) is uncommon. Here, we present a case of PCNSL treated using 5-ALA-induced fluorescence-guided resective surgery. A 70-year-old woman presented with cerebellar ataxia, and magnetic resonance imaging revealed an irregularly shaped and homogenously enhanced mass with surrounding brain edema in the vermis that extended to the right hemisphere of the cerebellum. Under the preoperative diagnosis of a malignant glioma in the cerebellum, the patient underwent 5-ALA-induced fluorescence-guided surgery. Under blue light illumination, the tumor revealed strong 5-ALA-induced fluorescence. The tumor was identified as a diffuse large B-cell lymphoma. After partial resection, the patient received adjuvant chemotherapy and radiotherapy. Importantly, the neurological deficit of the patient improved, and recurrence of the tumor was not observed 21 months post-surgery. Together with previous reports, this case study emphasizes the efficacy of the surgical application of 5-ALA for PCNSL.

Alleviation of salt-induced oxidative damage by 5-aminolevulinic acid in wheat seedlings

NASA Astrophysics Data System (ADS)

Genişel, Mucip; Erdal, Serkan

2016-04-01

The aim of this study was to elucidate how 5-aminolevulinic acid (ALA), the precursor of chlorophyll compounds, affects the defence mechanisms of wheat seedlings induced by salt stress. To determine the possible stimulative effects of ALA against salinity, 11-day old wheat seedlings were sprayed with ALA at two different concentrations (10 and 20 mg.l-1) and then stressed by exposure to salt (150 mM NaCl). The salt stress led to significant changes in the antioxidant activity. While guaiacol peroxidase activity decreased, the activities of superoxide dismutase, catalase, and ascorbate peroxidase markedly increased under salt stress. Compared to the salt stress alone, the application of ALA beforehand further increased the activity of these enzymes. This study is the first time the effects of ALA have been monitored with regard to protein content and the isoenzyme profiles of the antioxidant enzymes. Although the salt stress reduced both the soluble protein content and protein band intensities, pre-treating with ALA significantly mitigated these stress-induced reductions. The data for the isoenzyme profiles of the antioxidant enzymes paralleled that of the ALA-induced increases in antioxidant activity. As a consequence of the high antioxidant activity in the seedlings pre-treated with ALA, the stress-induced elevations in the reactive oxygen species, superoxide anion, and hydrogen peroxide contents and lipid peroxidation levels were markedly diminished. Taken together, this data demonstrated that pre-treating with ALA confers resistance to salt stress by modulating the protein synthesis and antioxidant activity in wheat seedlings.

Effects of gallic acid on delta - aminolevulinic dehydratase activity and in the biochemical, histological and oxidative stress parameters in the liver and kidney of diabetic rats.

PubMed

de Oliveira, Lizielle Souza; Thomé, Gustavo Roberto; Lopes, Thauan Faccin; Reichert, Karine Paula; de Oliveira, Juliana Sorraila; da Silva Pereira, Aline; Baldissareli, Jucimara; da Costa Krewer, Cristina; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa; Spanevello, Roselia Maria

2016-12-01

Diabetes mellitus (DM) is characterised by hyperglycaemia associated with the increase of oxidative stress. Gallic acid has potent antioxidant properties. The aim of this study was to evaluate the effect of gallic acid on the biochemical, histological and oxidative stress parameters in the liver and kidney of diabetic rats. Male rats were divided in groups: control, gallic acid, diabetic and diabetic plus gallic acid. DM was induced in the animals by intraperitoneal injection of streptozotocin (65mg/kg). Gallic acid (30mg/kg) was administered orally for 21days. Our results showed an increase in reactive species levels and lipid peroxidation, and a decrease in activity of the enzymes superoxide dismutase and delta-aminolevulinic acid dehydratase in the liver and kidney of the diabetic animals (P<0.05). Gallic acid treatment showed protective effects in these parameters evaluated, and also prevented a decrease in the activity of catalase and glutathione S-transferase, and vitamin C levels in the liver of diabetic rats. In addition, gallic acid reduced the number of nuclei and increased the area of the core in hepatic tissue, and increased the glomerular area in renal tissue. These results indicate that gallic acid can protect against oxidative stress-induced damage in the diabetic state. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Hydroxylamine hydrochloride-acetic acid-soluble and -insoluble fractions of pelagic sediment: Readsorption revisited

USGS Publications Warehouse

Piper, D.Z.; Wandless, G.A.

1992-01-01

The extraction of the rare earth elements (REE) from deep-ocean pelagic sediment, using hydroxylamine hydrochloride-acetic acid, leads to the separation of approximately 70% of the bulk REE content into the soluble fraction and 30% into the insoluble fraction. The REE pattern of the soluble fraction, i.e., the content of REE normalized to average shale on an element-by-element basis and plotted against atomic number, resembles the pattern for seawater, whereas the pattern, as well as the absolute concentrations, in the insoluble fraction resembles the North American shale composite. These results preclude significant readsorption of the REE by the insoluble phases during the leaching procedure.

Protopine hydrochloride.

PubMed

Dostál, J; Zák, Z; Necas, M; Slavík, J; Potácek, M

2001-05-01

Protopine hydrochloride (5,6,14,14a-tetrahydro-14a-hydroxy-7-methyl-8H-bis[1,3]benzodioxolo[5,6-a:4,5-g]quinolizinium chloride, C20H20NO5(+)-Cl(-)) is the salt of the isoquinoline alkaloid protopine. It is formed by the action of dilute hydrochloric acid on the protopine free base. The N-methyl and hydroxyl groups are in a trans configuration in the quinolizine ring and the central quinolizine N-C bond is unusually long [1.579 (2) A]. The crystal is a racemate.

Topical photodynamic therapy with 5-aminolevulinic acid in the treatment of actinic keratoses: a first clinical study

NASA Astrophysics Data System (ADS)

Karrer, Sigrid; Szeimies, Rolf-Markus; Sauerwald, Angela; Landthaler, Michael

1996-01-01

In this first clinical study performed according to GCP- (good clinical practice) guidelines, efficacy, and tolerability of topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) were tested in the treatment of actinic keratoses. Ten patients (6 f, 4 m) with 36 lesions (19 located on hands and arms, 17 on the head) received ALA-PDT once. Five to six hours after occlusive application of ALA (water-in-oil-emulsion containing 10% ALA) irradiation was performed with an incoherent light source. Up to 3 months after treatment patients were monitored. A score evaluating infiltration and keratosis of treated actinic keratoses allowed us to estimate therapeutic efficacy. Compared to the initial score (100%) significantly lower score-sums were observed at the 28 day follow-up at both localizations (head: 15%; hand: 67%). Complete remission (score sum 0) resulted in 71% of actinic keratoses localized on the head. Except for slight pain and burning sensations during and after irradiation there were no notable side effects. This study proved good efficacy and tolerability of topical PDT in the treatment of actinic keratoses. Whether PDT is able to compete with established treatment modalities remains to be shown in further studies.

A new model of the mechanism underlying lead poisoning: SNPs in miRNA target region influence the δ-aminolevulinic acid dehydratase expression level.

PubMed

Li, Chunping; Wang, Miaomiao; Wang, Yiqing; Zhang, Jinlong; Sun, Na

2017-11-01

To determine if SNPs located within the 3'-UTR of δ-aminolevulinic acid dehydratase (ALAD) can alter the risk of lead poisoning and the ALAD gene expression. A case-control study was carried out to find the SNPs in miRNA target region. Luciferase reporter gene assay, qRT-PCR and Western blot was used to determine the relationship between miRNA and SNPs. We found a significant association between rs818708 and the risk of lead poisoning. miR-545-5p was influenced by rs818708 variant and might result in a significant change in ALAD expression. rs818708 T > C can weaken the binding capability between miR-545-5p and 3'-UTR of ALAD and thus may alter the risk of lead poisoning.

Cinacalcet hydrochloride (Amgen).

PubMed

Iqbal, Jameel; Zaidi, Mone; Schneider, Adina E

2003-06-01

Amgen Inc and Kirin Brewery Co Ltd, under license from NPS Pharmaceuticals Inc, are developing cinacalcet hydrochloride, the lead compound in a series of calcimimetics, for the potential treatment of primary and secondary hyperparathyroidism. Tecalcet hydrochloride was the first compound from this class to be extensively studied and most of the pharmacological data disclosed is for this compound. Cinacalcet hydrochloride was developed in an effort to improve on the poor pharmacokinetics and metabolism of tecalcet hydrochloride.

Characterization and Influence of Green Synthesis of Nano-Sized Zinc Complex with 5-Aminolevulinic Acid on Bioactive Compounds of Aniseed.

PubMed

Tavallali, Vahid; Rahmati, Sadegh; Rowshan, Vahid

2017-11-01

A new water soluble zinc-aminolevulinic acid nano complex (n[Zn(ALA) 2 ]), which was characterized by TEM, IR, and EDX spectra, has been prepared via sonochemical method under green conditions in water. In the current study, the effectiveness of foliar Zn amendment using synthetic Zn-ALA nano complex, as a new introduced Zn-fertilizer here, was evaluated. As the model plant, Pimpinella anisum, the most valuable spice and medicinal plant grown in warm regions, was used. By using zinc nano complex, further twenty compounds were obtained in the essential oil of anise plants. Application of 0.2% (w/v) Zn-ALA nano complex increased the levels of (E)-anethole, β-bisabolene, germacrene D, methyl chavicol, and α-zingiberene in the essential oil. Nano Zn complex at the rate of 0.2% induced considerable high phenolic compounds and zinc content of shoots and seeds. Chlorogenic acid had the highest level between four detected phenolic compounds. The maximum antioxidant activity was monitored through the application of Zn nano complex. According to the results, nanoscale nutrients can be provided with further decreased doses for medicinal plants. Using Zn-ALA nano complex is a new and efficient method to improve the pharmaceutical and food properties of anise plants. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Delta-aminolevulinate dehydratase activity and oxidative stress markers in preeclampsia.

PubMed

de Lucca, Leidiane; Rodrigues, Fabiane; Jantsch, Letícia B; Kober, Helena; Neme, Walter S; Gallarreta, Francisco M P; Gonçalves, Thissiane L

2016-12-01

Preeclampsia is an important pregnancy-specific multisystem disorder characterized by the onset of hypertension and proteinuria. It is of unknown etiology and involves serious risks for the pregnant women and fetus. One of the main factors involved in the pathophysiology of preeclampsia is oxidative stress, where excess free radicals produce harmful effects, including damage to macromolecules such as lipids, proteins and DNA. In addition, the sulfhydryl delta-aminolevulinate dehydratase enzyme (δ-ALA-D) that is part of the heme biosynthetic pathway in pro-oxidant conditions can be inhibited, which may result in the accumulation of 5-aminolevulinic acid (ALA), associated with the overproduction of free radicals, suggesting it to be an indirect marker of oxidative stress. As hypertensive pregnancy complications are a major cause of morbidity and mortality maternal and fetal where oxidative stress appears to be an important factor involved in preeclampsia, the aim of this study was to evaluate the activity of δ-ALA-D and classic oxidative stress markers in the blood of pregnant women with mild and severe preeclampsia. The analysis and quantification of the following oxidative stress markers were performed: thiobarbituric acid-reactive species (TBARS); presence of protein and non-protein thiol group; quantification of vitamin C; Catalase and δ-ALA--D activities in samples of blood of pregnant women with mild preeclampsia (n=25), with severe preeclampsia (n=30) and in a control group of healthy pregnant women (n=30). TBARS was significantly higher in women with preeclampsia, while the presence of thiol groups, levels of vitamin C, catalase and δ-ALA-D activity were significantly lower in groups of pregnant women with preeclampsia compared with healthy women. In addition, the results showed no significant difference between groups of pregnant women with mild and severe preeclampsia. The data suggest a state of increased oxidative stress in pregnant women with

A Pilot Cost-Effectiveness Analysis of Treatments in Newly Diagnosed High-Grade Gliomas: The Example of 5-Aminolevulinic Acid Compared With White-Light Surgery

PubMed Central

Alves, Marta; Castel-Branco, Marta; Stummer, Walter

2015-01-01

BACKGROUND: High-grade gliomas are aggressive, incurable tumors characterized by extensive diffuse invasion of the normal brain parenchyma. Novel therapies at best prolong survival; their costs are formidable and benefit is marginal. Economic restrictions thus require knowledge of the cost-effectiveness of treatments. Here, we show the cost-effectiveness of enhanced resections in malignant glioma surgery using a well-characterized tool for intraoperative tumor visualization, 5-aminolevulinic acid (5-ALA). OBJECTIVE: To evaluate the cost-effectiveness of 5-ALA fluorescence-guided neurosurgery compared with white-light surgery in adult patients with newly diagnosed high-grade glioma, adopting the perspective of the Portuguese National Health Service. METHODS: We used a Markov model (cohort simulation). Transition probabilities were estimated with the use of data from 1 randomized clinical trial and 1 noninterventional prospective study. Utility values and resource use were obtained from published literature and expert opinion. Unit costs were taken from official Portuguese reimbursement lists (2012 values). The health outcomes considered were quality-adjusted life-years, life-years, and progression-free life-years. Extensive 1-way and probabilistic sensitivity analyses were performed. RESULTS: The incremental cost-effectiveness ratios are below €10 000 in all evaluated outcomes, being around €9100 per quality-adjusted life-year gained, €6700 per life-year gained, and €8800 per progression-free life-year gained. The probability of 5-ALA fluorescence-guided surgery cost-effectiveness at a threshold of €20000 is 96.0% for quality-adjusted life-year, 99.6% for life-year, and 98.8% for progression-free life-year. CONCLUSION: 5-ALA fluorescence-guided surgery appears to be cost-effective in newly diagnosed high-grade gliomas compared with white-light surgery. This example demonstrates cost-effectiveness analyses for malignant glioma surgery to be feasible on

Glucosamine Hydrochloride

MedlinePlus

... sulfate. People take glucosamine hydrochloride by mouth for osteoarthritis, rheumatoid arthritis, glaucoma, a jaw disorder called temporomandibular ... with chondroitin sulfate, shark cartilage, and camphor for osteoarthritis. Glucosamine hydrochloride is used parenterally and short-term ...

Comparative study of the bactericidal effects of 5-aminolevulinic acid with blue and red light on Propionibacterium acnes.

PubMed

Choi, Myoung-Soon; Yun, Sook Jung; Beom, Hee Ju; Park, Hyoung Ryun; Lee, Jee-Bum

2011-07-01

Propionibacterium acnes naturally produces endogenous porphyrins that are composed of coproporphyrin III (CPIII) and protoporphyrin IX (PpIX). Red light alone and photodynamic therapy (PDT) improve acne vulgaris clinically, but there remains a paucity of quantitative data that directly examine the bactericidal effects that result from PDT on P. acnes itself in vitro. The purpose of this study was to measure the difference of bactericidal effects of 5-aminolevulinic acid (ALA)-PDT with red and blue light on P. acnes. P. acnes were cultured under anaerobic conditions and divided into two groups (ALA-treated group and control group), and were then illuminated with blue (415 nm) and red (635 nm) lights using a light-emitting diode (LED). The cultured P. acnes were killed with both blue and red LED light illumination. The efficacy increased with larger doses of light and a greater number of consecutive illuminations. We demonstrated that red light phototherapy was less effective for the eradication of P. acnes than blue light phototherapy without the addition of ALA. However, pretreatment with ALA could enhance markedly the efficacy of red light phototherapy. © 2010 Japanese Dermatological Association.

Yohimbine hydrochloride as an antagonist to xylazine hydrochloride-ketamine hydrochloride immobilization of white-tailed deer

USGS Publications Warehouse

Mech, L.D.; DelGiudice, G.D.; Karns, P.D.; Seal, U.S.

1985-01-01

Thirteen captive and one free-ranging white-tailed deer (Odocoileus virginianus) were immobilized one to six times each with ketamine hydrochloride and xylazine hydrochloride during winter and spring in northern Minnesota. Administration of 0.09 to 0.53 mg of yohimbine hydrochloride per kg IV after each trial reversed the immobilization. The deer raised their heads within a median time of 2.0 min, stood in 6.0 min and walked away in 9.5 min. No adverse side effects were observed for several weeks following the immobilization.

5-aminolevulinic acid-mediated photodynamic therapy on Hep-2 and MCF-7c3 cells.

PubMed

Alvarez, María Gabriela; Lacelli, M S; Rivarola, Viviana; Batlle, Alcira; Fukuda, Haydée

2007-01-01

The cytotoxic effect of 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PPIX) on two human carcinoma cell lines, MCF-7c3 cells and Hep 2 cells, was studied. In both cell lines, PPIX content depends on the ALA concentration and incubation time. The maximal PPIX content was higher in the MCF-7c3 cells, reaching a value of 8 microg/10(6) cells, compared to the Hep-2 cells, which accumulated 3.2 microg/10(6) cells. Treatment of cells with the iron chelator desferrioxamine prior to ALA exposure enhances the amount of PPIX, consequently diminishing enzymatic activity of ferroquelatase. Photo sensitization of the cells was in correlation with the PPIX content; therefore, conditions leading to 80% cell death in the MCF-7c3 cells provoke a 50% cell death in the Hep 2 cells. Using fluorescence microscopy, cell morphology was analyzed after incubation with 1 mM ALA during 5 hr and irradiation with 54 Jcm(-2); 24 hr post-PDT, MCF-7c3 cells revealed the typical morphological changes of necrosis. Under the same conditions, Hep-2 cells produced chromatine fragmentation characteristic of apoptosis. PPIX accumulation was observed to occur in a perinuclear region in the MCF-7c3 cells; while in Hep-2 cells, it was localized in lysosomes. Different mechanisms of cell death were observed in both cell lines, depending on the different intracellular localization of PPIX.

A patient with scirrhous stomach cancer treated with combination of hyperthermotherapy and 5-aminolevulinic acid (ALA).

PubMed

Saito, Masashi; Yano, Kazuhito; Kamigaki, Takashi; Goto, Shigenori

2013-07-01

A 35-year-old female with scirrhous stomach cancer (stage IV) was treated with a combination of 5-aminolevulinic acid (ALA), sodium dichloroacetate (DCA), hyperthermotherapy, and immunotherapy as terminal care. The patient survived for one year and seven months, during which her quality of life was markedly improved and she returned to work. The patient was diagnosed with poorly-differentiated adenocarcinoma and progressive signet-ring cell carcinoma, accompanied by left ovarian metastasis, peritoneal dissemination, and right hydronephrosis stage IV, and treated with combination chemotherapy with tegafur-gimeracil-oteracil potassium (TS-1) and docetaxel. Oral ALA and DCA were concomitantly administered at 50 mg each three times a day (150 mg/day, respectively). In addition, hyperthermotherapy using thermotron was concomitantly performed at 2- to 3-week intervals. Cellular immunotherapy with αβ T- and immature dendritic cells was also performed. The disease did not progress for 11 months, her quality of life was markedly improved, and she was able to return to work. However, the signs of enlargement of the ovarian metastatic lesion were noted later, for which chemotherapy with four cycles of second-line paclitaxel and a half dose of irinotecan and cisplatin as third-line treatment were performed. Combination of ALA/DCA, hyperthermotherapy, and cellular immunotherapy may be a low-invasive palliative therapy superior in maintaining quality of life of tumor-bearing terminally ill individuals.

Aminolevulinic acid-mediated protoporphyrin IX and photodynamic therapy for breast cancers (Conference Presentation)

NASA Astrophysics Data System (ADS)

Chen, Bin

2017-02-01

Photodynamic therapy (PDT) involves the combination of a photosensitizer and light of a specific wavelength. Upon light activation in the presence of oxygen, photosensitizer molecules generate reactive oxygen species that cause cytotoxicity by inducing oxidative stress. Aminolevulinic acid (ALA) is a pro-drug used for the diagnosis and PDT treatment of various solid tumors based on endogenous production of heme precursor protoporphyrin IX (PpIX). Although nearly all types of human cells express heme biosynthesis enzymes and produce PpIX, tumor cells are found to have more PpIX production and accumulation than normal cells, allowing for the detection and treatment of solid tumors. The objective of my research is to explore therapeutic approaches to enhance ALA-based tumor detection and therapy. We have found that high ABCG2 transporter activity in triple negative breast cancer cells (TNBC) contributed to reduced PpIX levels in cells, causing them to be more resistant towards ALA-PDT. The administration of an ABCG2 inhibitor, Ko143, was able to reverse cell resistance to ALA-PDT by enhancing PpIX mitochondrial accumulation and sensitizing cancer cells to ALA-PDT. Ko143 treatment had little effect on PpIX production and ALA-PDT in normal and ER- or HER2-positive cells. Furthermore, since some tyrosine kinase inhibitors (TKI) are known to block ABCG2 transporter activity, we screened a panel of tyrosine kinase inhibitors to examine its effect on enhancing PpIX fluorescence and ALA-PDT efficacy. Several TKIs including lapatinib and gefitinib showed effectiveness in increasing ALA-PpIX fluorescence in TNBC leading to increased cell death after PDT administration. These results indicate that inhibiting ABCG2 transporter using TKIs is a promising approach for targeting TNBC with ALA-based modality.

Intra-operative visualization of brain tumors with 5-aminolevulinic acid-induced fluorescence.

PubMed

Widhalm, Georg

2014-01-01

Precise histopathological diagnosis of brain tumors is essential for the correct patient management. Furthermore, complete resection of brain tumors is associated with an improved patient prognosis. However, histopathological undergrading and incomplete tumor removal are not uncommon, especially due to insufficient intra-operative visualization of brain tumor tissue. The fluorescent dye 5-aminolevulinic acid (5-ALA) is currently applied for fluorescence-guided resections of high-grade gliomas. The value of 5-ALA-induced protoporphyrin (PpIX) fluorescence for intra-operative visualization of other tumors than high-grade gliomas remains unclear. Within the frame of this thesis, we found a significantly higher rate of complete resections of our high-grade gliomas as compared to control cases by using the newly established 5-ALA fluorescence technology at our department. Additionally, we showed that MRI spectroscopy-based chemical shift imaging (CSI) is capable to identify intratumoral high-grade glioma areas (= anaplastic foci) during navigation guided resections to avoid histopathological undergrading. However, the accuracy of navigation systems with integrated pre-operative imaging data such as CSI declines during resections due to intra-operative brainshift. In two further studies, we found that 5-ALA induced PpIX fluorescence is capable as a novel intra-operative marker to detect anaplastic foci within initially suspected low-grade gliomas independent of brainshift. Finally, we showed that the application of 5-ALA is also of relevance in needle biopsies for intra-operative identification of representative brain tumor tissue. These data indicate that 5-ALA is not only of major importance for resection of high-grade gliomas, but also for intra-operative visualization of anaplastic foci as well as representative brain tumor tissue in needle biopsies unaffected by brainshift. Consequently, this new technique might become a novel standard in brain tumor surgery that

Comparative evaluation of in vitro efficacy of colesevelam hydrochloride tablets.

PubMed

Krishnaiah, Yellela S R; Yang, Yongsheng; Bykadi, Srikant; Sayeed, Vilayat A; Khan, Mansoor A

2014-09-01

Colesevelam hydrochloride is used as an adjunct to diet and exercise to reduce elevated low-density lipoprotein (LDL) cholesterol in patients with primary hyperlipidemia as well as to improve glycemic control in patients with type 2 diabetes. This is likely to result in submission of abbreviated new drug applications (ANDA). This study was conducted to compare the efficacy of two tablet products of colesevelam hydrochloride based on the in vitro binding of bile acid sodium salts of glycocholic acid (GC), glycochenodeoxycholic acid (GCDA) and taurodeoxycholic acid (TDCA). Kinetic binding study was carried out with constant initial bile salt concentrations as a function of time. Equilibrium binding studies were conducted under conditions of constant incubation time and varying initial concentrations of bile acid sodium salts. The unbound concentration of bile salts was determined in the samples of these studies. Langmuir equation was utilized to calculate the binding constants k1 and k2. The amount of the three bile salts bound to both the products reached equilibrium at 3 h. The similarity factor (f2) was 99.5 based on the binding profile of total bile salts to the test and reference colesevelam tablets as a function of time. The 90% confidence interval for the test to reference ratio of k2 values were 96.06-112.07 which is within the acceptance criteria of 80-120%. It is concluded from the results that the test and reference tablets of colesevelam hydrochloride showed a similar in vitro binding profile and capacity to bile salts.

21 CFR 522.1222b - Ketamine hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... hydrochloride and aminopentamide hydrogen sulfate injection. 522.1222b Section 522.1222b Food and Drugs FOOD AND... hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection. (a) Chemical name... hydrochloride, 10-[3-(dimethylamino) propyl] phenothiazine monohydrochloride, and aminopentamide hydrogen...

21 CFR 522.1222b - Ketamine hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... hydrochloride and aminopentamide hydrogen sulfate injection. 522.1222b Section 522.1222b Food and Drugs FOOD AND... hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection. (a) Chemical name... hydrochloride, 10-[3-(dimethylamino) propyl] phenothiazine monohydrochloride, and aminopentamide hydrogen...

21 CFR 522.1222b - Ketamine hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... hydrochloride and aminopentamide hydrogen sulfate injection. 522.1222b Section 522.1222b Food and Drugs FOOD AND... hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection. (a) Chemical name... hydrochloride, 10-[3-(dimethylamino) propyl] phenothiazine monohydrochloride, and aminopentamide hydrogen...

21 CFR 522.1222b - Ketamine hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... hydrochloride and aminopentamide hydrogen sulfate injection. 522.1222b Section 522.1222b Food and Drugs FOOD AND... hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection. (a) Chemical name... hydrochloride, 10-[3-(dimethylamino) propyl] phenothiazine monohydrochloride, and aminopentamide hydrogen...

5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Inhibits RIPK1/RIPK3-Dependent Necroptosis in THP-1-Derived Foam Cells

PubMed Central

Tian, Fang; Yao, Jianting; Yan, Meng; Sun, Xin; Wang, Wei; Gao, Weiwei; Tian, Zhen; Guo, Shuyuan; Dong, Zengxiang; Li, Bicheng; Gao, Tielei; Shan, Peng; Liu, Bing; Wang, Haiyang; Cheng, Jiali; Gao, Qianping; Zhang, Zhiguo; Cao, Wenwu; Tian, Ye

2016-01-01

Necroptosis, or programmed necrosis, contributes to the formation of necrotic cores in atherosclerotic plaque in animal models. However, whether inhibition of necroptosis ameliorates atherosclerosis is largely unknown. In this study, we demonstrated that necroptosis occurred in clinical atherosclerotic samples, suggesting that it may also play an important role in human atherosclerosis. We established an in vitro necroptotic model in which necroptosis was induced in THP-1-derived foam cells by serum deprivation. With this model, we demonstrated that 5-aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) inhibited necroptosis while promoting apoptosis. ALA-SDT activated the caspase-3 and caspase-8 pathways in foam cells, which is responsible for the switch from necroptosis to apoptosis. The inhibition of either caspase-8 or caspase-3 abolished the anti-necroptotic effect of ALA-SDT. In addition, we found that caspase-3 activation peaked 4 hours after ALA-SDT treatment, 2 hours earlier than maximal caspase-8activation. Taken together, our data indicate that ALA-SDT mediates the switch from necroptosis to apoptosis by activating the caspase-3 and caspase-8 pathways and may improve the prognosis of atherosclerosis. PMID:26911899

Blood interference in fiber-optical based fluorescence guided resection of glioma using 5-aminolevulinic acid

NASA Astrophysics Data System (ADS)

Haj-Hosseini, Neda; Lowndes, Shannely; Salerud, Göran; Wårdell, Karin

2011-03-01

Fluorescence guidance in brain tumor resection is performed intra-operatively where bleeding is included. When using fiber-optical probes, the transmission of light to and from the tissue is totally or partially blocked if a small amount of blood appears in front of the probe. Sometimes even after rinsing with saline, the remnant blood cells on the optical probe head, disturb the measurements. In such a case, the corresponding spectrum cannot be reliably quantified and is therefore discarded. The optimal case would be to calculate and take out the blood effect systematically from the collected signals. However, the first step is to study the pattern of blood interference in the fluorescence spectrum. In this study, a fiber-optical based fluorescence spectroscopy system with a laser excitation light of 405 nm (1.4 J/cm2) was used during fluorescence guided brain tumor resection using 5-aminolevulinic acid (5-ALA). The blood interference pattern in the fluorescence spectrum collected from the brain was studied in two patients. The operation situation was modeled in the laboratory by placing blood drops from the finger tip on the skin of forearm and the data was compared to the brain in vivo measurements. Additionally, a theoretical model was developed to simulate the blood interference pattern on the skin autofluorescence. The blood affects the collected fluorescence intensity and leaves traces of oxy and deoxy-hemoglobin absorption peaks. According to the developed theoretical model, the autofluorescence signal is considered to be totally blocked by an approximately 500 μm thick blood layer.

5-Aminolevulinic Acid (ALA) Alleviated Salinity Stress in Cucumber Seedlings by Enhancing Chlorophyll Synthesis Pathway.

PubMed

Wu, Yue; Jin, Xin; Liao, Weibiao; Hu, Linli; Dawuda, Mohammed M; Zhao, Xingjie; Tang, Zhongqi; Gong, Tingyu; Yu, Jihua

2018-01-01

5-Aminolevulinic acid (ALA) is a common precursor of tetrapyrroles as well as a crucial growth regulator in higher plants. ALA has been proven to be effective in improving photosynthesis and alleviating the adverse effects of various abiotic stresses in higher plants. However, little is known about the mechanism of ALA in ameliorating the photosynthesis of plant under abiotic stress. In this paper, we studied the effects of exogenous ALA on salinity-induced damages of photosynthesis in cucumber ( Cucumis sativus L.) seedlings. We found that the morphology (plant height, leave area), light utilization capacity of PS II [qL, Y(II)] and gas exchange capacity (Pn, gs, Ci, and Tr) were significantly retarded under NaCl stress, but these parameters were all recovered by the foliar application of 25 mg L -1 ALA. Besides, salinity caused heme accumulation and up-regulation of gene expression of ferrochelatase ( HEMH ) with suppression of other genes involved in chlorophyll synthesis pathway. Exogenously application of ALA under salinity down-regulated the heme content and HEMH expression, but increased the gene expression levels of glutamyl-tRNA reductase ( HEMA1 ), Mg-chelatase ( CHLH ), and protochlorophyllide oxidoreductase ( POR ). Moreover, the contents of intermediates involved in chlorophyll branch were increased by ALA, including protoporphyrin IX (Proto IX), Mg-protoporphyrin IX (Mg-Proto IX, protochlorophyllide (Pchlide), and chlorophyll (Chl a and Chl b ) under salt stress. Ultrastructural observation of mesophyll cell showed that the damages of photosynthetic apparatus under salinity were fixed by ALA. Collectively, the chlorophyll biosynthesis pathway was enhanced by exogenous ALA to improve the tolerance of cucumber under salinity.

Photodynamic diagnostics of stress-induced gastrointestinal neoplasia in laboratory animals using 5-aminolevulinic acid and Al-phthalocyanine

NASA Astrophysics Data System (ADS)

Borisova, Ekaterina; Semyachkina-Glushkovskaya, Oxana; Navolokin, Nikita; Mantareva, Vanya; Angelov, Ivan; Agranovich, Ilana; Khorovodov, Alexander; Shushunova, Natalia; Bodrova, Anastasiya; Fedosov, Ivan; Namykin, Anton; Abdurashitov, Arkady; Avramov, Latchezar

2018-02-01

The main research objective is the development of innovative optical technologies for sensitive diagnosis of early stages of development of stomach cancer and monitoring of stress-induced appearance and development of tumors of the gastrointestinal tract by applying endogenous and exogenous fluorescence spectroscopy modalities. Different mechanisms solely and in combination for evaluation of the joint impact of bioenvironmental factors (stress, Helicobacter pillory, exo-toxins in the food, water, soil and air) were applied to induce gastrointestinal tract (GIT) neoplasia in rats. The transformation of damaged areas of the stomach mucosa into malignancies in all parts of gastrointestinal tract were detected using exogenous fluorescence of photosensitizers - 5-aminolevulinic acid (5-ALA) and aluminum phthalocyanine (Al-Pc). Fluorescent mapping of different organs (liver, spleen, lungs, brain) also was developed - to evaluate the distribution of the photosensitizers in the whole body on the second hour after photosensitizer application by intravenous injection. Fiber-optic probe was used to measure the organs investigated. Fluorescence spectra were detected by microspectrometer USB4000 (OceanOptics Inc., USA), and FS405 LED source on 405 nm was used as excitation source for both types of photosensitizers applied. Diagnostically-important parameters of oximetry, optical coherence tomography and speckle-imaging of the microcirculation of the stomach were also evaluated, to evaluate changes in the blood flow and vascular architecture, during the formation of the initial phases of the neoplasm development.

Dose-dependent effects of β-phenylglutamic acid hydrochloride (RGPU-135, neuroglutam) on animal behavior.

PubMed

Tyurenkov, I N; Bagmetova, V V; Chernyshova, Yu V; Merkushenkova, O V

2014-12-01

β-Phenylglutamic acid hydrochloride (RGPU-135, neuroglutam) in doses of 13-650 mg/kg suppressed depressive behavior of animals in the Porsolt test (i.e. produced antidepressant properties), reduced anxiety in the open-field, elevated plus maze, and Vogel conflict tests (i.e. produced anxiolytic effects). RGPU-135 in doses of 26-130 mg/kg exhibited more pronounced antidepressant action and in doses of 26 and 52 mg/kg had more pronounced anxiolytic effects. RGPU-135 in doses of 13-78 mg/kg increased locomotor and exploratory activity of animals in the open-field test. Activating effects of this agent decreased with increasing the dose. RGPU-135 in the subtoxic dose (650 mg/kg) suppressed locomotor activity of animals (produced sedative effect).

δ-Aminolevulinic Acid Dehydratase Single Nucleotide Polymorphism 2 (ALAD2) and Peptide Transporter 2*2 Haplotype (hPEPT2*2) Differently Influence Neurobehavior in Low-Level Lead Exposed Children

PubMed Central

Sobin, Christina; Gisel Flores-Montoya, Mayra; Gutierrez, Marisela; Parisi, Natali; Schaub, Tanner

2014-01-01

Delta-aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and peptide transporter haplotype 2*2 (hPEPT2*2) through different pathways can increase brain levels of delta-aminolevulinic acid and are associated with higher blood lead burden in young children. Past child and adult findings regarding ALAD2 and neurobehavior have been inconsistent, and the possible association of hPEPT2*2 and neurobehavior has not yet been examined. Mean blood lead level (BLL), genotype, and neurobehavioral function (fine motor dexterity, working memory, visual attention and short-term memory) were assessed in 206 males and 215 females ages 5.1 to 11.8 years. Ninety-six percent of children had BLLs < 5.0 µg/dL. After adjusting for covariates (sex, age and mother’s level of education) and sibling exclusion (N = 252), generalized linear mixed model analyses showed opposite effects for the ALAD2 and hPEPT2*2 genetic variants. Significant effects for ALAD2 were observed only as interactions with BLL and the results suggested that ALAD2 was neuroprotective. As BLL increased, ALAD2 was associated with enhanced visual attention and enhanced working memory (fewer commission errors). Independent of BLL, hPEPT2*2 predicted poorer motor dexterity and poorer working memory (more commission errors). BLL alone predicted poorer working memory from increased omission errors. The findings provided further substantiation that (independent of the genetic variants examined) lowest-level lead exposure disrupted early neurobehavioral function, and suggested that common genetic variants alter the neurotoxic potential of low-level lead. ALAD2 and hPEPT2*2 may be valuable markers of risk, and indicate novel mechanisms of lead-induced neurotoxicity. Longitudinal studies are needed to examine long-term influences of these genetic variants on neurobehavior. PMID:25514583

δ-Aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and peptide transporter 2*2 haplotype (hPEPT2*2) differently influence neurobehavior in low-level lead exposed children.

PubMed

Sobin, Christina; Flores-Montoya, Mayra Gisel; Gutierrez, Marisela; Parisi, Natali; Schaub, Tanner

2015-01-01

Delta-aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and peptide transporter haplotype 2*2 (hPEPT2*2) through different pathways can increase brain levels of delta-aminolevulinic acid and are associated with higher blood lead burden in young children. Past child and adult findings regarding ALAD2 and neurobehavior have been inconsistent, and the possible association of hPEPT2*2 and neurobehavior has not yet been examined. Mean blood lead level (BLL), genotype, and neurobehavioral function (fine motor dexterity, working memory, visual attention and short-term memory) were assessed in 206 males and 215 females ages 5.1-11.8years. Ninety-six percent of children had BLLs<5.0μg/dl. After adjusting for covariates (sex, age and mother's level of education) and sibling exclusion (N=252), generalized linear mixed model analyses showed opposite effects for the ALAD2 and hPEPT2*2 genetic variants. Significant effects for ALAD2 were observed only as interactions with BLL and the results suggested that ALAD2 was neuroprotective. As BLL increased, ALAD2 was associated with enhanced visual attention and enhanced working memory (fewer commission errors). Independent of BLL, hPEPT2*2 predicted poorer motor dexterity and poorer working memory (more commission errors). BLL alone predicted poorer working memory from increased omission errors. The findings provided further substantiation that (independent of the genetic variants examined) lowest-level lead exposure disrupted early neurobehavioral function, and suggested that common genetic variants alter the neurotoxic potential of low-level lead. ALAD2 and hPEPT2*2 may be valuable markers of risk, and indicate novel mechanisms of lead-induced neurotoxicity. Longitudinal studies are needed to examine long-term influences of these genetic variants on neurobehavior. Copyright © 2014 Elsevier Inc. All rights reserved.

Gemcitabine Hydrochloride-Loaded Functionalised Carbon Nanotubes as Potential Carriers for Tumour Targeting

PubMed Central

Das, Shilpee; Desai, Jagruti L.; Thakkar, Hetal P.

2013-01-01

The objective of the present work was to formulate gemcitabine hydrochloride loaded functionalised carbon nanotubes to achieve tumour targeted drug release and thereby reducing gemcitabine hydrochloride toxicity. Multiwalled carbon nanotubes were functionalised using 1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000. Optimised ratio 1:2 of carbon nanotubes:1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000 was taken for loading of gemcitabine hydrochloride. The formulation was evaluated for different parameters. The results showed that maximum drug loading efficiency achieved was 41.59% with an average particle size of 188.7 nm and zeta potential of −10−1 mV. Scanning electron microscopy and transmission electron microscopy images confirmed the tubular structure of the formulation. The carbon nanotubes were able to release gemcitabine hydrochloride faster in acidic pH than at neutral pH indicating its potential for tumour targeting. Gemcitabine hydrochloride release from carbon nanotubes was found to follow Korsmeyer-Peppas kinetic model with non-Fickian diffusion pattern. Cytotoxic activity of formulation on A549 cells was found to be higher in comparison to free gemcitabine hydrochloride. Stability studies indicated that lyophilised samples of the formulation were more stable for 3 months under refrigerated condition than at room temperature. Thus carbon nanotubes can be promising carrier for the anticancer drug gemcitabine hydrochloride. PMID:24591746

Desipramine hydrochloride overdose

MedlinePlus

... overdose To use the sharing features on this page, please enable JavaScript. Desipramine hydrochloride is a type of medicine called a tricyclic antidepressant. It is taken to relieve symptoms of depression. Desipramine hydrochloride overdose ...

[Simultaneous determination of five cold medicine ingredients in paracetamol triprolidine hydrochloride and pseudoephedrine hydrochloride tablets by pH/organic solvent double-gradient high performance liquid chromatography].

PubMed

Xuan, Xueyi; Huang, Lina; Pan, Xiaoling; Li, Ning

2013-02-01

A pH/organic solvent double-gradient mode in reversed-phase high performance liquid chromatography (HPLC) has been established as a new approach to the simultaneous determination of acetaminophen, caffeine, salicylamide, pseudoephedrine hydrochloride and triprolidine hydrochloride in paracetamol triprolidine hydrochloride and pseudoephedrine hydrochloride tablets. Through the optimization of the organic solvent gradient mode and pH/organic solvent double-gradient mode, the optimum double-gradient HPLC system of the five cold medicine ingredients has been built. The determination was carried out on a Diamonsiol C18 column (250 mm x 4.6 mm, 5 microm). The mobile phase consisted of methanol, 0.05 mol/L ammonium acetate solution and 0.08 mol/L acetic acid solution. The column temperature was set at 30 degrees C. The flow rate was 1.0 mL/min. The sample was measured at multiple wavelengths: 0-6 min, 280 nm; 6-7 min, 257 nm; 7-14 min, 280 nm; 14 min, 233 nm. The separation of the five cold medicine ingredients in the tablets was achieved in 25.5 min. The linear ranges of acetaminophen, pseudoephedrine hydrochloride, caffeine, salicylamide and triprolidine hydrochloride were 0.055 -0.998 g/L, 0.053-0.946 g/L, 0.007-0.129 g/L, 0.035-0.622 g/L and 0.002-0.039 g/L, respectively, with their correlation coefficients greater than 0.999 0. The detection limits (S/N = 3) were 0.09, 6, 0.02, 0.128 and 0.02 mg/L, respectively. Their mean recoveries were 97.9%-102.8%. The advantage of the method is the simultaneous determination of acidic, neutral and basic compounds. It also can improve the column efficiency of the analyte, compress the half-peak width and reduce the trailing. The optimized and validated method can be used for the simultaneous determination of the five cold medicine ingredients in the tablets.

Increased cutaneous oxygen availability by topical application of hydrogen peroxide cream enhances the photodynamic reaction to topical 5-aminolevulinic acid-methyl ester.

PubMed

Manifold, R N; Anderson, C D

2011-05-01

Topical 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) photodynamic therapy (PDT) of skin lesions is an accepted treatment for skin tumours but success rates need improvement. The effectiveness of PDT is influenced by availability of oxygen. The aim of this study was to demonstrate, in normal skin, whether a decrease in skin oxygen tension reduces the photodynamic reaction (PDR); and whether the addition of topical hydrogen peroxide can reverse the effect. Topical MAL and red light were administered to the inner forearms of 40 healthy volunteers. Skin oxygen availability was lowered during the illumination phase of the PDT, by applying blanching pressure with a plastic slide. Topical hydrogen peroxide was applied under the pressure slide, immediately prior to illumination, to reverse the effect. Erythema was assessed by naked eye and laser Doppler perfusion imaging (LDPI), at baseline and at 1, 5, 24 and 48 h following illumination. Decreasing oxygen availability by pressure altered the PDR with a larger number of subjects (17.5%) not demonstrating any visible erythema at any time point after plastic slide pressure compared to a PDR Control site (7.5%). The addition of topical hydrogen peroxide during pressure application, restored the number of subjects showing no visible erythema compared to that of PDR Control. LDPI data showed that there was a decrease in mean perfusion after plastic slide pressure when comparing the change from baseline to 24 h (P < 0.05) with the PDR Control. The addition of hydrogen peroxide not only restored but also increased the mean perfusion compared to that of PDR Control when comparing the change from baseline to 5 h and the change from baseline to 24 h (P < 0.001). Increasing oxygen availability increased the PDR in normal skin. The possibility that addition of topical hydrogen peroxide to PDT protocols for non-melanoma skin cancer may increase reactivity and, thus, be relevant for outcomes warrants further study.

Phyto-management of chromium contaminated soils through sunflower under exogenously applied 5-aminolevulinic acid.

PubMed

Farid, Mujahid; Ali, Shafaqat; Rizwan, Muhammad; Ali, Qasim; Saeed, Rashid; Nasir, Tauqir; Abbasi, Ghulam Hasan; Rehmani, Muhammad Ishaq Asif; Ata-Ul-Karim, Syed Tahir; Bukhari, Syed Asad Hussain; Ahmad, Tanvir

2018-04-30

Soil contamination with heavy metals is threatening the food security around the globe. Chromium (Cr) contamination results in poor quality and reduction in yield of crops. The present research was performed to figure out the Cr toxicity in sunflower and the ameliorative role of 5-aminolevulinic acid (ALA) as a plant growth regulator. The sunflower (FH-614) was grown under increasing concentration of Cr (0, 5, 10 and 20mgkg -1 ) alone and/or in combination with 5-ALA (0, 10 and 20mgL -1 ). Results showed that Cr suppressed the overall growth, biomass, gas exchange attributes and chlorophyll content of sunflower plants. Moreover, lower levels of Cr (5 and 10mgkg -1 ) increased the production of reactive oxygen species (ROS) and electrolyte leakage (EL) along with the activities of antioxidant enzymes i.e., superoxide dismutase (SOD), guaiacole peroxidase (POD), ascorbate (APX), catalase (CAT). But at higher concentration of Cr (20mgkg -1 ), the activities of these enzymes presented a declining trend. However, the addition of 5-ALA significantly alleviated the Cr-induced toxicity in sunflower plant and enhanced the plant growth and biomass parameters along with increased chlorophyll content, gas exchange attributes, soluble proteins and soil plant analysis development (SPAD) values by scavenging the ROS and lowering down the EL. The 5-ALA also enhanced the activities of antioxidant enzymes at all levels of Cr. The increase in Cr concentration in all plant parts such as leaf, root and stem was directly proportional to the Cr concentration in soil. The application of 5-ALA further enhanced the uptake of Cr and its concentration in the plants. To understand this variation in response of plants to 5-ALA, detailed studies are required on plant biochemistry and genetic modifications. Copyright © 2018 Elsevier Inc. All rights reserved.

In-Silico Analysis of Amotosalen Hydrochloride Binding to CD-61 of Platelets.

PubMed

Chaudhary, Hammad Tufail

2016-11-01

To determine the docking of Amotosalen hydrochloride (AH) at CD-61 of platelets, and to suggest the cause of bleeding in AH treated platelets transfusion. Descriptive study. Medical College, Taif University, Taif, Saudi Arabia, from October 2014 to May 2015. The study was carried out in-silico. PDB (protein data bank) code of Tirofiban bound to CD-61 was 2vdm. CD-61 was docked with Tirofiban using online docking tools, i.e. Patchdock and Firedock. Then, Amotosalen hydrochloride and CD-61 were also docked. Best docking poses to active sites of 2vdm were found. Ligplot of interactions of ligands and CD-61 were obtained. Then comparison of hydrogen bonds, hydrogen bond lengths, and hydrophobic bonds of 2vdm molecule and best poses of docking results were done. Patchdock and Firedock results of best poses were also analysed using SPSS version 16. More amino acids were involved in hydrogen and hydrophobic bonds in Patchdock and Firedock docking of Amotosalen hydrochloride with CD-61 than Patchdock and Firedock docking of CD-61 with Tirofiban. The binding energy was more in latter than former. Amotosalen hydrochloride binds to the active site of CD-61 with weaker binding force. Haemorrhage seen in Amotosalen hydrochloride-treated platelets might be due to binding of Amotosalen hydrochloride to CD-61.

Comparison of behavior in muscle fiber regeneration after bupivacaine hydrochloride- and acid anhydride-induced myonecrosis.

PubMed

Akiyama, C; Kobayashi, S; Nonaka, I

1992-01-01

We compared the morphologic characteristics of muscle fiber necrosis and subsequent regeneration after injury induced by intramuscular injections of bupivacaine hydrochloride (BPVC) and a variety of solutions at acid and alkaline pH (acetic anhydride, citric acid buffer, and sodium carbonate buffer). After BPVC injection the necrotic muscle fibers were rapidly invaded by phagocytic cells, followed by active regeneration and very little fibrous scar formation. The regenerating muscle fibers increased rapidly in size and attained complete fiber type differentiation and regained their initial fiber diameter within 1 month. Both alkaline and acid solutions induced muscle fiber necrosis followed by regeneration. Fiber necrosis induced by alkaline buffers and acetic anhydride solutions above pH 5.0 produced changes quite similar to that induced by BPVC. However, injection with 0.1 M acetic anhydride at pH below 4.0 resulted in coagulative necrosis of the injured muscle with very little phagocytic infiltration with poor regenerative activity and dense fibrous tissue scarring. Thus, pH 4.0 appears to be the critical pH determining the type of muscle injury and subsequent poor phagocytic and regenerative activities. This model of acidic acetic anhydride injury may lead to the identification of factors which interfere with regeneration and cause fibrous tissue scarring in human muscular dystrophy.

Catalytically active alkaline molten globular enzyme: Effect of pH and temperature on the structural integrity of 5-aminolevulinate synthase*

PubMed Central

Stojanovski, Bosko M.; Breydo, Leonid; Hunter, Gregory A.; Uversky, Vladimir N.; Ferreira, Gloria C.

2014-01-01

5-Aminolevulinate synthase (ALAS), a pyridoxal-5′phosphate (PLP)-dependent enzyme, catalyzes the first step of heme biosynthesis in mammals. Circular dichroism (CD) and fluorescence spectroscopies were used to examine the effects of pH (1.0–3.0 and 7.5–10.5) and temperature (20 and 37 °C) on the structural integrity of ALAS. The secondary structure, as deduced from far-UV CD, is mostly resilient to pH and temperature changes. Partial unfolding was observed at pH 2.0, but further decreasing pH resulted in acid-induced refolding of the secondary structure to nearly native levels. The tertiary structure rigidity, monitored by near-UV CD, is lost under acidic and specific alkaline conditions (pH 10.5 and pH 9.5/37 °C), where ALAS populates a molten globule state. As the enzyme becomes less structured with increased alkalinity, the chiral environment of the internal aldimine is also modified, with a shift from a 420 nm to 330 nm dichroic band. Under acidic conditions, the PLP cofactor dissociates from ALAS. Reaction with 8-anilino-1-naphtalenesulfonic acid corroborates increased exposure of hydrophobic clusters in the alkaline and acidic molten globules, although the reaction is more pronounced with the latter. Furthermore, quenching the intrinsic fluorescence of ALAS with acrylamide at pH 1.0 and 9.5 yielded subtly different dynamic quenching constants. The alkaline molten globule state of ALAS is catalytically active (pH 9.5/37 °C), although the kcat value is significantly decreased. Finally, the binding of 5-aminolevulinate restricts conformational fluctuations in the alkaline molten globule. Overall, our findings prove how the structural plasticity of ALAS contributes to reaching a functional enzyme. PMID:25240868

Catalytically active alkaline molten globular enzyme: Effect of pH and temperature on the structural integrity of 5-aminolevulinate synthase.

PubMed

Stojanovski, Bosko M; Breydo, Leonid; Hunter, Gregory A; Uversky, Vladimir N; Ferreira, Gloria C

2014-12-01

5-Aminolevulinate synthase (ALAS), a pyridoxal-5'phosphate (PLP)-dependent enzyme, catalyzes the first step of heme biosynthesis in mammals. Circular dichroism (CD) and fluorescence spectroscopies were used to examine the effects of pH (1.0-3.0 and 7.5-10.5) and temperature (20 and 37°C) on the structural integrity of ALAS. The secondary structure, as deduced from far-UV CD, is mostly resilient to pH and temperature changes. Partial unfolding was observed at pH2.0, but further decreasing pH resulted in acid-induced refolding of the secondary structure to nearly native levels. The tertiary structure rigidity, monitored by near-UV CD, is lost under acidic and specific alkaline conditions (pH10.5 and pH9.5/37°C), where ALAS populates a molten globule state. As the enzyme becomes less structured with increased alkalinity, the chiral environment of the internal aldimine is also modified, with a shift from a 420nm to 330nm dichroic band. Under acidic conditions, the PLP cofactor dissociates from ALAS. Reaction with 8-anilino-1-naphthalenesulfonic acid corroborates increased exposure of hydrophobic clusters in the alkaline and acidic molten globules, although the reaction is more pronounced with the latter. Furthermore, quenching the intrinsic fluorescence of ALAS with acrylamide at pH1.0 and 9.5 yielded subtly different dynamic quenching constants. The alkaline molten globule state of ALAS is catalytically active (pH9.5/37°C), although the kcat value is significantly decreased. Finally, the binding of 5-aminolevulinate restricts conformational fluctuations in the alkaline molten globule. Overall, our findings prove how the structural plasticity of ALAS contributes to reaching a functional enzyme. Copyright © 2014 Elsevier B.V. All rights reserved.

Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas.

PubMed

Sanai, Nader; Snyder, Laura A; Honea, Norissa J; Coons, Stephen W; Eschbacher, Jennifer M; Smith, Kris A; Spetzler, Robert F

2011-10-01

Greater extent of resection (EOR) for patients with low-grade glioma (LGG) corresponds with improved clinical outcome, yet remains a central challenge to the neurosurgical oncologist. Although 5-aminolevulinic acid (5-ALA)-induced tumor fluorescence is a strategy that can improve EOR in gliomas, only glioblastomas routinely fluoresce following 5-ALA administration. Intraoperative confocal microscopy adapts conventional confocal technology to a handheld probe that provides real-time fluorescent imaging at up to 1000× magnification. The authors report a combined approach in which intraoperative confocal microscopy is used to visualize 5-ALA tumor fluorescence in LGGs during the course of microsurgical resection. Following 5-ALA administration, patients with newly diagnosed LGG underwent microsurgical resection. Intraoperative confocal microscopy was conducted at the following points: 1) initial encounter with the tumor; 2) the midpoint of tumor resection; and 3) the presumed brain-tumor interface. Histopathological analysis of these sites correlated tumor infiltration with intraoperative cellular tumor fluorescence. Ten consecutive patients with WHO Grades I and II gliomas underwent microsurgical resection with 5-ALA and intraoperative confocal microscopy. Macroscopic tumor fluorescence was not evident in any patient. However, in each case, intraoperative confocal microscopy identified tumor fluorescence at a cellular level, a finding that corresponded to tumor infiltration on matched histological analyses. Intraoperative confocal microscopy can visualize cellular 5-ALA-induced tumor fluorescence within LGGs and at the brain-tumor interface. To assess the clinical value of 5-ALA for high-grade gliomas in conjunction with neuronavigation, and for LGGs in combination with intraoperative confocal microscopy and neuronavigation, a Phase IIIa randomized placebo-controlled trial (BALANCE) is underway at the authors' institution.

5-Aminolevulinic acid-induced protoporphyrin IX fluorescence in meningioma: qualitative and quantitative measurements in vivo.

PubMed

Valdes, Pablo A; Bekelis, Kimon; Harris, Brent T; Wilson, Brian C; Leblond, Frederic; Kim, Anthony; Simmons, Nathan E; Erkmen, Kadir; Paulsen, Keith D; Roberts, David W

2014-03-01

The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX. To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma. ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intraoperative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities. Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (cPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher cPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura. ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature.

5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence in Meningioma: Qualitative and Quantitative Measurements In Vivo

PubMed Central

Valdes, Pablo A.; Bekelis, Kimon; Harris, Brent T.; Wilson, Brian C.; Leblond, Frederic; Kim, Anthony; Simmons, Nathan E.; Erkmen, Kadir; Paulsen, Keith D.; Roberts, David W.

2014-01-01

BACKGROUND The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX. OBJECTIVE To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma. METHODS ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intra-operative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities. RESULTS Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (CPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher CPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura. CONCLUSION ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature. PMID:23887194

Metabolism of amosulalol hydrochloride in man: quantitative comparison with laboratory animals.

PubMed

Kamimura, H; Sasaki, H; Kawamura, S

1985-05-01

The metabolism of amosulalol hydrochloride, (+/-)-5-[1-hydroxy-2-[[2-(o-methoxyphenoxy)ethyl]amino]ethyl]-2- methylbenzenesulphonamide hydrochloride, was studied in man and laboratory animals. Humans excreted 30.1% of dose as unchanged drug, and the sulphate conjugate of a 5-hydroxy metabolite, (+/-)-5-[1-hydroxy-2-[[2-(5-hydroxy-2-methoxyphenoxy)ethyl]-amino] ethyl]-2-methylbenzenesulphonamide, was the major metabolite. Amosulalol hydrochloride was extensively metabolized in animals with 10% or less excreted as unchanged drug. Hydroxylation of the 2-methyl group and O-demethylation of the o-methoxyphenoxy group were preferred in rats, and oxidative C-N cleavage yielding o-methoxyphenoxyacetic acid (M-5) preceded other reactions in dogs. Monkeys excreted almost equal amounts of the 5-hydroxy and 4-hydroxy metabolites as well as M-5.

Study on the syhthesis process of tetracaine hydrochloride

NASA Astrophysics Data System (ADS)

Li, Wenli; Zhao, Jie; Cui, Yujie

2017-05-01

Tetrachloride hydrochloride is a local anesthetic with long-acting ester, and it is usually present in the form of a hydrochloride salt. Firsleb first synthesized the tetracaine by experiment in 1928, which is one of the recognized clinical potent anesthetics. This medicine has the advantages of stable physical and chemical properties, the rapid role and long maintenance. Tetracaine is also used for ophthalmic surface anesthesia as one of the main local anesthetic just like conduction block anesthesia, mucosal surface anesthesia and epidural anesthesia. So far, the research mainly engaged in its clinical application research, and the research strength is relatively small in the field of synthetic technology. The general cost of the existing production process is high, and the yield is low. In addition, the reaction time is long and the reaction conditions are harsh. In this paper, a new synthetic method was proposed for the synthesis of tetracaine hydrochloride. The reaction route has the advantages of few steps, high yield, short reaction time and mild reaction conditions. The cheap p-nitrobenzoic acid was selected as raw material. By esterification with ethanol and reaction with n-butyraldehyde (the reaction process includes nitro reduction, aldol condensation and hydrogenation reduction), the intermediate was transesterified with dimethylaminoethanol under basic conditions. Finally, the PH value was adjusted in the ethanol solvent. After experiencing 4 steps reaction, the crude tetracaine hydrochloride was obtained.

An In Vitro Model to Study the Effect of 5-Aminolevulinic Acid-mediated Photodynamic Therapy on Staphylococcus aureus Biofilm.

PubMed

Zhao, Ke-Qing; Wu, Yang; Yi, Yu-Xi; Feng, Si-Jia; Wei, Ruo-Yan; Ma, Ying; Zheng, Chun-Quan; Qu, Di

2018-04-16

Staphylococcus aureus (S. aureus) is a common human pathogen, which causes pyogenic and systemic infections. S. aureus infections are difficult to eradicate not only due to the emergence of antibiotic-resistant strains but also its ability to form biofilms. Recently, photodynamic therapy (PDT) has been indicated as one of the potential treatments for controlling biofilm infections. However, further studies are required to improve our knowledge of its effect on bacterial biofilms, as well as the underlying mechanisms. This manuscript describes an in vitro model of PDT with 5-aminolevulinic acid (5-ALA), a precursor of the actual photosensitizer, protoporphyrin IX (PpIX). Briefly, mature S. aureus biofilms were incubated with ALA and then exposed to light. Subsequently, the antibacterial effect of ALA-PDT on S. aureus biofilm was quantified by calculating the colony forming units (CFUs) and visualized by viability fluorescent staining via confocal laser scanning microscopy (CLSM). Representative results demonstrated a strong antibacterial effect of ALA-PDT on S. aureus biofilms. This protocol is simple and can be used to develop an in vitro model to study the treatment of S. aureus biofilms with ALA-PDT. In the future, it could also be referenced in PDT studies utilizing other photosensitizers for different bacterial strains with minimal adjustments.

Biomonitoring of lead-contaminated Missouri streams with an assay for erythrocyte δ-aminolevulinic acid dehydratase activity in fish blood

USGS Publications Warehouse

Schmitt, C.J.; Wildhaber, M.L.; Hunn, J.B.; Nash, T.; Tieger, M. N.; Steadman, B. L.

1993-01-01

The activity of the enzyme δ-aminolevulinic acid dehydratase (ALA-D) in erythrocytes has long been used as a biomarker of lead exposure in humans and waterfowl and, more recently, in fishes. The assay was tested for ALA-D activity in fishes from streams affected by lead in combination with other metals from lead-zinc mining and related activities. Fishes (mostly catostomids) were collected from sites affected by historic and current mining activities, and from sites considered to be unaffected by mining (reference sites). A group of potentially toxic elements was measured in blood and carcass samples of individual fish, as were ALA-D activity, total protein (TP), and hemoglobin (Hb) in blood. Concentrations of mining-related metals (lead, zinc, and cadmium) were significantly greater (P<0.05) in fish blood and carcass at sites affected by historic mining activities than at reference and active mining sites. When analyzed by multiple regression, ALA-D activity, Hb, and TP accounted for 66% of blood-lead and 69% of carcass-lead variability. Differences among species were small. ALA-D activity as a biomarker adequately distinguished sites affected by bioavailable environmental lead. Zinc was the only other metal that affected ALA-D activity; it appeared to ameliorate the inactivation of ALA-D by lead.

Enhancement of 5-aminolevulinic acid-based fluorescence detection of side population-defined glioma stem cells by iron chelation

PubMed Central

Wang, Wenqian; Tabu, Kouichi; Hagiya, Yuichiro; Sugiyama, Yuta; Kokubu, Yasuhiro; Murota, Yoshitaka; Ogura, Shun-ichiro; Taga, Tetsuya

2017-01-01

Cancer stem cells (CSCs) are dominantly responsible for tumor progression and chemo/radio-resistance, resulting in tumor recurrence. 5-aminolevulinic acid (ALA) is metabolized to fluorescent protoporphyrin IX (PpIX) specifically in tumor cells, and therefore clinically used as a reagent for photodynamic diagnosis (PDD) and therapy (PDT) of cancers including gliomas. However, it remains to be clarified whether this method could be effective for CSC detection. Here, using flow cytometry-based analysis, we show that side population (SP)-defined C6 glioma CSCs (GSCs) displayed much less 5-ALA-derived PpIX fluorescence than non-GSCs. Among the C6 GSCs, cells with ultralow PpIX fluorescence exhibited dramatically higher tumorigenicity when transplanted into the immune-deficient mouse brain. We further demonstrated that the low PpIX accumulation in the C6 GSCs was enhanced by deferoxamine (DFO)-mediated iron chelation, not by reserpine-mediated inhibition of PpIX-effluxing ABCG2. Finally, we found that the expression level of the gene for heme oxygenase-1 (HO-1), a heme degradation enzyme, was high in C6 GSCs, which was further up-regulated when treated with 5-ALA. Our results provide important new insights into 5-ALA-based PDD of gliomas, particularly photodetection of SP-defined GSCs by iron chelation based on their ALA-PpIX-Heme metabolism. PMID:28169355

Evaluation of Hydrogel Suppositories for Delivery of 5-Aminolevulinic Acid and Hematoporphyrin Monomethyl Ether to Rectal Tumors.

PubMed

Ye, Xuying; Yin, Huijuan; Lu, Yu; Zhang, Haixia; Wang, Han

2016-10-12

We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of SW837 rectal carcinoma cells. For comparison, ALA and HMME were also administered by three common photosensitizer delivery routes; local administration to the skin and intratumoral or intravenous injection. The concentration of ALA-induced protoporphyrin IX or HMME in the rectal wall, skin, and subcutaneous tumor was measured by fluorescence spectrophotometry, and their distribution in vertical sections of the tumor was measured using a fluorescence spectroscopy system. The concentration of ALA-induced protoporphyrin IX in the rectal wall after local administration of suppositories to the rectal cavity was 9.76-fold (1 h) and 5.8-fold (3 h) higher than in the skin after cutaneous administration. The maximal depth of ALA penetration in the tumor was ~3-6 mm at 2 h after cutaneous administration. Much lower levels of HMME were observed in the rectal wall after administration as a hydrogel suppository, and the maximal depth of tumor penetration was <2 mm after cutaneous administration. These data show that ALA more readily penetrates the mucosal barrier than the skin. Administration of ALA as an intrarectal hydrogel suppository is thus a potential delivery route for photodynamic therapy of rectal cancer.

[Simultaneous determination of scopolamine hydrobromide, atropine sulfate, ephedrine hydrochloride and pseudoephedrine hydrochloride in Zhichuanling oral liquid with HPLC].

PubMed

Zhang, Yu-Lin; Li, Yu-Ping

2013-10-01

To establish an HPLC method for determining the contents of scopolamine hydrobromide, atropine sulfate, ephedrine hydrochloride and pseudoephedrine hydrochloride in Zhichuanling oral liquid. Agela Durashell RP-C18 (4. 6 mm x250 mm, 5 microm) was adopted, with acetonitrile-sodium phosphate buffer solution (0. 07 mol L-1 sodium phosphate solution with 17.5 mmol L-1 sodium dodecylsulfate adjusted to pH 6.0 with phosphoric acid solution) (30:70) as the mobile phase. The flow rate was 0. 9 mL min -1, the detection wavelength was 207 nm, and the column temperature was 25 degree C. Scopolamine hydrobromide, atropine sulfate, ephedrine hlvdrochloride and pseudoephedrine hydrochloride showed good linear relations with peak areas within the concentration range of 0. 021 21-1. 060 5 pg (r =0. 999 3) , 0. 011 14-0. 557 microg (r = 0. 999 6) , 0. 200 56-10. 028 microg (r =0. 999 7) and 0.070 33-3. 516 5 gg (r =0. 999 6), respectively, with the average recoveries of 101.9% , 99. 80%, 100. 3%, 100. 2% (n=6). The method was so quick, simple, highly reproducible and specific that it could be used as one of quality control methods of Zhichuanling oral liquid.

21 CFR 522.2470 - Tiletamine hydrochloride and zolazepam hydrochloride for injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Tiletamine hydrochloride and zolazepam hydrochloride for injection. 522.2470 Section 522.2470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR...

Use of wood vinegar to enhance 5-aminolevulinic acid production by selected Rhodopseudomonas palustris in rubber sheet wastewater for agricultural use.

PubMed

Nunkaew, Tomorn; Kantachote, Duangporn; Chaiprapat, Sumate; Nitoda, Teruhiko; Kanzaki, Hiroshi

2018-05-01

This study aimed to produce inexpensive 5-aminolevulinic acid (ALA) in a non-sterile latex rubber sheet wastewater (RSW) by Rhodopseudomonas palustris TN114 and PP803 for the possibility to use in agricultural purposes by investigating the optimum conditions, and applying of wood vinegar (WV) as an economical source of levulinic acid to enhance ALA content. The Box-Behnken Design experiment was conducted under microaerobic-light conditions for 96 h with TN114, PP803 and their mixed culture (1:1) by varying initial pH, inoculum size (% v/v) and initial chemical oxygen demand (COD, mg/L). Results showed that the optimal condition (pH, % inoculum size, COD) of each set to produce extracellular ALA was found at 7.50, 6.00, 2000 for TN114; 7.50, 7.00, 3000 for PP803; and 7.50, 6.00, 4000 for a mixed culture; and each set achieved COD reduction as high as 63%, 71% and 75%, respectively. Addition of the optimal concentration of WV at mid log phase at 0.63% for TN114, and 1.25% for PP803 and the mixed culture significantly increased the ALA content by 3.7-4.2 times (128, 90 and 131 μM, respectively) compared to their controls. ALA production cost could be reduced approximately 31 times with WV on the basis of the amount of levulinic acid used. Effluent containing ALA for using in agriculture could be achieved by treating the RSW with the selected ALA producer R. palustris strains under the optimized condition with a little WV additive.

40 CFR Appendix B to Subpart Nnn... - Free Formaldehyde Analysis of Insulation Resins by Hydroxylamine Hydrochloride

Code of Federal Regulations, 2013 CFR

2013-07-01

... buffer. 3.350-mL burette for 1.0 N sodium hydroxide. 3.4Magnetic stirrer and stir bars. 3.5250-mL beaker... N sodium hydroxide solution. 4.2Hydroxylamine hydrochloride solution, 100 grams per liter, pH... hydrochloric acid, and 0.1 N sodium hydroxide. 5.5Add 50 mL of the hydroxylamine hydrochloride solution...

40 CFR Appendix B to Subpart Nnn... - Free Formaldehyde Analysis of Insulation Resins by Hydroxylamine Hydrochloride

Code of Federal Regulations, 2014 CFR

2014-07-01

... buffer. 3.350-mL burette for 1.0 N sodium hydroxide. 3.4Magnetic stirrer and stir bars. 3.5250-mL beaker... N sodium hydroxide solution. 4.2Hydroxylamine hydrochloride solution, 100 grams per liter, pH... hydrochloric acid, and 0.1 N sodium hydroxide. 5.5Add 50 mL of the hydroxylamine hydrochloride solution...

Alleviation of Lead Toxicity by 5-Aminolevulinic Acid Is Related to Elevated Growth, Photosynthesis, and Suppressed Ultrastructural Damages in Oilseed Rape

PubMed Central

Tian, Tian; Qin, Yebo; Gill, Rafaqat A.; Ali, Shafaqat

2014-01-01

Lead (Pb) is a widely spread pollutant and leads to diverse morphological and structural changes in the plants. In this study, alleviating role of 5-aminolevulinic acid (ALA) in oilseed rape (Brassica napus L.) was investigated with or without foliar application of ALA (25 mg L−1) in hydroponic environment under different Pb levels (0, 100, and 400 µM). Outcomes stated that plant morphology and photosynthetic attributes were reduced under the application of Pb alone. However, ALA application significantly increased the plant growth and photosynthetic parameters under Pb toxicity. Moreover, ALA also lowered the Pb concentration in shoots and roots under Pb toxicity. The microscopic studies depicted that exogenously applied ALA ameliorated the Pb stress and significantly improved the cell ultrastructures. After application of ALA under Pb stress, mesophyll cell had well-developed nucleus and chloroplast having a number of starch granules. Moreover, micrographs illustrated that root tip cell contained well-developed nucleus, a number of mitochondria, and golgi bodies. These results proposed that under 15-day Pb-induced stress, ALA improved the plant growth, chlorophyll content, photosynthetic parameters, and ultrastructural modifications in leaf mesophyll and root tip cells of the B. napus plants. PMID:24683549

High-performance liquid chromatographic analysis of methadone hydrochloride oral solution.

PubMed

Beasley, T H; Ziegler, H W

1977-12-01

A direct and rapid high-performance liquid chromatographic assay for methadone hydrochloride in a flavored oral solution dosage form is described. A syrup sample, one part diluted with three parts of water, is introduced onto a column packed with octadecylsilane bonded on 10 micrometer porous silica gel (reversed phase). A formic acid-ammonium formate-buffered mobile phase is linear programmed with acetonitrile. The absorbance is monitored continuously at 280 or 254 nm, using a flow-through, UV, double-beam photometer. An aqueous methadone hydrochloride solution is used for external standardization. The relative standard deviation was not more than 1.0%. Drug recovery from a syrup base was better than 99.8%.

Synthesis and evaluation of chitosan-graft-poly (2-hydroxyethyl methacrylate-co-itaconic acid) as a drug carrier for controlled release of tramadol hydrochloride

PubMed Central

Subramanian, Kaliappa gounder; Vijayakumar, Vediappan

2011-01-01

Chitosan-graft-poly (2-hydroxyethyl methacrylate-co-itaconic acid) has been synthesized for different feed ratios of 2-hydroxyethyl methacrylate and itaconic acid and characterized by FT-IR, thermogravimetry and swelling in simulated biological fluids (SBF) and evaluated as a drug carrier with model drug, tramadol hydrochloride (TRM). Grafting decreased the thermal stability of chitosan. FT-IR spectra of tablet did not reveal any molecular level (i.e. at <10 nm scale) drug–polymer interaction. But differential scanning calorimetric studies indicated a probable drug–polymer interaction at a scale >100 nm level. The observed Korsmeyer–Peppas’s power law exponents (0.19–1.21) for the in vitro release profiles of TRM in SBF and other drugs such as 5-fluorouracil (FU), paracetamol (PCM) and vanlafaxine hydrochloride (VNF) with the copolymer carriers revealed an anomalous drug release mechanism. The decreased release rates for the grafted chitosan and the enhanced release rate for the grafts with increasing itaconic acid content in the feed were more likely attributed to the enhanced drug–matrix interaction and polymer–SBF interactions, respectively. The different release profiles of FU, PCM, TRM and VNF with the copolymer matrix are attributed to the different chemical structures of drugs. The above features suggest the graft copolymer’s candidature for use as a promising oral drug delivery system. PMID:23960799

21 CFR 522.883 - Etorphine hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... milliliter of etorphine hydrochloride injection, veterinary, contains 1 mg of etorphine hydrochloride in... use the drug unless diprenorphine hydrochloride injection, veterinary, as provided for in § 522.723, is available for use in reversing the effects of etorphine hydrochloride injection, veterinary. (4...

21 CFR 522.883 - Etorphine hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... milliliter of etorphine hydrochloride injection, veterinary, contains 1 mg of etorphine hydrochloride in... use the drug unless diprenorphine hydrochloride injection, veterinary, as provided for in § 522.723, is available for use in reversing the effects of etorphine hydrochloride injection, veterinary. (4...

Comparative analysis of the effects of CO2 fractional laser and sonophoresis on human skin penetration with 5-aminolevulinic acid.

PubMed

Choi, J H; Shin, E J; Jeong, K H; Shin, M K

2017-11-01

Successful delivery of a photosensitizer into the skin is an important factor for effective photodynamic therapy (PDT). The effective method to increase drug penetration within short incubation time overcoming skin barrier have been investigated. This study was performed to analyze and compare the effectiveness of ablative fractional laser (FXL) pretreatment and/or sonophoresis for enhancing the penetration of 5-aminolevulinic acid (ALA) into human skin in vivo. Twenty-four identical 1 × 1 cm 2 treatment areas were mapped on the backs of ten healthy male subjects. Each area received FXL pretreatment and/or sonophoresis with different energy settings and ALA incubation times. After treatments, porphyrin fluorescence reflecting the ALA penetration were measured. Application of ablative CO 2 FXL pretreatment resulted to higher fluorescence intensities than the non-treatment group. Incubation times were positively correlated with the increments of ALA penetration. However, increasing pulse energy or combining with sonophoresis did not show additional positive effects on ALA penetration. Ablative CO 2 FXL pretreatment effectively facilitated ALA penetration in human skin in vivo. Ablative CO 2 FXL alone without sonophoresis setting pulse energy of 10 and 20 mJ with more than 60 min of ALA incubation time could be an ideal setting for ALA penetration.

Gateways to clinical trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2005-06-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, acyline, adalimumab, adenosine triphosphate, AEE-788, AIDSVAX gp120 B/B, AK-602, alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alprazolam, amdoxovir, AMG-162, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminophylline hydrate, anakinra, anecortave acetate, anti-CTLA-4 MAb, APC-8015, aripiprazole, aspirin, atazanavir sulfate, atomoxetine hydrochloride, atorvastatin calcium, atrasentan, AVE-5883, AZD-2171; Betamethasone dipropionate, bevacizumab, bimatoprost, biphasic human insulin (prb), bortezomib, BR-A-657, BRL-55730, budesonide, busulfan; Calcipotriol, calcipotriol/betamethasone dipropionate, calcium folinate, capecitabine, capravirine, carmustine, caspofungin acetate, cefdinir, certolizumab pegol, CG-53135, chlorambucil, ciclesonide, ciclosporin, cisplatin, clofarabine, clopidogrel hydrogensulfate, clozapine, co-trimoxazole, CP-122721, creatine, CY-2301, cyclophosphamide, cypher, cytarabine, cytolin; D0401, darbepoetin alfa, darifenacin hydrobromide, DASB, desipramine hydrochloride, desloratadine, desvenlafaxine succinate, dexamethasone, didanosine, diquafosol tetrasodium, docetaxel, doxorubicin hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecallantide, efalizumab, efavirenz, eletriptan, emtricitabine, enfuvirtide, enoxaparin sodium, estramustine phosphate sodium, etanercept, ethinylestradiol, etonogestrel, etonogestrel/ethinylestradiol, etoposide, exenatide; Famciclovir, fampridine, febuxostat, filgrastim, fludarabine phosphate, fluocinolone acetonide, fluorouracil, fluticasone propionate

Stability studies of lincomycin hydrochloride in aqueous solution and intravenous infusion fluids.

PubMed

Czarniak, Petra; Boddy, Michael; Sunderland, Bruce; Hughes, Jeff D

2016-01-01

The purpose of this study was to evaluate the chemical stability of Lincocin(®) (lincomycin hydrochloride) in commonly used intravenous fluids at room temperature (25°C), at accelerated-degradation temperatures and in selected buffer solutions. The stability of Lincocin(®) injection (containing lincomycin 600 mg/2 mL as the hydrochloride) stored at 25°C±0.1°C in sodium lactate (Hartmann's), 0.9% sodium chloride, 5% glucose, and 10% glucose solutions was investigated over 31 days. Forced degradation of Lincocin(®) in hydrochloric acid, sodium hydroxide, and hydrogen peroxide was performed at 60°C. The effect of pH on the degradation rate of lincomycin hydrochloride stored at 80°C was determined. Lincomycin hydrochloride w as found to maintain its shelf life at 25°C in sodium lactate (Hartmann's) solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution, with less than 5% lincomycin degradation occurring in all intravenous solutions over a 31-day period. Lincomycin hydrochloride showed less rapid degradation at 60°C in acid than in basic solution, but degraded rapidly in hydrogen peroxide. At all pH values tested, lincomycin followed first-order kinetics. It had the greatest stability near pH 4 when stored at 80°C (calculated shelf life of 4.59 days), and was least stable at pH 2 (calculated shelf life of 0.38 days). Lincocin(®) injection was chemically found to have a shelf life of at least 31 days at 25°C when added to sodium lactate (Hartmann's) solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution. Solutions prepared at approximately pH 4 are likely to have optimum stability.

Photosensitizer fluorescence and singlet oxygen luminescence as dosimetric predictors of topical 5-aminolevulinic acid photodynamic therapy induced clinical erythema.

PubMed

Mallidi, Srivalleesha; Anbil, Sriram; Lee, Seonkyung; Manstein, Dieter; Elrington, Stefan; Kositratna, Garuna; Schoenfeld, David; Pogue, Brian; Davis, Steven J; Hasan, Tayyaba

2014-02-01

The need for patient-specific photodynamic therapy (PDT) in dermatologic and oncologic applications has triggered several studies that explore the utility of surrogate parameters as predictive reporters of treatment outcome. Although photosensitizer (PS) fluorescence, a widely used parameter, can be viewed as emission from several fluorescent states of the PS (e.g., minimally aggregated and monomeric), we suggest that singlet oxygen luminescence (SOL) indicates only the active PS component responsible for the PDT. Here, the ability of discrete PS fluorescence-based metrics (absolute and percent PS photobleaching and PS re-accumulation post-PDT) to predict the clinical phototoxic response (erythema) resulting from 5-aminolevulinic acid PDT was compared with discrete SOL (DSOL)-based metrics (DSOL counts pre-PDT and change in DSOL counts pre/post-PDT) in healthy human skin. Receiver operating characteristic curve (ROC) analyses demonstrated that absolute fluorescence photobleaching metric (AFPM) exhibited the highest area under the curve (AUC) of all tested parameters, including DSOL based metrics. The combination of dose-metrics did not yield better AUC than AFPM alone. Although sophisticated real-time SOL measurements may improve the clinical utility of SOL-based dosimetry, discrete PS fluorescence-based metrics are easy to implement, and our results suggest that AFPM may sufficiently predict the PDT outcomes and identify treatment nonresponders with high specificity in clinical contexts.

Fluorescence Behavior and Dural Infiltration of Meningioma Analyzed by 5-Aminolevulinic Acid-Based Fluorescence: Operating Microscope Versus Mini-Spectrometer.

PubMed

Knipps, Johannes; Beseoglu, Kerim; Kamp, Marcel; Fischer, Igor; Felsberg, Joerg; Neumann, Lisa M; Steiger, Hans-Jakob; Cornelius, Jan F

2017-12-01

To compare fluorescence intensity of tumor specimens, as measured by a fluorescence-guided surgery microscope and a spectrometer, to evaluate tumor infiltration of dura mater around meningiomas with help of these 2 different 5-aminolevulinic acid (5-ALA)-based fluorescence tools, and to correlate fluorescence intensity with histopathologic data. In a clinical series, meningiomas were resected by 5-ALA fluorescence-guided surgery. Fluorescence intensity was semiquantitatively rated by the surgeon at predefined points. Biopsies were harvested and fluorescence intensity measured by a spectrometer and histopathologically analyzed. Sampling was realized at the level of the dura in a centrifugal direction. A total of 104 biopsies (n = 13 tumors) were analyzed. Specificity and sensitivity of the microscope were 0.96 and 0.53 and of the spectrometer 0.95 and 0.93, respectively. Fluorescence intensity as measured by the spectrometer was correlated to histologically confirmed tumor burden. In a centrifugal direction, tumor burden and fluorescence intensity continuously decreased (along the dural tail). Below a threshold value of 639 arbitrary units no tumor was histologically detectable. At the level of the dura the spectrometer was highly sensitive for detection of meningioma cells. The surgical microscope showed false negative results and missed residual tumor cells in more than one half of the cases. The complementary use of both fluorescence tools may improve resection quality. Copyright © 2017 Elsevier Inc. All rights reserved.

ABCG2 transporter inhibitor restores the sensitivity of triple negative breast cancer cells to aminolevulinic acid-mediated photodynamic therapy.

PubMed

Palasuberniam, Pratheeba; Yang, Xue; Kraus, Daniel; Jones, Patrick; Myers, Kenneth A; Chen, Bin

2015-08-18

Photosensitizer protoporphyrin IX (PpIX) fluorescence, intracellular localization and cell response to photodynamic therapy (PDT) were analyzed in MCF10A normal breast epithelial cells and a panel of human breast cancer cells including estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) positive and triple negative breast cancer (TNBC) cells after treatment with PpIX precursor aminolevulinic acid (ALA). Although PpIX fluorescence was heterogeneous in different cells, TNBC cells showed significantly lower PpIX level than MCF10A and ER- or HER2-positive cells. PpIX fluorescence in TNBC cells also had much less mitochondrial localization than other cells. There was an inverse correlation between PpIX fluorescence and cell viability after PDT. Breast cancer cells with the highest PpIX fluorescence were the most sensitive to ALA-PDT and TNBC cells with the lowest PpIX level were resistant to PDT. Treatment of TNBC cells with ABCG2 transporter inhibitor Ko143 significantly increased ALA-PpIX fluorescence, enhanced PpIX mitochondrial accumulation and sensitized cancer cells to ALA-PDT. Ko143 treatment had little effect on PpIX production and ALA-PDT in normal and ER- or HER2-positive cells. These results demonstrate that enhanced ABCG2 activity renders TNBC cell resistance to ALA-PDT and inhibiting ABCG2 transporter is a promising approach for targeting TNBC with ALA-based modality.

Low-Dose Topical 5-Aminolevulinic Acid Photodynamic Therapy in the Treatment of Different Severity of Acne Vulgaris.

PubMed

Tao, Shi-Qin; Li, Fei; Cao, Lei; Xia, Ru-Shan; Fan, Hua; Fan, Ying; Sun, Hui; Jing, Cheng; Yang, Li-Jia

2015-12-01

The objective of this article is to investigate the effectiveness and safety of photodynamic therapy (PDT) with 3.6 % topical aminolevulinic acid (ALA) and a short incubation time with red light in moderate to severe acne. One hundred and thirty-six patients with moderate to severe acne were treated with 3.6 % topical ALA-PDT for three sessions with an interval of 2 weeks. Patients were evaluated for efficacy and safety on week 2, 4, 6, 8, and 12 after the initial treatment. Most patients showed apparent clearance of acne lesions at the treated site after three sessions. The effective treatment rates were increased after the multiple therapies. The clinical outcomes are the best at 4 weeks after the final treatment. The total effectiveness rate and cure rate of the low-dose ALA-PDT procedure is 92.65 and 47.06 %, respectively. Thirty-one patients and nineteen patients showed apparent exacerbation of acne lesions before the 2nd and 3rd treatment, respectively, but all of them showed good or excellent improvement after a three-course treatment. A few patients showed mild relapse including papules and comedos at 8 weeks after the final treatment. No significant differences are found in the effects of different acne severity and different genders. Adverse reactions are mild and transient. A 3.6 % topical ALA-PDT with a short time incubation with red light is a simple and an effective treatment option for moderate to severe acne with mild side effects in Chinese people.

The proton-coupled oligopeptide transporter 1 plays a major role in the intestinal permeability and absorption of 5-aminolevulinic acid.

PubMed

Xie, Yehua; Hu, Yongjun; Smith, David E

2016-01-01

5-Aminolevulinic acid (5-ALA) has been widely used in photodynamic therapy and immunofluorescence of tumours. In the present study, the intestinal permeability and oral pharmacokinetics of 5-ALA were evaluated to probe the contribution of the proton-coupled oligopeptide transporter 1 (PEPT1) to the oral absorption and systemic exposure of this substrate. In situ single-pass intestinal perfusions and in vivo oral pharmacokinetic studies were performed in wildtype and Pept1 knockout mice. Perfusion studies were performed as a function of concentration dependence, specificity and permeability of 5-ALA in different intestinal segments. Pharmacokinetic studies were performed after 0.2 and 2.0 μmoL·g(-1) doses of 5-ALA. The permeability of 5-ALA was substantial in duodenal, jejunal and ileal regions of wildtype mice, but the residual permeability of 5-ALA in the small intestine from Pept1 knockout mice was only about 10% of that in wildtype animals. The permeability of 5-ALA in jejunum was specific for PEPT1 with no apparent contribution of other transporters, including the proton-coupled amino acid transporter 1 (PAT1). After oral dosing, the systemic exposure of 5-ALA was reduced by about twofold during PEPT1 ablation, and the pharmacokinetics were dose-proportional after the 0.2 and 2.0 µmol·g(-1) doses. PEPT1 had a minor effect on the disposition and peripheral tissue distribution of 5-ALA. Our findings suggested a major role of PEPT1 in the intestinal permeability and oral absorption of 5-ALA. In contrast, another proton-coupled transporter, PAT1, appeared to play a limited role, at best. © 2015 The British Pharmacological Society.

Amino Acid and Vitamin Requirements of Several Bacteroides Strains

PubMed Central

Quinto, Grace

1966-01-01

Nutritional studies were performed on nine Bacteroides strains, by use of the methodology and media of anaerobic rumen microbiology. Ristella perfoetens CCI required l-arginine hydrochloride, l-tryptophan, l-leucine, l-histidine hydrochloride, l-cysteine hydrochloride, dl-valine, dl-tyrosine, and the vitamin calcium-d-pantothenate, since scant turbidity developed in media without these nutrients. R. perfoetens was stimulated by glycine, dl-lysine hydrochloride, dl-isoleucine, l-proline, l-glutamic acid, dl-alanine, dl-phenylalanine, dl-methionine, and the vitamins nicotinamide and p-aminobenzoic acid, since maximal turbidity developed more slowly in media without these nutrients than in complete medium. Medium A-23, which was devised for R. perfoetens, contained salts, 0.0002% nicotinamide and calcium d-pantothenate, 0.00001% p-aminobenzoic acid, 0.044% l-tryptophan, 0.09% l-glutamic acid, and 0.1% of the other 13 amino acids listed above. Zuberella clostridiformis and seven strains of R. pseudoinsolita did not require vitamins, and showed no absolute requirement for any one amino acid. Various strains produced maximal turbidity more slowly in media deficient in l-proline, glycine, l-glutamic acid, dl-serine, l-histidine hydrochloride, dl-alanine, or l-cysteine hydrochloride, than in complete medium. These eight strains grew optimally in medium A-23 plus 0.1% dl-serine but without vitamins. PMID:16349673

Interaction between lidocaine hydrochloride (with and without adrenaline) and various irrigants: A nuclear magnetic resonance analysis

PubMed Central

Vidhya, Nirmal; Karthikeyan, Balasubramanian Saravana; Velmurugan, Natanasabapathy; Abarajithan, Mohan; Nithyanandan, Sivasankaran

2014-01-01

Background: Interaction between local anesthetic solution, lidocaine hydrochloride (with and without adrenaline), and root canal irrigants such as sodium hypochlorite (NaOCl), ethylene diamine tetra-acetic acid (EDTA), and chlorhexidine (CHX) has not been studied earlier. Hence, the purpose of this in vitro study was to evaluate the chemical interaction between 2% lidocaine hydrochloride (with and without adrenaline) and commonly used root canal irrigants, NaOCl, EDTA, and CHX. Materials and Methods: Samples were divided into eight experimental groups: Group I-Lidocaine hydrochloride (with adrenaline)/3% NaOCl, Group II-Lidocaine hydrochloride (with adrenaline)/17% EDTA, Group III- Lidocaine hydrochloride (with adrenaline)/2% CHX, Group IV-Lidocaine hydrochloride (without adrenaline)/3% NaOCl, Group V-Lidocaine hydrochloride (without adrenaline)/17% EDTA, Group VI-Lidocaine hydrochloride (without adrenaline)/2% CHX, and two control groups: Group VII-Lidocaine hydrochloride (with adrenaline)/deionized water and Group VIII-Lidocaine hydrochloride (without adrenaline)/deionized water. The respective solutions of various groups were mixed in equal proportions (1 ml each) and observed for precipitate formation. Chemical composition of the formed precipitate was then analysed by nuclear magnetic resonance spectroscopy (NMR) and confirmed with diazotation test. Results: In groups I and IV, a white precipitate was observed in all the samples on mixing the respective solutions, which showed a color change to reddish brown after 15 minutes. This precipitate was then analysed by NMR spectroscopy and was observed to be 2,6-xylidine, a reported toxic compound. The experimental groups II, III, V, and VI and control groups VII and VIII showed no precipitate formation in any of the respective samples, until 2 hours. Conclusion: Interaction between lidocaine hydrochloride (with and without adrenaline) and NaOCl showed precipitate formation containing 2,6-xylidine, a toxic compound

Photodynamic therapy using a new formulation of 5-aminolevulinic acid for wrinkles in Asian skin: A randomized controlled split face study.

PubMed

Shin, Hyun Tae; Kim, Jun Hwan; Shim, Joonho; Lee, Jong Hee; Lee, Dong Youn; Lee, Joo Heung; Yang, Jun Mo

2015-06-01

Photodynamic therapy (PDT) with intense pulsed light (IPL) was proven effective for photorejuvenation. Recently, a new formulation of 0.5% 5-aminolevulinic acid (ALA) liposomal spray has been available. We designed a randomized split face study to evaluate usefulness and safety of IPL-PDT using a liposomal spray for periorbital wrinkles in Asians. Patients received three treatments every 3 weeks. The half of the face was treated with IPL-PDT and the other half with long pulsed Nd:YAG laser (LPNY). Skin fluorescence was measured using a spectrophotometer for the guidance of PDT treatment. Wrinkle score was marked by two-blinded independent dermatologists. One patient dropped out due to 3-d lasting erythema on PDT side. The difference of mean reduction in lower and lateral periorbital wrinkle score on PDT side between the first and the last visit was statistically significant (p = 0.008 and p = 0.001, respectively). Lateral periorbital wrinkles treated with PDT showed better results than LPNY-treated sides. Twenty-five percent of patients reported good to excellent outcomes. This study demonstrated that PDT with a liposomal spray provided modest wrinkle reduction without serious adverse effect and it might be a promising treatment modality for wrinkle treatment in Asians.

Topical hexylaminolevulinate and aminolevulinic acid photodynamic therapy: complete arteriole vasoconstriction occurs frequently and depends on protoporphyrin IX concentration in vessel wall.

PubMed

Middelburg, T A; de Bruijn, H S; Tettero, L; van der Ploeg van den Heuvel, A; Neumann, H A M; de Haas, E R M; Robinson, D J

2013-09-05

Vascular responses to photodynamic therapy (PDT) may influence the availability of oxygen during PDT and the extent of tumor destruction after PDT. However, for topical PDT vascular effects are largely unknown. Arteriole and venule diameters were measured before and after hexylaminolevulinate (HAL) and aminolevulinic acid (ALA) PDT and related to the protoporphyrin IX (PpIX) concentration in the vessel wall. A mouse skin fold chamber model and an intravital confocal microscope allowed direct imaging of the subcutaneous vessels underlying the treated area. In both HAL and ALA groups over 60% of arterioles constricted completely, while venules generally did not respond, except for two larger veins that constricted partially. Arteriole vasoconstriction strongly correlated with PpIX fluorescence intensity in the arteriole wall. Total PpIX fluorescence intensity was significantly higher for HAL than ALA for the whole area that was imaged but not for the arteriole walls. In conclusion, complete arteriole vasoconstriction occurs frequently in both HAL and ALA based topical PDT, especially when relatively high PpIX concentrations in arteriole walls are reached. Vasoconstriction will likely influence PDT effect and should be considered in studies on topical HAL and ALA-PDT. Also, our results may redefine the vasculature as a potential secondary target for topical PDT. Copyright © 2013 Elsevier B.V. All rights reserved.

Inhibition of erythrocytes δ-aminolevulinic acid dehydratase (ALAD) activity in fish from waters affected by lead smelters

USGS Publications Warehouse

Schmitt, Christopher J.; Caldwell, Colleen A.; Olsen, Bill; Serdar, Dave; Coffey, Mike

2002-01-01

We assessed the effects on fish of lead (Pb) released to streamsby smelters located in Trail, BC (Canada), E. Helena, MT, Herculaneum, MO, and Glover, MO. Fish were collected by electrofishing from sites located downstream of smelters and from reference sites. Blood from each fish was analyzed for δ-aminolevulinic acid dehydratase (ALAD) activity and hemoglobin (Hb), and samples of blood, liver, or carcass were analyzed for Pb, zinc (Zn), or both. Fish collected downstreamof all four smelters sites had elevated Pb concentrations, decreased ALAD activity, or both relative to their respectivereference sites. At E. Helena, fish from the downstream site also had lower Hb concentrations than fish from upstream. Differences among taxa were also apparent. Consistent with previous studies, ALAD activity in catostomids (Pisces: Catostomidae-northern hog sucker,Hypentelium nigricans;river carpsucker, Carpiodes carpio; largescale sucker, Catostomus macrocheilus; and mountain sucker, C. platyrhynchus) seemed more sensitive to Pb-induced ALADinhibition than the salmonids (Pisces: Salmonidae-rainbow trout,Oncorhynchus mykiss; brook trout,Salvelinus fontinalis) or common carp (Cyprinus carpio). Some of these differences may have resulted from differential accumulation of Zn, which was not measured at all sites. We detected noALAD activity in channel catfish (Ictaluruspunctatus) from either site on the Mississippi River at Herculaneum, MO. Our findings confirmed that Pb is releasedto aquatic ecosystems by smelters and accumulated by fish, andwe documented potentially adverse effects of Pb in fish. We recommend that Zn be measured along with Pb when ALAD activityis used as a biomarker and the collection of at least 10 fish ofa species at each site to facilitate statistical analysis.

Combining 5-Aminolevulinic Acid Fluorescence and Intraoperative Magnetic Resonance Imaging in Glioblastoma Surgery: A Histology-Based Evaluation.

PubMed

Hauser, Sonja B; Kockro, Ralf A; Actor, Bertrand; Sarnthein, Johannes; Bernays, René-Ludwig

2016-04-01

Glioblastoma resection guided by 5-aminolevulinic acid (5-ALA) fluorescence and intraoperative magnetic resonance imaging (iMRI) may improve surgical results and prolong survival. To evaluate 5-ALA fluorescence combined with subsequent low-field iMRI for resection control in glioblastoma surgery. Fourteen patients with suspected glioblastoma suitable for complete resection of contrast-enhancing portions were enrolled. The surgery was carried out using 5-ALA-induced fluorescence and frameless navigation. Areas suspicious for tumor underwent biopsy. After complete resection of fluorescent tissue, low-field iMRI was performed. Areas suspicious for tumor remnant underwent biopsy under navigation guidance and were resected. The histological analysis was blinded. In 13 of 14 cases, the diagnosis was glioblastoma multiforme. One lymphoma and 1 case without fluorescence were excluded. In 11 of 12 operations, residual contrast enhancement on iMRI was found after complete resection of 5-ALA fluorescent tissue. In 1 case, the iMRI enhancement was in an eloquent area and did not undergo a biopsy. The 28 biopsies of areas suspicious for tumor on iMRI in the remaining 10 cases showed tumor in 39.3%, infiltration zone in 25%, reactive central nervous system tissue in 32.1%, and normal brain in 3.6%. Ninety-three fluorescent and 24 non-fluorescent tissue samples collected before iMRI contained tumor in 95.7% and 87.5%, respectively. 5-ALA fluorescence-guided resection may leave some glioblastoma tissue undetected. MRI might detect areas suspicious for tumor even after complete resection of all fluorescent tissue; however, due to the limited accuracy of iMRI in predicting tumor remnant (64.3%), resection of this tissue has to be considered with caution in eloquent regions.

Low-dose topical 5-aminolevulinic acid photodynamic therapy in the treatment of different severity of acne vulgaris.

PubMed

Ma, Li; Xiang, Lei-Hong; Yu, Bo; Yin, Rui; Chen, Lei; Wu, Yan; Tan, Zhi-Jian; Liu, Yong-Bin; Tian, Hong-Qing; Li, Hui-Zhong; Lin, Tong; Wang, Xiu-Li; Li, Yuan-Hong; Wang, Wei-Zheng; Yang, Hui-Lan; Lai, Wei

2013-12-01

To investigate the efficacy and safety of low-concentration 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of different severity of acne vulgaris and optimize the treatment regimen. A self-controlled multicenter clinical trial was carried out in 15 centers throughout China. A total of 397 acne patients of grade II-IV received 3- or 4-session PDT treatment. 5% ALA gel was applied topically to acne lesions for 1h incubation. The lesions were irradiated by a LED light of 633 nm at dose levels of 96-120 J/cm(2). Clinical assessment was conducted before and after every treatment up to 8 weeks. The effective rate overall and of grade II, III and IV are 82.1%, 71.6%, 79.6% and 88.2%, respectively. The effective rate rises significantly proportionally to the severity of acne (P<0.01). No significant differences are found in the efficacy between patients received 3-session and 4-session PDT treatments (P>0.05). The count of inflammatory and non-inflammatory acne lesions gradually decrease after each treatment (P<0.01) and during the 8-week follow up (P<0.01 or P<0.05). Maximum efficacy is obtained at 8 weeks after the treatment completion. A low-dose topical ALA-PDT regimen using 5% ALA, 1h incubation and red light source of 3 treatment sessions is suggested as optimal scheme for the treatment of different severity of acne vulgaris in Chinese patients. Superior efficacy is found in severe cystic acne of grade IV with mild side effects. Copyright © 2013 Elsevier B.V. All rights reserved.

Fluorescence-guided surgery with 5-aminolevulinic acid for resection of brain tumors in children--a technical report.

PubMed

Beez, Thomas; Sarikaya-Seiwert, Sevgi; Steiger, Hans-Jakob; Hänggi, Daniel

2014-03-01

5-aminolevulinic acid (5-ALA) can be used as an adjunct for the surgery of adult malignant glioma and improves the rate of gross total resection and patient survival. So far, only three casuistic reports of fluorescence-guided surgery used in children have been published. We report our pilot series of 16 pediatric brain tumors treated with 5-ALA. Sixteen patients (mean age 9 years, range 1-16 years) received a standardized 5-ALA dose according to the published protocol after informed parental consent. The fluorescence status (positive versus negative) in correlation with histology as well as blood samples and adverse clinical symptoms were recorded. Histology revealed pilocytic astrocytoma (n = 7), classical medulloblastoma (n = 4), anaplastic astrocytoma (n = 1), glioblastoma (n = 3) and anaplastic ependymoma (n = 1). Positive fluorescence was observed in cases of anaplastic astrocytoma, glioblastoma, and medulloblastoma, respectively. Significant increases were registered for alanine aminotransferase (14.92 ± 1.106 U/l vs. 37.70 ± 3.795 U/l, P = 0.0020) and gamma glutamyl transpeptidase (12.69 ± 1.638 U/l vs. 39.29 ± 6.342 U/l, P = 0.0156), correlated with young age. No further adverse reactions were evident. Positive fluorescence was observed in two high-grade gliomas and one medulloblastoma after oral administration of 5-ALA. Thus, 5-ALA appears capable of inducing fluorescence in pediatric high-grade tumors. Adverse reactions observed in children were similar to those reported for adults, although very young children might be at increased risk. Further studies are required to elucidate pharmacokinetic and pharmacodynamic properties of 5-ALA in children and to assess its prognostic role in the resection of pediatric brain tumors.

The influence of photodynamic therapy (PDT) with δ-aminolevulinic acid (ALA) on J-774A.1 macrophage cell line

NASA Astrophysics Data System (ADS)

Kawczyk-Krupka, Aleksandra; Czuba, Zenon; Ledwon, Aleksandra; Latos, Wojciech; Sliszka, Ewelina; Mianowska, Marta; Krol, Wojciech; Sieron, Aleksander

2008-02-01

Introduction. The whole mechanism of the cellular level of tumor destruction by photodynamic therapy (PDT) is still unknown. Despite necrotic and apoptotic ways of cell death, there is a variety of events leading to and magnifying the inactivation of tumor cells. Material and methods. J-774A.1 were incubated with δ-aminolevulinic acid (ALA) at different concentrations (125, 250, 500, 1000 μM) and then irradiated with VIS (400 - 750 nm) at the dose of 5,10 and 30 J/cm2 delivered from the incoherent light source. The effects of the application of ALA-PDT were evaluated on the basis of cell viability, nitric oxide (NO), tumor necrosis factor α- (TNF-α) and interleukin-1β (IL-1β) produced by the J-774A.1 cells. Results. The cell viability (assessed using MTT test) was comparable with control group at 5,10 and 30 J/cm2. At these doses of energy using different concentrations of ALA we have observed that at the higher energy doses, the greater increase of TNF-α release, lowering of the level of IL-1β production and decrease of NO release were observed. There was also observed the dependence of the secretional activity of the cells on the ALA concentrations. Conclusion. The cell viability and production of cytokines depended on ALA concentrations and energy doses of the light. The higher some cytokines' release after PDT could be an additional factor for the complete eradication of tumor.

In vitro bactericidal activity of 465-470 nm blue light phototherapy and aminolevulinic acid on Staphylococcus pseudintermedius.

PubMed

Bae, Seulgi; Oh, Taeho

2018-05-30

Staphylococcus pseudintermedius is the principal pathogen causing bacterial skin infections in dogs. Photodynamic therapy (PDT) involving the combination of light and a topical photosensitizer is used to treat human skin infections. Although the antimicrobial effects of PDT have been demonstrated using in vivo and in vitro studies in humans, its effects on dogs and their pathogens are unclear. The aim of this study was to demonstrate the in vitro efficacy of PDT over a 465-470 nm spectrum to kill S. pseudintermedius using δ-aminolevulinic acid (ALA) as the photosensitizer. Six S. pseudintermedius isolates from canine skin were exposed to blue light-emitting diodes (LEDs) at 465-470 nm, with or without ALA. The light doses were 18.4, 36.8 and 55.2 J/cm 2 . The number of colony-forming units and optical densities of broth cultures were measured and then compared with Dunnett's test. Bacterial viability was monitored using fluorescence microscopy and the fluorescence intensity values were compared with a paired Student's t-test. Blue light inhibited the growth of S. pseudintermedius; the effect significantly increased with the addition of ALA as a photosensitizer and with increasing light doses. Live/dead staining confirmed that PDT reduced bacterial viability and exerted an antibacterial effect. Blue light has a strong antibacterial effect on S. pseudintermedius in a light dose-dependent manner. ALA alone did not exhibit bactericidal action, but its combination with blue light increased the effect of PDT compared to blue light alone. © 2018 ESVD and ACVD.

Wavelength-dependent in-vitro and in-vivo photodynamic effects after sensitization with 5-aminolevulinic acid induced protoporphyrin IX

NASA Astrophysics Data System (ADS)

Szeimies, Rolf-Markus; Abels, Christoph; Fritsch, Clemens; Steinbach, Pia; Baeumler, Wolfgang; Messmann, Helmut; Goetz, Alwin E.; Goerz, Guenter; Landthaler, Michael

1996-01-01

Photodynamic therapy (PDT) with topically applied 5-aminolevulinic acid (ALA) is of growing interest, in particular in dermatology. Due to the fact that PDT with intravenously administered Photofrin is the only clinically approved sensitizer so far and is performed at a wavelength of 630 nm, this wavelength is also used in most experimental and clinical trials with ALA. In this study influence of irradiation with coherent light from a tunable dye laser at different wavelengths ranging from 625 to 649 nm was investigated. In in vitro experiments HaCaT immortalized human keratinocytes were sensitized with 30 (mu) g/ml ALA for 24 hrs. By determination of cell viability with the MTT test, best cell-killing effects were observed following irradiation at 635 nm. In an in vivo setting using an amelanotic melanoma (A-Mel-3) grown subcutaneously in Syrian Golden hamsters, these results were confirmed: tumor growth determined by measuring tumor volume increase after 28 days was less pronounced in animals treated with 100 mg/kg ALA i.v. and irradiated 2.5 hrs. later at 635 nm, as compared to animals receiving an equal dose and irradiated at 630 nm. This observation in vitro is probably due to large amounts of photosensitizing protoporphyrin IX (PP) localized in cell membranes which is visualized by confocal laser scanning microscopy (CLSM) and determined by HPLC analysis. These results suggest that in ALA-PDT when a coherent light source is used probably better results are achieved irradiating at 635 nm.

Is topical delta-aminolevulinic acid adequate for photodynamic therapy in Barrett's esophagus? A pilot study.

PubMed

Ortner, M -A; Zumbusch, K; Liebetruth, J; Ebert, B; Fleige, B; Dietel, M; Lochs, H

2002-08-01

The methods of endoscopic ablation of metaplastic and dysplastic areas in Barrett's esophagus so far described, are not satisfactory with respect to efficacy and safety. Therefore we investigated whether photodynamic therapy (PDT) with topical delta-aminolevulinic acid (delta-ALA) leads to ablation of specialized columnar epithelium and eradication of low-grade dysplasia while not producing phototoxicity and systemic side effects. 14 patients with histologically proven Barrett's esophagus, seven of whom had evidence of low-grade dysplasia, underwent endoscopic treatment with topical delta-ALA. Photoactivation (wavelength, 632 nm) was performed at 1.5 - 2 hours after drug administration using an argon dye laser. Patients received omeprazole 80 mg daily for 2 months; thereafter; maintenance therapy depended on reflux symptoms. Patients were endoscopically re-evaluated after 7 days, and subsequently at 3, 6, 12 and up to 48 months (mean follow up 33 months). Re-treatment with high-dose topical delta-ALA was offered to the 11 patients with remaining metaplasia and was carried out in five of them. Low-grade dysplasia was eradicated in all patients. One patient with no dysplasia before PDT developed a high-grade dysplasia after PDT. Complete ablation of Barrett's metaplasia was observed in 21 % of the patients after the first treatment session and in 20 % after the second treatment session. The mean reduction in the length of Barrett's metaplasia was 1.54 +/- 1.29 cm after the first PDT session and 1.02 +/- 0.80 cm after the second PDT session. Post-endoscopic pain and photosensitivity reactions were less frequent with low-dose delta-ALA PDT than with high-dose PDT (pain 15 %, 100 %, respectively; P = 0.001 by Fisher's exact test; phototoxicity, 0 %, 50 %, respectively; P = 0.021 by Fisher's exact test). Low-dose topical administration of delta-ALA provides ablation of low-grade dysplasia in the range obtained with oral delta-ALA. In addition, it is safe and well

Feasibility of ion-pair/supercritical fluid extraction of an ionic compound--pseudoephedrine hydrochloride.

PubMed

Eckard, P R; Taylor, L T

1997-02-01

The supercritical fluid extraction (SFE) of an ionic compound, pseudoephedrine hydrochloride, from a spiked-sand surface was successfully demonstrated. The effect of carbon dioxide density (CO2), supercritical fluid composition (pure vs. methanol modified), and the addition of a commonly used reversed-phase liquid chromatographic ion-pairing reagent, 1-heptanesulfonic acid, sodium salt, on extraction efficiency was examined. The extraction recoveries of pseudoephedrine hydrochloride with the addition of the ion-pairing reagent from a spiked-sand surface were shown to be statistically greater than the extraction recoveries without the ion-pairing reagent with both pure and methanol-modified carbon dioxide.

21 CFR 522.536 - Detomidine hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Detomidine hydrochloride injection. 522.536... § 522.536 Detomidine hydrochloride injection. (a) Specification. Each milliliter of sterile aqueous solution contains 10 milligrams of detomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of...

Randomized, Controlled Trial of Fractional Carbon Dioxide Laser Resurfacing Followed by Ultrashort Incubation Aminolevulinic Acid Blue Light Photodynamic Therapy for Actinic Keratosis.

PubMed

Alexiades, Macrene

2017-08-01

Aminolevulinic acid (ALA) photodynamic therapy (PDT) is an established treatment option for actinic keratosis (AK), and recently fractional carbon dioxide (CO2) laser was shown to improve outcomes; but studies of short incubation photosensitizer are lacking. Assess the efficacy of short incubation ALA followed by blue light PDT with and without previous fractional CO2 treatment for the treatment of AK. Randomized, paired split-design, controlled trial of fractional CO2 followed by ultrashort 15-minute versus 30-minute incubation ALA and blue light PDT for the treatment of AK on the face. The complete clearance rates (CRs) at 8 weeks after ALA PDT with and without FxCO2 at 30- and 15-minute ALA incubation times were 89.78% (+FxCO2) versus 71.20% CR (-FxCO2) at 30', and 86.38% (+FxCO2) versus 69.23% (-FxCO2) at 15' ALA incubation. All lesion improvements were statistically significant. This randomized, comparative paired group controlled clinical study demonstrates that ultrashort 15- and 30-minute incubation ALA PDTs are of limited efficacy for the treatment of AK. Pretreatment with fractional ablative resurfacing yields statistically significant greater AK clearance with ALA-PDT at ultrashort ALA incubations followed by blue light.

Simultaneous HPLC analysis of pseudophedrine hydrochloride, codeine phosphate, and triprolidine hydrochloride in liquid dosage forms.

PubMed

Manassra, Adnan; Khamis, Mustafa; El-Dakiky, Magdy; Abdel-Qader, Zuhair; Al-Rimawi, Fuad

2010-03-11

An HPLC method using UV detection is proposed for the simultaneous determination of pseudophedrine hydrochloride, codeine phosphate, and triprolidine hydrochloride in liquid formulation. C18 column (250mmx4.0mm) is used as the stationary phase with a mixture of methanol:acetate buffer:acetonitrile (85:5:10, v/v) as the mobile phase. The factors affecting column separation of the analytes were studied. The calibration graphs exhibited a linear concentration range of 0.06-1.0mg/ml for pseudophedrine hydrochloride, 0.02-1.0mg/ml for codeine phosphate, and 0.0025-1.0mg/ml for triprolidine hydrochloride for a sample size of 5microl with correlation coefficients of better than 0.999 for all active ingredients studied. The results demonstrate that this method is reliable, reproducible and suitable for routine use with analysis time of less than 4min. Copyright 2009 Elsevier B.V. All rights reserved.

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5875 Thiamine hydrochloride. (a) Product. Thiamine hydrochloride. (b) Conditions of use...

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5875 Thiamine hydrochloride. (a) Product. Thiamine hydrochloride. (b) Conditions of use...

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5875 Thiamine hydrochloride. (a) Product. Thiamine hydrochloride. (b) Conditions of use...

Effects of itopride hydrochloride and ranitidine in patients with functional dyspepsia: comparison between prokinetic and acid suppression therapies.

PubMed

Chiba, Toshimi; Tokunaga, Yumi; Ikeda, Keisei; Takagi, Ryo; Chishima, Raita; Terui, Torahiko; Kudara, Norihiko; Endo, Masaki; Inomata, Masaaki; Orii, Seishi; Suzuki, Kazuyuki

2007-09-01

The effect of itopride hydrochloride or ranitidine on the health-related quality of life (HRQoL) of functional dyspepsia is not well known. Our aim was to assess the HRQoL before and after administration of itopride hydrochloride or ranitidine in patients with functional dyspepsia. A total of 18 functional dyspepsia patients (12 women, 6 men; mean age 52.5 y.o.) were enrolled. We determined the HRQoL using two different inquiry systems: the 36 item short form of the Medical Outcome Study Questionnaire (SF-36) and the Gastrointestinal Symptom Rating Scale (GSRS). The HRQoL was determined before administration of drug, and two, four, and eight weeks after administration of drug. After administration of itopride hydrochloride, the SF-36 mental health scale and GSRS indigestion syndrome score and constipation syndrome score were significantly improved compared to before administration (p < 0.05). After the administration of ranitidine, the GSRS reflux syndrome score was significantly improved compared to before administration (p < 0.05). Itopride hydrochloride would be useful for the treatment of dysmotility-type functional dyspepsia, whereas ranitidine would be beneficial for ulcer-type functional dyspepsia.

Dual-labeling with 5-aminolevulinic acid and fluorescein for fluorescence-guided resection of high-grade gliomas: technical note.

PubMed

Suero Molina, Eric; Wölfer, Johannes; Ewelt, Christian; Ehrhardt, André; Brokinkel, Benjamin; Stummer, Walter

2018-02-01

OBJECTIVE Fluorescence guidance with 5-aminolevulinic acid (5-ALA) helps improve resections of malignant gliomas. However, one limitation is the low intensity of blue light for background illumination. Fluorescein has recently been reintroduced into neurosurgery, and novel microscope systems are available for visualizing this fluorochrome, which highlights all perfused tissues but has limited selectivity for tumor detection. Here, the authors investigate a combination of both fluorochromes: 5-ALA for distinguishing tumor and fluorescein for providing tissue fluorescence of adjacent brain tissue. METHODS The authors evaluated 6 patients who harbored cerebral lesions suggestive of high-grade glioma. Patients received 5-ALA (20 mg/kg) orally 4 hours before induction of anesthesia. Low-dose fluorescein (3 mg/kg intravenous) was injected immediately after anesthesia induction. Pentero microscopes (equipped either with Yellow 560 or Blue 400 filters) were used to visualize fluorescence. To simultaneously visualize both fluorochromes, the Yellow 560 module was combined with external blue light illumination (D-light C System). RESULTS Fluorescein-induced fluorescence created a useful background for protoporphyrin IX (PPIX) fluorescence, which appeared orange to red, surrounded by greenly fluorescent normal brain and edematous tissue. Green brain-tissue fluorescence was helpful in augmenting background. Levels of blue illumination that were too strong obscured PPIX fluorescence. Unspecific extravasation of fluorescein was noted at resection margins, which did not interfere with PPIX fluorescence detection. CONCLUSIONS Dual labeling with both PPIX and fluorescein fluorescence is feasible and gives superior background information during fluorescence-guided resections. The authors believe that this technique carries potential as a next step in fluorescence-guided resections if it is completely integrated into the surgical microscope.

Spectrophotometric determination of meclizine hydrochloride and pyridoxine hydrochloride in laboratory prepared mixtures and in their pharmaceutical preparation

NASA Astrophysics Data System (ADS)

Ibrahim, Maha M.; Elzanfaly, Eman S.; El-Zeiny, Mohamed B.; Ramadan, Nesreen K.; Kelani, Khadiga M.

2017-05-01

In this paper, three rapid, simple, accurate and precise spectrophotometric methods were developed for the determination of meclizine hydrochloride in the presence of pyridoxine hydrochloride without previous separation. The methods under study are dual wavelength (DWL), ratio difference (RD) and continuous wavelet transform (CWT). On the other hand, pyridoxine hydrochloride (PYH) was determined directly at 291 nm. The methods obey Beer's law in the range of (5-50 μg/mL) for both compounds. All the methods were validated according to the ICH guidelines where the accuracy was found to be 98.29, 99.59, 100.42 and 100.62% for DWL, RD, CWT and PYH; respectively. Moreover the precision of the methods were calculated in terms of %RSD and it was found to be 0.545, 0.372, 1.287 and 0.759 for DWL, RD,CWT and PYH; respectively. The selectivity of the proposed methods was tested using laboratory prepared mixtures and assessed by applying the standard addition technique. So, they can be used for the routine analysis of pyridoxine hydrochloride and meclizine hydrochloride in quality-control laboratories.

Differential antioxidant defense and detoxification mechanisms in photodynamically stressed rice plants treated with the deregulators of porphyrin biosynthesis, 5-aminolevulinic acid and oxyfluorfen.

PubMed

Phung, Thu-Ha; Jung, Sunyo

2015-04-03

This study focuses on differential molecular mechanisms of antioxidant and detoxification systems in rice plants under two different types of photodynamic stress imposed by porphyrin deregulators, 5-aminolevulinic acid (ALA) and oxyfluorfen (OF). The ALA-treated plants with white necrosis exhibited a greater decrease in photochemical quantum efficiency, Fv/Fm, as well as a greater increase in activity of superoxide dismutase, compared to the OF-treated plants. By contrast, the brown necrosis in OF-treated plants resulted in not only more widely dispersed H2O2 production and greater increases in H2O2-decomposing enzymes, catalase and peroxidase, but also lower ascorbate redox state. In addition, ALA- and OF-treated plants markedly up-regulated transcript levels of genes involved in detoxification processes including transport and movement, cellular homeostasis, and xenobiotic conjugation, with prominent up-regulation of serine/threonine kinase and chaperone only in ALA-treated plants. Our results demonstrate that different photodynamic stress imposed by ALA and OF developed differential actions of antioxidant enzymes and detoxification. Particularly, detoxification system may play potential roles in plant protection against photodynamic stress imposed by porphyrin deregulators, thereby contributing to alleviation of photodynamic damage. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of hot hydroxylamine hydrochloride and oxalic acid leaching of stream sediment and coated rock samples as anomaly enhancement techniques

USGS Publications Warehouse

Filipek, L.H.; Chao, T.T.; Theobald, P.K.

1982-01-01

A hot hydroxylamine hydrochloride (H-Hxl) extraction in 25% acetic acid is compared with the commonly used oxalic acid extraction as a method of anomaly enhancement for Cu and Zn in samples from two very different metal deposits and climatic environments. Results obtained on minus-80-mesh stream sediments from an area near the Magruder massive sulfide deposit in Lincoln County, Georgia, where the climate is humid subtropical, indicate that H-Hxl enhances the anomaly for Cu by a factor of 2 and for Zn by a factor of 1.5, compared to the oxalic method. Analyses of Fe oxide-coated rock samples from outcrops overlying the North Silver Bell porphyry copper deposit near Tucson, Arizona, where the climate is semi-arid to arid, indicate that both techniques effectively outline the zones of hydrothermal alteration. The H-Hxl extraction can also perform well in high-carbonate or high-clay environments, where other workers have suggested that oxalic acid is not very effective. Therefore, the H-Hxl method is recommended for general exploration use. ?? 1982.

21 CFR 520.1660b - Oxytetracycline hydrochloride capsules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride capsules. 520.1660b... Oxytetracycline hydrochloride capsules. (a) Specifications. The drug is in capsule form with each capsule containing 125 or 250 milligrams of oxytetracycline hydrochloride. Oxytetracycline is the antibiotic...

Stability of pilocarpine hydrochloride and pilocarpine nitrate ophthalmic solutions submitted by U.S. hospitals.

PubMed

Kreienbaum, M A; Page, D P

1986-01-01

The stability of pilocarpine hydrochloride and pilocarpine nitrate ophthalmic solutions stored in hospital pharmacies across the United States was studied. Through a voluntary drug stability program, FDA selected 252 samples (representing 11 manufacturers) from pharmacies representing an adequate cross section of the country. The samples were analyzed for strength, identification, pH, and isopilocarpine and pilocarpic acid impurities. All samples of pilocarpine nitrate met USP requirements. Eight samples of pilocarpine hydrochloride had tablets that exceeded the USP upper limit for strength. All of these samples were in 1- and 2-mL bottles. The amount of isopilocarpine found ranged from 1 to 6.4%, and the amount of pilocarpic acid from 1.5 to 10.1%. Although pilocarpine salts in ophthalmic solution decompose into isopilocarpine and pilocarpic acid under various conditions of storage, an amount of pilocarpine is maintained that is within the compendial limits. However, there is a problem of evaporation from some of the 1- and 2-mL containers in which this product is supplied.

Formulation and characterization of poly(ethylene glycol)-based, 5-aminolevulinic acid-loaded solid-dosage forms intended for photodynamic and photodiagnostic methodologies in the colorectal region.

PubMed

McCarron, Paul A; Andrews, Gavin P; Morrow, Desmond I J; Woolfson, A David; Donnelly, Ryan F

2007-01-01

Aminolevulinic acid-loaded, poly(ethylene glycol) disks prepared using three molecular weights (1000, 6000, and 10,000) were shown to be of potential for rectal administration as part of photodynamic and photodiagnostic colorectal procedures. The disk-shaped delivery system was mechanically robust, as judged by friability measurements. Calorimetric analysis confirmed that low concentrations of ALA (1% w/w) were dispersed completely throughout the PEG matrix, but higher concentrations (5% w/w and 10% w/w) formed crystalline suspensions. The molecular weight of the PEG determined the melting temperature, with PEG 1000 being suitable for melting around body temperature. The drug release kinetics were shown to be a function of both molecular weight and drug loading. Although the higher molecular weight PEG disks were resistant to surface erosion arising from an aqueous receptor phase, this effect was counterbalanced by more rapid and complete release when the ALA loading was increased. The lowest loading used (1% w/w) produced incomplete release, often not exceeding 30% of the total amount of drug. Results suggest that this simple formulation containing ALA can be administered directly to the colorectal area and is a feasible alternative to peroral dosing of ALA.

Immobilisation of impala (Aepyceros melampus) with a ketamine hydrochloride/medetomidine hydrochloride combination, and reversal with atipamezole hydrochloride.

PubMed

Bush, M; Raath, J P; Phillips, L G; Lance, W

2004-03-01

A combination of medetomidine hydrochloride (medetomidine) and ketamine hydrochloride (ketamine) was evaluated in 16 boma-confined and 19 free-ranging impalas (Aepyceros melampus) to develop a non-opiate immobilisation protocol. In free-ranging impala a dose of 220 +/- 34 microg/kg medetomidine and 4.4 +/- 0.7 mg/kg ketamine combined with 7500 IU of hyaluronidase induced recumbency within 4.5 +/- 1.5 min, with good muscle relaxation, a stable heart rate and blood pH. PaCO2 was maintained within acceptable ranges. The animals were hypoxic with reduced oxygen saturation and low PaO2 in the presence of an elevated respiration rate, therefore methods for respiratory support are indicated. The depth of sedation was adequate for minor manipulations but additional anaesthesia is indicated for painful manipulations. Immobilisation was reversed by 467 +/- 108 microg/kg atipamezole hydrochloride (atipamezole) intramuscularly, but re-sedation was observed several hours later, possibly due to a low atipamezole:medetomidine ratio of 2:1. Therefore, this immobilisation and reversal protocol would subject impalas to possible predation or conspecific aggression following reversal if they were released into the wild. If the protocol is used on free-ranging impala, an atipamezole:medetomidine ratio of 5:1 should probably be used to prevent re-sedation.

Potential efficacy of a delta 5-aminolevulinic acid thermosetting gel formulation for use in photodynamic therapy of lesions of the gastrointestinal tract.

PubMed

Bourre, Ludovic; Thibaut, Sonia; Briffaud, Amelie; Lajat, Youenn; Patrice, Thierry

2002-02-01

Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX may play a role in the treatment of dysplastic Barrett's oesophagus. An ALA thermosetting gel Pluronic F-127) was developed and evaluated in an in vivo mouse model for potential use in PDT of Barrett's mucosa. In vitro studies of the influence of Pluronic F-127 percentage on thermosetting gel temperature, followed by the influence of ALA concentration on thermosetting temperature and ALA-gel stability as a function of time or temperature were studied. In vivo relationships between ALA doses and fluorescence were studied to determine the optimal concentration. Fluorescence measurement in vivo showed that ALA concentration and time had a nonlinear influence on protoporphyrin IX synthesis. For ALA-gel applications longer than 30 min a plateau fluorescence was reached, the maximum fluorescence being obtained after 4 h whatever the time of contact. The maximum intensity (2824 counts s(-1)) was found with 40 mg mL(-1) ALA-gel, and fluorescence intensities differed with time, reaching a maximum after 3-4 h. ALA-Pluronic F-127 is a suitable formulation for treatment of Barrett's oesophagus, allowing easy application in liquid form at 4 degrees C and good adhesion in the oesophagus in gel form, with efficient diffusion of ALA into treated mucosa. Copyright 2002 Elsevier Science Ltd.

21 CFR 522.883 - Etorphine hydrochloride injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... § 522.883 Etorphine hydrochloride injection. (a) Chemical name. 6,7,8,14 - tetrahydro - alpha - methyl - alpha - propyl - 6,14 - endo-ethenooripavine-alpha-methanol hydrochloride. (b) Specifications. Each...

21 CFR 522.883 - Etorphine hydrochloride injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... § 522.883 Etorphine hydrochloride injection. (a) Chemical name. 6,7,8,14 - tetrahydro - alpha - methyl - alpha - propyl - 6,14 - endo-ethenooripavine-alpha-methanol hydrochloride. (b) Specifications. Each...

[Inhibition rate of gamma-aminolevulinic acid dehydratase activity in erythrocytes as a reliable index for individual workers of low lead exposure].

PubMed

Hirano, H; Omichi, M; Ohishi, H; Ishikawa, K; Hirashima, N

1983-09-01

As the delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocytes is decreased by lead exposure, we considered that a net reduction of ALAD activity by lead in blood should be the difference between the activity fully activated with zinc (Zn2+) and dithiothreitol (DTT) and that without activation. The optimal condition of activation of ALAD was found by addition of 0.25 mM of Zn2+ and 10 mM of DTT in the reaction mixture. Judging from our previous results that the amount of inhibition of ALAD activity can be represented as the rate of inhibition and is closely correlated with the dose of lead administered to rabbits, the inhibition rate of ALAD activity and lead content in blood (Pb-B) of lead workers were measured. The scatter diagram obtained from the inhibition rate and lead content in blood has two groups being divided at 50 micrograms/ml of Pb-B. In one group less than 50 micrograms/100 ml of Pb-B, the inhibition rate has been closely related to Pb-B., the regression equation being Y = 1.82 X + 11.7, and the correlation coefficient + 0.926. In another group more than 50 micrograms/100 ml of Pb-B the inhibition rate remained constant at the 90% level. Measurement of the inhibition rate suggests to have practical validity for monitoring lead exposure in workers, and by means of a nomograph lead content in blood can be estimated from the inhibition rate.

Regulation of Cadmium-Induced Proteomic and Metabolic Changes by 5-Aminolevulinic Acid in Leaves of Brassica napus L.

PubMed Central

Ali, Basharat; Gill, Rafaqat A.; Yang, Su; Gill, Muhammad B.; Farooq, Muhammad A.; Liu, Dan; Daud, Muhammad K.; Ali, Shafaqat; Zhou, Weijun

2015-01-01

It is evident from previous reports that 5-aminolevulinic acid (ALA), like other known plant growth regulators, is effective in countering the injurious effects of heavy metal-stress in oilseed rape (Brassica napus L.). The present study was carried out to explore the capability of ALA to improve cadmium (Cd2+) tolerance in B. napus through physiological, molecular, and proteomic analytical approaches. Results showed that application of ALA helped the plants to adjust Cd2+-induced metabolic and photosynthetic fluorescence changes in the leaves of B. napus under Cd2+ stress. The data revealed that ALA treatment enhanced the gene expressions of antioxidant enzyme activities substantially and could increase the expression to a certain degree under Cd2+ stress conditions. In the present study, 34 protein spots were identified that differentially regulated due to Cd2+ and/or ALA treatments. Among them, 18 proteins were significantly regulated by ALA, including the proteins associated with stress related, carbohydrate metabolism, catalysis, dehydration of damaged protein, CO2 assimilation/photosynthesis and protein synthesis/regulation. From these 18 ALA-regulated proteins, 12 proteins were significantly down-regulated and 6 proteins were up-regulated. Interestingly, it was observed that ALA-induced the up-regulation of dihydrolipoyl dehydrogenase, light harvesting complex photo-system II subunit 6 and 30S ribosomal proteins in the presence of Cd2+ stress. In addition, it was also observed that ALA-induced the down-regulation in thioredoxin-like protein, 2, 3-bisphosphoglycerate, proteasome and thiamine thiazole synthase proteins under Cd2+ stress. Taken together, the present study sheds light on molecular mechanisms involved in ALA-induced Cd2+ tolerance in B. napus leaves and suggests a more active involvement of ALA in plant physiological processes than previously proposed. PMID:25909456

5-Aminolevulinic acid-based photochemical internalization of the immunotoxin MOC31-gelonin generates synergistic cytotoxic effects in vitro.

PubMed

Selbo, P K; Kaalhus, O; Sivam, G; Berg, K

2001-08-01

Photochemical internalization (PCI) is a novel method for the endosomal or lysosomal release of membrane-impermeable molecules into the cytosol of target cells. This novel technology is based on the photodynamically induced rupture of endocytic vesicles preloaded with molecules of therapeutic interest. PCI of the ribosome-inactivating plant toxin gelonin and the immunotoxin monoclonal antibody 31 (MOC31) gelonin has been performed previously by the use of the endocytic vesicle-localizing photosensitizers TPPS2a and AIPcS2a and light, demonstrating synergistic toxicity against the more than 20 different cell lines tested, most of them of neoplastic origin. In this study we demonstrate that 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) is also capable of inducing PCI of MOC31-gelonin in the human colon adenocarcinoma cell line WiDr. The cells were incubated with 1 mM 5-ALA for up to 8 h in serum-free medium and from 24 to 96 h in serum-containing medium. Fluorescence microscopical studies indicate a partial plasma membrane localization of PpIX when 5-ALA was applied under serum-free conditions. This plasma membrane localization was not seen when 5-ALA was given in the presence of serum. There was a granular component of the PpIX localization in addition to a diffuse cytoplasmic localization. The granular component resembled the localization of the fluorescent dye conjugate Alexa-gelonin and the lysosomal localizing dye acridine orange. Our present results provide evidence for an endocytic vesicle-associated fraction of PpIX after 5-ALA incubation of the WiDr cells. We demonstrate that PCI, by combining 5-ALA, MOC31-gelonin and light, induces a synergistic cytotoxic effect against the WiDr cells.

5-aminolevulinic acid-mediated photodynamic therapy and its strain-dependent combined effect with antibiotics on Staphylococcus aureus biofilm.

PubMed

Zhang, Qing-Zhao; Zhao, Ke-Qing; Wu, Yang; Li, Xian-Hui; Yang, Chen; Guo, Li-Min; Liu, Chun-Hong; Qu, Di; Zheng, Chun-Quan

2017-01-01

Staphylococcus aureus (S. aureus) is hard to be eradicated, not only due to the emergence of antibiotic resistant strains but also because of its ability to form biofilm. Antibiotics are the major approach to treating biofilm infections, but their effects are unsatisfactory. One of the potential alternative treatments for controlling biofilm infections is photodynamic therapy (PDT), which requires the administration of photosensitizer, followed by light activation. 5-aminolevulinic acid (ALA), a natural photosensitizer prodrug, presents favorable characteristics, such as easy penetration and rapid clearance. These advantages enable ALA-based PDT (ALA-PDT) to be well-tolerated by patients and it can be repeatedly applied without cumulative toxicity or serious side effects. ALA-PDT has been proven to be an effective treatment for multidrug resistant pathogens; however, the study of its effect on S. aureus biofilm is limited. Here, we established our PDT system based on the utilization of ALA and a light-emitting diode, and we tested the effect of ALA-PDT on S. aureus biofilm as well as the combined effect of ALA-PDT and antibiotics on S. aureus biofilm. Our results showed that ALA-PDT has a strong antibacterial effect on S. aureus biofilm, which was confirmed by the confocal laser scanning microscope. We also found that lethal photosensitization occurred predominantly in the upper layer of the biofilm, while the residual live bacteria were located in the lower layer of the biofilm. In addition, the improved bactericidal effect was observed in the combined treatment group but in a strain-dependent manner. Our results suggest that ALA-PDT is a potential alternative approach for future clinical use to treat S. aureus biofilm-associated infections, and some patients may benefit from the combined treatment of ALA-PDT and antibiotics, but drug sensitivity testing should be performed in advance.

Promotive role of 5-aminolevulinic acid on chromium-induced morphological, photosynthetic, and oxidative changes in cauliflower (Brassica oleracea botrytis L.).

PubMed

Ahmad, Rehan; Ali, Shafaqat; Hannan, Fakhir; Rizwan, Muhammad; Iqbal, Muhammad; Hassan, Zaidul; Akram, Nudrat Aisha; Maqbool, Saliha; Abbas, Farhat

2017-03-01

Chromium (Cr) is among the most toxic pollutants in the environment that adversely affect the living organisms and physiological processes in different plants. The present study investigated the effect of 15 mg L -1 of 5-aminolevulinic acid (ALA) on morpho-physiological attributes of cauliflower (Brassica oleracea botrytis L.) under different Cr concentrations (0, 10, 100, and 200 μM) in the growth medium. The results showed that Cr stress decreased the growth, biomass, photosynthetic, and gas exchange parameters. Chromium stress enhanced the activities of enzymatic antioxidants, catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) in response to oxidative stress caused by the elevated levels of malondialdehyde (MDA), hydrogen peroxide (H 2 O 2 ), and electrolyte leakage (EL) in both roots and leaves of cauliflower. Chromium concentrations and total Cr uptake were increased in leaves, stems, and roots with increasing Cr levels in the culture medium. Foliar application of ALA increased the plant growth parameters, biomass, gas exchange parameters, and photosynthetic pigments under Cr stress compared to the treatments without ALA. Foliar application ALA decreased the levels of MDA, EL, and H 2 O 2 while further improved the performance of antioxidant in both leaves and roots compared to only Cr-stressed plant. Chromium concentrations and total Cr uptake were decreased by the ALA application compared to treatments without ALA application. The results of the present study indicated that foliar application of ALA might be beneficial in minimizing Cr uptake and its toxic effects in cauliflower.

Fluorescence-guided resection with 5-aminolevulinic Acid of subependymomas of the fourth ventricle: report of 2 cases: technical case report.

PubMed

Bernal García, Luis Miguel; Cabezudo Artero, José Manuel; Marcelo Zamorano, María Bella; Gilete Tejero, Ignacio

2015-06-01

The usefulness of 5-aminolevulinic acid (5-ALA) for resection of malignant astrocytomas has been established in recent years. In addition to these tumors, it has been reported that 5-ALA fluorescence could be elicited in other tumors such as intracranial and spinal meningiomas or posterior fossa and spinal cord ependymomas, resulting in improved resections. Here, we present 2 cases of subependymomas of the fourth ventricle that showed intense fluorescence after 5-ALA administration. To the best of our knowledge, these are the first reported cases of subependymomas in this location in which 5-ALA elicited useful fluorescence. Case 1 was a 61-year-old woman with a history of headaches accompanied by vomiting in the last month. Magnetic resonance imaging (MRI) revealed a tumor occupying the fourth ventricle with slight irregular enhancement. She was operated on after administration of 5-ALA. The tumor emitted intense red fluorescence when illuminated with blue light. An MRI performed 48 hours after surgery confirmed complete resection of the tumor. The pathological diagnosis was subependymoma. Case 2 was a 35-year-old man with a history of several months of headaches and vomiting. An MRI revealed a tumor occupying the caudal part of the fourth ventricle with moderate and irregular enhancement. He was operated on after administration of 5-ALA. The tumor showed intense fluorescence. An MRI performed 48 hours after surgery confirmed a complete resection of the tumor. The pathological diagnosis was subependymoma. Fluorescence-guided resection with 5-ALA may be useful for resection of subependymomas of the fourth ventricle. However, further studies are needed.

Prognostic value of residual fluorescent tissue in glioblastoma patients after gross total resection in 5-aminolevulinic Acid-guided surgery.

PubMed

Aldave, Guillermo; Tejada, Sonia; Pay, Eva; Marigil, Miguel; Bejarano, Bartolomé; Idoate, Miguel A; Díez-Valle, Ricardo

2013-06-01

There is evidence in the literature supporting that fluorescent tissue signal in fluorescence-guided surgery extends farther than tissue highlighted in gadolinium in T1 sequence magnetic resonance imaging (MRI), which is the standard to quantify the extent of resection. To study whether the presence of residual fluorescent tissue after surgery carries a different prognosis for glioblastoma (GBM) cases with complete resection confirmed by MRI. A retrospective review in our center found 118 consecutive patients with high-grade gliomas operated on with the use of fluorescence-guided surgery with 5-aminolevulinic acid. Within that series, the 52 patients with newly diagnosed GBM and complete resection of enhancing tumor (CRET) in early MRI were selected for analysis. We studied the influence of residual fluorescence in the surgical field on overall survival and neurological complication rate. Multivariate analysis included potential relevant factors: age, Karnofsky Performance Scale, O-methylguanine methyltransferase methylation promoter status, tumor eloquent location, preoperative tumor volume, and adjuvant therapy. The median overall survival was 27.0 months (confidence interval = 22.4-31.6) in patients with nonresidual fluorescence (n = 25) and 17.5 months (confidence interval = 12.5-22.5) for the group with residual fluorescence (n = 27) (P = .015). The influence of residual fluorescence was maintained in the multivariate analysis with all covariables, hazard ratio = 2.5 (P = .041). The neurological complication rate was 18.5% in patients with nonresidual fluorescence and 8% for the group with residual fluorescence (P = .267). GBM patients with CRET in early MRI and no fluorescent residual tissue had longer overall survival than patients with CRET and residual fluorescent tissue.

Nitric Oxide Mediates 5-Aminolevulinic Acid-Induced Antioxidant Defense in Leaves of Elymus nutans Griseb. Exposed to Chilling Stress

PubMed Central

Fu, Juanjuan; Chu, Xitong; Sun, Yongfang; Miao, Yanjun; Xu, Yuefei; Hu, Tianming

2015-01-01

Nitric oxide (NO) and 5-aminolevulinic acid (ALA) are both extremely important signalling molecules employed by plants to control many aspects of physiology. In the present study, the role of NO in ALA-induced antioxidant defense in leaves of two sources of Elymus nutans Griseb. (Damxung, DX and Zhengdao, ZD) was investigated. Chilling stress enhanced electrolyte leakage, accumulation of malondialdehyde (MDA), hydrogen peroxide (H2O2) and superoxide radical in two E. nutans, which were substantially alleviated by exogenous ALA and NO application. Pretreatment with NO scavenger PTIO or NOS inhibitor L-NNA alone and in combination with ALA induced enhancements in electrolyte leakage and the accumulation of MDA, H2O2 and superoxide radical in leaves of DX and ZD exposed to chilling stress, indicating that the inhibition of NO biosynthesis reduced the chilling resistance of E. nutans and the ALA-enhanced chilling resistance. Further analyses showed that ALA and NO enhanced antioxidant defense and activated plasma membrane (PM) H+-ATPase and decreased the accumulation of ROS induced by chilling stress. A pronounced increase in nitric oxide synthase (NOS) activity and NO release by exogenous ALA treatment was found in chilling-resistant DX plants exposed to chilling stress, while only a little increase was observed in chilling-sensitive ZD. Furthermore, inhibition of NO accumulation by PTIO or L-NNA blocked the protective effect of exogenous ALA, while both exogenous NO treatment and inhibition of endogenous NO accumulation did not induce ALA production. These results suggested that NO might be a downstream signal mediating ALA-induced chilling resistance in E. nutans. PMID:26151364

Lead concentration in plasma as a biomarker of exposure and risk, and modification of toxicity by δ-aminolevulinic acid dehydratase gene polymorphism.

PubMed

Tian, Liting; Zheng, Guang; Sommar, Johan Nilsson; Liang, Yihuai; Lundh, Tomas; Broberg, Karin; Lei, Lijian; Guo, Weijun; Li, Yulan; Tan, Mingguang; Skerfving, Staffan; Jin, Taiyi; Bergdahl, Ingvar A

2013-08-14

Blood lead concentration (B-Pb), the main biomarker of lead exposure and risk, is curvi-linearily related to exposure. We assessed plasma lead (P-Pb) as a marker for both lead exposure and toxic effects. We examined claims that δ-aminolevulinic acid dehydratase genotype (ALAD) can modify lead toxicity. In 290 lead-exposed and 91 unexposed Chinese workers, we determined P-Pb, B-Pb, urinary lead (U-Pb), ALAD polymorphism (rs1800435, ALAD1/2; TaqMan assay), and also toxic effects on heme synthesis (blood zinc protoporphyrin and hemoglobin, urinary δ-aminolevulic acid), on the kidneys (urinary albumin, β2-microglobulin and N-acetyl-β-d-glucosaminidase) and on the peripheral nervous system (sensory and motor conduction velocities). In exposed workers, median P-Pb was 4.10 (range 0.35-27)μg/L, B-Pb 401 (110-950)μg/L, and U-Pb 188 (22-590)μg/g creatinine. P-Pb had a higher ratio between exposed and unexposed workers (median 39, range 18-110) than B-Pb (19, 15-36; p<0.001) and U-Pb (28, 15-36; p<0.001). All three biomarkers were associated with all toxic effects (P-Pb: rS=-0.10 to 0.79; B-Pb: rS=-0.08 to 0.75; all p<0.05). In the exposed workers, B-Pb and U-Pb were significantly higher (p=0.04) in ALAD2 carriers (7% in the exposed population) than in ALAD1 homozygotes. P-Pb values were similar; ALAD1 homozygotes suffered higher kidney toxicity at the same P-Pb. (i) P-Pb has advantages over B-Pb as a biomarker of high Pb exposure, but it was not significantly better as an index of risk of toxicity. (ii) The ALAD genotype modifies toxicokinetics and toxicodynamics. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Levulinic Acid Biorefineries: New Challenges for Efficient Utilization of Biomass.

PubMed

Pileidis, Filoklis D; Titirici, Maria-Magdalena

2016-03-21

Levulinic acid is a sustainable platform molecule that can be upgraded to valuable chemicals and fuel additives. This article focuses on the catalytic upgrading of levulinic acid into various chemicals such as levulinate esters, δ-aminolevulinic acid, succinic acid, diphenolic acid, γ-valerolactone, and γ-valerolactone derivatives such valeric esters, 5-nonanone, α-methylene-γ valerolactone, and other various molecular-weight alkanes (C9 and C18-C27 olefins). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simultaneous voltammetry detection of dopamine and uric acid in human serum and urine with a poly(procaterol hydrochloride) modified glassy carbon electrode.

PubMed

Kong, Dexian; Zhuang, Qizhao; Han, Yejian; Xu, Lanping; Wang, Zeming; Jiang, Lili; Su, Jinwei; Lu, Chun-Hua; Chi, Yuwu

2018-08-01

In the present study, procaterol hydrochloride (ProH) was successfully electropolymerized onto a glass carbon electrode (GCE) with simply cyclic voltammetry scans to construct a poly(procaterol hydrochloride) (p-ProH) membrane modified electrode. Compared with the bare GCE, much higher oxidation peak current responses and better peak potentials separation could be obtained for the simultaneous oxidation of dopamine (DA) and uric acid (UA), owning to the excellent electrocatalytic ability of the p-ProH membrane. And it's based on that a square wave voltammetry (SWV) method was developed to selective and simultaneous measurement of DA and UA. Under the optimum conditions, the linear dependence of oxidation peak current on analyte concentrations were found to be 1.0-100 μmol/L and 2-100 μmol/L, giving detection limits of 0.3 μmol/L and 0.5 μmol/L for DA and UA, separately. The as prepared modified electrode shows simplicity in construction with the merits of good reproducibility, high stability, passable selectivity and nice sensitivity. Finally, the proposed p-ProH membrane modified electrode was successfully devoted to the detection of DA and UA in biological fluids such as human serum and urine with acceptable results. Copyright © 2018 Elsevier B.V. All rights reserved.

In vitro and in vivo genotoxicity assessment of the dopamine receptor antagonist molindone hydrochloride.

PubMed

Krishna, Gopala; Gopalakrishnan, Gopa; Goel, Saryu

2016-05-01

Molindone hydrochloride is a dihydroindolone neuroleptic with dopamine D2 and D5 receptor antagonist activity. As an integral component of its preclinical safety evaluation, molindone hydrochloride was evaluated in a series of in vitro and in vivo genetic toxicology assays. In the bacterial reverse gene mutation assays employing four Salmonella tester strains (TA98, TA100, TA1535, and TA1537) and the E. coli tester strain WP2uvrA, molindone hydrochloride was negative in all strains, except TA100, in which it induced a positive response (up to 3-fold) in the presence of rat liver S9. With human S9, a small (2-fold), but nonreproducible, increase in revertants was observed in TA100 at the highest concentration of molindone tested (5,000 µg/plate). The mutagenicity was completely abrogated by the addition of glutathione and UDP-glucuronic acid to rat liver S9, suggesting detoxification of the mutagenic metabolite(s) by Phase II conjugation reactions, pathways commonly operational in humans. Molindone hydrochloride did not induce chromosomal aberrations in human lymphocyte cultures, did not elicit a positive response in a rat bone marrow micronucleus test for clastogencity/aneugenicity, and did not give a positive response in the rat liver comet assay for DNA damage. Collectively, the weight of evidence from these studies, combined with a large margin of safety and efficient detoxification through Phase II conjugation supports the interpretation that molindone hydrochloride does not pose a genotoxic risk to humans at the anticipated clinical dose levels. © 2016 Wiley Periodicals, Inc.

21 CFR 520.1660c - Oxytetracycline hydrochloride tablets/boluses.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride tablets/boluses. 520....1660c Oxytetracycline hydrochloride tablets/boluses. (a) Specifications. Each tablet or bolus contains 250, 500, or 1,000 milligrams of oxytetracycline hydrochloride. (b) Sponsors. For sponsors in § 510...

EPR study of gamma-irradiated N-methyl-L-alanine, DL-2-methyl glutamic acid hemihydrate and Di-leucine hydrochloride in solid state

NASA Astrophysics Data System (ADS)

Sütçü, Kerem; Osmanoğlu, Y. Emre

2017-12-01

In this study, it was aimed to investigate ɣ-irradiated powders of N-methyl-L-alanine (NMLA), DL-2-methyl glutamic acid hemihydrate (DL2MGAH), and Di-leucine hydrochloride (DLHCl) at room temperature by electron paramagnetic resonance spectroscopy. After the γ-irradiation the samples indicated the existence of the CH3ĊNHCH3COOH, HOOCCH3NH2CĊHCH2COOH·1/2H2O and (CH3)2ĊCH2CH NHCOOHCOCH (NH2HCl) CH2CH (CH3)2 radicals, respectively. The spectral parameters of the radicals were determined. The results were compared with the earlier studies and discussed accordingly.

The Safety and Tolerability of 5-Aminolevulinic Acid Phosphate with Sodium Ferrous Citrate in Patients with Type 2 Diabetes Mellitus in Bahrain

PubMed Central

Al-Saber, Feryal; Aldosari, Waleed; Alselaiti, Mariam; Khalfan, Hesham; Kaladari, Ahmed; Khan, Ghulam; Harb, George; Rehani, Riyadh; Kudo, Sizuka; Koda, Aya; Tanaka, Tohru

2016-01-01

Type 2 diabetes mellitus is prevalent especially in Gulf countries and poses serious long-term risks to patients. A multifaceted treatment approach can include nutritional supplements with antioxidant properties such as 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC). This prospective, randomized, single-blind, placebo-controlled, dose escalating pilot clinical trial assessed the safety of 5-ALA with SFC at doses up to 200 mg 5-ALA/229.42 mg SFC per day in patients living in Bahrain with type 2 diabetes mellitus that was uncontrolled despite the use of one or more antidiabetic drugs. Fifty-three patients (n = 53) from 3 sites at one center were enrolled by Dr. Feryal (Site #01), Dr. Hesham (Site #02), and Dr. Waleed (Site #03) (n = 35, 5-ALA-SFC; n = 18, placebo). There was no significant difference in incidence of adverse events reported, and the most frequent events reported were gastrointestinal in nature, consistent with the known safety profile of 5-ALA in patients with diabetes. No significant changes in laboratory values and no difference in hypoglycemia between patients receiving 5-ALA and placebo were noted. Overall, the current results support that use of 5-ALA-SFC up to 200 mg per day taken as 2 divided doses is safe in patients taking concomitant oral antidiabetic medications and may offer benefits in the diabetic population. This trial is registered with ClinicalTrials.gov NCT02481141. PMID:27738640

Structure-based analysis reveals hydration changes induced by arginine hydrochloride.

PubMed

Nakakido, Makoto; Tanaka, Yoshikazu; Mitsuhori, Mariko; Kudou, Motonori; Ejima, Daisuke; Arakawa, Tsutomu; Tsumoto, Kouhei

2008-10-01

Arginine hydrochloride has been used to suppress protein aggregation during refolding and in various other applications. We investigated the structure of hen egg-white lysozyme (HEL) and solvent molecules in arginine hydrochloride solution by X-ray crystallography. Neither the backbone nor side-chain structure of HEL was altered by the presence of arginine hydrochloride. In addition, no stably bound arginine molecules were observed. The number of hydration water molecules, however, changed with the arginine hydrochloride concentration. We suggest that arginine hydrochloride suppresses protein aggregation by altering the hydration structure and the transient binding of arginine molecules that could not be observed.

Extractive determination of ephedrine hydrochloride and bromhexine hydrochloride in pure solutions, pharmaceutical dosage form and urine samples

NASA Astrophysics Data System (ADS)

Abdel-Ghani, N. T.; Rizk, M. S.; Mostafa, M.

2013-07-01

Simple, rapid, sensitive, precise and accurate spectrophotometeric methods for the determination of ephedrine hydrochloride (E-HCl) and bromhexine hydrochloride (Br-HCl) in bulk samples, dosage form and in spiked urine samples were investigated. The methods are based on the formation of a yellow colored ion-associates due to the interaction between the examined drugs with picric acid (PA), chlorophyllin coppered trisodium salt (CLPH), alizarin red (AR) and ammonium reineckate (Rk) reagents. A buffer solution had been used and the extraction was carried out using organic solvent, the ion associates exhibit absorption maxima at 410, 410, 430 and 530 nm of (Br-HCl)with PA, CLPH, AR and Rk respectively; 410, 410, 435 and 530 of (E-HCl) with PA, CLPH, AR and Rk respectively. (E-HCl) and (Br-HCl) could be determined up to 13, 121, 120 and 160; 25, 200, 92 and 206 μg mL-1, using PA, CLPH, AR and Rk respectively. The optimum reaction conditions for quantitative analysis were investigated. In addition, the molar absorptivity, Sandell sensitivity were determined for the investigated drug. The correlation coefficient was ⩾0.995 (n = 6) with a relative standard deviation (RSD) ⩽1.15 for five selected concentrations of the reagents. Therefore the concentration of Br-HCl and E-HCl drugs in their pharmaceutical formulations and spiked urine samples had been determined successfully.

Protoporphyrin IX induced by 5-aminolevulinic acid in bladder cancer cells in voided urine can be extracorporeally quantified using a spectrophotometer.

PubMed

Nakai, Yasushi; Anai, Satoshi; Onishi, Sayuri; Masaomi, Kuwada; Tatsumi, Yoshihiro; Miyake, Makito; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

2015-06-01

We evaluated the feasibility of photodynamic diagnosis of bladder cancer by spectrophotometric analysis of voided urine samples after extracorporeal treatment with 5-aminolevulinic acid (ALA). Sixty-one patients with bladder cancer, confirmed histologically after the transurethral resection of a bladder tumor, were recruited as the bladder cancer group, and 50 outpatients without history of urothelial carcinoma or cancer-related findings were recruited as the control group. Half of the voided urine sample was incubated with ALA (ALA-treated sample), and the rest was incubated without treatment (ALA-untreated sample). For detecting cellular protoporphyrin IX levels, intensity of the samples at the excitation wavelength of 405 nm was measured using a spectrophotometer. The difference between the intensity of the ALA-treated and ALA-untreated samples at 635 nm was calculated. The differences in the bladder cancer group were significantly greater than those in the control group (p < 0.001). These differences were also significantly greater in patients with high-grade tumors than in those with low-grade tumors (p = 0.004), and also in patients with invasive bladder cancer than in those with noninvasive bladder cancer (p = 0.007). The area under the curve was 0.84. Sensitivity and specificity of the method were 82% and 80%, respectively. We demonstrated that protoporphyrin IX levels in urinary cells treated with ALA could be quantitatively detected by spectrophotometer in patients with bladder cancer. Therefore, this cancer detection system has a potential for clinical use. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of L-ornithine hydrochloride ingestion on intermittent maximal anaerobic cycle ergometer performance and fatigue recovery after exercise.

PubMed

Demura, Shinichi; Morishita, Koji; Yamada, Takayoshi; Yamaji, Shunsuke; Komatsu, Miho

2011-11-01

L-Ornithine plays an important role in ammonia metabolism via the urea cycle. This study aimed to examine the effect of L-ornithine hydrochloride ingestion on ammonia metabolism and performance after intermittent maximal anaerobic cycle ergometer exercise. Ten healthy young adults (age, 23.8 ± 3.9 year; height, 172.3 ± 5.5 cm; body mass, 67.7 ± 6.1 kg) with regular training experience ingested L-ornithine hydrochloride (0.1 g/kg, body mass) or placebo after 30 s of maximal cycling exercise. Five sets of the same maximal cycling exercise were conducted 60 min after ingestion, and maximal cycling exercise was conducted after a 15 min rest. The intensity of cycling exercise was based on each subject's body mass (0.74 N kg(-1)). Work volume (watt), peak rpm (rpm) before and after intermittent maximal ergometer exercise and the following serum parameters were measured before ingestion, immediately after exercise and 15 min after exercise: ornithine, ammonia, urea, lactic acid and glutamate. Peak rpm was significantly greater with L-ornithine hydrochloride ingestion than with placebo ingestion. Serum ornithine level was significantly greater with L-ornithine hydrochloride ingestion than with placebo ingestion immediately and 15 min after intermittent maximal cycle ergometer exercise. In conclusion, although maximal anaerobic performance may be improved by L-ornithine hydrochloride ingestion before intermittent maximal anaerobic cycle ergometer exercise, the above may not depend on increase of ammonia metabolism with L-ornithine hydrochloride.

Two-Step Irradiance Treatment Can Achieve Excellent Pain Control During Red Light 5-Aminolevulinic Acid Photodynamic Therapy for Actinic Keratoses.

PubMed

Paragh, Gyorgy; Zeitouni, Nathalie C

2018-03-01

To evaluate the ability of two-step irradiance to maintain pain control during red light 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) for actinic keratoses (AK) and assess factors influencing pain. PDT provides excellent clinical and cosmetic results in the treatment AK and early basal cell carcinomas (BCC). Widespread use of PDT is limited, in part, by pain. A two-step irradiance method for PDT has previously been shown to significantly reduce PDT-associated pain during the treatment of BCC, but the ability of this method to limit pain during the treatment of AKs has not been reported. We performed a retrospective chart review to assess the level of pain during AK treatment by red light PDT (n = 99). Natural density filter was used to reduce the irradiance of the light source and initially 10 J/cm 2 dose was delivered at 35 mW/cm 2 and then, 65 J/cm 2 dose was delivered at 70 mW/cm 2 . Pain level was measured using a 10-point visual analog scale at three points during the procedure. Pain was low to moderate in most patients (mean ± standard error of the mean pain score: 2.35 ± 0.19). Higher pain was seen midprocedure versus at the beginning (p < 0.0001) and at the end (p = 0.003) of PDT. There was no significant difference in pain perception between genders and different treatment areas. Our results provide evidence that red light ALA PDT of AKs is very well tolerated with the two-step irradiance protocol.

High-pressure liquid chromatographic analysis of pramoxine hydrochloride in high lipoid aerosol foam dosage form.

PubMed

Weinberger, R; Mann, B; Posluszny, J

1980-04-01

A rapid and quantitative method for the determination of pramoxine hydrochloride by high-pressure liquid chromatography is presented. The drug is extracted as the salt from a preparation with a high lipoid composition by partitioning it to the aqueous phase of an ether-methanol-water-acetic acid system. The extract is chromatographed on an octadecylsilane bonded packing with a methanol-water-acetic acid-methanesulfonic acid mobile phase. The time required for each separation is approximately 6 min. Analytical recoveries of 100.4 +/- 1.5% were obtained.

Degree of corneal anaesthesia after topical application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle.

PubMed

Little, W B; Jean, G St; Sithole, F; Little, E; Jean, K Yvorchuk-St

2016-06-01

The use of corneal anaesthesia is necessary for a range of clinical purposes. Therefore, we assessed and compared the efficacy of corneal anaesthesia after application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle. The 24 clinically normal cows were allocated into two groups. Cows in group 1 (n = 12) received 0.2 mL of 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mL of sterile saline (0.9% NaCl) with fluorescein in the contralateral eye (control). Group 2 (n = 12) received 0.2 mL of 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mL of 0.5% proparacaine hydrochloride with fluorescein in the contralateral eye (control). In each group, corneal touch threshold was determined by Cochet-Bonnet aesthesiometer for both eyes immediately prior to topical administration of solutions, at 1 min and 5 min after administration of topical solutions and every 5 min thereafter for a total of 75 min. Significant corneal anaesthesia was noted immediately following topical application of both oxybuprocaine and proparacaine as compared with controls, with maximal corneal anaesthesia noted 1 min after administration. Both oxybuprocaine and proparacaine produced significant corneal anaesthesia for the duration of the 75-min study. Neither oxybuprocaine hydrochloride nor proparacaine hydrochloride treatment resulted in visible adverse effects. There are limited data available demonstrating the efficacy and duration of corneal anaesthetic agents in cattle. Both oxybuprocaine hydrochloride and proparacaine hydrochloride should be considered practical options for providing corneal anaesthesia in cattle in a clinical setting. © 2016 Australian Veterinary Association.

21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Ethylisobutrazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 50...

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Triflupromazine hydrochloride tablets. 520.2582 Section 520.2582 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Triflupromazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 25...

21 CFR 524.1662a - Oxytetracycline hydrochloride and hydrocortisone spray.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Oxytetracycline hydrochloride and hydrocortisone... NEW ANIMAL DRUGS § 524.1662a Oxytetracycline hydrochloride and hydrocortisone spray. (a) Specifications. Each 3-ounce unit of oxytetracycline hydrochloride and hydrocortisone spray contains 300...

21 CFR 524.1662a - Oxytetracycline hydrochloride and hydrocortisone spray.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Oxytetracycline hydrochloride and hydrocortisone... NEW ANIMAL DRUGS § 524.1662a Oxytetracycline hydrochloride and hydrocortisone spray. (a) Specifications. Each 3-ounce unit of oxytetracycline hydrochloride and hydrocortisone spray contains 300...

21 CFR 524.1662a - Oxytetracycline hydrochloride and hydrocortisone spray.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Oxytetracycline hydrochloride and hydrocortisone... NEW ANIMAL DRUGS § 524.1662a Oxytetracycline hydrochloride and hydrocortisone spray. (a) Specifications. Each 3-ounce unit of oxytetracycline hydrochloride and hydrocortisone spray contains 300...

21 CFR 524.1662a - Oxytetracycline hydrochloride and hydrocortisone spray.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride and hydrocortisone... NEW ANIMAL DRUGS § 524.1662a Oxytetracycline hydrochloride and hydrocortisone spray. (a) Specifications. Each 3-ounce unit of oxytetracycline hydrochloride and hydrocortisone spray contains 300...

The effect of L-cysteine and N-acetylcysteine on porphyrin/heme biosynthetic pathway in cells treated with 5-aminolevulinic acid and exposed to radiation.

PubMed

He, D; Behar, S; Roberts, J E; Lim, H W

1996-10-01

The effects of L-cysteine (LC) and N-acetylcysteine (NAC) on porphyrin accumulation in a human dermal microvascular endothelial cell line (HMEC-1) and a human epidermoid carcinoma cell line (A431) loaded with 5-aminolevulinic acid (ALA) and exposed to ultraviolet A (UVA) and blue light radiation were determined. Porphyrin accumulation was decreased in the presence of 0.1-7.5 mM LC (24.8%-31.4% suppression in HMEC-1 cell; 35.8%-48.9% suppression in A431 cells), and in the presence of 0.1-10.0 mM NAC (30.9%-58.0% suppression in HMEC-1 cells; 8.5%-45.3% in A431 cells). The suppression occurred in a LC or NAC dose-dependent fashion. The above was associated with partial reversal of suppression of ferrochelatase (FeC) activity in HMEC-1 cells and in A431 cells. As compared to FeC activity in cells treated with ALA and irradiation, enzyme activity was higher (by 31.9%-62.1%) in the presence of LC (1.0 mM or 5.0 mM) and in the presence of NAC (1.0 mM or 5.0 mM). These data indicate that LC and NAC have protective effects on porphyrin- and irradiation-induced diminution of FeC activity in HMEC-1 cells and A341 cells in vitro.

Pharmacokinetics of endogenous porphyrins induced by 5-aminolevulinic acid as observed by means of laser-induced fluorescence from several organs of tumor-bearing mice

NASA Astrophysics Data System (ADS)

Sroka, Ronald; Baumgartner, Reinhold; Beyer, Wolfgang; Gossner, Liebwin; Sassy, T.; Stocker, Susanne

1995-04-01

Photodynamic therapy (PDT) and photodynamic diagnosis (PDD) add support to efficient treatment modalities of superficial and early stage cancer. Recently 5-aminolevulinic acid (5-ALA), a precursor of hemoglobin in the hem biosynthetic pathway, was used to stimulate endogenous porphyrin production. The time dependency of 5-ALA induced porphyrin fluorescence has been investigated on several normal tissues as well as on a tumor in an in-vivo tumor model (human gastrointestinal adenocarcinoma Grade II, UICC IIa). 5-ALA has been administered intravenously at a concentration of 50 mg/(kg bw). With respect to a certain time schedule the animals were sacrificed and 12 different organs as well as the tumor were removed. Using laser-induced fluorescence techniques the emission spectra in the range of (lambda) equals (550-750) nm were detected from the tissues after excitation with light of the wavelength (lambda) equals (411 +/- 4) nm. For quantitative evaluation the integral fluorescence intensity at (lambda) equals (635 +/- 2) nm of the porphyrin specific spectra has been determined. All tissues showed porphyrin fluorescence, while brightest fluorescence has been detected from the tumor. With respect to the other tissues the relative tumor selectivity showed a maximum ratio at 406 h post injection. The kinetics of the porphyrin fluorescence intensity of the organs follow different time dependencies. Simple mathematical pharmacokinetic models are developed and discussed.

Real-time analysis of endogenous protoporphyrin IX fluorescence from δ-aminolevulinic acid and its derivatives reveals distinct time- and dose-dependent characteristics in vitro

NASA Astrophysics Data System (ADS)

Kiesslich, Tobias; Helander, Linda; Illig, Romana; Oberdanner, Christian; Wagner, Andrej; Lettner, Herbert; Jakab, Martin; Plaetzer, Kristjan

2014-08-01

Photodynamic therapy (PDT) and photodiagnosis based on the intracellular production of the photosensitizer protoporphyrin IX (PPIX) by administration of its metabolic precursor δ-aminolevulinic acid (ALA) achieved their breakthrough upon the clinical approval of MAL (ALA methyl ester) and HAL (ALA hexyl ester). For newly developed ALA derivatives or application in new tumor types, in vitro determination of PPIX formation involves multiparametric experiments covering variable pro-drug concentrations, medium composition, time points of analysis, and cell type(s). This study uses a fluorescence microplate reader with a built-in temperature and atmosphere control to investigate the high-resolution long-term kinetics (72 h) of cellular PPIX fueled by administration of either ALA, MAL, or HAL for each 10 different concentrations. For simultaneous proliferation correction, A431 cells were stably transfected with green fluorescent protein. The results indicate that the peak PPIX level is a function of both, incubation concentration and period: maximal PPIX is generated with 1 to 2-mM ALA/MAL or 0.125-mM HAL; also, the PPIX peak shifts to longer incubation periods with increasing pro-drug concentrations. The results underline the need for detailed temporal analysis of PPIX formation to optimize ALA (derivative)-based PDT or photodiagnosis and highlight the value of environment-controlled microplate readers for automated in vitro analysis.

UPLC and LC-MS studies on degradation behavior of irinotecan hydrochloride and development of a validated stability-indicating ultra-performance liquid chromatographic method for determination of irinotecan hydrochloride and its impurities in pharmaceutical dosage forms.

PubMed

Kumar, Navneet; Sangeetha, Dhanaraj; Reddy, Sunil P

2012-10-01

The objective of the current investigation was to study the degradation behavior of irinotecan hydrochloride under different International Conference on Harmonization (ICH) recommended stress conditions using ultra-performance liquid chromatography and liquid chromatography-mass spectrometry and to establish a validated stability-indicating reverse-phase ultra-performance liquid chromatographic method for the quantitative determination of irinotecan hydrochloride and its seven impurities and degradation products in pharmaceutical dosage forms. Irinotecan hydrochloride was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Irinotecan hydrochloride was found to degrade significantly in oxidative and base hydrolysis and photolytic degradation conditions. The degradation products were well resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. Chromatographic separation was achieved on a Waters Acquity BEH C8 (100 × 2.1 mm) 1.7-µm column with a mobile phase containing a gradient mixture of solvent A (0.02M KH(2)PO(4) buffer, pH 3.4) and solvent B (a mixture of acetonitrile and methanol in the ratio of 62:38 v/v). The mobile phase was delivered at a flow rate of 0.3 mL/min with ultraviolet detection at 220 nm. The run time was 8 min, within which irinotecan and its seven impurities and degradation products were satisfactorily separated. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. This method was also suitable for the assay determination of irinotecan hydrochloride in pharmaceutical dosage forms.

Accelerometric comparison of the locomotor pattern of horses sedated with xylazine hydrochloride, detomidine hydrochloride, or romifidine hydrochloride.

PubMed

López-Sanromán, F Javier; Holmbak-Petersen, Ronald; Varela, Marta; del Alamo, Ana M; Santiago, Isabel

2013-06-01

To evaluate the duration of effects on movement patterns of horses after sedation with equipotent doses of xylazine hydrochloride, detomidine hydrochloride, or romifidine hydrochloride and determine whether accelerometry can be used to quantify differences among drug treatments. 6 healthy horses. Each horse was injected IV with saline (0.9% NaCl) solution (10 mL), xylazine diluted in saline solution (0.5 mg/kg), detomidine diluted in saline solution (0.01 mg/kg), or romifidine diluted in saline solution (0.04 mg/kg) in random order. A triaxial accelerometric device was used for gait assessment 15 minutes before and 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after each treatment. Eight variables were calculated, including speed, stride frequency, stride length, regularity, dorsoventral power, propulsive power, mediolateral power, and total power; the force of acceleration and 3 components of power were then calculated. Significant differences were evident in stride frequency and regularity between treatments with saline solution and each α2-adrenoceptor agonist drug; in speed, dorsoventral power, propulsive power, total power, and force values between treatments with saline solution and detomidine or romifidine; and in mediolateral power between treatments with saline solution and detomidine. Stride length did not differ among treatments. Accelerometric evaluation of horses administered α2-adrenoceptor agonist drugs revealed more prolonged sedative effects of romifidine, compared with effects of xylazine or detomidine. Accelerometry could be useful in assessing the effects of other sedatives and analgesics. Accelerometric data may be helpful in drug selection for situations in which a horse's balance and coordination are important.

21 CFR 522.1662b - Oxytetracycline hydrochloride with lidocaine injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride with lidocaine... FORM NEW ANIMAL DRUGS § 522.1662b Oxytetracycline hydrochloride with lidocaine injection. (a) Specifications. The drug contains 50 or 100 milligrams of oxytetracycline hydrochloride and 2 percent lidocaine...

Compatibility of cholecalciferol, haloperidol, imipramine hydrochloride, levodopa/carbidopa, lorazepam, minocycline hydrochloride, tacrolimus monohydrate, terbinafine, tramadol hydrochloride and valsartan in SyrSpend SF PH4 oral suspensions.

PubMed

Polonini, H C; Silva, S L; Cunha, C N; Brandão, M A F; Ferreira, A O

2016-04-01

A challenge with compounding oral liquid formulations is the limited availability of data to support the physical, chemical and microbiological stability of the formulation. This poses a patient safety concern and a risk for medication errors. The objective of this study was to evaluate the compatibility of the following active pharmaceutical ingredients (APIs) in 10 oral suspensions, using SyrSpend SF PH4 (liquid) as the suspending vehicle: cholecalciferol 50,000 IU/mL, haloperidol 0.5 mg/mL, imipramine hydrochloride 5.0 mg/mL, levodopa/carbidopa 5.0/1.25 mg/mL, lorazepam 1.0 mg/mL, minocycline hydrochloride 10.0 mg/mL, tacrolimus monohydrate 1.0 mg/mL, terbinafine 25.0 mg/mL, tramadol hydrochloride 10.0 mg/mL and valsartan 4.0 mg/mL. The suspensions were stored both refrigerated (2 - 8 degrees C) and at controlled room temperature (20 - 25 degrees C). This is the first stability study for these APIs in SyrSpend SF PH4 (liquid). Further, the stability of haloperidol,ilmipramine hydrochloride, minocycline, and valsartan in oral suspension has not been previously reported in the literature. Compatibility was assessed by measuring percent recovery at varying time points throughout a 90 days period. Quantification of the APIs was performed by high performance liquid chromatography (HPLC-UV). Given the percentage of recovery of the APIs within the suspensions, the beyond-use date of the final preparations was found to be at least 90 days for most suspensions both refrigerated and at room temperature. Exceptions were: Minocycline hydrochloride at both storage temperatures (60 days), levodopa/carbidopa at room temperature (30 days), and lorazepam at room temperature (60 days). This suggests that compounded suspensions of APIs from different pharmacological classes in SyrSpend SF PH4 (liquid) are stable.

Effects of 5-aminolevulinic acid supplementation on home-based walking training achievement in middle-aged depressive women: randomized, double-blind, crossover pilot study.

PubMed

Suzuki, Hiroshi; Masuki, Shizue; Morikawa, Akiyo; Ogawa, Yu; Kamijo, Yoshi-Ichiro; Takahashi, Kiwamu; Nakajima, Motowo; Nose, Hiroshi

2018-05-08

Depressive patients often experience difficulty in performing exercise due to physical and psychological barriers. We examined the effects of 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) supplementation during home-based walking training in middle-aged depressive women. Nine outpatients [53 ± 8 (SD) yr] with major depressive disorder participated in the pilot study with randomized, placebo-controlled, double-blind crossover design. They underwent two trials for 7 days, each performing interval walking training (IWT) with ALA + SFC (ALA + SFC) or placebo supplement intake (PLC) intermittently with >a 10-day washout period. For the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. Before and after each trial, subjects underwent a graded cycling test, and lactate concentration in plasma ([Lac - ] p ), oxygen consumption rate ([Formula: see text]), and carbon dioxide production rate ([Formula: see text]) were measured with depression severity by the Montgomery-Åsberg Depression Rating Scale (MADRS). We found that the increases in [Lac - ] p , [Formula: see text] and [Formula: see text] during the test were attenuated only in ALA + SFC ([before vs. after] × workload; all, P < 0.01), accompanied by increased training days, impulse, and time at fast walking during IWT (all, P < 0.05) with decreased MADRS-score (P = 0.001). Thus, ALA + SFC supplementation increased IWT achievement to improve depressive symptoms in middle-aged women.

40 CFR Appendix A to Subpart Ddd... - Free Formaldehyde Analysis of Insulation Resins by the Hydroxylamine Hydrochloride Method

Code of Federal Regulations, 2013 CFR

2013-07-01

... buffer. 3.350-mL burette for 1.0 N sodium hydroxide. 3.4Magnetic stirrer and stir bars. 3.5250-mL beaker... N sodium hydroxide solution. 4.2Hydroxylamine hydrochloride solution, 100 grams per liter, pH... prestandardized pH meter, 1.0 N hydrochloric acid, 0.1 N hydrochloric acid, and 0.1 N sodium hydroxide. 5.5Add 50...

40 CFR Appendix A to Subpart Ddd... - Free Formaldehyde Analysis of Insulation Resins by the Hydroxylamine Hydrochloride Method

Code of Federal Regulations, 2012 CFR

2012-07-01

... buffer. 3.350-mL burette for 1.0 N sodium hydroxide. 3.4Magnetic stirrer and stir bars. 3.5250-mL beaker... N sodium hydroxide solution. 4.2Hydroxylamine hydrochloride solution, 100 grams per liter, pH... prestandardized pH meter, 1.0 N hydrochloric acid, 0.1 N hydrochloric acid, and 0.1 N sodium hydroxide. 5.5Add 50...

40 CFR Appendix A to Subpart Ddd... - Free Formaldehyde Analysis of Insulation Resins by the Hydroxylamine Hydrochloride Method

Code of Federal Regulations, 2014 CFR

2014-07-01

... buffer. 3.350-mL burette for 1.0 N sodium hydroxide. 3.4Magnetic stirrer and stir bars. 3.5250-mL beaker... N sodium hydroxide solution. 4.2Hydroxylamine hydrochloride solution, 100 grams per liter, pH... prestandardized pH meter, 1.0 N hydrochloric acid, 0.1 N hydrochloric acid, and 0.1 N sodium hydroxide. 5.5Add 50...

Extractive determination of ephedrine hydrochloride and bromhexine hydrochloride in pure solutions, pharmaceutical dosage form and urine samples.

PubMed

Abdel-Ghani, N T; Rizk, M S; Mostafa, M

2013-07-01

Simple, rapid, sensitive, precise and accurate spectrophotometeric methods for the determination of ephedrine hydrochloride (E-HCl) and bromhexine hydrochloride (Br-HCl) in bulk samples, dosage form and in spiked urine samples were investigated. The methods are based on the formation of a yellow colored ion-associates due to the interaction between the examined drugs with picric acid (PA), chlorophyllin coppered trisodium salt (CLPH), alizarin red (AR) and ammonium reineckate (Rk) reagents. A buffer solution had been used and the extraction was carried out using organic solvent, the ion associates exhibit absorption maxima at 410, 410, 430 and 530 nm of (Br-HCl)with PA, CLPH, AR and Rk respectively; 410, 410, 435 and 530 of (E-HCl) with PA, CLPH, AR and Rk respectively. (E-HCl) and (Br-HCl) could be determined up to 13, 121, 120 and 160; 25, 200, 92 and 206 μg mL(-1), using PA, CLPH, AR and Rk respectively. The optimum reaction conditions for quantitative analysis were investigated. In addition, the molar absorptivity, Sandell sensitivity were determined for the investigated drug. The correlation coefficient was ≥0.995 (n=6) with a relative standard deviation (RSD) ≤1.15 for five selected concentrations of the reagents. Therefore the concentration of Br-HCl and E-HCl drugs in their pharmaceutical formulations and spiked urine samples had been determined successfully. Copyright © 2013 Elsevier B.V. All rights reserved.

5-Aminolevulinic Acid Induced Fluorescence Is a Powerful Intraoperative Marker for Precise Histopathological Grading of Gliomas with Non-Significant Contrast-Enhancement

PubMed Central

Widhalm, Georg; Kiesel, Barbara; Woehrer, Adelheid; Traub-Weidinger, Tatjana; Preusser, Matthias; Marosi, Christine; Prayer, Daniela; Hainfellner, Johannes A.; Knosp, Engelbert; Wolfsberger, Stefan

2013-01-01

Background Intraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria. Methods We prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status. Results A total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%. Conclusions Our study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift. PMID:24204718

5-Aminolevulinic acid induced fluorescence is a powerful intraoperative marker for precise histopathological grading of gliomas with non-significant contrast-enhancement.

PubMed

Widhalm, Georg; Kiesel, Barbara; Woehrer, Adelheid; Traub-Weidinger, Tatjana; Preusser, Matthias; Marosi, Christine; Prayer, Daniela; Hainfellner, Johannes A; Knosp, Engelbert; Wolfsberger, Stefan

2013-01-01

Intraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria. We prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status. A total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%. Our study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift.

Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers.

PubMed

Yang, Deng-Fu; Lee, Jeng-Woei; Chen, Hsin-Ming; Hsu, Yih-Chih

2014-09-01

Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is effective for treatment of human oral precancerous lesions. This animal study aimed to assess whether topical methotrexate (MTX) pretreatment could enhance the therapeutic effect of topical ALA-PDT on hamster buccal pouch precancerous lesions. Twenty hamster buccal pouch precancerous lesions were treated with either topical ALA-PDT with topical MTX pretreatment (topical MTX-ALA-PDT group, n = 10) or topical ALA-PDT alone (topical ALA-PDT group, n = 10). The intracellular protoporphyrin IX (PpIX) level in another 12 precancerous lesions (n = 6 for either the topical MTX-ALA or topical ALA group) was monitored by fluorescence spectroscopy. The intracellular PpIX reached its peak level in precancerous lesions 6.5 hours and 2.5 hours after topical ALA application for the topical MTX-ALA group (5.63-fold higher in the lesion than in the normal mucosa) and topical ALA group (2.42-fold higher in the lesion than in the normal mucosa), respectively. The complete response rate of precancerous lesions was 80% for the topical MTX-ALA-PDT group and 70% for the topical ALA-PDT group. In addition, the topical MTX-ALA-PDT group required a significantly lower mean treatment number (2.1 ± 0.6) to achieve complete response than the topical ALA-PDT group (4.4 ± 1.3, p < 0.001)). Moreover, the topical MTX-ALA-PDT group had a lower recurrence rate (12.5%) than the topical ALA-PDT group (28.6%). We conclude that topical MTX-pretreatment can increase intracellular PpIX production in hamster buccal pouch precancerous lesions and significantly improves the outcomes of the precancerous lesions treated with topical ALA-PDT. Copyright © 2014. Published by Elsevier B.V.

Impact of 5-aminolevulinic acid with iron supplementation on exercise efficiency and home-based walking training achievement in older women

PubMed Central

Masuki, Shizue; Morita, Atsumi; Kamijo, Yoshi-ichiro; Ikegawa, Shigeki; Kataoka, Yufuko; Ogawa, Yu; Sumiyoshi, Eri; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo

2015-01-01

A reduction in exercise efficiency with aging limits daily living activities. We examined whether 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) increased exercise efficiency and voluntary achievement of interval walking training (IWT) in older women. Ten women [65 ± 3(SD) yr] who had performed IWT for >12 mo and were currently performing IWT participated in this study. The study was conducted in a placebo-controlled, double-blind crossover design. All subjects underwent two trials for 7 days each in which they performed IWT with ALA+SFC (100 and 115 mg/day, respectively) or placebo supplement intake (CNT), intermittently with a 2-wk washout period. Before and after each trial, subjects underwent a graded cycling test at 27.0°C atmospheric temperature and 50% relative humidity, and oxygen consumption rate, carbon dioxide production rate, and lactate concentration in plasma were measured. Furthermore, for the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. We found that, in the ALA+SFC trial, oxygen consumption rate and carbon dioxide production rate during graded cycling decreased by 12% (P < 0.001) and 11% (P = 0.001) at every workload, respectively, accompanied by a 16% reduction in lactate concentration in plasma (P < 0.001), although all remained unchanged in the CNT trial (P > 0.2). All of the reductions were significantly greater in the ALA+SFC than the CNT trial (P < 0.05). Furthermore, the training days, impulse, and time at fast walking were 42% (P = 0.028), 102% (P = 0.027), and 69% (P = 0.039) higher during the ALA+SFC than the CNT intake period, respectively. Thus ALA+SFC supplementation augmented exercise efficiency and thereby improved IWT achievement in older women. PMID:26514619

[Cetyltrimethylammonium bromide for fluorescence enhancement of anhydrotetracycline hydrochloride and iso-tetracycline].

PubMed

Zha, Jian-peng; Lin, Ying; Yang, Xing-hui; Hou, Hai-ni; Wei, Tie-jun; Chen, Xing-li

2002-06-01

Fluorescence enhancement of anhydrotetracycline hydrochloride and iso-tetracycline has been described. The fluorescence intensities of anhydrotetracycline hydrochloride and iso-tetracycline with cetyltrimethylammonium bromide (CTMAB) enhanced by micellar solution have been examined. It is found that fluorescence enhancement of anhydrotetracycline hydrochloride and iso-tetracycline depends on the concentration of CTMAB and pH of the solution. It can be used to develop sensitive methods for the determination of tetracycline hydrochloride and its decomposition product.

Stability of cefozopran hydrochloride in aqueous solutions.

PubMed

Zalewski, Przemysław; Skibiński, Robert; Paczkowska, Magdalena; Garbacki, Piotr; Talaczyńska, Alicja; Cielecka-Piontek, Judyta; Jelińska, Anna

2016-01-01

The influence of pH on the stability of cefozopran hydrochloride (CZH) was investigated in the pH range of 0.44-13.00. Six degradation products were identified with a hybrid ESI-Q-TOF mass spectrometer. The degradation of CZH as a result of hydrolysis was a pseudo-first-order reaction. As general acid-base hydrolysis of CZH was not occurred in the solutions of hydrochloric acid, sodium hydroxide, acetate, borate and phosphate buffers, kobs = kpH because specific acid-base catalysis was observed. Specific acid-base catalysis of CZH consisted of the following reactions: hydrolysis of CZH catalyzed by hydrogen ions (kH+), hydrolysis of dications (k1H2O), monocations (k2H2O) and zwitter ions (k3H2O) and hydrolysis of zwitter ions (k1OH-) and monoanions (k2OH-) of CZH catalyzed by hydroxide ions. The total rate of the reaction was equal to the sum of partial reactions: [Formula: see text]. CZH similarly like other fourth generation cephalosporin was most stable at slightly acidic and neutral pH and less stable in alkaline pH. The cleavage of the β-lactam ring resulting from a nucleophilic attack on the carbonyl carbon in the β-lactam moiety is the preferred degradation pathway of β-lactam antibiotics in aqueous solutions.

Comparative study of the bactericidal effects of indocyanine green- and methyl aminolevulinate-based photodynamic therapy on Propionibacterium acnes as a new treatment for acne.

PubMed

Choi, Seung-Hwan; Seo, Jeong-Wan; Kim, Ki-Ho

2018-05-03

Acne vulgaris is one of the most common dermatological problems, and its therapeutic options include topical and systemic retinoids and antibiotics. However, increase in problems associated with acne treatment, such as side-effects from conventional agents and bacterial resistance to antibiotics, has led to greater use of photodynamic therapy. The purpose of this study was to compare the bactericidal effects of indocyanine green- and methyl aminolevulinate-based photodynamic therapy on Propionibacterium acnes. P. acnes were cultured under anaerobic conditions; then they were divided into three groups (control, treated with indocyanine green and treated with methyl aminolevulinate) and illuminated with different lights (630-nm light-emitting diode, 805-nm diode laser and 830-nm light-emitting diode). The bactericidal effects were evaluated by comparing each group's colony-forming units. The cultured P. acnes were killed with an 805-nm diode laser and 830-nm light-emitting diode in the indocyanine green group. No bactericidal effects of methyl aminolevulinate-based photodynamic therapy were identified. The clinical efficacy of indocyanine green-based photodynamic therapy in 21 patients was retrospectively analyzed. The Korean Acne Grading System was used to evaluate treatment efficacy, which was significantly decreased after treatment. The difference in the efficacy of the 805-nm diode laser and 830-nm light-emitting diode was not statistically significant. Although the methyl aminolevulinate-based photodynamic therapy showed no bactericidal effect, the indocyanine green-based photodynamic therapy has bactericidal effect and clinical efficacy. © 2018 Japanese Dermatological Association.

Efficacy of ultra short sub-30 minute incubation of 5-aminolevulinic acid photodynamic therapy in vitro.

PubMed

Koo, Eugene; Austin, Evan; Mamalis, Andrew; Jagdeo, Jared

2017-08-01

The estimated incidence of cutaneous squamous cell carcinoma (SCC) is 700,000 cases per year. In the US, SCC incidence is highest among fair skinned adults older than 50 years of age. Thus, as the population ages, the reported number of SCCs will likely increase in the future. Photodynamic therapy (PDT) is an FDA approved therapy for treatment of actinic keratoses (AKs), a precursor to cutaneous SCC lesions. The FDA approved incubation time of the photosensitizing agent 5-aminolevulinic acid (ALA) is 14-18 hours. Recent studies have investigated short ALA incubation times of 1-3 hours with ALA and PDT demonstrating treatment success. Therefore, the question exists whether ALA incubation periods of less than 30 minutes are efficacious. Herein, we evaluate the efficacy of short ALA incubation periods by measuring apoptosis after 10, 15, and 20 minutes of ALA incubation. AG13145 normal human dermal fibroblasts HDFs were incubated with 10, 15, or 20 minute of ALA at various concentrations (0, 0.05, 0.075, 0.1, 0.25, 0.375, 0.5, 1, and 2 mM). After ALA incubation, samples were treated with 1,000 seconds (16 minutes 40 seconds) of Blu-U fluorescent blue light (417 ± 5 nm) for a fluence of 10 J/cm 2 . Immediately following treatment with blue light, samples were collected and stained for apoptosis and necrosis with annexin-V and 7-aminoactinomycin D (7-AAD), and then analyzed by flow cytometry. HDFs incubated with ALA for 10 minute at 36 °C followed by 10 J/cm 2 of blue light had no statistically significant changes in apoptosis. HDFs incubated with ALA for 15 or 20 minutes at 36 °C followed by 10 J/cm 2 of blue light had statistically significant increases in the percentages of cells positive for apoptosis in the 0.5, 1.0, and 2.0 mM ALA doses (P < 0.05). We found that incubation of ALA for at least 15 minutes followed by 10 J/cm 2 of blue light resulted in a statistically significant increase in apoptosis. Lasers Surg. Med. 49

Netupitant and Palonosetron Hydrochloride

Cancer.gov

This page contains brief information about netupitant and palonosetron hydrochloride and a collection of links to more information about the use of this combination drug, research results, and ongoing clinical trials.

Trifluridine and Tipiracil Hydrochloride

Cancer.gov

This page contains brief information about trifluridine and tipiracil hydrochloride and a collection of links to more information about the use of this combination drug, research results, and ongoing clinical trials.

A Strategy Using Photodynamic Therapy and Clofibric Acid to Treat Peritoneal Dissemination of Ovarian Cancer.

PubMed

Yokoyama, Yoshihito; Shigeto, Tatsuhiko; Miura, Rie; Kobayashi, Asami; Mizunuma, Makito; Yamauchi, Aisa; Futagami, Masayuki; Mizunuma, Hideki

2016-01-01

The current study examined the effectiveness of concurrent therapy using photodynamic therapy (PDT) and clofibric acid (CA) to treat peritoneal carcinomatosis resulting from ovarian cancer. Nude rats were used to create a model of peritoneal carcinomatosis resulting from ovarian cancer and the effectiveness of PDT with 5-aminolevulinic acid methyl ester hydrochloride (methyl-ALA-PDT) was determined. The survival time of rats receiving that therapy was compared to the survival time of a control group. Rats with peritoneal carcinomatosis resulting from ovarian cancer were divided into 3 groups: a group that received debulking surgery (DS) alone, a group that received DS+methyl-ALA-PDT, and a group that received DS+methyl-ALA-PDT+CA. The survival time of the 3 groups was compared. Protoporphyrin, a metabolite of methyl-ALA, produces a photochemical action when activated by light. The level of protoporphyrin (the concentration) that reached organs in the abdomen was measured with HPLC. Rats receiving methyl- ALA-PDT had a significantly longer survival time compared to the controls. Rats with peritoneal carcinomatosis that received DS+methyl-ALA-PDT+CA had a significantly longer survival time compared to the rats that received DS alone. Some of the rats that received concurrent therapy survived for a prolonged period. Protoporphyrin was highly concentrated in peritoneal metastases, but only small amounts reached major organs in the abdomen. PDT was not found to result in necrosis in the intestines. The results indicated that concurrent therapy consisting of PDT with methyl-ALA and CA is effective at treating peritoneal carcinomatosis resulting from ovarian cancer without damaging organs.

Simultaneous determination of nortriptyline hydrochloride and fluphenazine hydrochloride in microgram quantities from low dosage forms by liquid chromatography-UV detection.

PubMed

Ashour, Safwan; Kattan, Nuha

2012-12-01

A novel method for the simultaneous high-performance liquid chromatographic determination of nortriptyline hydrochloride and fluphenazine hydrochloride was developed and validated. Fluvastatin sodium was used as internal standard. The determination was performed on a Hypersil Gold C 8 column (250 mm × 4.6 mm i.d., 5 μm particle size) at 25 °C; the mobile phase, consisting of a mixture of formic acid (0.1 M, pH 2.16)-methanol (33:67, v / v), was delivered at a flow rate of 1.1 mL/min and detector wavelength at 251 nm. The retention time of nortriptyline, fluphenazine and fluvastatin was found to be 5.11, 8.05 and 11.38 min, respectively. Linearity ranges were 5.0-1350.0 and 10.0-1350.0 μg/mL with limit of detection values of 0.72 and 0.31 μg/mL, for nortriptyline and fluphenazine, respectively. Results of assay and recovery studies were statistically evaluated for its accuracy and precision. Correlation coefficients ( r 2 ) of the regression equations were greater than 0.999 in all cases. According to the validation results, the proposed method was found to be specific, accurate, precise and could be applied to the simultaneous quantitative analysis of nortriptyline and fluphenazine.

Chemical Immobilization of Sloth Bears (Melursus ursinus) with Ketamine Hydrochloride and Xylazine Hydrochloride: Hematology and Serum Biochemical Values

PubMed Central

Veeraselvam, M.; Sridhar, R.; Perumal, P.; Jayathangaraj, M. G.

2014-01-01

The present study was conducted to define the physiological responses of captive sloth bears immobilized with ketamine hydrochloride and xylazine hydrochloride and to determine and compare the values of hematology and serum biochemical parameters between sexes. A total of 15 sloth bears were immobilized using combination of ketamine hydrochloride and xylazine hydrochloride drugs at the dose rate of 5.0 milligram (mg) per kg body weight and 2.0 mg per kg body weight, respectively. The use of combination of these drugs was found satisfactory for the chemical immobilization of captive sloth bears. There were no significant differences observed in induction time and recovery time and physiological parameters such as heart rate, respiratory rate, and rectal temperature between sexes. Health related parameters comprising hematological values like packed cell volume (PCV), hemoglobin (Hb), red blood cell count (RBC), erythrocyte indices, and so forth and biochemical values like total protein, blood urea nitrogen (BUN), creatinine, alkaline amino-transferase (ALT), aspartate amino-transferase (AST), and so forth were estimated in 11 (5 males and 6 females) apparently healthy bears. Comparison between sexes revealed significant difference in PCV (P < 0.05) and mean corpuscular hemoglobin concentration (MCHC) (P < 0.05). The study might help to evaluate health profiles of sloth bears for appropriate line treatment. PMID:24876990

Fractional Ablative Laser Followed by Transdermal Acoustic Pressure Wave Device to Enhance the Drug Delivery of Aminolevulinic Acid: In Vivo Fluorescence Microscopy Study.

PubMed

Waibel, Jill S; Rudnick, Ashley; Nousari, Carlos; Bhanusali, Dhaval G

2016-01-01

Topical drug delivery is the foundation of all dermatological therapy. Laser-assisted drug delivery (LAD) using fractional ablative laser is an evolving modality that may allow for a greater precise depth of penetration by existing topical medications, as well as more efficient transcutaneous delivery of large drug molecules. Additional studies need to be performed using energy-driven methods that may enhance drug delivery in a synergistic manner. Processes such as iontophoresis, electroporation, sonophoresis, and the use of photomechanical waves aid in penetration. This study evaluated in vivo if there is increased efficacy of fractional CO2 ablative laser with immediate acoustic pressure wave device. Five patients were treated and biopsied at 4 treatment sites: 1) topically applied aminolevulinic acid (ALA) alone; 2) fractional ablative CO2 laser and topical ALA alone; 3) fractional ablative CO2 laser and transdermal acoustic pressure wave device delivery system; and 4) topical ALA with transdermal delivery system. The comparison of the difference in the magnitude of diffusion with both lateral spread of ALA and depth diffusion of ALA was measured by fluorescence microscopy. For fractional ablative CO2 laser, ALA, and transdermal acoustic pressure wave device, the protoporphyrin IX lateral fluorescence was 0.024 mm on average vs 0.0084 mm for fractional ablative CO2 laser and ALA alone. The diffusion for the acoustic pressure wave device was an order of magnitude greater. We found that our combined approach of fractional ablative CO2 laser paired with the transdermal acoustic pressure wave device increased the depth of penetration of ALA.

Bioavailability of Pb and Zn from mine tailings as indicated by erythrocyte aminolevulinic acid dehydratase (ALA-D) activity in suckers (Pisces: catostomidae)

USGS Publications Warehouse

Schmitt, Christopher J.; Dwyer, F. James; Finger, Susan E.

1984-01-01

The activity of the erythrocyte enzyme δ-aminolevulinic acid dehydratase (ALA-D) was measured in 35 catostomids (black redhorse, Moxostoma duquesnei; golden redhorse, M. erythrurum; northern hogsucker, Hypentelium nigricans) collected from three sites on a stream contaminated with Pb-, Cd-, and Zn-rich mine tailings and from an uncontaminated site upstream. Enzyme activity was expressed in terms of hemoglobin (Hb), DNA, and protein concentrations; these variables can be determined in the laboratory on once-frozen blood samples. Concentrations of Pb and Zn in blood and of Pb in edible tissues were significantly higher, and ALA-D activity was significantly lower, at all three contaminated sites than upstream. At the most contaminated site, ALA-D activity was 62–67% lower than upstream. Lead concentrations in the edible tissues and in blood were positively correlated (r = 0.80), whereas ALA-D activity was negatively correlated with Pb in blood (r = −0.70) and in edible tissues (r = −0.59). Five statistically significant relations between Pb and Zn in blood and ALA-D activity were determined. The two models that explained the highest percentage (> 74%) of the total variance also included factors related to Hb concentration. All five significant models included negative coefficients for variables that represented Pb in blood and positive coefficients for Zn in blood. The ALA-D assay with results standardized to Hb concentration represents an expedient alternative to the more traditional hematocrit standardization, and the measurement of ALA-D activity by this method can be used to document exposure of fish to environmental Pb.

Polymorphisms of delta-aminolevulinic acid dehydratase (ALAD) and peptide transporter 2 (PEPT2) genes in children with low-level lead exposure

PubMed Central

Sobin, Christina; Gutierrez, Marisela; Alterio, Heather

2009-01-01

Low-level lead exposure during early childhood has long been associated with altered neurocognitive development and diminished cognitive functions. Over nine thousand U.S. industrial facilities annually emit significant amounts of lead, creating exposure risk particularly for minority children. The mechanisms by which low-level lead exerts neurotoxic effects are poorly understood. Once absorbed, the only intervention is source removal, thus primary prevention is key. Genetic biomarkers could provide an efficient means of identifying children at greatest risk. Common functional variants of genes that alter lead's neurotoxic potential have been identified and include delta-aminolevulinic acid dehydratase (ALAD2) and peptide transporter 2 (PEPT2*2). These polymorphisms have not been examined previously in Hispanic minority samples, or with regard to lowest level lead exposure. In 116 children of Mexican-American/Hispanic descent residing in zip codes previously designated as “high risk” for lead exposure (mean age = 8.1, S.D. = 1.9), blood lead level was measured at three time points over a 3-month period and averaged. DNA extraction was completed using buccal swab samples. The frequencies of the ALAD2 and PEPT2*2 polymorphisms observed in this sample closely approximated those previously reported for Anglo, European and Asian samples. As compared to children heterozygous for the PEPT2*2 polymorphism, and without the PEPT2*2 polymorphism, the geometric mean blood lead level of children homozygous for the PEPT2*2 polymorphism was significantly higher. In contrast to past studies, mean blood lead level of children heterozygous and homozygous for the ALAD2 polymorphism in this sample did not differ from that of children without the ALAD2 polymorphism. Higher blood lead burden in children with the PEPT2*2 mutation may suggest that this common genetic variant is a biomarker of increased vulnerability to the neurotoxic effects of lowest level lead exposure. PMID

[Simultaneous determination of ephedrine hydrochloride, D-pseudoephedrine and amygdalin in xiao'er pingchuan qutan granule by HPLC].

PubMed

Yang, De-Bin; Tong, Yan; Ma, Zhen-Shan; Wang, Lin; Dong, Mei-Hong; Li, Yan-Ling; Wang, Jin-Yu

2013-03-01

To establish an HPLC method for the determination of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin in Xiao'er Pingchuan Qutan granule. Pheny ether chromatographic column (4.6 mm x 250 mm, 5 microm) was adopted, with acetonitrile-0.1% phosphoric acid (containing 0.1% three ethylamine) (3:97) as the mobile phase. The UV detection wavelength was at 210 nm, with the flow rate of 1 mL x min(-1), and column temperature was at 35 degrees C. The linearity of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin ranged between 0.078 60-3.144 microg (r = 1.000 0), 0.103 4-2.068 microg (r = 0.999 7) and 0.430 5-3.157 microg (r = 0.999 8), respectively. Their average recoveries were 98.46% (RSD 1.1%), 103.0% (RSD 1.5%) and 97.15% (RSD 2.1%), respectively. The method is simple, stable and reliable that it can be used to determine the content of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin in Xiao'er Pingchuan Qutan granule.

Preparation and adsorption behavior of berberine hydrochloride imprinted polymers by using silica gel as sacrificed support material

NASA Astrophysics Data System (ADS)

Li, Hui; Li, Yuzhuo; Li, Zhiping; Peng, Xiyang; Li, Yanan; Li, Gui; Tan, Xianzhou; Chen, Gongxi

2012-03-01

Preparation of berberine hydrochloride (B-Cl) imprinted polymers (MIPs) based on surface imprinting technique with silica gel as sacrificial support material was performed successfully by using B-Cl as template, methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) as functional monomer and cross-linker, respectively. The prepared polymers were characterized by Fourier transmission infrared spectrometry (FTIR) and scanning electron microscopy (SEM). Adsorption behavior of the MIPs for the template and its structural analogues was investigated. Sites distribution on the surface of MIPs was explored by using different isotherm adsorption models and thermodynamic parameters for the adsorption of B-Cl on the MIPs determined. Sample application and reusability for the MIPs was also evaluated. Results indicated the strong adsorption and high selectivity of the MIPs for B-Cl. Saturated adsorption capacity reached 27.2 μmol g-1 and the selectivity coefficient of the MIPs for B-Cl relative to jatrorrhizine hydrochloride (J-Cl) and palmatine palmatus hydrochloride (P-Cl) are 3.70 and 6.03, respectively. In addition, the MIPs were shown with good reusability and selectively retention ability in sample application.

The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors

PubMed Central

Jaber, Mohammed; Wölfer, Johannes; Ewelt, Christian; Holling, Markus; Hasselblatt, Martin; Niederstadt, Thomas; Zoubi, Tarek; Weckesser, Matthias

2015-01-01

BACKGROUND: Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [18F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and 18F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and 18F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. CONCLUSION: Age, tumor volume, and 18F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased

Suppressive effects of acid-forming diet against the tumorigenic potential of pioglitazone hydrochloride in the urinary bladder of male rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sato, Keiichiro, E-mail: Sato_Keiichiro@takeda.co.jp; Awasaki, Yasuyuki; Kandori, Hitoshi

Pioglitazone hydrochloride (PIO), a peroxisome proliferator-activated receptor gamma (PPAR{gamma}) agonist, was administered orally for 85 weeks at 16 mg/kg/day to male rats fed either a diet containing 1.5% ammonium chloride (acid-forming diet) or a control diet to investigate the effects of urinary acidification induced by the acid-forming diet on the tumorigenic potential of PIO in the urinary bladder. The surviving animals at the end of the administration period were followed to the end of the 2-year study period without changes in the diet and were subjected to terminal necropsy on Week 104. The number of urinary microcrystals, evaluated by manualmore » counting with light microscopy and by an objective method with a laser diffraction particle size analyzer, was increased by PIO on Weeks 12 and 25 and the increases were markedly suppressed by urinary acidification. Urinary citrate was decreased by PIO throughout the study period, but no changes were seen in urinary oxalate at any timepoint. The incidences of PIO-treated males bearing at least one of the advanced proliferative changes consisting of papillary hyperplasia, nodular hyperplasia, papilloma or carcinoma were significantly decreased from 11 of 82 males fed the control diet to 2 of 80 males fed the acid-forming diet. The acid-forming diet did not show any effects on the toxicokinetic parameters of PIO and its metabolites. Microcrystalluria appears to be involved in the development of the advanced stage proliferative lesions in bladder tumorigenesis induced by PIO in male rats.« less

Suppressive effects of acid-forming diet against the tumorigenic potential of pioglitazone hydrochloride in the urinary bladder of male rats.

PubMed

Sato, Keiichiro; Awasaki, Yasuyuki; Kandori, Hitoshi; Tanakamaru, Zen-Yo; Nagai, Hirofumi; Baron, David; Yamamoto, Masaki

2011-03-15

Pioglitazone hydrochloride (PIO), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, was administered orally for 85 weeks at 16 mg/kg/day to male rats fed either a diet containing 1.5% ammonium chloride (acid-forming diet) or a control diet to investigate the effects of urinary acidification induced by the acid-forming diet on the tumorigenic potential of PIO in the urinary bladder. The surviving animals at the end of the administration period were followed to the end of the 2-year study period without changes in the diet and were subjected to terminal necropsy on Week 104. The number of urinary microcrystals, evaluated by manual counting with light microscopy and by an objective method with a laser diffraction particle size analyzer, was increased by PIO on Weeks 12 and 25 and the increases were markedly suppressed by urinary acidification. Urinary citrate was decreased by PIO throughout the study period, but no changes were seen in urinary oxalate at any timepoint. The incidences of PIO-treated males bearing at least one of the advanced proliferative changes consisting of papillary hyperplasia, nodular hyperplasia, papilloma or carcinoma were significantly decreased from 11 of 82 males fed the control diet to 2 of 80 males fed the acid-forming diet. The acid-forming diet did not show any effects on the toxicokinetic parameters of PIO and its metabolites. Microcrystalluria appears to be involved in the development of the advanced stage proliferative lesions in bladder tumorigenesis induced by PIO in male rats. Copyright © 2011 Elsevier Inc. All rights reserved.

Developmental rates of immatures of three Chrysomya species (Diptera: Calliphoridae) under the effect of methylphenidate hydrochloride, phenobarbital, and methylphenidate hydrochloride associated with phenobarbital.

PubMed

Rezende, Fábio; Alonso, Marcela A; Souza, Carina M; Thyssen, Patrícia J; Linhares, Arício X

2014-05-01

Entomotoxicology is focused on obtaining data on necrophagous entomofauna, for criminal investigations purposes. This study aimed to evaluate the effect of different concentrations of methylphenidate hydrochloride, phenobarbital, and their association on the developmental rate, larval and pupal survivorship, and the interval of emergence of adults of Chrysomya albiceps (Wiedemann), Chrysomya megacephala (Fabricius), and Chrysomya putoria (Wiedemann) (Diptera: Calliphoridae). Considering the therapeutic dose (TD) of methylphenidate hydrochloride (0.29 mg/Kg), the concentrations tested were 10× TD, 50× TD, and 100× TD. For phenobarbital, the concentrations used were 1× TD (=150 mg/Kg), 3.3× TD, and 6.7× TD. For the association of the drugs, the combinations used were 10× TD-methylphenidate hydrochloride plus 1× TD-phenobarbital, 50× TD-methylphenidate hydrochloride plus 3.3× TD-phenobarbital, and 100× TD-methylphenidate hydrochloride plus 6.7× TD-phenobarbital. The control group, without addition of drug, was maintained under the same conditions of temperature (25 ± 1 °C), humidity (70 ± 10%), and photoperiod (12 h). Specimens of each group were weighed every 12 h until pupariation. The developmental rate of the three Chrysomya species immatures was monitored. For C. albiceps the developmental time was delayed in 24 h for methylphenidate hydrochloride group and in 12 h for the phenobarbital and the drugs association groups. The effect was observed only at specific ages for C. megacephala, without altering the developmental time. For C. putoria, the developmental time was delayed in 12 h for methylphenidate hydrochloride group and in 24 h for the phenobarbital and the drugs association groups. The emergence interval was similar among all experimental groups, but larval and pupal viabilities were affected in different ways.

Temperature-dependent THz vibrational spectra of clenbuterol hydrochloride

NASA Astrophysics Data System (ADS)

Yang, YuPing; Lei, XiangYun; Yue, Ai; Zhang, Zhenwei

2013-04-01

Using the high-resolution Terahertz Time-domain spectroscopy (THz-TDS) and the standard sample pellet technique, the far-infrared vibrational spectra of clenbuterol hydrochloride (CH), a β 2-adrenergic agonist for decreasing fat deposition and enhancing protein accretion, were measured in temperature range of 77-295 K. Between 0.2 and 3.6 THz (6.6-120.0 cm-1), seven highly resolved spectral features, strong line-narrowing and a frequency blue-shift were observed with cooling. However, ractopamine hydrochloride, with some structural and pharmacological similarities to clenbuterol hydrochloride, showed no spectral features, indicating high sensitivity and strong specificity of THz-TDS. These results could be used for the rapid and nondestructive CH residual detection in food safety control.

Indirect spectrophotometric determination of propranolol hydrochloride and piroxicam in pure and pharmaceutical formulations.

PubMed

Gowda, Babu G; Seetharamappa, Jaldappa; Melwanki, Mahaveer B

2002-06-01

Two simple and sensitive indirect spectrophotometric methods for the assay of propranolol hydrochloride (PPH) and piroxicam (PX) in pure and pharmaceutical formulations have been proposed. The methods are based on the oxidation of PPH by a known excess of standard N-bromosuccinimide (NBS) and PX by ceric ammonium sulfate (CAS) in an acidic medium followed by the reaction of excess oxidant with promethazine hydrochloride (PMH) and methdilazine hydrochloride (MDH) to yield red-colored products. The absorbance values decreased linearly with increasing concentration of the drugs. The systems obeyed Beer's law over the concentration ranges of 0.5 - 12.5 and 0.3 - 16.0 microg/ml for PPH, and 0.4 - 7.5 and 0.2 - 10 microg/ml for PX with PMH and MDH, respectively. Molar absorptivity values, as calculated from Beer's law data, were found to be 1.36 x 10(4) and 2.55 x 10(4) l mol(-1) cm(-1) for PPH, and 2.08 x 10(4) and 2.05 x 10(4) l mol(-1) cm(-1) for PX with PMH and MDH, respectively. The common excipients and additives did not interfere with their determinations. The proposed methods have been successfully applied to the determinations of PPH and PX in various dosage forms. The results obtained by the proposed methods compare favorably with those of official methods.

Construction and performance characteristics of new ion selective electrodes based on carbon nanotubes for determination of meclofenoxate hydrochloride.

PubMed

El-Nashar, Rasha M; Abdel Ghani, Nour T; Hassan, Sherif M

2012-06-12

This work offers construction and comparative evaluation the performance characteristics of conventional polymer (I), carbon paste (II) and carbon nanotubes chemically modified carbon paste ion selective electrodes (III) for meclofenoxate hydrochloride are described. These electrodes depend mainly on the incorporation of the ion pair of meclofenoxate hydrochloride with phosphomolybdic acid (PMA) or phosphotungestic acid (PTA). They showed near Nernestian responses over usable concentration range 1.0 × 10(-5) to 1.0 × 10(-2)M with slopes in the range 55.15-59.74 mV(concentrationdecade)(-1). These developed electrodes were fully characterized in terms of their composition, response time, working concentration range, life span, usable pH and temperature range. The electrodes showed a very good selectivity for Meclo with respect to a large number of inorganic cations, sugars and in the presence of the degradation product of the drug (p-chloro phenoxy acetic acid). The standard additions method was applied to the determination of MecloCl in pure solution, pharmaceutical preparations and biological samples. Dissolution testing was also applied using the proposed sensors. Copyright © 2011 Elsevier B.V. All rights reserved.

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

New copper(II) complexes with dopamine hydrochloride and vanillymandelic acid: Spectroscopic and thermal characterization

NASA Astrophysics Data System (ADS)

Mohamed, Gehad G.; Nour El-Dien, F. A.; El-Nahas, R. G.

2011-10-01

The dopamine derivatives participate in the regulation of wide variety of physiological functions in the human body and in medication life. Increase and/or decrease in the concentration of dopamine in human body reflect an indication for diseases such as Schizophrenia and/or Parkinson diseases. The Cu(II) chelates with coupled products of dopamine hydrochloride (DO.HCl) and vanillymandelic acid (VMA) with 4-aminoantipyrine (4-AAP) are prepared and characterized. Different physico-chemical techniques namely IR, magnetic and UV-vis spectra are used to investigate the structure of these chelates. Cu(II) forms 1:1 (Cu:DO) and 1:2 (Cu:VMA) chelates. DO behave as a uninegative tridentate ligand in binding to the Cu(II) ion while VMA behaves as a uninegative bidentate ligand. IR spectra show that the DO is coordinated to the Cu(II) ion in a tridentate manner with ONO donor sites of the phenolic- OH, -NH and carbonyl- O, while VMA is coordinated with OO donor sites of the phenolic- OH and -NH. Magnetic moment measurements reveal the presence of Cu(II) chelates in octahedral and square planar geometries with DO and VMA, respectively. The thermal decomposition of Cu(II) complexes is studied using thermogravimetric (TG) and differential thermal analysis (DTA) techniques. The activation thermodynamic parameters, such as, energy of activation, enthalpy, entropy and free energy change of the complexes are evaluated and the relative thermal stability of the complexes are discussed.

Fundamentals of ionic conductivity relaxation gained from study of procaine hydrochloride and procainamide hydrochloride at ambient and elevated pressure.

PubMed

Wojnarowska, Z; Swiety-Pospiech, A; Grzybowska, K; Hawelek, L; Paluch, M; Ngai, K L

2012-04-28

The pharmaceuticals, procaine hydrochloride and procainamide hydrochloride, are glass-forming as well as ionically conducting materials. We have made dielectric measurements at ambient and elevated pressures to characterize the dynamics of the ion conductivity relaxation in these pharmaceuticals, and calorimetric measurements for the structural relaxation. Perhaps due to their special chemical and physical structures, novel features are found in the ionic conductivity relaxation of these pharmaceuticals. Data of conductivity relaxation in most ionic conductors when represented by the electric loss modulus usually show a single resolved peak in the electric modulus loss M(")(f) spectra. However, in procaine hydrochloride and procainamide hydrochloride we find in addition another resolved loss peak at higher frequencies over a temperature range spanning across T(g). The situation is analogous to many non-ionic glass-formers showing the presence of the structural α-relaxation together with the Johari-Goldstein (JG) β-relaxation. Naturally the analogy leads us to name the slower and faster processes resolved in procaine hydrochloride and procainamide hydrochloride as the primary α-conductivity relaxation and the secondary β-conductivity relaxation, respectively. The analogy of the β-conductivity relaxation in procaine HCl and procainamide HCl with JG β-relaxation in non-ionic glass-formers goes further by the finding that the β-conductivity is strongly related to the α-conductivity relaxation at temperatures above and below T(g). At elevated pressure but compensated by raising temperature to maintain α-conductivity relaxation time constant, the data show invariance of the ratio between the β- and the α-conductivity relaxation times to changes of thermodynamic condition. This property indicates that the β-conductivity relaxation has fundamental importance and is indispensable as the precursor of the α-conductivity relaxation, analogous to the relation found

Gadolinium and 5-Aminolevulinic Acid-induced Protoporphyrin IX Levels in Human Gliomas: An Ex Vivo Quantitative Study to Correlate Protoporphyrin IX Levels and Blood-Brain Barrier Breakdown

PubMed Central

Valdés, Pablo A.; Moses, Ziev B.; Kim, Anthony; Belden, Clifford J.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.; Harris, Brent T.

2012-01-01

In recent years, 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence guidance has been used as a surgical adjunct to improve the extent of resection of gliomas. Exogenous administration of ALA prior to surgery leads to the accumulation of red fluorescent PpIX in tumor tissue that the surgeon can visualize and thereby discriminate between normal and tumor tissue. Selective accumulation of PpIX has been linked to numerous factors, of which blood-brain barrier (BBB) breakdown has been suggested to be a key factor. To test the hypothesis that PpIX concentration (CPpIX) positively correlates with gadolinium (Gd) concentrations (CGd), we performed ex vivo measurements of PpIX and of Gd using Inductively-Coupled Plasma Mass Spectrometry (ICP-MS) the latter as a quantitative biomarker of BBB breakdown; this was corroborated with immunohistochemistry of microvascular density in surgical biopsies of patients undergoing fluorescence guided surgery for glioma .We found positive correlations between CPpIX and CGd (r = 0.58, p < 0.0001), and between CPpIX and microvascular density (r = 0.55, p < 0.0001), suggesting a significant, yet limited association between BBB breakdown and ALA-induced PpIX fluorescence. To our knowledge, this is the first time that Gd measurements by ICP-MS have been used in human gliomas. PMID:22878664

Pediatric oral solutions with propranolol hydrochloride for extemporaneous compounding: the formulation and stability study.

PubMed

Klovrzová, Sylva; Zahálka, Lukáš; Matysová, Ludmila; Horák, Petr; Sklubalová, Zdenka

2013-02-01

The aim of this study is to formulate an extemporaneous pediatric oral solution of propranolol hydrochloride (PRO) 2 mg/ml for the therapy of infantile haemangioma or hypertension in a target age group of 1 month to school children and to evaluate its stability. A citric acid solution and/or a citrate-phosphate buffer solution, respectively, were used as the vehicles to achieve pH value of about 3, optimal for the stability of PRO. In order to mask the bitter taste of PRO, simple syrup was used as the sweetener. All solutions were stored in tightly closed brown glass bottles at 5 ± 3 °C and/or 25 ± 3 °C, respectively. The validated HPLC method was used to evaluate the concentration of PRO and a preservative, sodium benzoate, at time intervals of 0-180 days. All preparations were stable at both storage temperatures with pH values in the range of 2.8-3.2. According to pharmacopoeial requirements, the efficacy of sodium benzoate 0.05 % w/v was proved (Ph.Eur., 5.1.3). The preparation formulated with the citrate-phosphate buffer, in our experience, had better palatability than that formulated with the citric acid solution. propranolol hydrochloride pediatric preparation extemporaneous preparation solution stability testing HPLC.

Differential antioxidant defense and detoxification mechanisms in photodynamically stressed rice plants treated with the deregulators of porphyrin biosynthesis, 5-aminolevulinic acid and oxyfluorfen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phung, Thu-Ha; Jung, Sunyo, E-mail: sjung@knu.ac.kr

This study focuses on differential molecular mechanisms of antioxidant and detoxification systems in rice plants under two different types of photodynamic stress imposed by porphyrin deregulators, 5-aminolevulinic acid (ALA) and oxyfluorfen (OF). The ALA-treated plants with white necrosis exhibited a greater decrease in photochemical quantum efficiency, F{sub v}/F{sub m}, as well as a greater increase in activity of superoxide dismutase, compared to the OF-treated plants. By contrast, the brown necrosis in OF-treated plants resulted in not only more widely dispersed H{sub 2}O{sub 2} production and greater increases in H{sub 2}O{sub 2}-decomposing enzymes, catalase and peroxidase, but also lower ascorbate redoxmore » state. In addition, ALA- and OF-treated plants markedly up-regulated transcript levels of genes involved in detoxification processes including transport and movement, cellular homeostasis, and xenobiotic conjugation, with prominent up-regulation of serine/threonine kinase and chaperone only in ALA-treated plants. Our results demonstrate that different photodynamic stress imposed by ALA and OF developed differential actions of antioxidant enzymes and detoxification. Particularly, detoxification system may play potential roles in plant protection against photodynamic stress imposed by porphyrin deregulators, thereby contributing to alleviation of photodynamic damage. - Highlights: • We employ two different types of photodynamic stress, white and brown necrosis. • We examine molecular mechanisms of antioxidative and detoxification systems. • ALA and OF develop differential actions of antioxidant and detoxification systems. • Coordinated mechanism of antioxidants and detoxification works against toxic ROS. • Detoxification system plays critical roles in protection against photodynamic stress.« less

Oil components modulate the skin delivery of 5-aminolevulinic acid and its ester prodrug from oil-in-water and water-in-oil nanoemulsions

PubMed Central

Zhang, Li-Wen; Al-Suwayeh, Saleh A; Hung, Chi-Feng; Chen, Chih-Chieh; Fang, Jia-You

2011-01-01

The study evaluated the potential of nanoemulsions for the topical delivery of 5-aminolevulinic acid (ALA) and methyl ALA (mALA). The drugs were incorporated in oil-in-water (O/W) and water-in-oil (W/O) formulations obtained by using soybean oil or squalene as the oil phase. The droplet size, zeta potential, and environmental polarity of the nanocarriers were assessed as physicochemical properties. The O/W and W/O emulsions showed diameters of 216–256 and 18–125 nm, which, respectively, were within the range of submicron- and nano-sized dispersions. In vitro diffusion experiments using Franz-type cells and porcine skin were performed. Nude mice were used, and skin fluorescence derived from protoporphyrin IX was documented by confocal laser scanning microscopy (CLSM). The loading of ALA or mALA into the emulsions resulted in slower release across cellulose membranes. The release rate and skin flux of topical drug application were adjusted by changing the type of nanocarrier, the soybean oil O/W systems showing the highest skin permeation. This formulation increased ALA flux via porcine skin to 180 nmol/cm2/h, which was 2.6-fold that of the aqueous control. The CLSM results showed that soybean oil systems promoted mALA permeation to deeper layers of the skin from ∼100 μm to ∼140 μm, which would be beneficial for treating subepidermal and subcutaneous lesions. Drug permeation from W/O systems did not surpass that from the aqueous solution. An in vivo dermal irritation test indicated that the emulsions were safe for topical administration of ALA and mALA. PMID:21556344

Daunorubicin Hydrochloride and Cytarabine Liposome

Cancer.gov

This page contains brief information about daunorubicin hydrochloride and cytarabine liposome and a collection of links to more information about the use of this drug, research results, and ongoing clinical trials.

5-Aminolevulinic acid loaded ethosomal vesicles with high entrapment efficiency for in vitro topical transdermal delivery and photodynamic therapy of hypertrophic scars.

PubMed

Zhang, Zheng; Chen, Yunsheng; Xu, Heng; Wo, Yan; Zhang, Zhen; Liu, Ying; Su, Weijie; Cui, Daxiang; Zhang, Yixin

2016-11-24

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an alternative therapy for hypertrophic scars (HS), which destroys human hypertrophic scar fibroblasts (HSF). However, the poor permeability of ALA both in HS tissue and HSF significantly restricts the PDT of HS. To overcome these barriers, ALA-loaded ethosomal vesicles (ALA-ES) were developed by a pH gradient active loading method and characterized by morphology, entrapment efficiency (EE) and stability. Results show that prepared ALA-ES are homogenous spherical lamellar vesicles, 53 ± 7 nm in size, 50.6 ± 2.3% in EE and have excellent stability. In vitro transdermal delivery studies through HS tissue were carried out by using Franz diffusion cells. Compared to the traditional ALA hydroalcoholic solution (ALA-HA), ALA-ES achieve higher drug retention in less administration time, and fluorescence microscopy showed that ALA-ES penetrate into the deeper dermis of HS in a shorter time, indicating that ALA-ES can enhance the penetration of ALA into HS. Additionally, ALA-ES was visualized in HS tissue for the first time by transmission electron microscopy (TEM). The irregular and collapsed ALA-ES suggest that they can squeeze through narrow spaces to the target area and release ALA into HS. Taking HSF as the target, the transcellular delivery of ALA-ES into HSF cells was investigated by intracellular protoporphyrin IX (PpIX) accumulation. The efficiency of PDT for HSF cells, including the formation of reactive oxygen species (ROS) and cell apoptosis, were also well investigated. Furthermore, the detailed changes of HSF were observed by TEM. The results strongly indicate that ALA-ES can facilitate ALA penetration into HSF cells, and can cause a higher level of cell apoptosis or necrosis than ALA-HA. ALA-ES with high EE is therefore a promising transdermal delivery system for topical ALA administration and has great potential in ALA-PDT of HS.

5-Aminolevulinic Acid Protects against Cisplatin-Induced Nephrotoxicity without Compromising the Anticancer Efficiency of Cisplatin in Rats In Vitro and In Vivo

PubMed Central

Matsumoto, Tatsuki; Ishihara, Masayuki; Hamada, Kazu; Shimamura, Yoshiko; Ogata, Koji; Inoue, Kosuke; Taniguchi, Yoshinori; Horino, Taro; Karashima, Takashi; Tamura, Kenji; Fukuhara, Hideo; Fujimoto, Shimpei; Tsuda, Masayuki; Shuin, Taro

2013-01-01

Background/Aims Nephrotoxicity is a frequent and major limitation in cisplatin (CDDP)-based chemotherapy. 5-Aminolevulinic acid (ALA) is widely distributed in animal cells, and it is a precursor of tetrapyrole compounds such as heme that is fundamentally important in aerobic energy metabolism. The aim of this study is to evaluate the protective role of ALA in CDDP-induced acute kidney injury (AKI). Method We used CDDP-induced AKI rat model and cultured renal tubular cells (NRK-52E). We divided four groups of rats: control, CDDP only, CDDP + ALA(post);(ALA 10 mg/kg + Fe in drinking water) after CDDP, CDDP + ALA(pre & post). Result CDDP increased Cr up to 6.5 mg/dl, BUN up to 230 mg/dl, and ALA significantly reduced these changes. ALA ameliorates CDDP-induced morphological renal damages, and reduced tubular apoptosis evaluated by TUNEL staining and cleaved caspase 3. Protein and mRNA levels of ATP5α, complex(COX) IV, UCP2, PGC-1α in renal tissue were significantly decreased by CDDP, and ALA ameliorates reduction of these enzymes. In contrast, Heme Oxigenase (HO)-1 level is induced by CDDP treatment, and ALA treatment further up-regulates HO-1 levels. In NRK-52E cells, the CDDP-induced reduction of protein and mRNA levels of mitochondrial enzymes was significantly recovered by ALA + Fe. CDDP-induced apoptosis were ameliorated by ALA + Fe treatment. Furthermore, we evaluated the size of transplantated bladder carcinoma to the rat skin, and ALA did not change the anti cancer effects of CDDP. Conclusion These data suggested that the protective role of ALA in cisplatin-induced AKI is via protection of mitochondrial viability and prevents tubular apoptosis. Also there are no significant effects of ALA on anticancer efficiency of CDDP in rats. Thus, ALA has the potential to prevent CDDP nephrotoxicity without compromising its anticancer efficacy. PMID:24324635

pH-sensing properties of cascaded long- and short-period fiber grating with poly acrylic acid/poly allylamine hydrochloride thin-film overlays

NASA Astrophysics Data System (ADS)

Yang, Ying

2014-11-01

Based on coupled-mode theory and transfer matrix method, the mode coupling mechanism and the reflection spectral properties of coated cascaded long- and short-period gratings (CLBG) are discussed. The effects of the thin-film parameters (film refractive index and film thickness) on the reflection spectra of the coated CLBG are simulated. By using electrostatic self-assembly method, poly acrylic acid (PAA) and poly allylamine hydrochloride (PAH) multilayer molecular pH-sensitive thin-films are assembled on the surface of the partial corroded CLBG. When the CLBG coated with PAA/PAH films are used to sense pH values, the resonant wavelengths of the CLBG have almost no shift, whereas the resonance peak reflectivities change with pH values. In addition, the sensitivities of the resonance peak reflectivities responding to pH values are improved by an order of magnitude.

Surgery combined with local 5-aminolevulinic acid-photodynamic therapy on skin cancer and its effect on the expression of cyclophilin A, cyclophilin B and CD147

PubMed Central

Guo, Ling; Han, Yingsheng

2017-01-01

The study evaluated an approach to treat skin cancer using surgery combined with local 5-aminolevulinic acid-photodynamic therapy (ALA-PDT). Seventy-six patients with skin cancer who were admitted to the Liaocheng People's Hospital from May 2014 to April 2015 were randomly divided into a control and an observation group (38 cases in each). The patients in the control group were treated with ALA-PDT alone. Those in the observation group were first subjected to surgical treatment, and then treated with ALA-PDT. The treatment efficacies of the two groups were compared. The expression of cancer markers CyPA, CyPB and CD147 were detected by immunohistochemical methods before and after the treatment. Our results showed the average healing time of the wounds of patients in the observation group was shorter, the number of treatments needed was less, the efficacy rate and the lesion appearance satisfaction were significantly higher, and the recurrence rate at 12 months after treatment and the incidence of adverse reactions were both significantly lower. Additionally, the levels of CyPA, CyPB and CD147 were reduced to a significantly higher degree after treatment in the observation group. No difference was found in the recurrence rate between the two groups at 6 months after treatment. We conclude that surgery combined with ALA-PDT is a safe and reliable treatment method, which can increase the survival rate while improving the recovery rate and appearance satisfaction in patients with skin cancer. PMID:28789363

Surgery combined with local 5-aminolevulinic acid-photodynamic therapy on skin cancer and its effect on the expression of cyclophilin A, cyclophilin B and CD147.

PubMed

Guo, Ling; Han, Yingsheng

2017-08-01

The study evaluated an approach to treat skin cancer using surgery combined with local 5-aminolevulinic acid-photodynamic therapy (ALA-PDT). Seventy-six patients with skin cancer who were admitted to the Liaocheng People's Hospital from May 2014 to April 2015 were randomly divided into a control and an observation group (38 cases in each). The patients in the control group were treated with ALA-PDT alone. Those in the observation group were first subjected to surgical treatment, and then treated with ALA-PDT. The treatment efficacies of the two groups were compared. The expression of cancer markers CyPA, CyPB and CD147 were detected by immunohistochemical methods before and after the treatment. Our results showed the average healing time of the wounds of patients in the observation group was shorter, the number of treatments needed was less, the efficacy rate and the lesion appearance satisfaction were significantly higher, and the recurrence rate at 12 months after treatment and the incidence of adverse reactions were both significantly lower. Additionally, the levels of CyPA, CyPB and CD147 were reduced to a significantly higher degree after treatment in the observation group. No difference was found in the recurrence rate between the two groups at 6 months after treatment. We conclude that surgery combined with ALA-PDT is a safe and reliable treatment method, which can increase the survival rate while improving the recovery rate and appearance satisfaction in patients with skin cancer.

Spectrophotometric determination of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride by flow injection analysis.

PubMed

Seno, Kunihiko; Matumura, Kazuki; Oshima, Mitsuko; Motomizu, Shoji

2008-04-01

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl) is a very useful agent to form amide bonds (peptide bonds) in an aqueous medium. A simple and fast detection system was developed using the reaction with pyridine and ethylenediamine in acidic aqueous solution and spectrophotometric flow injection analysis. The absorbances were measured at 400 nm and the reaction was accelerated at 40 degrees C. The calibration graph showed good linearity from 0 to 10% of EDC.HCl solutions: the regression equation was y=3.15x10(4)x (y, peak area; x, % concentration of EDC.HCl). The RSD was under 1.0%. Sample throughput was 15 h(-1). This method was applied to monitoring the EDC.HCl concentration that remained after the anhydration of phthalic acid in water, esterification of acetic acid in methanol or dehydration condensation of malonic acid and ethylenediamine in water.

Metabolomic Analyses of Blood Plasma after Oral Administration of D-Glucosamine Hydrochloride to Dogs

PubMed Central

Osaki, Tomohiro; Azuma, Kazuo; Kurozumi, Seiji; Takamori, Yoshimori; Tsuka, Takeshi; Imagawa, Tomohiro; Okamoto, Yoshiharu; Minami, Saburo

2012-01-01

D-Glucosamine hydrochloride (GlcN∙HCl) is an endogenous amino monosaccharide synthesized from glucose that is useful in the treatment of joint diseases in both humans and animals. The aim of this study was to examine amino acid metabolism in dogs after oral administration of GlcN∙HCl. Accelerated fumarate respiration and elevated plasma levels of lactic acid and alanine were observed after administration. These results suggest that oral administration of GlcN∙HCl induces anaerobic respiration and starvation in cells, and we hypothesize that these conditions promote cartilage regeneration. Further studies are required to evaluate the expression of transforming growth factor-beta (TGF-β). PMID:23015778

Quantification of bupivacaine hydrochloride and isoflupredone acetate residues in porcine muscle, beef, milk, egg, shrimp, flatfish, and eel using a simplified extraction method coupled with liquid chromatography-triple quadrupole tandem mass spectrometry.

PubMed

Cho, Sang-Hyun; Park, Jin-A; Zheng, Weijia; Abd El-Aty, A M; Kim, Seong-Kwan; Choi, Jeong-Min; Yi, Hee; Cho, Soo-Min; Afifi, Nehal A; Shim, Jae-Han; Chang, Byung-Joon; Kim, Jin-Suk; Shin, Ho-Chul

2017-10-15

In this study, a simple analytical approach has been developed and validated for the determination of bupivacaine hydrochloride and isoflupredone acetate residues in porcine muscle, beef, milk, egg, shrimp, flatfish, and eel using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A 0.1% solution of acetic acid in acetonitrile combined with n-hexane was used for deproteinization and defatting of all tested matrices and the target drugs were well separated on a Waters Xbridge™ C18 analytical column using a mobile phase consisting of 0.1% acetic acid (A) and 0.1% solution of acetic acid in methanol (B). The linearity estimated from six-point matrix-matched calibrations was good, with coefficients of determination ≥0.9873. The limits of quantification (LOQs) for bupivacaine hydrochloride and isoflupredone acetate were 1 and 2ngg -1 , respectively. Recovery percentages in the ranges of 72.51-112.39% (bupivacaine hydrochloride) and 72.58-114.56% (isoflupredone acetate) were obtained from three different fortification concentrations with relative standard deviations (RSDs) of <15.14%. All samples for the experimental work and method application were collected from the local markets in Seoul, Republic of Korea, and none of them tested positive for the target drugs. In conclusion, a simple method using a 0.1% solution of acetic acid in acetonitrile and n-hexane followed by LC-MS/MS could effectively extract bupivacaine hydrochloride and isoflupredone acetate from porcine muscle, beef, milk, egg, shrimp, flatfish, and eel samples. Copyright © 2017 Elsevier B.V. All rights reserved.

21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... an aqueous solution which contains in each fluid ounce 0.36 gram of levamisole hydrochloride and piperazine dihydrochloride equivalent to 3.98 grams of piperazine base. (2) The drug is a soluble powder which when reconstituted with water contains in each fluid ounce 0.45 gram of levamisole hydrochloride...

21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... an aqueous solution which contains in each fluid ounce 0.36 gram of levamisole hydrochloride and piperazine dihydrochloride equivalent to 3.98 grams of piperazine base. (2) The drug is a soluble powder which when reconstituted with water contains in each fluid ounce 0.45 gram of levamisole hydrochloride...

21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... an aqueous solution which contains in each fluid ounce 0.36 gram of levamisole hydrochloride and piperazine dihydrochloride equivalent to 3.98 grams of piperazine base. (2) The drug is a soluble powder which when reconstituted with water contains in each fluid ounce 0.45 gram of levamisole hydrochloride...

Improving contrast enhancement in magnetic resonance imaging using 5-aminolevulinic acid-induced protoporphyrin IX for high-grade gliomas.

PubMed

Yamamoto, Junkoh; Kakeda, Shingo; Yoneda, Tetsuya; Ogura, Shun-Ichiro; Shimajiri, Shohei; Tanaka, Tohru; Korogi, Yukunori; Nishizawa, Shigeru

2017-03-01

Magnetic resonance imaging (MRI) with a gadolinium-based contrast agent is the gold standard for high-grade gliomas (HGGs). The compound 5-aminolevulinic acid (5-ALA) undergoes a high rate of cellular uptake, particularly in cancer cells. In addition, fluorescence-guided resection with 5-ALA is widely used for imaging HGGs. 5-ALA is water soluble, while protoporphyrin IX (PpIX) is water insoluble. It was speculated whether converting from 5-ALA to PpIX may relatively increase intracellular water content, and consequently, might enhance the T2 signal intensity in HGG. The aim of the present study was to assess whether 5-ALA-induced PpIX enhances the T2 signal intensity in patients with HGGs. A total of 4 patients who were candidates for HGG surgical treatment were prospectively analyzed with preoperative MRI. Patients received oral doses of 5-ALA (20 mg/kg) 3 h prior to anesthesia. At 2.5 h post-5-ALA administration, T2-weighted images (T2WIs) were obtained from all patients. Subsequently, tumors were evaluated via fluorescence using a modified operating microscope. Fluorescent tumor tissues were obtained to analyze the accumulation of 5-ALA-induced PpIX within the tumors, which was confirmed quantitatively by high-performance liquid chromatography (HPLC) analysis. The MRI T2 signal intensity within the tumors was evaluated prior to and following 5-ALA administration. Three glioblastoma multiformes (GBMs) and 1 anaplastic oligodendroglioma (AO) were included in the analysis. Intraoperatively, all GBMs exhibited strong fluorescence of 5-ALA-induced PpIX, whilst no fluorescence was observed in the AO sample. HPLC analysis indicated a higher accumulation of 5-ALA-induced PpIX in the GBM samples compared with the AO sample. In total, 48 regions of interest were identified within the tumors from T2-WIs. In the GBM group, the relative T2 signal intensity value within the tumors following 5-ALA administration was significantly increased compared with the T2 signal

Perturbed porphyrin biosynthesis contributes to differential herbicidal symptoms in photodynamically stressed rice (Oryza sativa) treated with 5-aminolevulinic acid and oxyfluorfen.

PubMed

Phung, Thu-Ha; Jung, Sunyo

2014-11-01

This paper focuses on the molecular mechanism of deregulated porphyrin biosynthesis in rice plants under photodynamic stress imposed by an exogenous supply of 5-aminolevulinic acid (ALA) and oxyfluorfen (OF). Plants treated with 5 mM ALA or 50 µM OF exhibited differential herbicidal symptoms as characterized by white and brown necrosis, respectively, with substantial increases in cellular leakage and malondialdehyde production. Protoporphyrin IX accumulated to higher levels after 1 day of ALA and OF treatment, whereas it decreased to the control level after 2 days of ALA treatment. Plants responded to OF by greatly decreasing the levels of Mg-protoporphyrin IX (MgProto IX), MgProto IX methyl ester, and protochlorophyllide to levels lower than control, whereas their levels drastically increased 1 day after ALA treatment and then disappeared 2 days after the treatment. Enzyme activity and transcript levels of HEMA1, GSA and ALAD for ALA synthesis greatly decreased in ALA- and OF-treated plants. Transcript levels of PPO1, CHLH, CHLI, and PORB genes involving Mg-porphyrin synthesis continuously decreased in ALA- and OF-treated plants, with greater decreases in ALA-treated plants. By contrast, up-regulation of FC2 and HO2 genes in Fe-porphyrin branch was noticeable in ALA and OF-treated plants 1 day and 2 days after the treatments, respectively. Decreased transcript levels of nuclear-encoded genes Lhcb1, Lhcb6, and RbcS were accompanied by disappearance of MgProto IX in ALA- and OF-treated plants after 2 days of the treatments. Under photodynamic stress imposed by ALA and OF, tight control of porphyrin biosynthesis prevents accumulation of toxic metabolic intermediates not only by down-regulation of their biosynthesis but also by photodynamic degradation. The up-regulation of FC2 and HO2 also appears to compensate for the photodynamic stress-induced damage. Copyright © 2014 Elsevier Inc. All rights reserved.

The effect of polymorphism on powder compaction and dissolution properties of chemically equivalent oxytetracycline hydrochloride powders.

PubMed

Liebenberg, W; de Villiers, M M; Wurster, D E; Swanepoel, E; Dekker, T G; Lötter, A P

1999-09-01

In South Africa, oxytetracycline is identified as an essential drug; many generic products are on the market, and many more are being developed. In this study, six oxytetracycline hydrochloride powders were obtained randomly from manufacturers, and suppliers were compared. It was found that compliance to a pharmacopoeial monograph was insufficient to ensure the optimum dissolution performance of a simple tablet formulation. Comparative physicochemical raw material analysis showed no major differences with regard to differential scanning calorimetry (DSC), infrared (IR) spectroscopy, powder dissolution, and particle size. However, the samples could be divided into two distinct types with respect to X-ray powder diffraction (XRD) and thus polymorphism. The two polymorphic forms had different dissolution properties in water or 0.1 N hydrochloride acid. This difference became substantial when the dissolution from tablets was compared. The powders containing form A were less soluble than that containing form B.

Postulated deficiency of hepatic heme and repair by hematin infusions in the "inducible" hepatic porphyrias.

PubMed Central

Watson, C J; Pierach, C A; Bossenmaier, I; Cardinal, R

1977-01-01

There is compelling, indirect evidence of hepatic heme deficiency due primarily to the respective genetic errors of the three inducible hepatic porphyrias, acute intermittent porphyria, porphyria variegata, and hereditary coproporphyria. The induction is enhanced by exogenous inducers such as barbiturate, estrogens and other "porphyrogenic" chemicals and factors, including glucose deprivation. The newer knowledge of the induction of delta-aminolevulinic acid synthetase [delta-aminolevulinate synthase; succinyl--CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37] in relation to inadequate heme, and repression by heme, stimulated early trials of hematin infusions to overcome the acute relapse in the foregoing inducible porphyrias. Recently this experience has been considerably expanded, 143 infusions of hematin having been given in 22 cases. Studies of the effect on the serum concentrations of delta-aminolevulinic acid and porphobilinogen have shown a highly significant decline, often to 0, especially of delta-aminolevulinic acid. A distinct relationship to the clinical severity of the attack has been evident in the frequency and magnitude of decline of serum delta-aminolevulinic acid and porphobilinogen. This was regularly associated with objective clinical improvement. PMID:266732

Infrared and Raman spectroscopy and DFT calculations of DL amino acids: Valine and lysine hydrochloride

NASA Astrophysics Data System (ADS)

Paiva, F. M.; Batista, J. C.; Rêgo, F. S. C.; Lima, J. A.; Freire, P. T. C.; Melo, F. E. A.; Mendes Filho, J.; de Menezes, A. S.; Nogueira, C. E. S.

2017-01-01

Single crystals of DL-valine and DL-lysine hydrochloride were grown by slow evaporation method and the crystallographic structure were confirmed by X-ray diffraction experiment and Rietveld method. These two crystals have been studied by Raman spectroscopy in the 25-3600 cm-1 spectral range and by infrared spectroscopy through the interval 375-4000 cm-1 at room temperature. Experimental and theoretical vibrational spectra were compared and a complete analysis of the modes was done in terms of the Potential Energy Distribution (PED).

Postpartum immobilization of adult female moose using xylazine, ketamine and yohimbine hydrochlorides.

PubMed

Garner, D L; Addison, E M

1994-01-01

Twenty-two free-ranging adult female moose (Alces alces) were immobilized with a 1:4 mixture of xylazine hydrochloride (XH) and ketamine hydrochloride (KH). Mean (SD) dosages/animal for XH and KH were 419 (148) and 1565 (433) mg, respectively. Mean (SD) induction time was 18.4 (9.7) minutes. Reversal with yohimbine hydrochloride using a mean dosage of 83 mg/animal resulted in a mean (SD) recovery time of 22.8 (28.5) minutes.

Development and Validation of a Rapid RP-UPLC Method for the Simultaneous Estimation of Bambuterol Hydrochloride and Montelukast Sodium from Tablets

PubMed Central

Yanamandra, R.; Vadla, C. S.; Puppala, U. M.; Patro, B.; Murthy, Y. L. N.; Parimi, A. R.

2012-01-01

A rapid, simple, sensitive and selective analytical method was developed by using reverse phase ultra performance liquid chromatographic technique for the simultaneous estimation of bambuterol hydrochloride and montelukast sodium in combined tablet dosage form. The developed method is superior in technology to conventional high performance liquid chromatography with respect to speed, resolution, solvent consumption, time, and cost of analysis. Elution time for the separation was 6 min and ultra violet detection was carried out at 210 nm. Efficient separation was achieved on BEH C18 sub-2-μm Acquity UPLC column using 0.025% (v/v) trifluoro acetic acid in water and acetonitrile as organic solvent in a linear gradient program. Resolutions between bambuterol hydrochloride and montelukast sodium were found to be more than 31. The active pharmaceutical ingredient was extracted from tablet dosage from using a mixture of methanol, acetonitrile and water as diluent. The calibration graphs were linear for bambuterol hydrochloride and montelukast sodium in the range of 6.25-37.5 μg/ml. The percentage recoveries for bambuterol hydrochloride and montelukast sodium were found to be in the range of 99.1-100.0% and 98.0-101.6%, respectively. The test solution was found to be stable for 7 days when stored in the refrigerator between 2-8°. Developed UPLC method was validated as per International Conference on Harmonization specifications for method validation. This method can be successfully employed for simultaneous estimation of bambuterol hydrochloride and montelukast sodium in bulk drugs and formulations. PMID:23325991

Validated Colorimetric Assay of Clonidine Hydrochloride from Pharmaceutical Preparations

PubMed Central

Corciova, Andreia

2016-01-01

Clonidine hydrochloride is an antihypertensive agent used for migraine prophylaxis, attention deficit hyperactivity disorder, menopausal flushing and Tourette syndrome. The quantity of the active substance in pharmaceutical preparations must be within specific limits, in agreement with the respective label claim. Therefore, the aim of this study was to establish the conditions for two spectrophotometric methods for clonidine determination, based on the formation of the ion pair complex between clonidine hydrochloride and thymol blue/bromophenol blue. A Jasco UV-Vis 530 spectrophotometer was used for the analysis and the maxim absorbance was measured at 418 nm/448 nm against blank solution. After validation, the methods were used for quantification of clonidine hydrochloride in two commercial samples (tablets). The recovery of active substance varies between 98.06 and 100.13 % without interferences from the excipients. PMID:27610155

Inhibition of VDAC1 prevents Ca²⁺-mediated oxidative stress and apoptosis induced by 5-aminolevulinic acid mediated sonodynamic therapy in THP-1 macrophages.

PubMed

Chen, Haibo; Gao, Weiwei; Yang, Yang; Guo, Shuyuan; Wang, Huan; Wang, Wei; Zhang, Shuisheng; Zhou, Qi; Xu, Haobo; Yao, Jianting; Tian, Zhen; Li, Bicheng; Cao, Wenwu; Zhang, Zhiguo; Tian, Ye

2014-12-01

Ultrasound combined with endogenous protoporphyrin IX derived from 5-aminolevulinic acid (ALA-SDT) is known to induce apoptosis in multiple cancer cells and macrophages. Persistent retention of macrophages in the plaque has been implicated in the pathophysiology and progression of atherosclerosis. Here we investigated the effects of inhibition of voltage-dependent anion channel 1 (VDAC1) on ALA-SDT-induced THP-1 macrophages apoptosis. Cells were pre-treated with VDAC1 inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) disodium salt for 1 h or downregulated VDAC1 expression by small interfering RNA and exposed to ultrasound. Cell viability was assessed by MTT assay, and cell apoptosis along with necrosis was evaluated by Hoechst 33342/propidium iodide staining and flow cytometry. Levels of cytochrome c release was assessed by confocal microscope and Western blot. The levels of full length caspases, caspase activation, and VDAC isoforms were analyzed by Western blot. Intracellular reactive oxygen species generation, mitochondrial membrane permeability, and intracellular Ca(2+) [Ca(2+)]i levels were measured with fluorescent probes. We confirmed that the pharmacological inhibition of VDAC1 by DIDS notably prevented ALA-SDT-induced cell apoptosis in THP-1 macrophages. Additionally, DIDS significantly inhibited intracellular ROS generation and apoptotic biochemical changes such as inner mitochondrial membrane permeabilization, loss of mitochondrial membrane potential, cytochrome c release and activation of caspase-3 and caspase-9. Moreover, ALA-SDT elevated the [Ca(2+)]i levels and it was also notably reduced by DIDS. Furthermore, both of intracellular ROS generation and cell apoptosis were predominately inhibited by Ca(2+) chelating reagent BAPTA-AM. Intriguingly, ALA-treatment markedly augmented VDAC1 protein levels exclusively, and the downregulation of VDAC1 expression by specific siRNA also significantly abolished cell apoptosis. Altogether, these

Synthesis, spectroscopic, thermal and antimicrobial investigations of charge-transfer complexes formed from the drug procaine hydrochloride with quinol, picric acid and TCNQ

NASA Astrophysics Data System (ADS)

Adam, Abdel Majid A.

2012-12-01

Intermolecular charge-transfer or proton-transfer complexes between the drug procaine hydrochloride (PC-HCl) as a donor and quinol (QL), picric acid (PA) or 7,7',8,8'-tetracyanoquinodimethane (TCNQ) as a π-acceptor have been synthesized and spectroscopically studied in methanol at room temperature. Based on elemental analyses and photometric titrations, the stoichiometry of the complexes (donor:acceptor molar ratios) was determined to be 1:1 for all three complexes. The formation constant (KCT), molar extinction coefficient (ɛCT) and other spectroscopic data have been determined using the Benesi-Hildebrand method and its modifications. The newly synthesized CT complexes have been characterized via elemental analysis, IR, Raman, 1H NMR, and electronic absorption spectroscopy. The morphological features of these complexes were investigated using scanning electron microscopy (SEM), and the sharp, well-defined Bragg reflections at specific 2θ angles have been identified from the powder X-ray diffraction patterns. Thermogravimetric analyses (TGAs) and kinetic thermodynamic parameters were also used to investigate the thermal stability of the synthesized solid CT complexes. Finally, the CT complexes were screened for their antibacterial and antifungal activities against various bacterial and fungal strains, and only the complex obtained using picric acid exhibited moderate antibacterial activity against all of the tested strains.

40 CFR Appendix B to Subpart Nnn... - Free Formaldehyde Analysis of Insulation Resins by Hydroxylamine Hydrochloride

Code of Federal Regulations, 2011 CFR

2011-07-01

... 4.0 with pH 4.0 buffer and pH 7 with pH 7.0 buffer. 3.350-mL burette for 1.0 N sodium hydroxide. 3... hydrochloride solution, 100 grams per liter, pH adjusted to 4.00. 4.3Hydrochloric acid solution, 1.0 N and 0.1 N... magnetic stirrer. Confirm that the resin has dissolved. 5.4Adjust the resin/solvent solution to pH 4.0...

40 CFR Appendix B to Subpart Nnn... - Free Formaldehyde Analysis of Insulation Resins by Hydroxylamine Hydrochloride

Code of Federal Regulations, 2010 CFR

2010-07-01

... 4.0 with pH 4.0 buffer and pH 7 with pH 7.0 buffer. 3.350-mL burette for 1.0 N sodium hydroxide. 3... hydrochloride solution, 100 grams per liter, pH adjusted to 4.00. 4.3Hydrochloric acid solution, 1.0 N and 0.1 N... magnetic stirrer. Confirm that the resin has dissolved. 5.4Adjust the resin/solvent solution to pH 4.0...

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride.

PubMed

Plöger, Gerlinde F; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, Dirk W; Langguth, Peter; Mehta, Mehul U; Parr, Alan; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Dressman, Jennifer B

2018-07-01

Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To elucidate the Biopharmaceutics Classification System (BCS) classification, experimental solubility and dissolution studies were also carried out. The antimalarial proguanil hydrochloride, effective via the parent compound proguanil and the metabolite cycloguanil, is not considered to be a narrow therapeutic index drug. Proguanil hydrochloride salt was shown to be highly soluble according to the U.S. Food and Drug Administration, World Health Organization, and European Medicines Agency guidelines, but data for permeability are inconclusive. Therefore, proguanil hydrochloride is conservatively classified as a BCS class 3 substance. In view of this information and the assessment of risks associated with a false positive decision, a BCS-based biowaiver approval procedure can be recommended for orally administered solid immediate release products containing proguanil hydrochloride, provided well-known excipients are used in usual amounts and provided the in vitro dissolution of the test and reference products is very rapid (85% or more are dissolved in 15 min at pH 1.2, 4.5, and 6.8) and is performed according to the current requirements for BCS-based biowaivers. Copyright © 2018 American Pharmacists Association®. All rights reserved.

Analgesic Effect of Intraperitoneal Bupivacaine Hydrochloride After Laparoscopic Sleeve Gastrectomy: a Randomized Clinical Trial.

PubMed

Alamdari, Nasser Malekpour; Bakhtiyari, Mahmood; Gholizadeh, Barmak; Shariati, Catrine

2018-03-01

The indications for sleeve gastrectomy as a primary procedure for the surgical treatment of morbid obesity have increased worldwide. Pain is the most common complaint for patients on the first day after laparoscopic sleeve gastrectomy. There are various methods for decreasing pain after laparoscopic sleeve gastrectomy such as the use of intraperitoneal bupivacaine hydrochloride. This clinical trial was an attempt to discover the effects of intraperitoneal bupivacaine hydrochloride on alleviating postoperative pain after laparoscopic sleeve gastrectomy. In general, 120 patients meeting the inclusion criteria were enrolled. Patients were randomly allocated into two interventions and control groups using a balanced block randomization technique. One group received intraperitoneal bupivacaine hydrochloride (30 cm 3 ), and the other group served as the control one and did not receive bupivacaine hydrochloride. Diclofenac suppository and paracetamol injection were administered to both groups for postoperative pain management. The mean subjective postoperative pain score was significantly decreased in patients who received intraperitoneal bupivacaine hydrochloride within the first 24 h after the surgery; thus, the instillation of bupivacaine hydrochloride was beneficial in managing postoperative pain. The intraoperative peritoneal irrigation of bupivacaine hydrochloride (30 cm 3 , 0.25%) in sleeve gastrectomy patients was safe and effective in reducing postoperative pain, nausea, and vomiting (IRCT2016120329181N4).

[Effect of phenformin hydrochloride on pharmacokinetics of puerarin in rats].

PubMed

Deng, Ying; Li, Ning; Cui, Mei; Xiong, Zhi-li; Li, Fa-mei

2012-10-01

To study the effect of phenformin hydrochloride that may be illegally added in traditional Chinese medicine preparations on the pharmacokinetics of puerarin in rats. Rats were randomly divided into the single pueraria group and the phenformin hydrochloride combined with pueraria group. After oral administration in the two groups, their bloods were sampled at different time points to determine the drug concentration of puerarin in rat blood and calculate pharmacokinetic parameters. After oral administration with pueraria extracts and phenformin hydrochloride combined with pueraria extracts, the two groups showed main pharmacokinetic parameters as follows: Cmax were (2.39 +/- 1.01), (1.03 +/- 0.35) mg x L(-1), respectively; Tmax were (0.50 +/- 0.09), (1.5 +/- 0.5) h, respectively; Ke were (0.153 +/- 0.028), (0.172 +/- 0.042) h(-1), respectively; t(1/2) were (4.65 +/- 0.86), (4.20 +/- 0.81) h, respectively; AUC(0-t), were (5.73 +/- 2.60), (5.45 +/- 1.81) mg x h x L(-1), respectively; AUC(0-infinity) were (6.72 +/- 2.89), (6.26 +/- 1.88) mg x h x L(-1), respectively. Compared with the single puerarin group, the Cmax was significantly decreased (P < 0.05) and the Tmax was markedly longer (P < 0.01) than the hydrochloride combined with pueraria group. Phenformin hydrochloride can slow down the absorption process of puerarin and change the pharmacokinetic process of puerarin to some extent.

The radiolysis and radioracemization of amino acids on clays

NASA Technical Reports Server (NTRS)

Bonner, W. A.; Hall, H.; Chow, G.; Yi, L.; Lemmon, R. M.

1985-01-01

The effects of the surfaces of kaolinite and bentonite clays on the radiolysis and radioracemization of L-leucine and its hydrochloride salt have been investigated experimentally. L-leucine and its hydrochloride salt were deposited on the clays and the amino acid/clay preparations were irradiated by a Co-60 gamma-ray source which induced 2-89 percent radiolysis. The efficiency of radiolysis and radioracemization were measured using gas chromatography. Results were obtained for leucine in 0.1 M aqueous solution for comparison with the clay-deposted leucine and leucine hydrochloride. It is found that radiolysis and radioracemization in the samples occurred according to a pseudo-first-order rate law. Comparison of the specific rate constants showed that leucine and its hydrochloride salt were the most resistant to both radiolysis and radioracemization, followed by leucine and its hydrochloride salt on kaolin. Leucine and its HCl salt on bentonite, and leucine in aqueous solution were found to be the least resistant to radiolysis and radioracemization. The experimental results are intepreted with respect to the Vester-Ulbricht mechanism for the origin of optical activity.

21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or injectable...

Stability-indicating spectrofluorimetric method for determination of itopride hydrochloride in raw material and pharmaceutical formulations.

PubMed

Walash, Mohamed I; Ibrahim, Fawzia; Eid, Manal I; El Abass, Samah Abo

2013-11-01

A simple, sensitive and rapid spectrofluorimetric method for determination of itopride hydrochloride in raw material and tablets has been developed. The proposed method is based on the measurement of the native fluorescence of the drug in water at 363 nm after excitation at 255 nm. The relative fluorescence intensity-concentration plot was rectilinear over the range of 0.1-2 μg/mL (2.5 × 10(-7)-5.06 × 10(-6) mole/L), with good correlation (r = 0.9999), limit of detection of 0.015 μg/mL and a lower limit of quantification of 0.045 μg/mL. The described method was successfully applied for the determination of itopride hydrochloride in its commercial tablets with average percentage recovery of 100.11 ± 0.32 without interference from common excipients. Additionally, the proposed method can be applied for determination of itopride in combined tablets with rabeprazole or pantoprazole without prior separation. The method was extended to stability study of itopride. The drug was exposed to acidic, alkaline, oxidative and photolytic degradation according to ICH guidelines. Moreover, the method was utilized to investigate the kinetics of the alkaline, acidic and oxidative degradation of the drug. A proposal for the degradation pathways was postulated.

The effect of tramadol hydrochloride on early life stages of fish.

PubMed

Sehonova, Pavla; Plhalova, Lucie; Blahova, Jana; Berankova, Petra; Doubkova, Veronika; Prokes, Miroslav; Tichy, Frantisek; Vecerek, Vladimir; Svobodova, Zdenka

2016-06-01

The aim of this study was to perform the fish embryo acute toxicity test (FET) on zebrafish (Danio rerio) and the early-life stage toxicity test on common carp (Cyprinus carpio) with tramadol hydrochloride. The FET was performed using the method inspired by the OECD guideline 236. Newly fertilized zebrafish eggs were exposed to tramadol hydrochloride at concentrations of 10; 50; 100 and 200μg/l for a period of 144h. An embryo-larval toxicity test on C. carpio was performed according to OECD guideline 210 also with tramadol hydrochloride at concentrations 10; 50; 100 and 200μg/l for a period of 32 days. Hatching was significantly influenced in both acute and subchronic toxicity assays. Subchronic exposure also influenced early ontogeny, both morphometric and condition characteristics and caused changes in antioxidant enzyme activity. The LOEC value was found to be 10μg/l tramadol hydrochloride. Copyright © 2016 Elsevier B.V. All rights reserved.

Immobilization of swift foxes with ketamine hydrochloride-xylazine hydrochloride

USGS Publications Warehouse

Telesco, R.L.; Sovada, Marsha A.

2002-01-01

There is an increasing need to develop field immobilization techniques that allow researchers to handle safely swift foxes (Vulpes velox) with minimal risk of stress or injury. We immobilized captive swift foxes to determine the safety and effectiveness of ketamine hydrochloride and xylazine hydrochloride at different dosages. We attempted to determine appropriate dosages to immobilize swift foxes for an adequate field-handling period based on three anesthesia intervals (induction period, immobilization period, and recovery period) and physiologic responses (rectal temperature, respiration rate, and heart rate). Between October 1998–July 1999, we conducted four trials, evaluating three different dosage ratios of ketamine and xylazine (2.27:1.2, 5.68:1.2, and 11.4:1.2 mg/kg ketamine:mg/kg xylazine, respectively), followed by a fourth trial with a higher dosage at the median ratio (11.4 mg/kg ketamine:2.4 mg/kg xylazine). We found little difference in induction and recovery periods among trials 1–3, but immobilization time increased with increasing dosage (P<0.08). Both the immobilization period and recovery period increased in trial 4 compared with trials 1–3 (P≤0.03). There was a high variation in responses of individual foxes across trials, making it difficult to identify an appropriate dosage for field handling. Heart rate and respiration rates were depressed but all physiologic measures remained within normal parameters established for domestic canids. We recommend a dosage ratio of 10 mg/kg ketamine to 1 mg/kg xylazine to immobilize swift foxes for field handling.

Anti-Inflammatory Effects of Berberine Hydrochloride in an LPS-Induced Murine Model of Mastitis

PubMed Central

Feng, Shibin; Ding, Nana; He, Yanting; Li, Cheng; Li, Manman; Ding, Xuedong; Ding, Hongyan; Li, Jinchun

2018-01-01

Berberine hydrochloride is an isoquinoline type alkaloid extracted from Berberidaceae, Rutaceae, and other plants. Previous reports have shown that berberine hydrochloride has anti-inflammatory properties. However, the underlying molecular mechanisms remain unclear. In this study, a lipopolysaccharide- (LPS-) induced murine model of mastitis was established to explore the anti-inflammatory action of berberine hydrochloride. Sixty mice that had been lactating for 5–7 days were randomly divided into six groups, including control, LPS, three berberine hydrochloride treatment groups (5, 10, and 20 mg/kg), and a dexamethasone (DEX) (5 mg/kg) group. Berberine hydrochloride was administered intraperitoneally 1 h before and 12 h after LPS-induced mastitis, and all mice were sacrificed 24 h after LPS induction. The pathological and histopathological changes of the mammary glands were observed. The concentrations and mRNA expressions of TNF-α, IL-1β, and IL-6 were measured by ELISA and qRT-PCR. The activation of TLR4 and NF-κB signaling pathways was analyzed by Western blot. Results indicated that berberine hydrochloride significantly attenuated neutrophil infiltration and dose-dependently decreased the secretion and mRNA expressions of TNF-α, IL-1β, and IL-6 within a certain range. Furthermore, berberine hydrochloride suppressed LPS-induced TLR4 and NF-κB p65 activation and the phosphorylation of I-κB. Berberine hydrochloride can provide mice robust protection from LPS-induced mastitis, potentially via the TLR4 and NF-κB pathway.

A pilot cost-effectiveness analysis of treatments in newly diagnosed high-grade gliomas: the example of 5-aminolevulinic Acid compared with white-light surgery.

PubMed

Esteves, Susana; Alves, Marta; Castel-Branco, Marta; Stummer, Walter

2015-05-01

High-grade gliomas are aggressive, incurable tumors characterized by extensive diffuse invasion of the normal brain parenchyma. Novel therapies at best prolong survival; their costs are formidable and benefit is marginal. Economic restrictions thus require knowledge of the cost-effectiveness of treatments. Here, we show the cost-effectiveness of enhanced resections in malignant glioma surgery using a well-characterized tool for intraoperative tumor visualization, 5-aminolevulinic acid (5-ALA). To evaluate the cost-effectiveness of 5-ALA fluorescence-guided neurosurgery compared with white-light surgery in adult patients with newly diagnosed high-grade glioma, adopting the perspective of the Portuguese National Health Service. We used a Markov model (cohort simulation). Transition probabilities were estimated with the use of data from 1 randomized clinical trial and 1 noninterventional prospective study. Utility values and resource use were obtained from published literature and expert opinion. Unit costs were taken from official Portuguese reimbursement lists (2012 values). The health outcomes considered were quality-adjusted life-years, life-years, and progression-free life-years. Extensive 1-way and probabilistic sensitivity analyses were performed. The incremental cost-effectiveness ratios are below &OV0556;10 000 in all evaluated outcomes, being around &OV0556;9100 per quality-adjusted life-year gained, &OV0556;6700 per life-year gained, and &OV0556;8800 per progression-free life-year gained. The probability of 5-ALA fluorescence-guided surgery cost-effectiveness at a threshold of &OV0556;20000 is 96.0% for quality-adjusted life-year, 99.6% for life-year, and 98.8% for progression-free life-year. 5-ALA fluorescence-guided surgery appears to be cost-effective in newly diagnosed high-grade gliomas compared with white-light surgery. This example demonstrates cost-effectiveness analyses for malignant glioma surgery to be feasible on the basis of existing data.

21 CFR 524.1484b - Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride, and myristyl-gamma-picolinium...

Code of Federal Regulations, 2010 CFR

2010-04-01

..., tetracaine hydrochloride, and myristyl-gamma-picolinium chloride, topical powder. 524.1484b Section 524.1484b... Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride, and myristyl-gamma-picolinium chloride... hydrochloride and .2 milligram of myristyl-gamma-picolinium chloride in each gram of the product in a special...

21 CFR 524.1662 - Oxytetracycline hydrochloride ophthalmic and topical dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride ophthalmic and topical dosage forms. 524.1662 Section 524.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1662 Oxytetracycline hydrochloride ophthalmic and topical dosage forms. ...

IR, FT-ICR-MS studies on (1'S, 6'S)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0] non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride salt.

PubMed

Lin, Zhiwei

2014-01-01

The infrared spectra of (1'S, 6'S)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0] non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride salt (CLF-HCl) were studied and compared with free base. Their fragmentation pathways were investigated using tandem mass spectrometric (MS/MS) techniques on Fourier-transform ion cyclotron resonance spectrum, and many characteristic fragment ions were found. Copyright © 2013 Elsevier B.V. All rights reserved.

Electron beam-induced graft polymerization of acrylic acid and immobilization of arginine-glycine-aspartic acid-containing peptide onto nanopatterned polycaprolactone.

PubMed

Sun, Hui; Wirsén, Anders; Albertsson, Ann-Christine

2004-01-01

Electron beam- (EB-) induced graft polymerization of acrylic acid and the subsequent immobilization of arginine-glycine-aspartic acid (RGD) peptide onto nanopatterned polycaprolactone with parallel grooves is reported. A high concentration of carboxylic groups was introduced onto the polymer substrate by EB-induced polymerization of acrylic acid. In the coupling of the RGD peptide to the carboxylated polymer surface, a three-step peptide immobilization process was used. This process included the activation of surface carboxylic acid into an active ester intermediate by use of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), the introduction of disulfide groups by use of 2-(2-pyridinyldithio)ethanamine hydrochloride (PDEA), and final immobilization of the peptide via a thiol-disulfide exchange reaction. The extent of coupling was measured by UV spectroscopy. A preliminary study of the in vitro behavior of keratinocytes (NCTC 2544) cultured on the acrylic acid-grafted and RGD peptide-coupled surface showed that most cells grown on the coupled samples had a spread-rounded appearance, while the majority of cells tended to be elongated along the grooves on uncoupled substrates.

21 CFR 184.1676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... hydrochloride that is prepared by chemical synthesis. (b) The ingredient meets the specifications of the Food...)(31) of this chapter; plant protein products as defined in § 170.3(n)(33) of this chapter; and snack...

21 CFR 520.1263a - Lincomycin hydrochloride monohydrate tablets and sirup.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Lincomycin hydrochloride monohydrate tablets and sirup. 520.1263a Section 520.1263a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1263a Lincomycin hydrochloride monohydrate tablets and sirup. (a) Specifications. The sirup...

A comparative study on the aggregating effects of guanidine thiocyanate, guanidine hydrochloride and urea on lysozyme aggregation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Emadi, Saeed, E-mail: emadi@iasbs.ac.ir; Behzadi, Maliheh

Highlights: • Lysozyme aggregated in guanidine thiocyanate (1.0 and 2.0 M). • Lysozyme aggregated in guanidine hydrochloride (4 and 5 M). • Lysozyme did not aggregated at any concentration (0.5–5 M) of urea. • Unfolding pathway is more important than unfolding per se in aggregation. - Abstract: Protein aggregation and its subsequent deposition in different tissues culminate in a diverse range of diseases collectively known as amyloidoses. Aggregation of hen or human lysozyme depends on certain conditions, namely acidic pH or the presence of additives. In the present study, the effects on the aggregation of hen egg-white lysozyme via incubationmore » in concentrated solutions of three different chaotropic agents namely guanidine thiocyanate, guanidine hydrochloride and urea were investigated. Here we used three different methods for the detection of the aggregates, thioflavin T fluorescence, circular dichroism spectroscopy and atomic force microscopy. Our results showed that upon incubation with different concentrations (0.5, 1.0, 2.0, 3.0, 4.0, 5.0 M) of the chemical denaturants, lysozyme was aggregated at low concentrations of guanidine thiocyanate (1.0 and 2.0 M) and at high concentrations of guanidine hydrochloride (4 and 5 M), although no fibril formation was detected. In the case of urea, no aggregation was observed at any concentration.« less

21 CFR 520.1242b - Levamisole hydrochloride tablet or oblet (bolus).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Levamisole hydrochloride tablet or oblet (bolus... § 520.1242b Levamisole hydrochloride tablet or oblet (bolus). (a) Chemical name. (-)-2,3,5,6-Tetrahydro... using in severely debilitated animals. (2) It is used in a tablet for sheep as follows: (i) Amount. 0...

A novel kind of TSV slurry with guanidine hydrochloride

NASA Astrophysics Data System (ADS)

Jiao, Hong; Yuling, Liu; Baoguo, Zhang; Xinhuan, Niu; Liying, Han

2015-10-01

The effect of a novel alkaline TSV (through-silicon-via) slurry with guanidine hydrochloride (GH) on CMP (chemical mechanical polishing) was investigated. The novel alkaline TSV slurry was free of any inhibitors. During the polishing process, the guanidine hydrochloride serves as an effective surface-complexing agent for TSV CMP applications, the removal rate of barrier (Ti) can be chemically controlled through tuned selectivity with respect to the removal rate of copper and dielectric, which is helpful to modifying the dishing and gaining an excellent topography performance in TSV manufacturing. In this paper, we mainly studied the working mechanism of the components of slurry and the skillful application guanidine hydrochloride in the TSV slurry. Project supported by the Major National Science and Technology Special Projects (No. 2009ZX02308), the Fund Project of Hebei Provincial Department of Education, China (No. QN2014208), the Natural Science Foundation of Hebei Province, China (No. E2013202247), and Colleges and Universities Scientific research project of Hebei Province, China (No. Z2014088).

Validation of an HPLC method for the quantification of ambroxol hydrochloride and benzoic acid in a syrup as pharmaceutical form stress test for stability evaluation.

PubMed

Heinänen, M; Barbas, C

2001-03-01

A method is described for ambroxol, trans-4-(2-amino-3,5-dibromobenzylamino) cyclohexanol hydrochloride, and benzoic acid separation by HPLC with UV detection at 247 nm in a syrup as pharmaceutical presentation. Optimal conditions were: Column Symmetry Shield RPC8, 5 microm 250 x 4.6 mm, and methanol/(H(3)PO(4) 8.5 mM/triethylamine pH=2.8) 40:60 v/v. Validation was performed using standards and the pharmaceutical preparation which contains the compounds described above. Results from both standards and samples show suitable validation parameters. The pharmaceutical grade substances were tested by factors that could influence the chemical stability. These reaction mixtures were analysed to evaluate the capability of the method to separate degradation products. Degradation products did not interfere with the determination of the substances tested by the assay.

Synthesis of silver nanoparticles in the presence of diethylaminoethyl-dextran hydrochloride polymer and their SERS activity

NASA Astrophysics Data System (ADS)

Mikac, L.; Jurkin, T.; Štefanić, G.; Ivanda, Mile; Gotić, Marijan

2017-09-01

The silver nanoparticles (AgNPs) were synthesized upon γ-irradiation of AgNO3 precursor suspensions in the presence of diethylaminoethyl-dextran hydrochloride (DEAE-dextran) cationic polymer as a stabilizer. The dose rate of γ-irradiation was 32 kGy h-1, and absorbed doses were 30 and 60 kGy. The γ-irradiation of the precursor suspension at acidic or neutral pH conditions produced predominantly the silver(I) chloride (AgCl) particles, because of the poor solubility of AgCl already present in the precursor suspension. The origin of AgCl in the precursor suspension was due to the presence of chloride ions in DEAE-dextran hydrochloride polymer. The addition of ammonia to the precursor suspension dissolved the AgCl precipitate, and the γ-irradiation of such colourless suspension at alkali pH produced a stable aqueous suspension with rather uniform spherical AgNPs of approximately 30 nm in size. The size of AgNPs was controlled by varying the AgNO3/DEAE-dextran concentration in the suspensions. The surface-enhanced Raman scattering (SERS) activities of synthesized AgNPs were examined using organic molecules rhodamine 6G, pyridine and 4-mercaptobenzoic acid (4-MBA). The NaBH4 was used as SERS aggregation agent. The SERS results have shown that in the presence of synthesized AgNPs, it was possible to detect low concentration of tested compounds.

5-aminolevulinic acid (5-ALA) fluorescence guided surgery of high-grade gliomas in eloquent areas assisted by functional mapping. Our experience and review of the literature.

PubMed

Della Puppa, Alessandro; De Pellegrin, Serena; d'Avella, Elena; Gioffrè, Giorgio; Rossetto, Marta; Gerardi, Alessandra; Lombardi, Giuseppe; Manara, Renzo; Munari, Marina; Saladini, Marina; Scienza, Renato

2013-06-01

Only few data are available on the specific topic of 5-aminolevulinic acid (5-ALA) guided surgery of high-grade gliomas (HGG) located in eloquent areas. Studies focusing specifically on the post-operative clinical outcome of such patients are yet not available, and it has not been so far explored whether such approach could be more suitable for some particular subgroups of patients. Patients affected by HGG in eloquent areas who underwent surgery assisted by 5-ALA fluorescence and intra-operative monitoring were prospectively recruited in our Department between June 2011 and August 2012. Resection rate was reported as complete resection of enhancing tumor (CRET), gross total resection (GTR) >98 % and GTR > 90 %. Clinical outcome was evaluated at 7, 30, and 90 days after surgery. Thirty-one patients were enrolled. Resection was complete (CRET) in 74 % of patients. Tumor removal was stopped to avoid neurological impairment in 26 % of cases. GTR > 98 % and GTR > 90 % was achieved in 93 % and 100 % of cases, respectively. First surgery and awake surgery had a CRET rate of 80 % and 83 %, respectively. Even though at the first-week assessment 64 % of patients presented neurological impairment, there was a 3 % rate of severe morbidity at the 90th day assessment. Newly diagnosed patients had a significantly lower morbidity (0 %) and post-operative higher median KPS. Both pre-operative neurological condition and improvement after corticosteroids resulted significantly predictive of post-operative functional outcome. 5-ALA surgery assisted by functional mapping makes high HGG resection in eloquent areas feasible , through a reasonable rate of late morbidity. This emerges even more remarkably for selected patients.

Stability of methadone hydrochloride in 0.9% sodium chloride injection in single-dose plastic containers.

PubMed

Denson, D D; Crews, J C; Grummich, K W; Stirm, E J; Sue, C A

1991-03-01

The stability of methadone hydrochloride in 0.9% sodium chloride injection in flexible polyvinyl chloride containers was studied. Commercially available methadone hydrochloride 20 mg/mL and 25-mL single-dose bags of 0.9% sodium chloride injection were used. Six samples each were prepared at methadone hydrochloride concentrations of 1, 2, and 5 mg/mL. The solutions were stored at room temperature and were not protected from light. Immediately after preparation and after two, three, and four weeks of storage, each of the 18 samples was divided into three aliquots, each of which was analyzed in duplicate for methadone hydrochloride concentration by gas chromatography. There was less than 10% change in methadone hydrochloride concentration in any sample throughout the four-week study period. Methadone hydrochloride at concentrations of 1, 2, and 5 mg/mL prepared in commercially available flexible polyvinyl chloride containers of 0.9% sodium chloride injection and stored at room temperature without deliberate protection from light is stable for at least four weeks.

Formulation of bi-layer matrix tablets of tramadol hydrochloride: Comparison of rate retarding ability of the incorporated hydrophilic polymers.

PubMed

Arif, Hasanul; Al-Masum, Abdullah; Sharmin, Florida; Reza, Selim; Sm Islam, Sm Ashraful

2015-05-01

Bi-layer tablets of tramadol hydrochloride were prepared by direct compression technique. Each tablet contains an instant release layer with a sustained release layer. The instant release layer was found to release the initial dose immediately within minutes. The instant release layer was combined with sustained release matrix made of varying quantity of Methocel K4M, Methocel K15MCR and Carbomer 974P. Bi-layer tablets were evaluated for various physical tests including weight variation, thickness and diameter, hardness and percent friability. Drug release from bi-layer tablet was studied in acidic medium and buffer medium for two and six hours respectively. Sustained release of tramadol hydrochloride was observed with a controlled fashion that was characteristic to the type and extent of polymer used. % Drug release from eight-hour dissolution study was fitted with several kinetic models. Mean dissolution time (MDT) and fractional dissolution values (T25%, T50% and T80%) were also calculated as well, to compare the retarding ability of the polymers. Methocel K15MCR was found to be the most effective in rate retardation of freely water-soluble tramadol hydrochloride compared to Methocel K4M and Capbomer 974P, when incorporated at equal ratio in the formulation.

21 CFR 520.2345h - Tetracycline hydrochloride, sodium novobiocin, and prednisolone tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... prednisolone tablets. 520.2345h Section 520.2345h Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... ANIMAL DRUGS § 520.2345h Tetracycline hydrochloride, sodium novobiocin, and prednisolone tablets. (a) Specifications. Each tablet contains the equivalent of 60 milligrams of tetracycline hydrochloride, 60 milligrams...

New thermoresistant polymorph from CO2 recrystallization of minocycline hydrochloride.

PubMed

Rodrigues, Miguel A; Tiago, João M; Padrela, Luis; Matos, Henrique A; Nunes, Teresa G; Pinheiro, Lídia; Almeida, António J; de Azevedo, Edmundo Gomes

2014-11-01

To prepare and thoroughly characterize a new polymorph of the broad-spectrum antibiotic minocycline from its hydrochloride dehydrate salts. The new minocycline hydrochloride polymorph was prepared by means of the antisolvent effect caused by carbon dioxide. Minocycline recrystallized as a red crystalline hydrochloride salt, starting from solutions or suspensions containing CO2 and ethanol under defined conditions of temperature, pressure and composition. This novel polymorph (β-minocycline) revealed characteristic PXRD and FTIR patterns and a high melting point (of 247 ºC) compared to the initial minocycline hydrochloride hydrates (α-minocycline). Upon dissolution the new polymorph showed full anti-microbial activity. Solid-state NMR and DSC studies evidenced the higher chemical stability and crystalline homogeneity of β-minocycline compared to the commercial chlorohydrate powders. Molecular structures of both minocyclines present relevant differences as shown by multinuclear solid-state NMR. This work describes a new crystalline structure of minocycline and evidences the ability of ethanol-CO2 system in removing water molecules from the crystalline structure of this API, at modest pressure, temperature and relatively short time (2 h), while controlling the crystal habit. This process has therefore the potential to become a consistent alternative towards the control of the solid form of APIs.

Study on fluorescence characteristics of duloxetine hydrochloride

NASA Astrophysics Data System (ADS)

Liu, Xiangping; Du, Yingxiang; Wu, Xiulan

2008-12-01

The fluorescence characteristics of duloxetine hydrochloride are studied in this paper. The fluorescence emission spectra of duloxetine demonstrate that intramolecular charge-transfer takes place between thiophene ring and napthalenyloxy group upon irradiation. The effects of excitation light, solvent system, variation of solution pH value, metal ions and vitamin C on the fluorescence spectra of duloxetine hydrochloride are elucidated, respectively. A spectrofluorometric method of quantitative determination of duloxetine in dosage form is reported for the first time, the linear range is 7.14 × 10 -8 mol/L to 1.43 × 10 -5 mol/L, the linear correlation coefficient r is equal to 0.9997, and the detection limit is 3.5 × 10 -8 mol/L. The accuracy and the precision are satisfactory.

Chemical stability of diphenhydramine hydrochloride from an elixir and lidocaine hydrochloride from a viscous solution when mixed together.

PubMed

Gupta, Vishnu D

2006-01-01

The stability of diphenhydramine hydrochloride (from an elixir) and lidocaine hydrochloride (from a viscous solution) in a mixture (1:1) was studied using a stability-indicating high-peformance liquid chromatographic assay method. The concentrations of the drugs were related directly to peak heights and the percent relative standard deviations based on five injections were 1.4 for diphenhydramine and 1.3 for lidocaine. The products of hydrolysis from the both the drugs and a number of excipients present in the dosage forms did not interfere with the developed assay procedure. The mixture was stable for at least 21 days when stored in amber-colored bottles at room temperature. The pH value of the mixture remained constant, and the physical appearance did not change during the study period.

5-Aminolevulinic acid with sodium ferrous citrate induces autophagy and protects cardiomyocytes from hypoxia-induced cellular injury through MAPK-Nrf-2-HO-1 signaling cascade

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Mingyi; Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou; Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha

Background: Hypoxia causes cardiac disease via oxidative stress and mitochondrial dysfunction. 5-Aminolevulinic acid in combination with sodium ferrous citrate (ALA/SFC) has been shown to up-regulate heme oxygenase-1 (HO-1) and decrease macrophage infiltration and renal cell apoptosis in renal ischemia injury mice. However, its underlying mechanism remains largely unknown. The aim of this study was to investigate whether ALA/SFC could protect cardiomyocytes from hypoxia-induced apoptosis by autophagy via HO-1 signaling. Materials & methods: Murine atrial cardiomyocyte HL-1 cells were pretreated with ALA/SFC and then exposed to hypoxia. Results: ALA/SFC pretreatment significantly attenuated hypoxia-induced cardiomyocyte apoptosis, reactive oxygen species production, and mitochondrial injury,more » while it increased cell viability and autophagy levels. HO-1 expression by ALA/SFC was associated with up-regulation and nuclear translocation of Nrf-2, whereas Nrf-2 siRNA dramatically reduced HO-1 expression. ERK1/2, p38, and SAPK/JNK pathways were activated by ALA/SFC and their specific inhibitors significantly reduced ALA/SFC-mediated HO-1 upregulation. Silencing of either Nrf-2 or HO-1and LY294002, inhibitor of autophagy, abolished the protective ability of ALA/AFC against hypoxia-induced injury and reduced ALA/SFC-induced autophagy. Conclusion: Taken together, our data suggest that ALA/SFC induces autophagy via activation of MAPK/Nrf-2/HO-1 signaling pathway to protect cardiomyocytes from hypoxia-induced apoptosis. - Highlights: • ALA/SFC attenuates hypoxia-induced cardiomyocyte apoptosis, reactive oxygen species production, and mitochondrial injury. • ALA/SFC increases the heme oxygenase-1 expression via Nrf-2 and ERK1/2, p38, and SAPK/JNK pathways. • ALA/SFC induces autophagy and inhibition of autophagy prevent ALA/SFC-mediated suppression of hypoxia-induced injury.« less

An evaluation of the influence of medetomidine hydrochloride and atipamezole hydrochloride on the arrhythmogenic dose of epinephrine in dogs during halothane anesthesia.

PubMed Central

Pettifer, G R; Dyson, D H; McDonell, W N

1996-01-01

Alterations in the arrhythmogenic dose of epinephrine (ADE) were determined following administration of medetomidine hydrochloride (750 micrograms/M2) and a saline placebo, or medetomidine hydrochloride (750 micrograms/M2), followed by specific medetomidine reversal agent, atipamezole hydrochloride (50 micrograms/kg) 20 min later, in halothane-anesthetized dogs (n = 6). ADE determinations were made prior to the administration of either treatment, 20 min and 4 h following medetomidine/saline or medetomidine/atipamezole administration. Epinephrine was infused for 3 min at increasing dose rates (2.5 and 5.0 micrograms/kg/min) until the arrhythmia criterion (4 or more intermittent or continuous premature ventricular contractions) was reached. The interinfusion interval was 20 min. There were no significant differences in the amount of epinephrine required to reach the arrhythmia criterion following the administration of either treatment. In addition, the ADE at each determination was not different between treatment groups. In this study, the administration of medetomidine to halothane-anesthetized dogs did not alter their arrhythmogenic response to infused epinephrine. PMID:8825986

Acute dermal toxicity of guanidine hydrochloride in rabbits. Report for 18 May-1 August 1984

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hiatt, G.F.; Sanso, S.K.; Korte, D.W.

1989-12-01

The acute dermal toxicity of guanidine hydrochloride was evaluated in five male and five female New Zealand White rabbits. Guanidine hydrochloride (2 g/kg) was applied topically to the clipped dorsal skin surface for 24 hours. No compound-related deaths or clinical signs were observed; however, guanidine hydrochloride did produce dermal irritation, necrosis, and eschar formation under conditions of the study.

[The effectiveness of cevimeline hydrochloride on dry cough in Sjögren's syndrome].

PubMed

Nishinarita, Makoto; Hanzawa, Midori; Iikuni, Noriko; Ota, Syuji

2004-04-01

Dry cough in Sjögren syndrome (SS) is not an uncommon symptom observed in clinical fields. However, effective treatments for the cough have not been established. The recently introduced cevimeline hydrochloride, a muscarinic receptor stimulant, has been confirmed to be definitely effective for xerostomia of SS. In the present study, the effectiveness of cevimeline hydrochloride on dry cough was studied in 9 Sjögren patients and evaluated using the visual analog scale (VAS) and face scale. Improvement of dry cough was observed in 8 out of the 9 patients, suggesting the effectiveness of cevimeline hydrochloride. Although the detailed etiology of dry cough in SS is unknown, the result of the study suggested the mechanism that cevimeline hydrochloride increased the secretion in the airway mucus, improving dry bronchial conditions. Further studies are needed with more subjects.

Physical and chemical stability of palonosetron hydrochloride with five opiate agonists during simulated Y-site administration.

PubMed

Trissel, Lawrence A; Trusley, Craig; Ben, Michel; Kupiec, Thomas C

2007-06-01

The physical and chemical compatibility of palonosetron hydrochloride with fentanyl citrate, hydromorphone hydrochloride, meperidine hydrochloride, morphine sulfate, and sufentanil citrate during simulated Y-site administration was studied. Test samples were prepared in triplicate by mixing 7.5-mL samples of undiluted palonosetron 50 microg/mL (of palonosetron) with 7.5-mL samples of fentanyl citrate 50 microg/mL, morphine sulfate 15 mg/mL, hydromorphone hydrochloride 0.5 mg/mL, meperidine hydrochloride 10 mg/mL, and sufentanil citrate 12.5 microg/mL (of sufentanil) per milliliter individually in colorless 15-mL borosilicate glass screw-cap culture tubes with polypropylene caps. Physical stability of the admixtures was assessed by visual examination and by measuring turbidity and particle size and content. Chemical stability was assessed by stability-indicating high-performance liquid chromatography. Evaluations were performed immediately and one and four hours after mixing. All of the admixtures were initially clear and colorless in normal fluorescent room light and when viewed with a high-intensity monodirectional light (Tyndall beam) and were essentially without haze. Changes in turbidity were minor throughout the study. Particulates measuring 10 microm or larger were few in all samples throughout the observation period. The admixtures remained colorless throughout the study. No loss of palonosetron hydrochloride occurred with any of the opiate agonists tested over the four-hour period. Similarly, little or no loss of the opiate agonists occurred over the four-hour period. Palonosetron hydrochloride was physically and chemically stable with fentanyl citrate, hydromorphone hydrochloride, meperidine hydrochloride, morphine sulfate, and sufentanil citrate during simulated Y-site administration.

Effects of ambroxol hydrochloride on concentrations of paclitaxel and carboplatin in lung cancer patients at different administration times.

PubMed

Li, J; Yi, W; Jiang, P; Sun, R; Li, T

2016-11-30

Our previous preliminary study revealed a synergistic effect of ambroxol hydrochloride with chemotherapeutic agents such as paclitaxel and carboplatin in lung cancer. However, the optimal conditions such as administration time and drug concentration of ambroxol hydrochloride to achieve the maximum synergistic effect remained unclear. Therefore, concentration changes of the chemotherapy drugs paclitaxel and carboplatin in the sputum were observed after ambroxol hydrochloride administration at different times in order to determine the most effective time frame of ambroxol hydrochloride administration. In this study, 470 cases of non-small cell lung cancer (NSCLC) were divided into different groups with ambroxol hydrochloride administered at different time points prior to chemotherapy, while another 171 cases received no ambroxol hydrochloride prior to chemotherapy. The results showed the concentrations of paclitaxel and carboplatin in sputum of patients treated with ambroxol hydrochloride were significantly higher than those of the control group, suggesting that ambroxol hydrochloride significantly increased the local concentrations of chemotherapeutic agents in lung tissues of NSCLC. Furthermore, the intravenous administration of ambroxol hydrochloride more than 48 hours before chemotherapy showed an optimized schedule and much greater efficacy in increasing drug concentrations than that of the control group. No statistical differences were found in the rates of grade 2 or above myelosuppression between the ambroxol intervention and control groups. Taken together, these results demonstrate that ambroxol hydrochloride administered intravenously more than 48 hours prior to chemotherapy optimally increased the concentrations of paclitaxel and carboplatin in lung tissue without significantly increasing hematologic toxicity.

76 FR 53907 - Determination That TALWIN COMPOUND (Aspirin; Pentazocine Hydrochloride) Tablets, 325 Milligrams...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

...] Determination That TALWIN COMPOUND (Aspirin; Pentazocine Hydrochloride) Tablets, 325 Milligrams; Equivalent to... determined that TALWIN COMPOUND (aspirin; pentazocine hydrochloride (HCl)) tablets, 325 milligrams (mg... determination will allow FDA to approve abbreviated new drug applications (ANDAs) for aspirin; pentazocine HCl...

Use of xylazine hydrochloride-ketamine hydrochloride for immobilization of wild leopards (Panthera pardus fusca) in emergency situations.

PubMed

Belsare, Aniruddha V; Athreya, Vidya R

2010-06-01

In India, leopards (Panthera pardus fusca) inhabit human-dominated landscapes, resulting in encounters that require interventions to prevent harm to people, as well as the leopards. Immobilization is a prerequisite for any such intervention. Such emergency field immobilizations have to be carried out with limited tools, often amidst large uncontrollable crowds. An effective and practicable approach is discussed, based on 55 wild leopard immobilizations undertaken between January 2003 and April 2008. A xylazine hydrochloride (1.4 +/- 0.3 mg/kg)--ketamine hydrochloride (5 +/- 2 mg/kg) mixture was used for immobilization of leopards, based on estimated body weight. When weight could not be estimated, a standard initial dose of 50 mg of xylazine--150 mg of ketamine was used. Supplemental doses (50-75 mg) of only ketamine were used as required. No life-threatening adverse effects of immobilization were documented for at least 1 mo postimmobilization.

21 CFR 522.723 - Diprenorphine hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Specifications. Each milliliter of diprenorphine hydrochloride injection, veterinary, contains 2 mg of... injection, veterinary, the use of which is provided for in § 522.883, in wild and exotic animals. (2) It is...

21 CFR 556.580 - Robenidine hydrochloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.580 Robenidine hydrochloride. Tolerances are established...

21 CFR 556.580 - Robenidine hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.580 Robenidine hydrochloride. Tolerances are established...

21 CFR 556.580 - Robenidine hydrochloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.580 Robenidine hydrochloride. Tolerances are established...

21 CFR 556.580 - Robenidine hydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.580 Robenidine hydrochloride. Tolerances are established...

21 CFR 556.580 - Robenidine hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.580 Robenidine hydrochloride. Tolerances are established...

Niosomal encapsulation of ethambutol hydrochloride for increasing its efficacy and safety.

PubMed

El-Ridy, Mohammed Shafik; Yehia, Soad Aly; Kassem, Mahfouz Abd-El-Megeid; Mostafa, Dina Mahmoud; Nasr, Essam Amin; Asfour, Marwa Hasanin

2015-01-01

Tuberculosis (TB) is a worldwide health concern. In 2011, about 8.7 million new cases developed TB and 1.4 million people died from it. Enhancement of ethambutol hydrochloride activity and safety in treatment of TB through niosomal encapsulation. Niosomes were prepared by the thin-film hydration method. They were characterized, investigated for in vitro release, lung disposition and in vivo biological evaluation. Entrapment efficiency of ethambutol hydrochloride ranged from 12.20% to 25.81%. Zeta potential values inferred stability of neutral and negatively charged formulations. In vitro release was biphasic. Lung targeting was increased by niosomal encapsulation. Biological evaluation revealed superiority of niosomal ethambutol hydrochloride over the free drug. Neutral and negatively charged niosomal vesicles are dispersed homogenously unlike positively charged vesicles. Niosomal encapsulation results in controlled drug release. Niosomal formulations targeted more drugs to mice lungs for a prolonged period of time resulting in: decreased root-specific lung weight, bacterial counts in lung homogenates and optimizing pathological effect on guinea pigs lungs, livers and spleens. Encapsulation of ethambutol hydrochloride in niosomal formulations for the treatment of TB provides higher efficacy and safety compared with the free drug.

[Pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in Beagle dogs].

PubMed

Chen, He-Li; Zhang, Wen-Ping; Yang, Fu-Ying; Wang, Xin-Yu; Yang, Wen-Cheng; Dang, Hong-Wan

2013-05-01

The object of this study is to investigate the pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in healthy adult Beagle dogs following single and multiple oral dose administration. A randomized, cross-over study was conducted with nine healthy adult Beagle dogs assigned to three groups. Each group was arranged to take atorvastatin calcium (A), pioglitazone hydrochloride (B), atorvastatin calcium and pioglitazone hydrochloride (C) orally in the first period, to take B, C, A in the second period, and to take C, A, B in the third period for 6 days respectively. The blood samples were collected at the first and the sixth day after the administration, plasma drug concentrations were determined by LC-MS/MS, a one-week wash-out period was needed between each period. The pharmacokinetic parameters of drug combination group and the drug alone group were calculated by statistical moment method, calculation of C(max) and AUC(0-t) was done by using 90% confidence interval method of the bioequivalence and bioavailability degree module DAS 3.2.1 software statistics. Compared with the separate administration, the main pharmacokinetic parameters (C(max) and AUC(0-t)) of joint use of pioglitazone hydrochloride and atorvastatin calcium within 90% confidence intervals for bioequivalence statistics were unqualified, the mean t(max) with standard deviation used paired Wilcoxon test resulted P > 0.05. There was no significant difference within t1/2, CL(int), MRT, V/F. Pioglitazone hydrochloride and atorvastatin calcium had pharmacokinetic interaction in healthy adult Beagle dogs.

21 CFR 582.5676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Pyridoxine hydrochloride. 582.5676 Section 582.5676 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

21 CFR 582.5676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Pyridoxine hydrochloride. 582.5676 Section 582.5676 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

21 CFR 582.5676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Pyridoxine hydrochloride. 582.5676 Section 582.5676 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

21 CFR 582.5676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Pyridoxine hydrochloride. 582.5676 Section 582.5676 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

21 CFR 582.5676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Pyridoxine hydrochloride. 582.5676 Section 582.5676 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

The concentration of some metals (Pb, Cd, Zn and Cu) and delta aminolevulinic acid dehydratase activity of fruit fly (Drosophila melanogaster) living near lead and zinc smelter ``Trepça'' in Kosova

NASA Astrophysics Data System (ADS)

Elezaj, I. R.; Letaj, K. Rr.; Selimi, Q. I.; Zhushi-Etemi, F.

2003-05-01

The concentration of Pb, Cd, Zn and Cu, δ-aminolevulinic acid dehydratase activity (ALA-D: EC.4.2.1.24) hemoglobin and protein amount have been determined in three different populations of fruit fly (Drosophila melanogaster) caught at two urban sites (Mitrovica town, which is situated close to smelter of “Trepça” don close and Prishtina the capital of Kosova) and in Luki village as uncontaminated area. The results show that in the fruit fly of Mitrovica the concentration of Pb, Cd and Zn was significantly higher (P<0.00l) in comparison with that on the f-Liit fly of Prishtina and Luki. The concentration of Pb of fruit fly from Mitrovica was 3.1 times higher in comparison with that on fruit fly of Prishtina and 4.9 times higher in comparison with uncontaminated group of fruit fly. The ALA-D activity was significantly inhibited in the homogenate of fruit fly from Mitrovica in comparison with Prishtina and Luki localities (P<0.00l). ALA-D activity was also inhibited in the homogenate of Prishtina fruit fly in comparison with Luki group (P<0.00l). The amount of proteins was significantly lower in Mitrovica fruit fly in comparison with that in control and Prishtina group. The hemoglobin value was relatively unchanged.

Photoacoustic imaging to detect rat brain activation after cocaine hydrochloride injection

NASA Astrophysics Data System (ADS)

Jo, Janggun; Yang, Xinmai

2011-03-01

Photoacoustic imaging (PAI) was employed to detect small animal brain activation after the administration of cocaine hydrochloride. Sprague Dawley rats were injected with different concentrations (2.5, 3.0, and 5.0 mg per kg body) of cocaine hydrochloride in saline solution through tail veins. The brain functional response to the injection was monitored by photoacoustic tomography (PAT) system with horizontal scanning of cerebral cortex of rat brain. Photoacoustic microscopy (PAM) was also used for coronal view images. The modified PAT system used multiple ultrasonic detectors to reduce the scanning time and maintain a good signal-to-noise ratio (SNR). The measured photoacoustic signal changes confirmed that cocaine hydrochloride injection excited high blood volume in brain. This result shows PAI can be used to monitor drug abuse-induced brain activation.

21 CFR 522.1335 - Medetomidine hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... solution contains 1.0 milligram of medetomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of... diseases, dogs in shock, dogs which are severly debilitated, or dogs which are stressed due to extreme heat...

21 CFR 522.1335 - Medetomidine hydrochloride injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... solution contains 1.0 milligram of medetomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of... diseases, dogs in shock, dogs which are severly debilitated, or dogs which are stressed due to extreme heat...

21 CFR 522.1335 - Medetomidine hydrochloride injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... solution contains 1.0 milligram of medetomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of... diseases, dogs in shock, dogs which are severly debilitated, or dogs which are stressed due to extreme heat...

21 CFR 522.1335 - Medetomidine hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... solution contains 1.0 milligram of medetomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of... diseases, dogs in shock, dogs which are severly debilitated, or dogs which are stressed due to extreme heat...

21 CFR 556.350 - Levamisole hydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.350 Levamisole hydrochloride. A tolerance of 0.1 part per...

21 CFR 556.350 - Levamisole hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.350 Levamisole hydrochloride. A tolerance of 0.1 part per...

21 CFR 556.350 - Levamisole hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.350 Levamisole hydrochloride. A tolerance of 0.1 part per...

21 CFR 556.410 - Metoserpate hydrochloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.410 Metoserpate hydrochloride. A tolerance of 0.02 part per...

21 CFR 556.410 - Metoserpate hydrochloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.410 Metoserpate hydrochloride. A tolerance of 0.02 part per...

21 CFR 556.410 - Metoserpate hydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.410 Metoserpate hydrochloride. A tolerance of 0.02 part per...

21 CFR 556.350 - Levamisole hydrochloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.350 Levamisole hydrochloride. A tolerance of 0.1 part per...

21 CFR 556.350 - Levamisole hydrochloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.350 Levamisole hydrochloride. A tolerance of 0.1 part per...

21 CFR 556.410 - Metoserpate hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.410 Metoserpate hydrochloride. A tolerance of 0.02 part per...

21 CFR 556.410 - Metoserpate hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.410 Metoserpate hydrochloride. A tolerance of 0.02 part per...

21 CFR 522.234 - Butamisole hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Butamisole hydrochloride. 522.234 Section 522.234 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... a solution consisting of 70 percent propylene glycol, 4 percent benzyl alcohol and distilled water...

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Thiamine hydrochloride. 582.5875 Section 582.5875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary...

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Thiamine hydrochloride. 582.5875 Section 582.5875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary...

Crystal and molecular structures of 3-amino-4-hydroxy benzenesulfonamide and its hydrochloride: Quantum-chemical study of their tautomerism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kovalchukova, O. V., E-mail: okovalchukova@mail.ru; Strashnova, S. B.; Romashkina, E. P.

2013-03-15

3-amino-4-hydroxy benzenesulfonamide and its hydrochloride have been isolated in the crystalline state. Their crystal and molecular structures are determined by X-ray diffraction. The equilibrium between neutral tautomeric forms of the 3-amino-4-hydroxy benzenesulfonamide molecule is studied within the approximation of density functional theory (B3LYP/aug-cc-pVDZ). The constants of acid-base equilibrium of 3-amino-4-hydroxy benzenesulfonamide are deter-mined using spectrophotometry.

SU-F-J-215: Non-Thermal Pulsed High Intensity Focused Ultrasound Therapy Combined with 5-Aminolevulinic Acid: An in Vivo Pilot Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, B; He, W; Cvetkovic, D

Purpose: It has recently been shown that non-thermal pulsed high intensity focused ultrasound (pHIFU) has a cell-killing effect. The purpose of the study is to investigate the sonosensitizing effect of 5-Aminolevulinic Acid (5-ALA) in non-thermal pHIFU cancer therapy. Methods: FaDu human head and neck squamous cell carcinoma cells were injected subcutaneously in the flanks of nude mice. After one to two weeks, the tumors reached the volume of 112 ± 8 mm3 and were assigned randomly into a non-thermal pHIFU group (n=9) and a non-thermal sonodynamic therapy (pHIFU after 5-ALA administration) group (n=7). The pHIFU treatments (parameters: 1 MHz frequency;more » 25 W acoustic power; 0.1 duty cycle; 60 seconds duration) were delivered using an InSightec ExAblate 2000 system with a GE Signa 1.5T MR scanner. The mice in the non-thermal sonodynamic group received 5-ALA tail-vein injection 4 hours prior to the pHIFU treatment. The tumor growth was monitored using the CT scanner on a Sofie-Biosciences G8 PET/CT system. Results: The tumors in this study grew very aggressively and about 60% of the tumors in this study developed ulcerations at various stages. Tumor growth delay after treatments was observed by comparing the treated (n=9 in pHIFU group; n=7 in sonodynamic group) and untreated tumors (n=17). However, no statistically significant differences were found between the non-thermal pHIFU and non-thermal sonodynamic group. The mean normalized tumor volume of the untreated tumors on Day 7 after their first CT scans was 7.05 ± 0.54, while the normalized volume of the treated tumors on Day 7 after treatment was 5.89 ± 0.79 and 6.27 ± 0.47 for the sonodynamic group and pHIFU group, respectively. Conclusion: In this study, no significant sonosensitizing effects of 5-ALA were obtained on aggressive FaDu tumors despite apparent tumor growth delay in some mice treated with non-thermal sonodynamic therapy.« less

Determination of itopride hydrochloride in human plasma by RP-HPLC with fluorescence detection and its use in bioequivalence study.

PubMed

Ma, Jing; Yuan, Li-Hua; Ding, Mei-Juan; Zhang, Jun; Zhang, Qing; Xu, Qun-Wei; Zhou, Xue-Min

2009-03-01

A sensitive, selective and simple method using a precipitation of protein with 10% perchloric acid, followed by high-performance liquid chromatography (HPLC) with fluorescence detection was developed for the determination of itopride hydrochloride in human plasma, using levofloxacin as the internal standard (IS). Chromatographic separation was obtained within 7.0 min using a reverse phase Hypersil BDS C(18) (250 mm x 4.6 mm, 5 microm) column and an isocratic mobile phase, constituting of a mixture of 0.1 mol/l ammonium acetate-methanol (30:70, v/v) flowing at 1.1 ml/min. The excitation and emission wavelengths were set at 304 and 344 nm, respectively. The method was validated over the concentration range of 5 ng/ml to 1000.0 ng/ml. The lower limit of quantitation (LLOQ) was 5 ng/ml. The extractive recovery of itopride hydrochloride from the biological matrix was more than 80.77%. The intra-day accuracy of the drug containing serum samples was more than 82.94% with a precision of 2.81-4.37%. The inter-day accuracy was 82.91% or more, with a precision of 6.89-9.54%. The limit we have used (70-143%) is based on the local regulatory authority (SFDA). The developed method was validated and successfully applied to bioequivalence studies of itopride hydrochloride in healthy male volunteers.

Physical and chemical stability of palonosetron hydrochloride with five common parenteral drugs during simulated Y-site administration.

PubMed

Kupie, Thomas C; Trusley, Craig; Ben, Michel; Trissel, Lawrence A

2008-09-15

The physical and chemical compatibility of palonosetron hydrochloride with atropine sulfate, famotidine, heparin sodium, lidocaine hydrochloride, and potassium chloride during simulated Y-site administration were studied. Test samples were prepared in duplicate by separately mixing 7.5-mL samples of undiluted palonosetron hydrochloride 50 microg/mL with 7.5-mL samples of atropine sulfate 0.4 mg/mL, famotidine 2 mg/mL, undiluted heparin sodium 100 units/mL, lidocaine hydrochloride 10 mg/mL, and potassium chloride 0.1 meq/mL diluted in 5% dextrose in colorless 15-mL borosilicate glass screw-cap culture tubes with polypropylene caps. Physical stability of the admixtures was assessed by visual examination and by measuring turbidity and particle size and content. Chemical stability of atropine sulfate, famotidine, heparin sodium, and lidocaine hydrochloride was assessed by stability-indicating high-performance liquid chromatography. Potassium chloride concentration was determined by indirect potentiometry using a potassiumion selective electrode. All of the samples of palonosetron hydrochloride with the test drugs were initially clear and colorless in normal fluorescent room light and when viewed with a Tyndall beam. Changes in turbidity for the samples were minor throughout the study. Measured particulates of 10 mum or larger were found to be few in number in all samples and remained so throughout the observation period. The admixtures remained colorless throughout the study. No loss of palonosetron hydrochloride occurred with any of the drugs over four hours. Similarly, little or no loss of the other drugs occurred in four hours. Palonosetron hydrochloride is physically and chemically stable with atropine sulfate, famotidine, heparin sodium, lidocaine hydrochloride, and potassium chloride during simulated Y-site administration.

21 CFR 184.1676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... hydrochloride that is prepared by chemical synthesis. (b) The ingredient meets the specifications of the Food... manufacturing practice conditions of use: (1) The ingredient is used as a nutrient supplement as defined in... exceed current good manufacturing practice: baked goods as defined in § 170.3(n)(1) of this chapter...

Oxygen isotope ratio measurements on carbon dioxide generated by reaction of microliter quantities of biological fluids with guanidine hydrochloride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, W.W.; Lee, L.S.; Klein, P.D.

1987-03-01

Guanidine hydrochloride was used to convert water in biological fluids to carbon dioxide for oxygen isotope ratio measurements. Five 10-..mu..L aliquots each of five different saliva, urine, plasma, and human milk samples were allowed to react with 100 mg of guanidine hydrochloride at 260/sup 0/C to produce ammonia and carbon dioxide. Ammonia was removed with 100% phosphoric acid and carbon dioxide was cryogenically purified before isotope ratio measurement. At natural abundances, the delta/sup 18/O values of the biological fluids were reproducible to within 0.16% (standard deviation) and accurate to within 0.11 +/- 0.73% (x vector +/- SD) of the H/submore » 2/O-CO/sub 2/ equilibration values. At a 250% enrichment level of /sup 18/O, the delta/sup 18/O values of the biological fluids were reproducible to within 0.95% and accurate to -1.27 +/- 2.25%.« less

21 CFR 520.2345a - Tetracycline hydrochloride capsules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... organisms sensitive to tetracycline hydrochloride, such as bacterial gastroenteritis due to E. coli and urinary tract infections due to Staphylococcus spp. and E. coli. (3) Limitations. Federal law restricts...

21 CFR 520.2345a - Tetracycline hydrochloride capsules.

Code of Federal Regulations, 2011 CFR

2011-04-01

... organisms sensitive to tetracycline hydrochloride, such as bacterial gastroenteritis due to E. coli and urinary tract infections due to Staphylococcus spp. and E. coli. (3) Limitations. Federal law restricts...

Hexyl aminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: a critical review of the current literature.

PubMed

Rink, Michael; Babjuk, Marko; Catto, James W F; Jichlinski, Patrice; Shariat, Shahrokh F; Stenzl, Arnulf; Stepp, Herbert; Zaak, Dirk; Witjes, J Alfred

2013-10-01

Controversy exists regarding the therapeutic benefit and cost effectiveness of photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) or hexyl aminolevulinate (HAL) in addition to white-light cystoscopy (WLC) in the management of non-muscle-invasive bladder cancer (NMIBC). To systematically evaluate evidence regarding the therapeutic benefits and economic considerations of PDD in NMIBC detection and treatment. We performed a critical review of PubMed/Medline, Embase, and the Cochrane Library in October 2012 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT) and Standards for the Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forty-four publications were selected for inclusion in this analysis. Included reports used 5-ALA (in 26 studies), HAL (15 studies), or both (three studies) as photosensitising agents. PDD increased the detection of both papillary tumours (by 7-29%) and flat carcinoma in situ (CIS; by 25-30%) and reduced the rate of residual tumours after transurethral resection of bladder tumour (TURBT; by an average of 20%) compared to WLC alone. Superior recurrence-free survival (RFS) rates and prolonged RFS intervals were reported for PDD, compared to WLC in most studies. PDD did not appear to reduce disease progression. Our findings are limited by tumour heterogeneity and a lack of NMIBC risk stratification in many reports or adjustment for intravesical therapy use in most studies. Although cost effectiveness has been demonstrated for 5-ALA, it has not been studied for HAL. Moderately strong evidence exists that PDD improves tumour detection and reduces residual disease after TURBT compared with WLC. This has been shown to improve RFS but not progression to more advanced disease. Further work to evaluate cost effectiveness of PDD is required. Copyright © 2013 European Association of

Determination of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride by flow-injection analysis based on a specific condensation reaction between malonic acid and ethylenediamine.

PubMed

Seno, Kunihiko; Matumura, Kazuki; Oshita, Koji; Oshima, Mitsuko; Motomizu, Shoji

2009-03-01

A sensitive and rapid flow-injection analysis was developed for the determination of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl), which was used for the formation of amide (peptide) and esters as a dehydration or condensation reagent. The EDC.HCl could be determined by the flow-injection analysis based on a specific condensation reaction between malonic acid and ethylenediamine in aquatic media. The reaction was accelerated at 60 degrees C, and the absorbance of the product was detected at 262 nm. The calibration graph of EDC.HCl showed good linearity in the range from 0 to 0.1% (0 to 0.0005 M), whose regression equation was y = 1.52 x 10(9)x (y, peak area; x, % concentration of EDC.HCl). The proposed method allowed high-throughput analysis; the sample throughput was 12 samples per hour. The limit of detection (LOD) and the relative standard deviation (RSD) were 2 x 10(-6) M and 1.0%, respectively. This reaction is proceeded in aqueous solution and specific for EDC.HCl.

1,5-Diaminonaphthalene hydrochloride assisted laser desorption/ionization mass spectrometry imaging of small molecules in tissues following focal cerebral ischemia.

PubMed

Liu, Huihui; Chen, Rui; Wang, Jiyun; Chen, Suming; Xiong, Caiqiao; Wang, Jianing; Hou, Jian; He, Qing; Zhang, Ning; Nie, Zongxiu; Mao, Lanqun

2014-10-21

A sensitive analytical technique for visualizing small endogenous molecules simultaneously is of great significance for clearly elucidating metabolic mechanisms during pathological progression. In the present study, 1,5-naphthalenediamine (1,5-DAN) hydrochloride was prepared for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) of small molecules in liver, brain, and kidneys from mice. Furthermore, 1,5-DAN hydrochloride assisted LDI MSI of small molecules in brain tissue of rats subjected to middle cerebral artery occlusion (MCAO) was carried out to investigate the altered metabolic pathways and mechanisms underlying the development of ischemic brain damage. Our results suggested that the newly prepared matrix possessed brilliant features including low cost, strong ultraviolet absorption, high salt tolerance capacity, and fewer background signals especially in the low mass range (typically m/z < 500), which permitted us to visualize the spatial distribution of a broad range of small molecule metabolites including metal ions, amino acids, carboxylic acids, nucleotide derivatives, peptide, and lipids simultaneously. Nineteen endogenous metabolites involved in metabolic networks such as ATP metabolism, tricarboxylic acid (TCA) cycle, glutamate-glutamine cycle, and malate-aspartate shuttle, together with metal ions and phospholipids as well as antioxidants underwent relatively obvious changes after 24 h of MCAO. The results were highly consistent with the data obtained by MRM MS analysis. These findings highlighted the promising potential of the organic salt matrix for application in the field of biomedical research.

78 FR 16685 - Impax Laboratories, Inc.; Withdrawal of Approval of Bupropion Hydrochloride Extended-Release...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-18

...] Impax Laboratories, Inc.; Withdrawal of Approval of Bupropion Hydrochloride Extended-Release Tablets... Administration (FDA) is withdrawing approval of Bupropion Hydrochloride (HCl) Extended-Release Tablets, 300 Milligrams (mg) (Bupropion HCl Extended-Release Tablets 300 mg), under Abbreviated New Drug Application (ANDA...

NTP toxicity studies of dimethylaminopropyl chloride, hydrochloride (CAS No. 5407-04-5) administered by Gavage to F344/N rats and B6C3F1 mice.

PubMed

Abdo, Km

2007-07-01

included lethargy in one 50 mg/kg male and one 100 mg/kg male, tremors in one 100 mg/kg male, and ataxia in one 50 mg/kg male and two 100 mg/kg males. Absolute lung weights in the 25, 50, and 100 mg/kg groups of female mice were significantly less than those of the vehicle controls. Total serum bile acid concentrations were increased in 50 mg/kg male rats and 100 mg/kg male and female rats. The incidence of goblet cell hypertrophy of the nose was significantly increased in 100 mg/kg male rats compared to the vehicle controls. There were no significant histopathologic findings in mice. Dimethylaminopropyl chloride, hydrochloride was mutagenic in the Salmonella typhimurium base substitution strains TA100 and TA1535, with and without hamster or rat liver S9 activation enzymes; no mutagenic activity was seen in TA97 or TA98. No increase in the frequency of micronucleated erythrocytes was seen in peripheral blood of male or female mice administered dimethylaminopropyl chloride, hydrochloride for 3 months by gavage. In summary, dimethylaminopropyl chloride, hydrochloride caused increased incidences of goblet cell hypertrophy in the nose of male rats and increased serum bile acid concentrations in male and female rats. In mice, dimethylaminopropyl chloride, hydrochloride caused deaths in females administered 100 mg/kg. The estimated no-observed-effect levels were 50 mg/kg per day for male rats and female mice, 100 to 200 mg/kg per day for female rats, and greater than 100 mg/kg per day for male mice. Synonyms: 3-Chloropropyldimethyl-ammonium chloride; (3-chloropropyl)dimethylamine, hydrochloride; N-(3-chloropropyl)-N,N-dimethylammonium chloride; 3-dimethylamino-1-propyl chloride hydrochloride; 3-dimethylaminopropyl chloride hydrochloride; DMPC; 1-propylamine, 3-chloro-N,N-dimethyl-, hydrochloride.

Spectrophotometric determination of dopamine hydrochloride in pharmaceutical, banana, urine and serum samples by potassium ferricyanide-Fe(III).

PubMed

Guo, Li; Zhang, Yan; Li, Quanmin

2009-12-01

In the present work, we developed a simple, sensitive and inexpensive method to determine dopamine hydrochloride using potassium ferricyanide-Fe(III) by spectrophotometry. The results show that Fe(III) is deoxidized to Fe(II) by dopamine hydrochloride at pH 4.0, and then Fe(II) reacts with potassium ferricyanide to form a soluble prussian blue (KFe(III)[Fe(II)(CN)6]). The absorbance of this product was monitored over time using a spectrophotometer at an absorption maximum of 735 nm, and the amount of dopamine hydrochloride could be calculated based on the absorbance. A good linear relationship of the concentration of dopamine hydrochloride versus absorbance was observed, and a linear regression equation of A = 0.022 + 0.16921C (microg mL(-1)) was obtained. Moreover, the apparent molar absorption coefficient for the indirect determination of dopamine hydrochloride was 3.2 x 10(4) L mol(-1) cm(-1). This described method has been used to determine dopamine hydrochloride in pharmaceutical, banana, urine and serum samples with satisfactory results.

Stability of ondansetron hydrochloride injection in various beverages.

PubMed

Yamreudeewong, W; Danthi, S N; Hill, R A; Fox, J L

1995-09-15

The stability of ondansetron hydrochloride injection in beverages likely to be acceptable to patients was studied. Ondansetron hydrochloride injection (containing ondansetron 2 mg/mL) was added to apple juice, fruit punch, cherry-flavored drink, carbonated soft drinks, and hot tea to provide a nominal ondansetron concentration of 32.8, 64.5, or 95.2 micrograms/mL. Samples were stored at -3 to 28 degrees C (noncarbonated-beverage mixtures except tea), 2 to 28 degrees C (carbonated-beverage mixtures), and 25 degrees C (tea) and assayed for ondansetron concentration by high-performance liquid chromatography at 6, 24, 48, and 72 hours (noncarbonated-beverage mixtures except tea); 6, 24, and 48 hours (carbonated-beverage mixtures); and 1 hour (tea). More than 95% of the initial ondansetron concentration was retained in apple juice, fruit punch, cherry-flavored drink, Sprite, and Diet Coke throughout the periods studied. A precipitate formed immediately after ondansetron was added to hot tea, but the drug was chemically stable for at least one hour in this preparation. Ondansetron hydrochloride injection 32.7, 64.5, and 95.2 micrograms/mL (expressed as free base) was stable in various beverages when stored at -3 to 28 degrees C for up to 72 hours. Ondansetron at these same concentrations precipitated in hot tea preparations but was chemically stable for at least one hour.

Studies on battery repair and recycling workers occupationally exposed to lead in Karachi.

PubMed

Haider, Muhammad Jamal; Qureshi, Naeemullah

2013-01-01

OBJECTIVE. The present study was carried out to investigate the effects of occupational lead exposure on the hematological and biochemical parameters in occupationally exposed and non exposed inhabitants of Karachi. MATERIAL AND METHODS. In 100 lead exposed subjects recruited from automobile workshops, lead battery repair and recycling units located in Karachi and in 100 control subjects the general health status, hematological parameters and exposure markers for lead were measured. RESULTS. Results indicated that the mean values of blood lead level and delta-aminolevulinic acid were significantly higher (P<0.05) while the activity of delta-aminolevulinic acid dehydratase were significantly decreased (P<0.05) among battery repair and recycling workers as compared to controls. The abnormalities in the blood lead level, delta-aminolevulinic acid and delta-aminolevulinic acid dehydratase were more frequent in lead exposed battery repair workers when compared with control subjects. The blood lead levels and deltaaminolevulinic acid were positively correlated while delta-aminolevulinic acid dehydratase was found to be negatively correlated with age, years of exposure and years of employment. Blood lead level was positively correlated with hemoglobin and RBC count while delta-aminolevulinic acid dehydratase was negatively correlated with hemoglobin concentration. The work related symptoms, droopiness, nasal symptoms and muscular pain were more frequent among battery repair workers as compared to control group. The findings of present study confirmed that occupational exposure to lead is associated with deviation in important hematological parameters and biological markers of exposure to lead among lead exposed workers, and also confirms the impact of lead exposure in the development of adverse effects among lead exposed workers. The study provides the data for risk assessment in lead battery repair workers of Karachi and suggests the need for preventive measures for

Hypercrosslinked poly(styrene-co-divinylbenzene) resin as a specific polymeric adsorbent for purification of berberine hydrochloride from aqueous solutions.

PubMed

Li, Yin; Cao, Ruofan; Wu, Xiaofei; Huang, Jianhan; Deng, Shuguang; Lu, Xiuyang

2013-06-15

A hypercrosslinked poly(styrene-co-divinylbenzene) resin (TEPA) was synthesized and characterized as a specific polymeric adsorbent for concentrating berberine hydrochloride from aqueous solutions. Three organic molecules of different sizes (2-naphthol, berberine hydrochloride, and Congo red) were used as target molecules to elucidate the molecular sieving effect of the TEPA adsorbent. Because the TEPA adsorbent has a pore structure consisting mainly of micropores and mesopores, the adsorption of 2-naphthol from aqueous solutions is very efficient due to the micropore filling effect. The adsorption of berberine hydrochloride mostly takes place in the mesopores as well as macropores, while the adsorption of Congo red mainly occurs in the macropores. The smaller adsorbate molecule (2-naphthol) reaches the adsorption equilibrium much faster than the larger ones (berberine hydrochloride and Congo red). An adsorption breakthrough experiment with an aqueous solution containing 2-naphthol and berberine hydrochloride demonstrated that the TEPA adsorbent could effectively remove 2-naphthol from berberine hydrochloride at 0-107 BV (bed volume, 1 BV=10 ml), and the berberine hydrochloride concentration was increased from 66.7% to 99.4%, suggesting that this polymeric adsorbent is promising for purifying berberine hydrochloride and similar alkaloids from herbal plant extracts. Copyright © 2013 Elsevier Inc. All rights reserved.

Simultaneous HPTLC Determination of Rabeprazole and Itopride Hydrochloride From Their Combined Dosage Form

PubMed Central

Suganthi, A.; John, Sofiya; Ravi, T. K.

2008-01-01

A simple, precise, sensitive, rapid and reproducible HPTLC method for the simultaneous estimation of the rabeprazole and itopride hydrochloride in tablets was developed and validated. This method involves separation of the components by TLC on precoated silica gel G60F254 plate with solvent system of n-butanol, toluene and ammonia (8.5:0.5:1 v/v/v) and detection was carried out densitometrically using a UV detector at 288 nm in absorbance mode. This system was found to give compact spots for rabeprazole (Rf value of 0.23 0.02) and for itopride hydrochloride (Rf value of 0.75±0.02). Linearity was found to be in the range of 40-200 ng/spot and 300-1500 ng/spot for rabeprazole and itopride hydrochloride. The limit of detection and limit of quantification for rabeprazole were 10 and 20 ng/spot and for itopride hydrochloride were 50 and 100 ng/spot, respectively. The method was found to be beneficial for the routine analysis of combined dosage form. PMID:20046748

Simultaneous HPTLC Determination of Rabeprazole and Itopride Hydrochloride From Their Combined Dosage Form.

PubMed

Suganthi, A; John, Sofiya; Ravi, T K

2008-01-01

A simple, precise, sensitive, rapid and reproducible HPTLC method for the simultaneous estimation of the rabeprazole and itopride hydrochloride in tablets was developed and validated. This method involves separation of the components by TLC on precoated silica gel G60F254 plate with solvent system of n-butanol, toluene and ammonia (8.5:0.5:1 v/v/v) and detection was carried out densitometrically using a UV detector at 288 nm in absorbance mode. This system was found to give compact spots for rabeprazole (Rf value of 0.23 0.02) and for itopride hydrochloride (Rf value of 0.75+/-0.02). Linearity was found to be in the range of 40-200 ng/spot and 300-1500 ng/spot for rabeprazole and itopride hydrochloride. The limit of detection and limit of quantification for rabeprazole were 10 and 20 ng/spot and for itopride hydrochloride were 50 and 100 ng/spot, respectively. The method was found to be beneficial for the routine analysis of combined dosage form.

Identification and assessment of permeability enhancing vehicles for transdermal delivery of glucosamine hydrochloride.

PubMed

Han, In Hee; Choi, Sung-Up; Nam, Dae Young; Park, Young Mi; Kang, Myung Joo; Kang, Kyoung Hoon; Kim, Yong Min; Bae, Gunho; Oh, Il Young; Park, Jong Hyeok; Ye, Jin Soo; Choi, Yoon Bae; Kim, Duk Ki; Lee, Jaehwi; Choi, Young Wook

2010-02-01

As an initial step to develop the transdermal delivery system of glucosamine hydrochloride (GL-HCl), the permeation study across the rat skin in vitro was performed to identify the most efficient vehicle with regard to the ability to deliver GL-HCl transdermally. The GL-HCl formulations such as o/w cream, liposome suspension, liposomal gel, and liquid crystalline vehicles were prepared and compared for transdermal flux of GL-HCl. The liquid crystalline vehicles were more effective in increasing the skin permeation of GL-HCl than o/w cream and liposomal vehicles. Of the liquid crystalline vehicles tested, the permeation enhancing ability of the cubic phase was greater than that of the hexagonal phase when the nanoparticle dispersion was used. The skin permeation enhancing ability of the cubic nanoparticles for GL-HCl was further increased by employing both oleic acid and polyethylene glycol 200. Therefore, the cubic liquid crystalline nanodispersion containing oleic acid and PEG 200 can provide a possibility of clinical application of transdermal GL-HCl.

Molecular weight of Escherichia coli β-galactosidase in concentrated solutions of guanidine hydrochloride

PubMed Central

Erickson, Robert P.

1970-01-01

The molecular weight of Escherichia coli β-galactosidase was determined in 6m- and 8m-guanidine hydrochloride by meniscus-depletion sedimentation equilibrium, sedimentation velocity and viscosity. Sedimentation equilibrium revealed heterogeneity with the smallest component having a molecular weight of about 50000. At lower speeds, the apparent weight-average molecular weight is about 80000. By use of a calculation based on an empirical correlation for proteins that are random coils in 6m-guanidine hydrochloride, sedimentation velocity gave a molecular weight of 91000, and the intrinsic viscosity indicated a viscosity-average molecular weight of 84000. Heating in 6m-guanidine hydrochloride lowered the viscosity of β-galactosidase in a variable manner. PMID:4924171

Twisted intramolecular charge transfer investigation of semi organic L-Glutamic acid hydrochloride single crystal for organic light-emitting and optical limiting applications

NASA Astrophysics Data System (ADS)

Joy, Lija K.; George, Merin; Alex, Javeesh; Aravind, Arun; Sajan, D.; Vinitha, G.

2018-03-01

Single crystals of L-Glutamic acid hydrochloride (LGHCl) were grown by slow evaporation solution technique and good crystalline perfection was confirmed by Powder X-ray diffraction studies. The complete vibrational studies of the compound were analyzed by FT-IR, FT-Raman and UV-visible spectra combined with Normal Coordinate Analysis (NCA) following the scaled quantum mechanical force field methodology and density functional theory (DFT). Twisted Intramolecular Charge Transfer (ICT) occurs due to the presence of strong ionic intra-molecular Nsbnd H⋯O hydrogen bonding was confirmed by Hirshfeld Surface analysis. The existence of intermolecular Nsbnd H⋯Cl hydrogen bonds due to the interaction between the lone pair of oxygen with the antibonding orbital was established by NBO analysis. The Z-scan result indicated that the title molecule exhibits saturable absorption behavior. The attractive third-order nonlinear properties suggest that LGHCl can be a promising candidate for the design and development devices for optical limiting applications. LGHCL exhibits distinct emission in the blue region of the fluorescence lifetime which proves to be a potential candidate for blue- Organic light-emitting diodes (OLEDs) fabrication.

Outcome of patients affected by newly diagnosed glioblastoma undergoing surgery assisted by 5-aminolevulinic acid guided resection followed by BCNU wafers implantation: a 3-year follow-up.

PubMed

Della Puppa, Alessandro; Lombardi, Giuseppe; Rossetto, Marta; Rustemi, Oriela; Berti, Franco; Cecchin, Diego; Gardiman, Marina Paola; Rolma, Giuseppe; Persano, Luca; Zagonel, Vittorina; Scienza, Renato

2017-01-01

The purpose of the study was to evaluate the clinical outcome of the association of BCNU wafers implantation and 5-aminolevulinic acid (5-ALA) fluorescence in the treatment of patients with newly diagnosed glioblastoma (ndGBM). Clinical and surgical data from patients who underwent 5-ALA surgery followed by BCNU wafers implantation were retrospectively evaluated (20 patients, Group I) and compared with data of patients undergoing surgery with BCNU wafers alone (42 patients, Group II) and 5-ALA alone (59 patients, Group III). Patients undergoing 5-ALA assisted resection followed by BCNU wafers implantation (Group I) resulted long survivors (>3 years) in 15 % of cases and showed a median PFS and MS of 11 and 22 months, respectively. Patients treated with BCNU wafers presented a significantly higher survival when tumor was removed with the assistance of 5-ALA (22 months with vs 18 months without 5-ALA, p < 0.0001); these data could be partially explained by the significantly higher CRET achieved in patients operated with 5-ALA assistance (80 % with vs 47 %% without 5-ALA). Moreover, patients of Group I showed a significant increased survival compared with Group III (5-ALA without BCNU) (22 months with vs 21 months without BCNU wafers, p = 0.0025) even with a comparable CRET (80 % vs 76 %, respectively). The occurrence of adverse events related to wafers did not significantly increase with 5-ALA (20 % with and 19 % without 5-ALA) and did not impact in survival outcome. In conclusion, our experience shows that on selected ndGBM patients 5-ALA technology and BCNU wafers implantation show a synergic action on patients' outcome without increasing adverse events occurrence.

21 CFR 184.1676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... exceed current good manufacturing practice: baked goods as defined in § 170.3(n)(1) of this chapter...)(31) of this chapter; plant protein products as defined in § 170.3(n)(33) of this chapter; and snack... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Pyridoxine hydrochloride. 184.1676 Section 184...

Stability of sotalol hydrochloride in extemporaneously prepared oral suspension formulations.

PubMed

Sidhom, Madiha B; Rivera, Nadya; Almoazen, Hassan; Taft, David R; Kirschenbaum, Harold L

2005-01-01

The physical, chemical, and microbial stabilities of extemporaneously compounded oral liquid formulations of sotalol hydrochloride were studied. Sotalol hydrochloride oral liquid suspensions (5mg/mL) were prepared from commercially available tablets (Betapace) in a 1:1 mixture of Ora-Plus: Ora-Sweet, a 1:1 mixture of Ora-Plus:Ora-Sweet SF, and a 1:2.4 mixture of simple syrup:methylcellulose vehicle. Six batches of each formulation were prepared; three were stored at refrigerated temperature (2 deg to 8 deg C) and three at room temperature (20 deg to 25 deg C). Samples were collected from each batch weekly for 6 weeks, and again at 12 weeks. Samples were analyzed by means of a high-performance liquid chromatographic method, and the concentrations obtained were compared to the theoretical time zero value. Samples were examined for pH, odor, color, and consistency changes. The suspensions also were evaluated for their microbial stability. Sotalol hydrochloride oral liquid suspensions (5mg/mL) were chemically stable for 12 weeks regardless of storage conditions (room temperature or refrigerated). Bacterial growth was not supported by any of the formulations. Suspensions stored at refrigerated temperature retained better physical quality (e.g., odor, color, and consistency) than suspensions stored at room temperature. Overall, this study demonstrates that oral formulations of sotalol hydrochloride can be readily prepared with commercially available vehicles. The method of preparation is relatively simple, the materials are relatively inexpensive, and the products have a shelf-life of at least 12 weeks.

Doxycycline potentiates antitumor effect of 5-aminolevulinic acid-mediated photodynamic therapy in malignant peripheral nerve sheath tumor cells

PubMed Central

Lee, Ming-Jen; Hung, Shih-Hsuan; Huang, Mu-Ching; Tsai, Tsuimin

2017-01-01

Neurofibromatosis type 1 (NF1) is one of the most common neurocutaneous disorders. Some NF1 patients develop benign large plexiform neurofibroma(s) at birth, which can then transform into a malignant peripheral nerve sheath tumor (MPNST). There is no curative treatment for this rapidly progressive and easily metastatic neurofibrosarcoma. Photodynamic therapy (PDT) has been developed as an anti-cancer treatment, and 5-aminolevulinic (ALA) mediated PDT (ALA-PDT) has been used to treat cutaneous skin and oral neoplasms. Doxycycline, a tetracycline derivative, can substantially reduce the tumor burden in human and animal models, in addition to its antimicrobial effects. The purpose of this study was to evaluate the effect and to investigate the mechanism of action of combined doxycycline and ALA-PDT treatment of MPNST cells. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the combination of ALA-PDT and doxycycline significantly reduce MPNST survival rate, compared to cells treated with each therapy alone. Isobologram analysis showed that the combined treatment had a synergistic effect. The increased cytotoxic activity could be seen by an increase in cellular protoporphyrin IX (PpIX) accumulation. Furthermore, we found that the higher retention of PpIX was mainly due to increasing ALA uptake, rather than activity changes of the enzymes porphobilinogen deaminase and ferrochelatase. The combined treatment inhibited tumor growth in different tumor cell lines, but not in normal human Schwann cells or fibroblasts. Similarly, a synergistic interaction was also found in cells treated with ALA-PDT combined with minocycline, but not tetracycline. In summary, doxycycline can potentiate the effect of ALA-PDT to kill tumor cells. This increased potency allows for a dose reduction of doxycycline and photodynamic radiation, reducing the occurrence of toxic side effects in vivo. PMID:28558025

Doxycycline potentiates antitumor effect of 5-aminolevulinic acid-mediated photodynamic therapy in malignant peripheral nerve sheath tumor cells.

PubMed

Lee, Ming-Jen; Hung, Shih-Hsuan; Huang, Mu-Ching; Tsai, Tsuimin; Chen, Chin-Tin

2017-01-01

Neurofibromatosis type 1 (NF1) is one of the most common neurocutaneous disorders. Some NF1 patients develop benign large plexiform neurofibroma(s) at birth, which can then transform into a malignant peripheral nerve sheath tumor (MPNST). There is no curative treatment for this rapidly progressive and easily metastatic neurofibrosarcoma. Photodynamic therapy (PDT) has been developed as an anti-cancer treatment, and 5-aminolevulinic (ALA) mediated PDT (ALA-PDT) has been used to treat cutaneous skin and oral neoplasms. Doxycycline, a tetracycline derivative, can substantially reduce the tumor burden in human and animal models, in addition to its antimicrobial effects. The purpose of this study was to evaluate the effect and to investigate the mechanism of action of combined doxycycline and ALA-PDT treatment of MPNST cells. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the combination of ALA-PDT and doxycycline significantly reduce MPNST survival rate, compared to cells treated with each therapy alone. Isobologram analysis showed that the combined treatment had a synergistic effect. The increased cytotoxic activity could be seen by an increase in cellular protoporphyrin IX (PpIX) accumulation. Furthermore, we found that the higher retention of PpIX was mainly due to increasing ALA uptake, rather than activity changes of the enzymes porphobilinogen deaminase and ferrochelatase. The combined treatment inhibited tumor growth in different tumor cell lines, but not in normal human Schwann cells or fibroblasts. Similarly, a synergistic interaction was also found in cells treated with ALA-PDT combined with minocycline, but not tetracycline. In summary, doxycycline can potentiate the effect of ALA-PDT to kill tumor cells. This increased potency allows for a dose reduction of doxycycline and photodynamic radiation, reducing the occurrence of toxic side effects in vivo.

Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study. Clinical article.

PubMed

Stummer, Walter; Tonn, Jörg-Christian; Mehdorn, Hubertus Maximilian; Nestler, Ulf; Franz, Kea; Goetz, Claudia; Bink, Andrea; Pichlmeier, Uwe

2011-03-01

Accumulating data suggest more aggressive surgery in patients with malignant glioma to improve outcome. However, extended surgery may increase morbidity. The randomized Phase III 5-aminolevulinic acid (ALA) study investigated 5-ALA-induced fluorescence as a tool for improving resections. An interim analysis demonstrated more frequent complete resections with longer progression-free survival (PFS). However, marginal differences were found regarding neurological deterioration and the frequency of additional therapies. Presently, the authors focus on the latter aspects in the final study population, and attempt to determine how safety might be affected by cytoreductive surgery. Patients with malignant gliomas were randomized for fluorescence-guided (ALA group) or conventional white light (WL) (WL group) microsurgery. The final intent-to-treat population consisted of 176 patients in the ALA and 173 in the WL group. Primary efficacy variables were contrast-enhancing tumor on early MR imaging and 6-month PFS. Among secondary outcome measures, the National Institutes of Health Stroke Scale (NIH-SS) score and the Karnofsky Performance Scale (KPS) score were used for assessing neurological function. More frequent complete resections and improved PFS were confirmed, with higher median residual tumor volumes in the WL group (0.5 vs 0 cm(3), p = 0.001). Patients in the ALA group had more frequent deterioration on the NIH-SS at 48 hours. Patients at risk were those with deficits unresponsive to steroids. No differences were found in the KPS score. Regarding outcome, a combined end point of risks and neurological deficits was attempted, which demonstrated results in patients in the ALA group to be superior to those in participants in the WL group. Interestingly, the cumulative incidence of repeat surgery was significantly reduced in ALA patients. When stratified by completeness of resection, patients with incomplete resections were quicker to deteriorate neurologically (p = 0

p53, Bcl-2 and cox-2 are involved in berberine hydrochloride-induced apoptosis of HeLa229 cells.

PubMed

Wang, Hai-Yan; Yu, Hai-Zhong; Huang, Sheng-Mou; Zheng, Yu-Lan

2016-10-01

The present study aimed to investigate the effects of berberine hydrochloride on the proliferation and apoptosis of HeLa229 human cervical cancer cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to examine the cytotoxicity of berberine hydrochloride against HeLa229 cells. The effects of berberine hydrochloride on the apoptosis of HeLa229 cells was detected by immunofluorescence and flow cytometry, and the mRNA expression levels of p53, B‑cell lymphoma 2 (Bcl‑2) and cyclooxygenase‑2 (cox‑2) were analyzed by reverse transcription-quantitative polymerase chain reaction. Berberine hydrochloride inhibited the proliferation of HeLa229 cells in a dose‑dependent manner; minimum cell viability (3.61%) was detected following treatment with 215.164 µmol/l berberine hydrochloride and the half maximal inhibitory concentration value was 42.93 µmol/l following treatment for 72 h. In addition, berberine hydrochloride induced apoptosis in HeLa229 cells in a dose‑ and time‑dependent manner. Berberine hydrochloride upregulated the mRNA expression levels of p53, and downregulated mRNA expression levels of Bcl‑2 and cox‑2, in a dose‑dependent manner. In conclusion, berberine hydrochloride inhibited the proliferation and induced apoptosis of HeLa229 cells, potentially via the upregulation of p53 and the downregulation of Bcl‑2 and cox‑2 mRNA expression levels.

40 CFR 721.1025 - Benzenamine, 4-chloro-2-methyl-; benzenamine, 4-chloro-2-methyl-, hydrochloride; and ben-zenamine...

Code of Federal Regulations, 2010 CFR

2010-07-01

...-; benzenamine, 4-chloro-2-methyl-, hydrochloride; and ben-zenamine, 2-chloro-6-methyl-. 721.1025 Section 721... Benzenamine, 4-chloro-2-methyl-; benzenamine, 4-chloro-2-methyl-, hydrochloride; and ben-zenamine, 2-chloro-6...-, hydrochloride (CAS Number 3165-93-3); and benzenamine, 2-chloro-6-methyl- (CAS Number 87-63-8) are subject to...

Syntheses and structure characterization of ten acid-base hybrid crystals based on N-containing aromatic brønsted bases and mineral acids

NASA Astrophysics Data System (ADS)

Lin, Zhihao; Jin, Shouwen; Li, Xiaoliang; Xiao, Xiao; Hu, Kaikai; Guo, Ming; Chi, Xinchen; Liu, Hui; Wang, Daqi

2017-10-01

Cocrystallization of the aromatic brønsted bases with a series of mineral acids gave a total of ten hybrid salts with the compositions: (2-methylquinoline)2: (hydrochloride acid): 3H2O [(HL1)+. (L1)·· (Cl-) · (H2O)3] (1), (6-bromobenzo[d]thiazol-2-amine): (hydrochloride acid) [(HL2)+. (Cl-)] (2), (6-bromobenzo[d]thiazol-2-amine): (nitric acid) [(HL2)+. (NO3-)] (3), (6-bromobenzo[d]thiazol-2-amine): (sulfuric acid) [(HL2)+ · (HSO4)-] (4), (6-bromobenzo[d]thiazol-2-amine): (phosphoric acid) [(HL2)+ · (H2PO4)-] (5), (5,7-dimethyl-1,8-naphthyridine-2-amine): (hydrochloride acid): 3H2O [(HL3)+ · (Cl-) (H2O)3] (6), (5,7-dimethyl-1,8-naphthyridine-2-amine): (hydrobromic acid): CH3OH [(HL3)+ · (Br)- · CH3OH] (7), (5,7-dimethyl-1,8-naphthyridine-2-amine): (sulfuric acid): H2O [(HL3)+ · (HSO4)- · H2O] (8), (2-aminophenol): (phosphoric acid) [(HL4)+ · (H2PO4)-] (9), and (2-amino-4-chlorophenol): (phosphoric acid) [(HL5)+ · (H2PO4)-] (10). The ten salts have been characterized by X-ray diffraction analysis, IR, and elemental analysis, and the melting points of all the salts were also reported. And their structural and supramolecular aspects are fully analyzed. The result reveals that among the ten investigated crystals the ring N of the heterocycle or the NH2 in the aminophenol are protonated when the acids are deprotonated, and the crystal packing is interpreted in terms of the strong charge-assisted classical hydrogen bonds between the NH+/NH3+ and deprotonated acidic groups. Further analysis of the crystal packing of the salts indicated that a different family of additional CHsbnd O, CHsbnd Cl, CH3sbnd N, CH3sbnd O, CHsbnd Br, CH3sbnd Br, Brsbnd Cl, Clsbnd S, Osbnd S, Osbnd O, Brsbnd S, Hsbnd H, and π-π associations contribute to the stabilization and expansion of the total high-dimensional frameworks. For the coexistence of the various weak nonbonding interactions these structures adopted homo or hetero supramolecular synthons or both. Some classical

Development and Validation of RP-HPLC Method for the Estimation of Ivabradine Hydrochloride in Tablets

PubMed Central

Seerapu, Sunitha; Srinivasan, B. P.

2010-01-01

A simple, sensitive, precise and robust reverse–phase high-performance liquid chromatographic method for analysis of ivabradine hydrochloride in pharmaceutical formulations was developed and validated as per ICH guidelines. The separation was performed on SS Wakosil C18AR, 250×4.6 mm, 5 μm column with methanol:25 mM phosphate buffer (60:40 v/v), adjusted to pH 6.5 with orthophosphoric acid, added drop wise, as mobile phase. A well defined chromatographic peak of Ivabradine hydrochloride was exhibited with a retention time of 6.55±0.05 min and tailing factor of 1.14 at the flow rate of 0.8 ml/min and at ambient temperature, when monitored at 285 nm. The linear regression analysis data for calibration plots showed good linear relationship with R=0.9998 in the concentration range of 30-210 μg/ml. The method was validated for precision, recovery and robustness. Intra and Inter-day precision (% relative standard deviation) were always less than 2%. The method showed the mean % recovery of 99.00 and 98.55 % for Ivabrad and Inapure tablets, respectively. The proposed method has been successfully applied to the commercial tablets without any interference of excipients. PMID:21695008

21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.863...

21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.863...

21 CFR 522.1462 - Naloxone hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Naloxone hydrochloride injection. 522.1462 Section 522.1462 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... antagonist in dogs. (2) It is administered by intravenous, intramuscular, or subcutaneous injection at an...

21 CFR 522.1462 - Naloxone hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Naloxone hydrochloride injection. 522.1462 Section 522.1462 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... antagonist in dogs. (2) It is administered by intravenous, intramuscular, or subcutaneous injection at an...

21 CFR 522.2615 - Tripelennamine hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Tripelennamine hydrochloride injection. 522.2615 Section 522.2615 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS...

Formulation of a stable parenteral product; Clonidine Hydrochloride Injection.

PubMed

Kostecka, D; Duncan, M R; Wagenknecht, D

1998-01-01

formulation pH was minimal. In addition, the stopper compatibility of the product is enhanced by the absence of chelating agents, preservatives, acids, and bases. Since the dilute concentrations of both the active and excipient are well below their solubility limits, no solubility related issues would be expected upon freezing and subsequent thawing. Clonidine Hydrochloride Injection, as formulated, does not require protection from light, oxygen, or freezing. The product shows acceptable stability within the pH range, and the rubber closure is compatible with the product. Real time stability data combined with statistical projections support a 36-month expiration date.

Ambulant photodynamic therapy of superficial malignomas with 5-ALA in combination with folic acid and use of noncoherent light.

PubMed

Jindra, R H; Kubin, A; Kolbabek, H; Alth, G; Dobrowsky, W

1999-01-01

This study reports our first results of ambulant photodynamic treatment with 5-aminolevulinic acid (5-ALA) in combination with folic acid and subsequent illumination with a noncoherent light source. The compound was topically applied to avoid total body skin sensitivity which occurs in the case of systemic administration. If no therapeutic response could be proved, we added folic acid to 5-ALA for a further treatment attempt. Illumination was performed by broad band red thermic light to also excitate reaction products with absorption bands located near to that of the sensitizer. As a result, we observed a response in all cases, however, in some cases only after the addition of folic acid.

Facilitatory effect of AC-iontophoresis of lidocaine hydrochloride on the permeability of human enamel and dentine in extracted teeth.

PubMed

Ikeda, Hideharu; Suda, Hideaki

2013-04-01

The objectives of the present study were to quantitatively evaluate chemical permeability through human enamel/dentine using conductometry and to clarify if alternating current (AC) iontophoresis facilitates such permeability. Electrical impedance of different concentrations of lidocaine hydrochloride was measured using a bipolar platinum impedance probe. A quadratic curve closely fitted to the response functions between conductance and lidocaine hydrochloride. For analysis of the passage of lidocaine hydrochloride through human enamel/dentine, eight premolars that were extracted for orthodontic treatment were sectioned at the cemento-enamel junction. The tooth crowns were held between two chambers with a double O-ring. The enamel-side chamber was filled with lidocaine hydrochloride, and the pulp-side chamber was filled with extrapure water. Two platinum plate electrodes were set at the end of each chamber to pass alternating current. A simulated interstitial pulp pressure was applied to the pulp-side chamber. The change in the concentration of lidocaine hydrochloride in the pulp-side chamber was measured every 2min using a platinum recording probe positioned at the centre of the pulp-side chamber. Passive entry without iontophoresis was used as a control. The level of lidocaine hydrochloride that passed through enamel/dentine against the dentinal fluid flow increased with time. Electrical conductance (G, mho) correlated closely to the concentration (x, mmol/L) of lidocaine hydrochloride (G=2.16x(2)+0.0289x+0.000376, r(2)=0.999). Lidocaine hydrochloride can pass through enamel/dentine. Conductometry showed that the level of lidocaine hydrochloride that passed through enamel/dentine was increased by AC iontophoresis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Naratriptan hydrochloride in extemporaneosly compounded oral suspensions.

PubMed

Zhang, Y P; Trissel, L A; Fox, J L

2000-01-01

The purpose of this study was to determine the pharmaceutical acceptability and chemical stability of naratriptan hydrochloride in three extemporaneously compounded suspension formulations. The naratriptan-hydrochloride oral suspensions were prepared from 2.5-mg commercial tablets yielding a nominal naratriptan concentration of 0.5 mg/mL. The suspension vehicles selected for testing were Syrpalta, an equal-parts mixture of Ora-Plus and Ora-Sweet, and an equal-parts mixture of Ora-Plus and Ora-Sweet SF. The tablets were crushed and thoroughly triturated to a fine powder using a porcelain mortar and pestle. The powder was incorporated into a portion of the Syrpalta or Ora-Plus suspension vehicle and mixed until homogeneous. The mixtures were then brought to volume with Syrpalta, Ora-Sweet or Ora-Sweet SF, as appropriate. The suspensions were packaged in amber, plastic, screw-cap prescription bottles and stored at 23 deg C for seven days and 4 deg C for 90 days. An adequate suspension was never achieved in Syrpalta. The crushed-tablet powder did not produce a uniformly dispersed mixture and exhibited clumping and a high rate of sedimentation. A distinct layer of the solid tablet material settled immediately after shaking. Over the next four hours, a densely packed, yellow, caked layer formed at the bottom of the containers, making resuspension difficult. During storage, the caking became worse. Chemical analysis was not performed. The Ora-Plus and Ora-Sweet or Ora-Sweet SF suspensions had a slight greenish cast and were resuspended without difficulty by shaking for approximately ten seconds, yielding easily poured and homogeneous mixtures throughout the study. Visible settling and layering did not begin for four hours with the Ora-Sweet suspension and 24 hours for the Ora-Sweet SF suspension. High pressure liquid chromatographic analysis found that the naratriptan concentration in both suspension-vehicle combinations exhibited little or no loss for seven days at 23

Optimization of mesoporous carbons for efficient adsorption of berberine hydrochloride from aqueous solutions.

PubMed

Li, Yin; Fu, Jie; Deng, Shuguang; Lu, Xiuyang

2014-06-15

Sixteen mesoporous carbon adsorbents were synthesized by varying the ratio of soft to hard templates in order to optimize the pore textural properties of these adsorbents. The mesoporous carbon adsorbents have a high BET specific surface area (1590.3-2193.5 m(2)/g), large pore volume (1.72-2.56 cm(3)/g), and uniform pore size distribution with a median pore diameter ranging from 3.51 nm to 4.52 nm. It was observed that pore textural properties of the carbon adsorbents critically depend on the molar ratio of carbon sources to templates, and the hard template plays a more important role than the soft template in manipulating the pore textures. Adsorption isotherms of berberine hydrochloride at 303 K were measured to evaluate the adsorption efficacy of these adsorbents. The adsorption of berberine hydrochloride from aqueous solutions on the sixteen mesoporous carbon adsorbents synthesized in this work is very efficient, and the adsorption equilibrium capacities on all samples are more than double the adsorption capacities of berberine hydrochloride of the benchmark adsorbents (polymer resins and spherical activated carbons) at similar conditions. It was observed from the adsorption experiments that the equilibrium adsorption amounts of berberine hydrochloride are strongly correlated with the BET specific surface area and pore volume of the adsorbents. The adsorbent with the highest BET of 2193.5 m(2)/g displayed the largest adsorption capacity of 574 mg/g at an equilibrium concentration of 0.10mg/mL of berberine hydrochloride in an aqueous solution. Copyright © 2014 Elsevier Inc. All rights reserved.

Quantification of antioxidants by using chlorpromazine hydrochloride: application of the method to food and medicinal plant samples.

PubMed

Nagaraja, Padmarajaiah; Aradhana, Narayanan; Suma, Aandamurthy; Shivakumar, Anantharaman; Chamaraja, Nelligere Arkeshwaraiah

2014-01-01

Chlorpromazine hydrochloride (CPH) (3-(2-chloro-phenothiazine-10-yl)-propyl] dimethylamine hydrochloride) has been the subject of a large number of studies employing a broad spectrum of oxidants, and chosen to examine the course of electron transfer reactions. We report on a method to determine the antioxidant activity of some food and medicinal plants using the oxidation of CPH by chromium(VI) to form a stable CPH radical in the 1:1 orthophosphoric acid-ethyl alcohol (OPA-EtOH) medium. The pink color of the control solution was measured at λ(max) of 530 nm. Nine standard antioxidants have been studied by this method, along with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The EC50, TEC50, antioxidant efficacy and the stoichiometric values for antioxidants have been evaluated. The radical scavenging activity expressed as EC50 ranged from 9.2 μg/mL in Camellia sinensis to 448.18 μg/mL in Cuminum cyminum. The application of a simple and versatile antioxidant capacity assay for dietary polyphenols and medicinal plant extracts, which are commonly used in Ayurveda opens its relevance in the field of antioxidant analysis.

Carrier-mediated γ-aminobutyric acid transport across the basolateral membrane of human intestinal Caco-2 cell monolayers.

PubMed

Nielsen, Carsten Uhd; Carstensen, Mette; Brodin, Birger

2012-06-01

The aim of the present study was to investigate the transport of γ-aminobutyric acid (GABA) across the basolateral membrane of intestinal cells. The proton-coupled amino acid transporter, hPAT1, mediates the influx of GABA and GABA mimetic drug substances such as vigabatrin and gaboxadol and the anticancer prodrug δ-aminolevulinic acid across the apical membrane of small intestinal enterocytes. Little is however known about the basolateral transport of these substances. We investigated basolateral transport of GABA in mature Caco-2 cell monolayers using isotope studies. Here we report that, at least two transporters seem to be involved in the basolateral transport of GABA. The basolateral uptake consisted of a high-affinity system with a K(m) of 290 μM and V(max) of 75 pmol cm(-2) min(-1) and a low affinity system with a K(m) of approximately 64 mM and V(max) of 1.6 nmol cm(-2) min(-1). The high-affinity transporter is Na(+) and Cl(-) dependent. The substrate specificity of the high-affinity transporter was further studied and Gly-Sar, Leucine, gaboxadol, sarcosine, lysine, betaine, 5-hydroxythryptophan, proline and glycine reduced the GABA uptake to approximately 44-70% of the GABA uptake in the absence of inhibitor. Other substances such as β-alanine, GABA, 5-aminovaleric acid, taurine and δ-aminolevulinic acid reduced the basolateral GABA uptake to 6-25% of the uptake in the absence of inhibitor. Our results indicate that the distance between the charged amino- and acid-groups is particular important for inhibition of basolateral GABA uptake. Thus, there seems to be a partial substrate overlap between the basolateral GABA transporter and hPAT1, which may prove important for understanding drug interactions at the level of intestinal transport. Copyright © 2012 Elsevier B.V. All rights reserved.

78 FR 38053 - Determination That OPANA ER (Oxymorphone Hydrochloride) Drug Products Covered by New Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-25

...] Determination That OPANA ER (Oxymorphone Hydrochloride) Drug Products Covered by New Drug Application 21-610... (oxymorphone hydrochloride (HCl)) Extended-Release Tablet products approved under new drug application (NDA) 21... refer to these drug products, and it will allow FDA to continue to approve ANDAs for oxymorphone HCl...

21 CFR 522.723 - Diprenorphine hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diprenorphine hydrochloride injection. 522.723 Section 522.723 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... use in wild or exotic animals only. Do not use in domestic food-producing animals. Do not use 30 days...

Daylight photodynamic therapy with methyl-aminolevulinate for the treatment of actinic cheilitis.

PubMed

Fai, Dario; Romanello, Eugenio; Brumana, Marta Benedetta; Fai, Carlotta; Vena, Gino Antonio; Cassano, Nicoletta; Piaserico, Stefano

2015-01-01

Actinic cheilitis (AC) is a common premalignant condition that requires an effective treatment to reduce the risk of malignant transformation. Photodynamic therapy (PDT) has been recently added to the armamentarium available for AC treatment. Daylight PDT (D-PDT) is a novel PDT modality in which the activation of the topical photosensitizer is induced by the exposure to natural daylight instead of artificial light sources without preliminary occlusion. This simplified procedure was found to be more tolerated as compared to conventional PDT. We report our preliminary experience on the use of D-PDT using methyl-aminolevulinate cream in 10 patients with refractory AC of the lower lip. Patients received two consecutive D-PDT sessions with an interval of 7-14 days. At 3 months after therapy, a complete response was observed in seven patients, with sustained results in five patients over an observational period of 6-12 months. Treatment was well tolerated. © 2015 Wiley Periodicals, Inc.

78 FR 27971 - Determination That REV-EYES (Dapiprazole Hydrochloride Ophthalmic Solution), 0.5%, Was Not...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-13

...] Determination That REV-EYES (Dapiprazole Hydrochloride Ophthalmic Solution), 0.5%, Was Not Withdrawn From Sale.... SUMMARY: The Food and Drug Administration (FDA) has determined that REV-EYES (dapiprazole hydrochloride... CFR 314.161)). FDA may not approve an ANDA that does not refer to a listed drug. REV-EYES (dapiprazole...

Synthesis, spectral, and anti-microbial studies of thioiminium iodides and amine hydrochlorides.

PubMed

Britto, Sebastian; Renaud, Philippe; Nallu, Maruthai

2014-01-01

To avoid the undesired deprotonation during the addition of organolithium and organomagnesium reagents to ketones, the thioiminium salts, easily prepared from lactams and amides are converted into 2,2-disubstituted and 2-monosubstituted amines by reaction with simple nucleophiles such as organocerium and organocopper reagents. The reaction of thioiminium iodides with organocerium reagents derived by transmetalation of corresponding lithium reagents with anhydrous cerium(III) chloride has been investigated. These thioiminium iodides act as good electrophiles and accept alkylceriums towards bisaddition. The newly synthesized amines have been characterized by 1H and 13C NMR, IR and mass spectra. The amines have been converted into their hydrochlorides and characterized by COSY. These hydrochlorides have been subjected to antimicrobial screening with clinically isolated microorganisms, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi and Candida albicans. The hydrochlorides show quite good activity against these bacteria and fungus. Copyright © 2013 Elsevier B.V. All rights reserved.

Stability of Clindamycin Hydrochloride in PCCA Base SuspendIt.

PubMed

Pramar, Yashoda V; Graves, Richard A; Ledet, Grace A; Phan, Kelly V; Bostanian, Levon A; Mandal, Tarun K

2016-01-01

Clindamycin is an effective antibiotic in the treatment of infections caused by certain gram-positive and gram-negative anaerobic microorganisms. While manufactured forms of the drug for pediatric use are available, there are instances when a compounded liquid dosage form is essential to meet unique patient needs. The purpose of this study was to determine the chemical stability of clindamycin hydrochloride in the PCCA base SuspendIt, a sugar-free, paraben- free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. It thickens upon standing to minimize settling of any insoluble drug particles and becomes fluid upon shaking to allow convenient pouring during administration to the patient. A robust stability-indicating high-performance liquid chromatographic assay for the determination of clindamycin hydrochloride in SuspendIt was developed and validated. This assay was used to determine the chemical stability of the drug in SuspendIt. Samples were prepared and stored under three different temperature conditions (5°C, 25°C, and 40°C), and assayed using the high-performance liquid chromatographic assay at pre-determined intervals over an extended period of time as follows: 7, 14, 30, 45, 60, 91, 120, and 182 days at each designated temperature. Physical data such as pH, viscosity, and appearance were also monitored. The study showed that drug concentration did not go below 90% of the label claim (initial drug concentration) at all three temperatures studied, barring isolated experimental errors. Viscosity and pH values also did not change significantly. Some variations in viscosity were attributed to the thixotropic nature of the vehicle. This study demonstrates that clindamycin hydrochloride is physically and chemically stable in SuspendIt for 182 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for clindamycin hydrochloride in a liquid dosage form, with an

Microparticulate drug delivery system containing tramadol hydrochloride for pain treatment.

PubMed

Ciurba, Adriana; Todoran, Nicoleta; Vari, C E; Lazăr, Luminita; Al Hussein, Stela; Hancu, G

2014-01-01

The current trend of replacing conventional pharmaceutical forms is justified because most substances administered in this form give fluctuations of therapeutic concentrations and often outside the therapeutic range. In addition, these formulations offer a reduction in the dose or the number of administrations, thus increasing patient compliance. In the experiment, we developed an appropriate technology for the preparation of gelatin microspheres containing tramadol hydrochloride by emulsification/cross-linking method. The formulated microspheres were characterized by product yield, size distribution, encapsulation efficiency and in vitro release of tramadol hydrochloride. Data obtained from in vitro release studies were fitted to various mathematical models to elucidate the transport mechanisms. The kinetic models used were zero-order, first-order, Higuchi Korsmeyer-Peppas and Hopfenberg. Spherical microspheres were obtained, with free-flowing properties. The entrapment efficiency of tramadol hydrochloride in microparticles was 79.91% and product yield -94.92%. As the microsphere size was increased, the entrapment efficiency increased. This was 67.56, 70.03, 79.91% for formulations MT80-250, MT8-500 and, MT250-500. High entrapment efficiency was observed for MT250-500 formulation. The gelatin microspheres had particle sizes ranging from 80 to 500 microm. The drug was released for a period of 12 hours with a maximum release of 96.02%. Of the three proposed formulations, MT250-500 presented desirable properties and optimal characteristics for the therapy of pain. Release of tramadol hydrochloridi was best fitted to Korsmeyer-Peppas equation because the Akaike Information Criterion had the lowest values for this kinetic model. These results suggest the opportunity to influence the therapeutic characteristics of gelatin microspheres to obtain a suitable drug delivery system for the oral administration of tramadol hydrochloride.

Amides and Hydrazides from Amine and Hydrazine Hydrochlorides.

ERIC Educational Resources Information Center

Shama, Sami A.; Tran, Thuan L.

1978-01-01

This safe and efficient procedure for the synthesis of N-substituted amides and hydrazides is a modification of the Schotten-Bausmann procedure in which the amine or hydrazide is replaced by the corresponding hydrochloride salt, and the use of alkali is eliminated. (Author/BB)

Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects.

PubMed

Cynober, L; Coudray-Lucas, C; de Bandt, J P; Guéchot, J; Aussel, C; Salvucci, M; Giboudeau, J

1990-02-01

Ornithine alpha-ketoglutarate (OKG) has been useful as an adjuvant of enteral and parenteral nutrition. However, its metabolism and mechanism of action remain unclear although it is known that alpha-ketoglutarate (alpha KG) and ornithine (ORN) follow, in part, common metabolic pathways. Six fasting healthy male subjects underwent three separate oral load tests: (i) they received 10 g of OKG (i.e., 3.6 g of alpha KG and 6.4 g of ORN); (ii) 6.4 g of ORN as ornithine hydrochloride, and (iii) 3.6 g of alpha KG as calcium alpha-ketoglutarate. Blood was drawn 15 times over a five-hour period for measurements of plasma amino acids, alpha KG, insulin, and glucagon. After OKG and ORN administration, plasma ORN peaked at 60-75 min (494 +/- 91 and 541 +/- 85 mumol/L). The increase in plasma alpha KG was very small. OKG, alpha KG, and ORN all increased glutamate concentrations at 60 min (mean: +43%, +68%, +68%, respectively, p less than 0.05 compared to basal values). However, only OKG increased proline and arginine levels at 60 min (mean: +35%, p less than 0.01 and mean: +41%, p less than 0.05). Furthermore, glutamate, proline, and arginine concentrations correlated linearly with ornithine levels at 60 min. Finally, OKG increased insulinemia and glucagonemia (mean: +24% at 15 min, p less than 0.05 and +30% at 60 min, p less than 0.01, respectively). These data provide evidence that the combination of ORN and alpha KG modifies amino acid metabolism in a way which is not observed when they are administered separately. In addition, the OKG-mediated increase in insulin levels probably does not appear to result from a direct action of ORN on pancreatic secretion.

Effects of MK-467 hydrochloride and hyoscine butylbromide on cardiorespiratory and gastrointestinal changes induced by detomidine hydrochloride in horses.

PubMed

Tapio, Heidi A; Raekallio, Marja R; Mykkänen, Anna; Mama, Khursheed; Mendez-Angulo, Jóse L; Hautajärvi, Heidi; Vainio, Outi M

2018-04-01

OBJECTIVE To compare the effects of MK-467 and hyoscine butylbromide on detomidine hydrochloride-induced cardiorespiratory and gastrointestinal changes in horses. ANIMALS 6 healthy adult horses. PROCEDURES Horses received detomidine hydrochloride (20 μg/kg, IV), followed 10 minutes later by MK-467 hydrochloride (150 μg/kg; DET-MK), hyoscine butylbromide (0.2 mg/kg; DET-HYO), or saline (0.9% NaCl) solution (DET-S), IV, in a Latin square design. Heart rate, respiratory rate, rectal temperature, arterial and venous blood pressures, and cardiac output were measured; blood gases and arterial plasma drug concentrations were analyzed; selected cardiopulmonary variables were calculated; and sedation and gastrointestinal borborygmi were scored at predetermined time points. Differences among treatments or within treatments over time were analyzed statistically. RESULTS With DET-MK, detomidine-induced hypertension and bradycardia were reversed shortly after MK-467 injection. Marked tachycardia and hypertension were observed with DET-HYO. Mean heart rate and mean arterial blood pressure differed significantly among all treatments from 15 to 35 and 15 to 40 minutes after detomidine injection, respectively. Cardiac output was greater with DET-MK and DET-HYO than with DET-S 15 minutes after detomidine injection, but left ventricular workload was significantly higher with DET-HYO. Borborygmus score, reduced with all treatments, was most rapidly restored with DET-MK. Sedation scores and pharmacokinetic parameters of detomidine did not differ between DET-S and DET-MK. CONCLUSIONS AND CLINICAL RELEVANCE MK-467 reversed or attenuated cardiovascular and gastrointestinal effects of detomidine without notable adverse effects or alterations in detomidine-induced sedation in horses. Further research is needed to determine whether these advantages are found in clinical patients and to assess whether the drug influences analgesic effects of detomidine.

Spectrophotometric simultaneous determination of Rabeprazole Sodium and Itopride Hydrochloride in capsule dosage form

NASA Astrophysics Data System (ADS)

Sabnis, Shweta S.; Dhavale, Nilesh D.; Jadhav, Vijay. Y.; Gandhi, Santosh V.

2008-03-01

A new simple, economical, rapid, precise and accurate method for simultaneous determination of rabeprazole sodium and itopride hydrochloride in capsule dosage form has been developed. The method is based on ratio spectra derivative spectrophotometry. The amplitudes in the first derivative of the corresponding ratio spectra at 231 nm (minima) and 260 nm were selected to determine rabeprazole sodium and itopride hydrochloride, respectively. The method was validated with respect to linearity, precision and accuracy.

Spectrophotometric simultaneous determination of rabeprazole sodium and itopride hydrochloride in capsule dosage form.

PubMed

Sabnis, Shweta S; Dhavale, Nilesh D; Jadhav, Vijay Y; Gandhi, Santosh V

2008-03-01

A new simple, economical, rapid, precise and accurate method for simultaneous determination of rabeprazole sodium and itopride hydrochloride in capsule dosage form has been developed. The method is based on ratio spectra derivative spectrophotometry. The amplitudes in the first derivative of the corresponding ratio spectra at 231nm (minima) and 260nm were selected to determine rabeprazole sodium and itopride hydrochloride, respectively. The method was validated with respect to linearity, precision and accuracy.

Determination of losartan potassium, quinapril hydrochloride and hydrochlorothiazide in pharmaceutical preparations using derivative spectrophotometry and chromatographic-densitometric method.

PubMed

Stolarczyk, Mariusz; Maślanka, Anna; Apola, Anna; Krzek, Jan

2013-01-01

Two methods, spectrophotometric and chromatographic-densitometric ones, were developed for determination of losartan potassium, quinapril hydrochloride and hydrochlorothiazide in pharmaceutical preparations. Spectrophotometric method involved derivative spectrophotometry and zero order spectrophotometry. The measurements were carried out at lambda = 224.0 nm for quinapril, lambda = 261.0 nm for hydrochlorothiazide and lambda = 270.0 nm for losartan when the derivative spectrophotometry was applied and lambda = 317.0 nm when zero order spectrophotometry was applied for the determination of hydrochlorothiazide. In chromatographic-densitometric studies high performance thin layer chromatography (HPTLC) plates were used as stationary phase and a mixture of solvents n-butanol : acetic acid : water (15 : 5 : 1, v/v/v) as mobile phase. Under the established conditions good resolution of examined constituents was obtained. Retardation factor for quinapril hydrochloride was R(f) - 0.70, for losartan potassium R(f) - 0.85 and for hydrochlorothiazide R(f) - 0.78. The developed methods are characterized by high sensitivity and accuracy. For quantitative analysis, densitometric measurements were carried out at lambda = 218.0 nm for quinapril, lambda = 275.0 nm for hydrochlorothiazide and = 232.0 nm for losartan.

A validated high performance thin layer chromatography method for determination of yohimbine hydrochloride in pharmaceutical preparations

PubMed Central

Badr, Jihan M.

2013-01-01

Background: Yohimbine is an indole alkaloid used as a promising therapy for erectile dysfunction. A number of methods were reported for the analysis of yohimbine in the bark or in pharmaceutical preparations. Materials and Method: In the present work, a simple and sensitive high performance thin layer chromatographic method is developed for determination of yohimbine (occurring as yohimbine hydrochloride) in pharmaceutical preparations and validated according to International Conference of Harmonization (ICH) guidelines. The method employed thin layer chromatography aluminum sheets precoated with silica gel as the stationary phase and the mobile phase consisted of chloroform:methanol:ammonia (97:3:0.2), which gave compact bands of yohimbine hydrochloride. Results: Linear regression data for the calibration curves of standard yohimbine hydrochloride showed a good linear relationship over a concentration range of 80–1000 ng/spot with respect to the area and correlation coefficient (R2) was 0.9965. The method was evaluated regarding accuracy, precision, selectivity, and robustness. Limits of detection and quantitation were recorded as 5 and 40 ng/spot, respectively. The proposed method efficiently separated yohimbine hydrochloride from other components even in complex mixture containing powdered plants. The amount of yohimbine hydrochloride ranged from 2.3 to 5.2 mg/tablet or capsule in preparations containing the pure alkaloid, while it varied from zero (0) to 1.5–1.8 mg/capsule in dietary supplements containing powdered yohimbe bark. Conclusion: We concluded that this method employing high performance thin layer chromatography (HPTLC) in quantitative determination of yohimbine hydrochloride in pharmaceutical preparations is efficient, simple, accurate, and validated. PMID:23661986

A validated high performance thin layer chromatography method for determination of yohimbine hydrochloride in pharmaceutical preparations.

PubMed

Badr, Jihan M

2013-01-01

Yohimbine is an indole alkaloid used as a promising therapy for erectile dysfunction. A number of methods were reported for the analysis of yohimbine in the bark or in pharmaceutical preparations. In the present work, a simple and sensitive high performance thin layer chromatographic method is developed for determination of yohimbine (occurring as yohimbine hydrochloride) in pharmaceutical preparations and validated according to International Conference of Harmonization (ICH) guidelines. The method employed thin layer chromatography aluminum sheets precoated with silica gel as the stationary phase and the mobile phase consisted of chloroform:methanol:ammonia (97:3:0.2), which gave compact bands of yohimbine hydrochloride. Linear regression data for the calibration curves of standard yohimbine hydrochloride showed a good linear relationship over a concentration range of 80-1000 ng/spot with respect to the area and correlation coefficient (R(2)) was 0.9965. The method was evaluated regarding accuracy, precision, selectivity, and robustness. Limits of detection and quantitation were recorded as 5 and 40 ng/spot, respectively. The proposed method efficiently separated yohimbine hydrochloride from other components even in complex mixture containing powdered plants. The amount of yohimbine hydrochloride ranged from 2.3 to 5.2 mg/tablet or capsule in preparations containing the pure alkaloid, while it varied from zero (0) to 1.5-1.8 mg/capsule in dietary supplements containing powdered yohimbe bark. We concluded that this method employing high performance thin layer chromatography (HPTLC) in quantitative determination of yohimbine hydrochloride in pharmaceutical preparations is efficient, simple, accurate, and validated.

[Clinical observation of icotinib hydrochloride for patients with advanced non-small cell lung cancer].

PubMed

Li, Xi; Yang, Xin-jie; Sun, Yi-fen; Qin, Na; Lü, Jia-lin; Wu, Yu-hua; Zhang, Hui; Zhang, Quan; Zhang, Shu-cai

2012-08-01

To explore the efficacy and side effects of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The efficacy and side effects of icotinib hydrochloride in treatment of 59 cases with stage IV NSCIC and followed-up from March 2009 to January 2012 were retrospectively analyzed. Twenty seven patients (45.8%) showed partial response (PR), 17 patients (28.8%) achieved SD, and 15 (25.4%) had progressive disease. The objective response rate (ORR) was 45.8% (27/59), and disease control rate (DCR) was 74.6% (44/59). Among the 23 patients with EGFR mutation, ORR was 73.9% (17/23), and DCR was 95.7% (22/23). Thirty six patients (61.0%) achieved remission of symptoms to varying degrees. The main symptoms relieved were cough, asthmatic suffocating, pain and hoarseness. The major adverse events were mild skin rash (35.6%) and diarrhea (15.3%). Others were dry skin, nausea and stomach problems. The efficacy of icotinib hydrochloride were related to the ECOG performance status, smoking history, EGFR mutation and rash significantly (P < 0.05). Monotherapy with icotinib hydrochloride is effective and tolerable for patients with advanced NSCLC, especially with EGFR mutation.

Formulation and Evaluation of Multilayered Tablets of Pioglitazone Hydrochloride and Metformin Hydrochloride

PubMed Central

Chowdary, Y. Ankamma; Raparla, Ramakrishna; Madhuri, Muramshetty

2014-01-01

In the treatment of type 2 diabetes mellitus a continuous therapy is required which is a more complex one. As in these patients there may be a defect in both insulin secretion and insulin action exists. Hence, the treatment depends on the pathophysiology and the disease state. In the present study, multilayered tablets of pioglitazone hydrochloride 15 mg and metformin hydrochloride 500 mg were prepared in an attempt for combination therapy for the treatment of type 2 diabetes mellitus. Pioglitazone HCl was formulated as immediate release layer to show immediate action by direct compression method using combination of superdisintegrants, namely, crospovidone and avicel PH 102. Crospovidone at 20% concentration showed good drug release profile at 2 hrs. Metformin HCl was formulated as controlled release layer to prolong the drug action by incorporating hydrophilic polymers such as HPMC K4M by direct compression method and guar gum by wet granulation method in order to sustain the drug release from the tablets and maintain its integrity so as to provide a suitable formulation. The multilayered tablets were prepared after carrying out the optimization of immediate release layer and were evaluated for various precompression and postcompression parameters. Formulation F13 showed 99.97% of pioglitazone release at 2 hrs in 0.1 N HCl and metformin showed 98.81% drug release at 10 hrs of dissolution in 6.8 pH phosphate buffer. The developed formulation is equivalent to innovator product in view of in vitro drug release profile. The results of all these evaluation tests are within the standards. The procedure followed for the formulation of these tablets was found to be reproducible and all the formulations were stable after accelerated stability studies. Hence, multilayered tablets of pioglitazone HCl and metformin HCl can be a better alternative way to conventional dosage forms. PMID:26556204

Effects of metomindate hydrochloride and tricaine methanesulfonate on the short term cortisol response in channel catfish

USDA-ARS?s Scientific Manuscript database

The effects of metomidate hydrochloride and tricaine methanesulfonate (MS-222) on cortisol stress response of channel catfish, Ictalurus punctatus, were examined during 10 minutes of sedation. Channel catfish were assigned to three treatments: 1. Metomidate hydrochloride (12.5 mg/L), 2. MS-222 (100...

Evaluation of the potential carcinogenicity of 4-chloro-o-toluidine hydrochloride (3165-93-3). Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1988-06-01

4-Chloro-o-toluidine hydrochloride is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment. Evidence on potential carcinogenicity from animal studies is Sufficient, and the evidence from human studies is No Data. The potency factor (F) for 4-chloro-o-toluidine hydrochloride is estimated to be 0.40 (mg/kg/day)(-1), placing it in potency group 3 according to the CAG's methodology for evaluating potential carcinogens. Combining the weight-of-evidence group and the potency group, 4-chloro-o-toluidine hydrochloride is assigned a LOW hazard ranking.

Antinociceptive effects after oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Sanchez-Migallon Guzman, David; Souza, Marcy J; Braun, Jana M; Cox, Sherry K; Keuler, Nicholas S; Paul-Murphy, Joanne R

2012-08-01

To evaluate antinociceptive effects on thermal thresholds after oral administration of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals-15 healthy adult Hispaniolan Amazon parrots. 2 crossover experiments were conducted. In the first experiment, 15 parrots received 3 treatments (tramadol at 2 doses [10 and 20 mg/kg] and a control suspension) administered orally. In the second experiment, 11 parrots received 2 treatments (tramadol hydrochloride [30 mg/kg] and a control suspension) administered orally. Baseline thermal foot withdrawal threshold was measured 1 hour before drug or control suspension administration; thermal foot withdrawal threshold was measured after administration at 0.5, 1.5, 3, and 6 hours (both experiments) and also at 9 hours (second experiment only). For the first experiment, there were no overall effects of treatment, hour, period, or any interactions. For the second experiment, there was an overall effect of treatment, with a significant difference between tramadol hydrochloride and control suspension (mean change from baseline, 2.00° and -0.09°C, respectively). There also was a significant change from baseline for tramadol hydrochloride at 0.5, 1.5, and 6 hours after administration but not at 3 or 9 hours after administration. Tramadol at a dose of 30 mg/kg, PO, induced thermal antinociception in Hispaniolan Amazon parrots. This dose was necessary for induction of significant and sustained analgesic effects, with duration of action up to 6 hours. Further studies with other types of noxious stimulation, dosages, and intervals are needed to fully evaluate the analgesic effects of tramadol hydrochloride in psittacines.

Influence of stereoelectronic effects on the non-opioid analgesics gaboxadol and gaboxadol hydrochloride: Spectral and DFT study

NASA Astrophysics Data System (ADS)

Leenaraj, D. R.; Joe, I. Hubert

2018-05-01

The stereoelectronic properties of the molecular structure of most stable conformers of gaboxadol and gaboxadol hydrochloride have been studied using DFT/B3P86-LANL2DZ methodology. The energies of stable conformers of gaboxadol and gaboxadol hydrochloride are -494.2689 and -510.0117 hartrees, respectively. The stability of the molecules arising from stereoelectronic interactions, leading to its bioactivity, has been confirmed using natural bond orbital analysis. The natural bond orbital analysis of donor-acceptor (σ→σ* and n→σ*) interactions showed that the stereoelectronic hyperconjugative and anomeric interactions are exhibited in gaboxadol hydrochloride and gaboxadol, respectively. Lengthening of the axial and equatorial C-H bond lengths and natural population analysis support these results. Spectral features of gaboxadol hydrochloride have been explored by the Fourier transform infrared, Raman and Nuclear magnetic resonance spectroscopic techniques combined with density functional theory computations. NH+ … Cl- hydrogen bonding has been noticeable as a broad and strong absorption in the 2800-2400 cm-1 region. Broad peaks obtained by proton NMR are a result of the quadrupole effect of the N+ atom. Docking studies using representative GABA receptor crystal structures revealed that molecules containing azinane and isoxazole cores fit within the ligand binding domains, and the gaboxadol hydrochloride molecule shows the best binding energy with the 3D32 GABA receptor. Also, gaboxadol hydrochloride has obtained a high value of HOMO energy and a narrow HOMO- LUMO energy gap, which enhances reactivity.

Red versus blue light illumination in hexyl 5-aminolevulinate photodynamic therapy: the influence of light color and irradiance on the treatment outcome in vitro

NASA Astrophysics Data System (ADS)

Helander, Linda; Krokan, Hans E.; Johnsson, Anders; Gederaas, Odrun A.; Plaetzer, Kristjan

2014-08-01

Hexyl 5-aminolevulinate (HAL) is a lipophilic derivative of 5-aminolevulinate, a key intermediate in biosynthesis of the photosensitizer protoporphyrin IX (PpIX). The photodynamic efficacy and cell death mode after red versus blue light illumination of HAL-induced PpIX have been examined and compared using five different cancer cell lines. LED arrays emitting at 410 and 624 nm served as homogenous and adjustable light sources. Our results show that the response after HAL-PDT is cell line specific, both regarding the shape of the dose-survival curve, the overall dose required for efficient cell killing, and the relative amount of apoptosis. The ratio between 410 and 624 nm in absorption coefficient correlates well with the difference in cell killing at the same wavelengths. In general, the PDT efficacy was several folds higher for blue light as compared with red light, as expected. However, HAL-PDT624 induced more apoptosis than HAL-PDT410 and illumination with low irradiance resulted in more apoptosis than high irradiance at the same lethal dose. This indicates differences in death modes after low and high irradiance after similar total light doses. From a treatment perspective, these differences may be important.

Red versus blue light illumination in hexyl 5-aminolevulinate photodynamic therapy: the influence of light color and irradiance on the treatment outcome in vitro.

PubMed

Helander, Linda; Krokan, Hans E; Johnsson, Anders; Gederaas, Odrun A; Plaetzer, Kristjan

2014-08-01

Hexyl 5-aminolevulinate (HAL) is a lipophilic derivative of 5-aminolevulinate, a key intermediate in biosynthesis of the photosensitizer protoporphyrin IX (PpIX). The photodynamic efficacy and cell death mode after red versus blue light illumination of HAL-induced PpIX have been examined and compared using five different cancer cell lines. LED arrays emitting at 410 and 624 nm served as homogenous and adjustable light sources. Our results show that the response after HAL-PDT is cell line specific, both regarding the shape of the dose-survival curve, the overall dose required for efficient cell killing, and the relative amount of apoptosis. The ratio between 410 and 624 nm in absorption coefficient correlates well with the difference in cell killing at the same wavelengths. In general, the PDT efficacy was several folds higher for blue light as compared with red light, as expected. However, HAL-PDT₆₂₄ induced more apoptosis than HAL-PDT₄₁₀ and illumination with low irradiance resulted in more apoptosis than high irradiance at the same lethal dose. This indicates differences in death modes after low and high irradiance after similar total light doses. From a treatment perspective, these differences may be important.

Study on the binding of procaine hydrochloride to DNA/DNA bases and the effect of CdS nanoparticles on the binding behavior.

PubMed

Ping, Gang; Lv, Gang; Gutmann, Sebastian; Chen, Chen; Zhang, Renyun; Wang, Xuemei

2006-01-01

The interaction between procaine hydrochloride and DNA/DNA bases in the absence and presence of cadmium sulfide (CdS) nanoparticles has been explored in this study by using differential pulse voltammetry, atomic force microscopy (AFM) and so on, which illustrates the different binding behaviors of procaine hydrochloride with different DNA bases. The results clearly indicate that the binding of purines to procaine hydrochloride is stronger than that of pyrimidines and the binding affinity is in the order of G > A > T > C. In addition, it was observed that the presence of CdS nanoparticles could remarkably enhance the probing sensitivity for the interaction between procaine hydrochloride and DNA/DNA bases. Furthermore, AFM study illustrates that procaine hydrochloride can bind to some specific sites of DNA chains, which indicates that procaine hydrochloride may interact with some special sequences of DNA.

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.

Code of Federal Regulations, 2013 CFR

2013-04-01

... milligrams of triflupromazine hydrochloride. (b) Sponsor. See No. 053501 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs and cats to relieve anxiety and to help control psychomotor... preanesthetic.1 (2) The drug is administered orally to dogs and cats at a dosage level of 1 to 2 milligrams per...

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... milligrams of triflupromazine hydrochloride. (b) Sponsor. See No. 053501 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs and cats to relieve anxiety and to help control psychomotor... preanesthetic.1 (2) The drug is administered orally to dogs and cats at a dosage level of 1 to 2 milligrams per...

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

... milligrams of triflupromazine hydrochloride. (b) Sponsor. See No. 053501 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs and cats to relieve anxiety and to help control psychomotor... preanesthetic.1 (2) The drug is administered orally to dogs and cats at a dosage level of 1 to 2 milligrams per...

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... milligrams of triflupromazine hydrochloride. (b) Sponsor. See No. 053501 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs and cats to relieve anxiety and to help control psychomotor... preanesthetic.1 (2) The drug is administered orally to dogs and cats at a dosage level of 1 to 2 milligrams per...

EFFECT OF MAGNESIUM STEARATE CONCENTRATION ON DISSOLUTION PROPERTIES OF RANITIDINE HYDROCHLORIDE COATED TABLETS

PubMed Central

Uzunović, Alija; Vranić, Edina

2007-01-01

Most pharmaceutical formulations also include a certain amount of lubricant to improve their flowability and prevent their adhesion to the surfaces of processing equipment. Magnesium stearate is an additive that is most frequently used as a lubricant. Magnesium stearate is capable of forming films on other tablet excipients during prolonged mixing, leading to a prolonged drug liberation time, a decrease in hardness, and an increase in disintegration time. It is hydrophobic, and there are many reports in the literature concerning its adverse effect on dissolution rates. The objective of this study was to evaluate the effects of two different concentrations of magnesium stearate on dissolution properties of ranitidine hydrochloride coated tablet formulations labeled to contain 150 mg. The uniformity content was also checked. During the drug formulation development, several samples were designed for choice of the formulation. For this study, two formulations containing 0,77 and 1,1% of magnesium stearate added in the manufacture of cores were chosen. Fraction of ranitidine hydrochloride released in dissolution medium was calculated from calibration curves. The data were analyzed using pharmaco-peial test for similarity of dissolution profiles (f2 equation), previously proposed by Moore and Flanner. Application of f2 equation showed differences in time-course of ranitidine hydrochloride dissolution properties. The obtained values indicate differences in drug release from analyzed ranitidine hydrochloride formulations and could cause differences in therapeutic response. PMID:17848158

Effects of cyanobacterial extracellular products and gibberellic acid on salinity tolerance in Oryza sativa L

PubMed Central

Rodríguez, AA; Stella, AM; Storni, MM; Zulpa, G; Zaccaro, MC

2006-01-01

Salt stress is one of the most serious factors limiting the productivity of rice, the staple diet in many countries. Gibberellic acid has been reported to reduce NaCl-induced growth inhibition in some plants including rice. Most paddy soils have a natural population of Cyanobacteria, prokaryotic photosynthethic microorganisms, which synthesize and liberate plant growth regulators such as gibberellins that could exert a natural beneficial effect on salt stressed rice plants. The aim of this work was to evaluate the effect of the cyanobacterium Scytonema hofmanni extracellular products on the growth of rice seedlings inhibited by NaCl and to compare it with the effect of the gibberellic acid in the same stress condition. Growth (length and weight of the seedlings) and biochemical parameters (5-aminolevulinate dehydratase activity, total free porphyrin and pigments content) were evaluated. Salt exposure negatively affected all parameters measured, with the exception of chlorophyll. Chlrorophyll concentrations nearly doubled upon exposure to high salt. Gibberellic acid counteracted the effect of salt on the length and dry weight of the shoot, and on carotenoid and chlorophyll b contents. Extracellular products nullified the salt effect on shoot dry weight and carotenoid content; partially counteracted the effect on shoot length (from 54% to 38% decrease), root dry weight (from 59% to 41% decrease) and total free porphyrin (from 31 to 13% decrease); reduced by 35% the salt increase of chlorophyll a; had no effect on root length and chlorophyll b. Gibberellic acid and extracellular products increased 5-aminolevulinate dehydratase activity over the control without salt. When coincident with high salinity, exposure to either EP or GA3, resulted in a reversal of shoot-related responses to salt stress. We propose that Scytonema hofmanni extracellular products may counteract altered hormone homeostasis of rice seedlings under salt stress by producing gibberellin-like plant

40 CFR 180.499 - Propamocarb hydrochloride, tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... for residues. 180.499 Section 180.499 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.499 Propamocarb hydrochloride, tolerances for residues. (a) General. Tolerances are...

40 CFR 180.499 - Propamocarb hydrochloride, tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... for residues. 180.499 Section 180.499 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.499 Propamocarb hydrochloride, tolerances for residues. (a) General. Tolerances are...

Influence of limonene on the bioavailability of nicardipine hydrochloride from membrane-moderated transdermal therapeutic systems in human volunteers.

PubMed

Krishnaiah, Y S R; Satyanarayana, V; Bhaskar, P

2002-10-24

The aim of the present study was to develop a membrane-moderated transdermal therapeutic system (TTS) of nicardipine hydrochloride using 2%w/w hydroxy propyl cellulose (HPC) gel as a reservoir system containing 4%w/w of limonene as a penetration enhancer. The permeability flux of nicardipine hydrochloride through ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate (VA) content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38 or TACKWHITE A 4MED) on the permeability of nicardipine hydrochloride through EVA membrane 2825 (28% w/w VA) or membrane/skin composite was also studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE 4A MED/skin composite was higher than that coated with MA-31or MA-38. Thus a new TTS for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE 4A MED and 2%w/w HPC gel as reservoir containing 4%w/w of limonene as a penetration enhancer. The bioavailability studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady state plasma concentration of the drug with minimal fluctuations for 20 h with improved bioavailability in comparison with the immediate release capsule dosage form. Copyright 2002 Elsevier Science B.V.

[Clinical observation of icotinib hydrochloride in first-line therapy for pulmonary adenocarcinoma].

PubMed

Yang, Xinjie; Zhang, Hui; Qin, Na; Li, Xi; Nong, Jingying; Lv, Jialin; Wu, Yuhua; Zhang, Quan; Zhang, Shucai

2013-07-01

It has been proven that icotinib hydrochloride, as a molecule targeted drug, can be safely and efficiently used to treat advanced non-small cell lung cancer (NSCLC) for second-line or third-line. This research was aimed to investigate the efficacy and toxicity of icotinib hydrochloride as the first-line therapy for pulmonary adenocarcinoma. Among the 56 patients, the tumor objective response rate (ORR) and disease control rate (DCR) was 46.4% (26/56) and 78.6% (46/56), respectively. Among the 20 patients with EGFR analyses, 18 patients were positive for a mutation, ORR was 66.7% (12/18), DCR was 94.4% (17/18) respectively. The ORR with no history of smoke. EGFR positive mutation and appearance of rash were significantly higher than those with smoker, wild type EGFR, no information about EGFR and no appearance of rash (P<0.05). The most common drug-related adverse events were mild skin rash (28.5%) and diarrhea (12%). Single agent treatment with icotinib hydrochloride is effective and tolerable in first-line therapy for pulmonary adenocarcinoma, especially with EGFR mutation.

Vitamin D as a potential enhancer of aminolevulinate-based photodynamic therapy for nonmelanoma skin cancer

NASA Astrophysics Data System (ADS)

Maytin, Edward V.; Anand, Sanjay; Atanaskova, Natasha; Wilson, Clara

2010-02-01

Vitamin D3 (Vit D3) is a hormone essential for normal bone and cardiovascular health, and may participate in preventing nonmelanoma skin cancers (NMSC). Calcitriol (1,25 dihydroxyD3) is the active form of the hormone. We showed previously that calcitriol is a potent inducer of protoporphyrin IX (PpIX) in skin keratinocytes grown in organotypic cultures. Here, we investigated the ability of Vit D3 to enhance PpIX levels within skin tumors in vivo. Squamous tumors, generated by chemical carcinogenesis in mice, were pretreated for 3 days with topical calcitriol. Then 5-aminolevulinic acid (5-ALA) was applied topically, and PpIX levels were measured by noninvasive fluorimetry and in biopsied tissue. Calcitriol pretreatment resulted in a 3 to 4-fold elevation of PpIX in tumors, relative to no pretreatmen, providing significantly more photosensitizer available for tumor destruction. For deep tumors, topical calcitriol may not penetrate sufficiently. Therefore we explored whether systemic Vit D3, given short-term (3 days), might elevate PpIX within NMSC in a deep tumor model (subcutaneously-implanted A431 human squamous carcinoma cells). Defined amounts of calcitriol were injected into the mice for 3 d, followed by systemic 5-ALA, tissue biopsy, and confocal microscopic measurement of PpIX in frozen tissues. PpIX was clearly elevated after systemically delivered calcitriol. More work is needed, but if the amount of calcitriol required to elevate PpIX levels proves to be small, then the approach may ultimately prove attractive. Since most Americans are currently Vitamin D deficient, a small increase in calcitriol might be possible without risk of hypercalcemia.

A novel dressing for the combined delivery of platelet lysate and vancomycin hydrochloride to chronic skin ulcers: Hyaluronic acid particles in alginate matrices.

PubMed

Rossi, S; Mori, M; Vigani, B; Bonferoni, M C; Sandri, G; Riva, F; Caramella, C; Ferrari, F

2018-06-15

The aim of the present work was to develop a medication allowing for the combined delivery of platelet lysate (PL) and an anti-infective model drug, vancomycin hydrochloride (VCM), to chronic skin ulcers. A simple method was set up for the preparation of hyaluronic acid (HA) core-shell particles, loaded with PL and coated with calcium alginate, embedded in a VCM containing alginate matrix. Two different CaCl 2 concentrations were investigated to allow for HA/PL core-shell particle formation. The resulting dressings were characterized for mechanical and hydration properties and tested in vitro (on fibroblasts) and ex-vivo (on skin biopsies) for biological activity. They were found of sufficient mechanical strength to withstand packaging and handling stress and able to absorb a high amount of wound exudate and to form a protective gel on the lesion area. The CaCl 2 concentration used for shell formation did not affect VCM release from the alginate matrix, but strongly modified the release of PGFAB (chosen as representative of growth factors present in PL) from HA particles. In vitro and ex vivo tests provided sufficient proof of concept of the ability of dressings to improve skin ulcers healing. Copyright © 2018 Elsevier B.V. All rights reserved.

Health and environmental effects profile for 2,4-dimethylaniline and 2,4-dimethylaniline hydrochloride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1987-01-01

The Health and Environmental Effects Profile for 2-4-Dimethylaniline and 2,4-Dimethylaniline Hydrochloride was prepared to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and information obtained from Agency program office files were evaluated as they pertained to potential human-health, aquatic-life and environmental effects of hazardous-waste constituents. The human carcinogen potency factors (q1*) for 2-4-dimethylaniline and 2,4-dimethylaniline hydrochloride are 0.75 and 0.58/(mg/kg/day) respectively,more » for oral exposure. The Reportable Quantity (RQ) value for 2-4-dimethylaniline and 2,4-dimethylaniline Hydrochloride is 1000.« less

Solution blow spun Poly(lactic acid)/Hydroxypropyl methylcellulose nanofibers with antimicrobial properties

USDA-ARS?s Scientific Manuscript database

Poly(lactic acid) (PLA) nanofibers containing hydroxypropyl methylcellulose (HPMC) and tetracycline hydrochloride (THC) were solution blow spun from two different solvents, chloroform/acetone (CA, 80:20 v/v) and 2,2,2-triflouroethanol (TFE). The diameter distribution, chemical, thermal, thermal stab...

Lead and PCB's in canvasback ducks: Relationship between enzyme levels and residues in blood

USGS Publications Warehouse

Dieter, M.P.; Perry, M.C.; Mulhern, B.M.

1976-01-01

Blood samples were taken for two successive years from canvasback ducks trapped in the Chesapeake Bay. The first winter (1972?1973) five plasma enzymes known to respond to organochlorine poisoning were examined. Abnormal enzyme elevations suggested that 20% of the population sampled (23/115 ducks) might contain organochlorine contaminants, but no residue analyses were performed. The second winter (1974) two of the same enzymes, aspartate aminotransferase and lactate dehydrogenase, and a third enzyme known to be specifically inhibited by lead, delta-aminolevulinic acid dehydratase, were assayed in 95 blood samples. Blood residues of organochlorine compounds and of lead were determined in representative samples, and the correlations between residue levels and enzyme changes were examined. The enzyme bioassays in 1974 indicated that lead was a more prevalent environmental contaminant than organochlorine compounds in canvasback ducks; 17% of the blood samples had less than one-half of the normal delta-aminolevulinic acid dehydratase activity, but only 11% exhibited abnormal aspartate aminotransferase or lactate dehydrogenase activities. These findings were confirmed by residue analyses that demonstrated lead concentrations four times higher than background levels, but only relatively low organochlorine concentrations. There was a highly significant inverse correlation between delta-aminolevulinic acid dehydratase activity and blood lead concentrations (P<0.01), and a weaker but significant correlation between plasma aspartate aminotransferase activity and blood PCB concentrations (P<0.05). It was apparent that delta-aminolevulinic acid dehydratase activity in the blood provided a sensitive and precise estimate of lead contamination in waterfowl. In canvasback ducks 200 ppb of lead in the blood caused a 75% decrease in delta-aminolevulinic acid dehydratase activity, a magnitude of enzyme inhibition that disturbs heme synthesis and is regarded as detrimental in humans.

Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

NASA Astrophysics Data System (ADS)

Bhunia, Tridib; Goswami, Luna; Chattopadhyay, Dipankar; Bandyopadhyay, Abhijit

2011-08-01

Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

Disposable screen-printed sensors for determination of duloxetine hydrochloride

PubMed Central

2012-01-01

A screen-printed disposable electrode system for the determination of duloxetine hydrochloride (DL) was developed using screen-printing technology. Homemade printing has been characterized and optimized on the basis of effects of the modifier and plasticizers. The fabricated bi-electrode potentiometric strip containing both working and reference electrodes was used as duloxetine hydrochloride sensor. The proposed sensors worked satisfactorily in the concentration range from 1.0 × 10-6-1.0 × 10-2 mol L-1 with detection limit reaching 5.0 × 10-7 mol L-1 and adequate shelf life of 6 months. The method is accurate, precise and economical. The proposed method has been applied successfully for the analysis of the drug in pure and in its dosage forms. In this method, there is no interference from any common pharmaceutical additives and diluents. Results of the analysis were validated statistically by recovery studies. PMID:22264225

Degradation chemistry of gemcitabine hydrochloride, a new antitumor agent.

PubMed

Anliker, S L; McClure, M S; Britton, T C; Stephan, E A; Maple, S R; Cooke, G G

1994-05-01

The anti-tumor agent gemcitabine hydrochloride, a beta-difluoronucleoside, is remarkably stable in the solid state. In 0.1 N HCI solution at 40 degrees C, deamination of gemcitabine occurs, yielding its uridine analogue. Approximately 86% of the initial gemcitabine remains after 4 weeks under these conditions. Cleavage of the N-glycosidic bond of gemcitabine or conversion to its alpha-anomer in 0.1 N HCI solution is not observed over a 4-week period. However, this work has shown that gemcitabine hydrochloride anomerizes in 0.1 N NaOH at 40 degrees C. Approximately 72% of the initial gemcitabine remains after 4 weeks under the basic conditions used. Uridine hydrolysis products are also formed under these conditions. The anormerization reaction, which is unusual under basic conditions, has been confirmed by characterization of the chromatographically isolated alpha-anomer by NMR and mass spectrometry. A mechanism involving an acyclic intermediate is proposed.

Tranexamic acid attenuates oleic-acid-induced pulmonary extravasation.

PubMed

Moriuchi, H; Arai, I; Yuizono, T

1995-12-01

Activation of fibrinolysis is implicated in the development of vascular injury in certain lung injuries. It has yet to be reported that activation of plasmin is involved in extravasation caused by oleic acid (OA). We examined whether or not plasmin is involved in pulmonary extravasation by OA. Prospective trial. University laboratory. A total of 78 guinea pigs (498.9 +/- 10.6 g). Evans blue (EB) was administered to anesthetized guinea pigs. Subsequently four protocols were followed: (1) After 1 min, 60 micro l/kg of OA was injected. Perfusion was performed 30, 60 or 90 min after OA injection to wash out intravascular EB. (2) After 1 min, 15, 30 or 60 micro l/kg of OA was injected. (3) Tranexamic acid (TA) (2 g/kg) or saline was administered 30 min before OA (15 micro l/kg) injection. (4) Diphenhydramine hydrochloride (2.9 mg/kg) or saline was administered 7 min before OA (15 micro l/kg) injection. Except in protocol 1, the chest cavity was opened 90 min after OA injection. Perfusion was then performed. Airway was separated into four parts from trachea to distal bronchus. EB was extracted from the tissues and measured. OA caused an extravasation throughout airways in a time- and dose-dependent manner. Extravasation was more conspicuous in peripheral tissues. TA significantly attenuated extravasation, while diphenhydramine hydrochloride did not. It is suggested that plasmin, but not histamine, is involved in extravasation by OA. Inhibition of plasmin can be an effective strategy for treatment of this kind of lung injury.

Toxicity of naproxen sodium and its mixture with tramadol hydrochloride on fish early life stages.

PubMed

Sehonova, Pavla; Plhalova, Lucie; Blahova, Jana; Doubkova, Veronika; Prokes, Miroslav; Tichy, Frantisek; Fiorino, Emma; Faggio, Caterina; Svobodova, Zdenka

2017-12-01

Pharmaceuticals occur in water bodies as a consequence of their incomplete removal during waste water treatment processes. The occurence of pharmaceuticals in surface waters as well as their possible impact on aquatic vertebrates have received considerable attention in recent years. However, there is still a lack of informations on the chronic effects of widely used drugs as well as their possible mixture toxicity on non-target aquatic vertebrates as well as their possible mixture toxicity. The aim of this study was to assess the effects of naproxen sodium on early life stages of fish and evaluate its mixture toxicity with tramadol hydrochloride, which was assessed in our earlier study as a single substance. Two embryo-larval toxicity tests with common carp (Cyprinus carpio) were performed according to the OECD guideline 210 (Fish, Early-life Stage Toxicity Test) in order to assess the subchronic toxicity of naproxen sodium and tramadol hydrochlorid-naproxen sodium mixture at the concentrations of 10; 50; 100 and 200 μg/L. These experiments were conducted for 32 days. The subchronic exposure to naproxen sodium and naproxen sodium and tramadol hydrochloride mixture had a strong effect on the early life stages of common carp. Hatching, developmental rate, morphology, histopathology and, in the case of the naproxen sodium and tramadol hydrochloride mixture, mortality were influenced. The bioindicators of oxidative stress were also influenced. The LOEC was determined at 10 μg/L for both naproxen sodium and naproxen sodium and tramadol hydrochloride mixture. Copyright © 2017 Elsevier Ltd. All rights reserved.

Benzydamine hydrochloride in prevention and management of pain in oral mucositis associated with radiation therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Epstein, J.B.; Stevenson-Moore, P.

1986-08-01

Benzydamine hydrochloride rinse reduced pain associated with radiation mucositis when it was used during the course of radiation therapy. Fewer patients using benzydamine rinse required systemic analgesics. All patients using benzydamine tolerated the rinse well and continued with regular rinsing throughout the course of radiation therapy. Benzydamine hydrochloride is currently undergoing clinical trials in the United States for application for approval from the Food and Drug Administration.

Solid-state and solution /sup 13/C NMR in the conformational analysis of methadone-hydrochloride and related narcotic analgesics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sumner, S.C.J.

1986-01-01

Solid state and solution /sup 13/C NMR have been used to study the conformations of the racemic mixtures and single enantiomers of methadone hydrochloride, alpha and beta methadol hydrochloride, and alpha and beta acetylmethadol hydrochloride. The NMR spectra acquired for the compounds as solids, and in polar and nonpolar solvents are compared, in order to determine the conformation of the molecules in solution. To determine the reliability of assigning solution conformations by comparing solution and solid state chemical shift data, three bond coupling constants measured in solution are compared with those calculated from X-ray data. The conformations of the racemicmore » mixture and plus enantiomer of methadone hydrochloride have been shown to be very similar in the solid state, where minor differences in conformation can be seen by comparing NMR spectra obtained for the solids. Also shown is that the molecules of methadone hydrochloride have conformations in polar and in nonpolar solvents which are very similar to the conformation of the molecules in the solid state.« less

A novel drug delivery gel of terbinafine hydrochloride with high penetration for external use.

PubMed

Yang, Yan; Ou, Rujing; Guan, Shixia; Ye, Xiaoling; Hu, Bo; Zhang, Yi; Lu, Shufan; Zhou, Yubin; Yuan, Zhongwen; Zhang, Jun; Li, Qing-Guo

2015-12-01

Terbinafine hydrochloride is an antifungal drug for onychomycosis. Poor permeability of its external preparation leads to poor curative effect. Transfersomes, also known as flexible liposome, could improve transmission of drug for local external use. Terbinafine hydrochloride-loaded liposome is expected to become a breakthrough on the treatment of onychomycosis. This study is aimed to prepare high skin penetration terbinafine hydrochloride transfersomes with high encapsulation efficiency, appropriate drug loading and good stability. Taking entrapment efficiency as the main indicator, the formulations and the processes of preparation were investigated. Transfersomes with different surfactants were prepared in the optimization processes, and the formulations were optimized through the transdermal test in vitro. As a result, a gel contained transfersomes was obtained with a brief evaluation. Its pharmacokinetic properties of going through the skin were studied by using the micro dialysis technology and liquid chromatography-mass spectrometry to assay the penetration behavior of terbinafine. Mean particle size of the terbinafine hydrochloride transfersomes was 69.6 ± 1.23 nm, and the entrapment efficiency was 95.4% ± 0.51. The content of the gel was 4.45 ± 0.15 mg/g. The accumulated permeation of the transfersomes gel in 12 h was 88.52 ± 4.06 µg cm -2 and the intracutaneous drug detention was 94.38 ± 5.26 µg cm -2 . The results of pharmacokinetic studies showed the C max and area under the curve (AUC) were apparently higher than the commercial cream. The terbinafine hydrochloride transfersomes was highly absorbed by the skin. The absorption rate was significantly higher than that of the commercial cream either in the transdermal test in vitro or in the pharmacokinetic studies in vivo.

Combination photodynamic therapy using 5-fluorouracil and aminolevulinate enhances tumor-selective production of protoporphyrin IX and improves treatment efficacy of squamous skin cancers and precancers

NASA Astrophysics Data System (ADS)

Maytin, Edward V.; Anand, Sanjay

2016-03-01

In combination photodynamic therapy (cPDT), a small-molecule drug is used to modulate the physiological state of tumor cells prior to giving aminolevulinate (ALA; a precursor for protoporphyrin IX, PpIX). In our laboratory we have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can enhance therapeutic effectiveness of ALAbased photodynamic therapy for cutaneous squamous cell carcinoma (SCC). However, only one (5-fluorouracil; 5-FU) is FDA-approved for skin cancer management. Here, we describe animal and human studies on 5-FU mechanisms of action, in terms of how 5-FU pretreatment leads to enhanced PpIX accumulation and improves selectivity of ALA-PDT treatment. In A431 subcutaneous tumors in mice, 5-FU changed expression of heme enzyme (upregulating coproporphyrinogen oxidase, and down-regulating ferrochelatase), inhibited tumor cell proliferation (Ki-67), enhanced differentiation (E-cadherin), and led to strong, tumor-selective increases in apoptosis. Interestingly, enhancement of apoptosis by 5-FU correlated strongly with an increased accumulation of p53 in tumor cells that persisted for 24 h post- PDT. In a clinical trial using a split-body, bilaterally controlled study design, human subjects with actinic keratoses (AK; preneoplastic precursors of SCC) were pretreated on one side of the face, scalp, or forearms with 5-FU cream for 6 days, while the control side received no 5-FU. On the seventh day, the levels of PpIX in 4 test lesions were measured by noninvasive fluorescence dosimetry, and then all lesions were treated with PDT using methyl-aminolevulinate (MAL) and red light (635 nm). Relative amounts of PpIX were found to be increased ~2-fold in 5-FU pretreated lesions relative to controls. At 3 months after PDT, the overall clinical response to PDT (reduction in lesion counts) was 2- to 3-fold better for the 5-FU pretreated lesions, a clinically important result. In summary, 5-FU is a useful adjuvant to aminolevulinate-based PDT

Quantitative HPLC Analysis of a Psychotherapeutic Medication: Simultaneous Determination of Amitriptyline Hydrochloride and Perphenazine

NASA Astrophysics Data System (ADS)

Ferguson, Glenda K.

1998-12-01

A quantitative high-performance liquid chromatography (HPLC) laboratory experiment which entails the isocratic separation and simultaneous determination of the two active components of a commercial antipsychotic tablet has been developed. The prescription formulation used in this experiment contains amitriptyline hydrochloride (a tricyclic antidepressant) and perphenazine (a tranquilizer). Our experiment makes use of a straightforward HPLC separation on a cyanopropyl-packed column with an acetonitrile:methanol:aqueous monopotassium phosphate mobile phase pumped at a flow rate of 2.0 mL/min. Analytes are detected by UV absorbance at 215 nm. These conditions yield highly symmetrical and well-resolved peaks in less than 5 min after the injection of a mixture. In the experiment, students are given amitriptyline hydrochloride-perphenazine tablets without the manufacturer's labeled composition claim and a stock solution mixture with known concentrations of amitriptyline hydrochloride and perphenazine. They prepare four standards and a pharmaceutical sample of unknown concentration, assay each solution in quadruplicate, and plot average peak areas of the concentrations of the known solutions in the construction of a standard curve. From the mathematical relationships that result, the average masses of amitriptyline hydrochloride and perphenazine in the prescription tablet are determined. Finally, the standard deviations of the mean masses are calculated. The entire laboratory procedure and statistical data analysis can be completed in a single 3-hour period.

Nifekalant hydrochloride suppresses severe electrical storm in patients with malignant ventricular tachyarrhythmias.

PubMed

Washizuka, Takashi; Chinushi, Masaomi; Watanabe, Hiroshi; Hosaka, Yukio; Komura, Satoru; Sugiura, Hirotaka; Hirono, Takashi; Furushima, Hiroshi; Tanabe, Yasutaka; Aizawa, Yoshifusa

2005-12-01

Some patients with an implantable cardioverter-defibrillator (ICD) suffer from burst of inappropriate multiple discharges (severe electrical storm), and because the current therapeutic options are limited, the effect of nifekalant hydrochloride, a new class III drug, on severe electrical storm was investigated in the present study. Ninety-one consecutive patients treated with ICD were included in the study (M 70; mean age 58 years; left ventricular ejection fraction 45+/-15%). Severe electrical storm was defined as more than 10 ICD discharges within 1 h. During a mean follow-up period of 30+/-13 months, 41/91 (45%) patients had appropriate ICD therapy for arrhythmias and severe electrical storm occurred in 11 of them (12%) at 20+/-18 months after ICD implantation. The mean number of ICD discharges/h during severe electrical storm was 18+/-12. In 4 of 10 patients, severe electrical storm was successfully suppressed by a combination of deep sedation and beta-blocking agent; 6 other patients were refractory to this treatment, but severe electrical storm was successfully suppressed by intravenous administration of nifekalant hydrochloride with no adverse effects. Nifekalant hydrochloride is an effective and safe treatment for severe electrical storm.

Vibrational spectra of ketamine hydrochloride and 3, 4-methylenedioxymethamphetamine in terahertz range

NASA Astrophysics Data System (ADS)

Wang, Guangqin; Shen, Jingling; Jia, Yan

2007-07-01

The terahertz spectrum of ketamine hydrochloride at room temperature, in the range of 0.2-2.6THz, has been measured by terahertz time-domain spectroscopy (TDS). Full-geometry optimizations and frequency calculations using the density functional theory (DFT) are also applied to predict the absorption spectra of ketamine hydrochloride and 3, 4-methylenedioxymethamphetamine (MDMA). The results of the simulation show qualitative agreement with the experimental data especially for MDMA, and the observed spectra features are assigned based on the DFT calculation. The results suggest that use of the terahertz TDS technique can be an effective method for the detection and inspection of illicit drugs.

Differences in the Pathways of Proteins Unfolding Induced by Urea and Guanidine Hydrochloride: Molten Globule State and Aggregates

PubMed Central

Povarova, Olga I.; Kuznetsova, Irina M.; Turoverov, Konstantin K.

2010-01-01

It was shown that at low concentrations guanidine hydrochloride (GdnHCl) can cause aggregation of proteins in partially folded state and that fluorescent dye 1-anilinonaphthalene-8-sulfonic acid (ANS) binds with these aggregates rather than with hydrophobic clusters on the surface of protein in molten globule state. That is why the increase in ANS fluorescence intensity is often recorded in the pathway of protein denaturation by GdnHCl, but not by urea. So what was previously believed to be the molten globule state in the pathway of protein denaturation by GdnHCl, in reality, for some proteins represents the aggregates of partially folded molecules. PMID:21152408

Relationship between Photoconvertible and Nonphotoconvertible Protochlorophyllides.

PubMed

Murray, A E; Klein, A O

1971-10-01

Two forms of protochlorophyllide are found in dark-grown bean (Phaseolus vulgaris, var. Black Velentine) leaves, one (protochlorophyllide(650)) which is directly photoconvertible to chlorophyllide and another (protochlorophyllide(632)) which is not. Dark-grown leaves placed in solutions of delta-aminolevulinic acid accumulate protochlorophyllide(632). Protochlorophyllide(650) and protochlorophyllide(632) can be partially separated on sucrose density gradients. A nitrogen atmosphere blocks chlorophyll synthesis in light or the regeneration of protochlorophyllide(650) in the dark, even in the presence of excess delta-aminolevulinic acid, except when a stockpile of protochlorophyllide(632) is present in the leaf. Under the latter conditions chlorophyll synthesis or protochlorophyllide(650) regeneration is accompanied by a decrease in protochlorophyllide(632). These experiments suggest that protochlorophyllide(632) may be converted to protochlorophyllide(650).Cycloheximide inhibited greening only after an "action-dependent" delay, requiring a predictable minimal period of illumination. This inhibition could be relieved for a time by feeding delta-aminolevulinic acid.

Ambroxol Hydrochloride Combined with Fluconazole Reverses the Resistance of Candida albicans to Fluconazole.

PubMed

Li, Xiuyun; Zhao, Yuanhao; Huang, Xin; Yu, Cuixiang; Yang, Yilei; Sun, Shujuan

2017-01-01

In this study, we found that ambroxol hydrochloride (128 μg/mL) exhibits synergistic antifungal effects in combination with fluconazole (2 μg/mL) against resistant planktonic Candida albicans ( C. albicans ) cells. This combination also exhibited synergistic effects against resistant C. albicans biofilms in different stages (4, 8, and 12 h) according to the microdilution method. In vitro data were further confirmed by the success of this combination in treating Galleria mellonella infected by resistant C. albicans . With respect to the synergistic mechanism, our result revealed that ambroxol hydrochloride has an effect on the drug transporters of resistant C. albicans , increasing the uptake and decreasing the efflux of rhodamine 6G, a fluorescent alternate of fluconazole. This is the first study to investigate the in vitro and in vivo antifungal effects, as well as the possible synergistic mechanism of ambroxol hydrochloride in combination with fluconazole against resistant C. albicans . The results show the potential role for this drug combination as a therapeutic alternative to treat resistant C. albicans and provide insights into the development of antifungal targets and new antifungal agents.

Chromatographic determination of itopride hydrochloride in the presence of its degradation products.

PubMed

Kaul, Neeraj; Agrawal, Himani; Maske, Pravin; Rao, Janhavi Ramchandra; Mahadik, Kakasaheb Ramoo; Kadam, Shivajirao S

2005-08-01

Two sensitive and reproducible methods are described for the quantitative determination of itopride hydrochloride (IH) in the presence of its degradation products. The first method is based on HPLC separation on a reversed phase Kromasil column [C18 (5-microm, 25 cm x 4.6 mm, ID)] at ambient temperature using a mobile phase consisting of methanol and water (70:30, v/v) adjusted to pH 4.0 with orthophosphoric acid with UV detection at 258 nm. The flow rate was 1.0 mL per min with an average operating pressure of 180 kg/cm2. The second method is based on HPTLC separation on silica gel 60 F254 using toluene:methanol:chloroform:10% ammonia (5.0:3.0:6.0:0.1, v/v/v/v) as mobile phase at 270 nm. The analysis of variance (ANOVA) and Student's t-test were applied to correlate the results of IH determination in dosage form by means of HPLC and HPTLC methods. The drug was subjected to acid and alkali hydrolysis, oxidation, dry heat, wet heat treatment, UV, and photodegradation. The proposed HPLC method was utilized to investigate the kinetics of the acidic, alkaline, and oxidative degradation processes at different temperatures and the apparent pseudo-first-order rate constant, half-life, and activation energy were calculated. In addition the pH-rate profile of degradation of IH in constant ionic strength buffer solutions in the pH range 2-11 was studied.

Photodynamic therapy using a novel irradiation source, LED lamp, is similarly effective to photodynamic therapy using diode laser or metal-halide lamp on DMBA- and TPA-induced mouse skin papillomas.

PubMed

Takahashi, Hidetoshi; Nakajima, Susumu; Ogasawara, Koji; Asano, Ryuji; Nakae, Yoshinori; Sakata, Isao; Iizuka, Hajime

2014-08-01

Photodynamic therapy (PDT) is useful for superficial skin tumors such as actinic keratosis and Bowen disease. Although PDT is non-surgical and easily-performed treatment modality, irradiation apparatus is large and expensive. Using 7, 12-dimethylbenz[a]anthracene (DMBA) and 12-ο-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin papilloma model, we compared the efficacy of TONS501- and ALA-PDT with a LED lamp, a diode laser lamp or a metal-halide lamp on the skin tumor regression. TONS501-PDT using 660 nm LED lamp showed anti-tumor effect at 1 day following the irradiation and the maximal anti-tumor effect was observed at 3 days following the irradiation. There was no significant difference in the anti-tumor effects among TONS501-PDT using LED, TONS501-PDT using diode laser, and 5-aminolevulinic acid hydrochloride (ALA)-PDT using metal-halide lamp. Potent anti-tumor effect on DMBA- and TPA-induced mouse skin papilloma was observed by TONS501-PDT using 660 nm LED, which might be more useful for clinical applications. © 2014 Japanese Dermatological Association.

A Stability-Indicating HPLC Method for the Determination of Memantine Hydrochloride in Dosage Forms through Derivatization with 1-Fluoro-2,4-dinitrobenzene

PubMed Central

Jalalizadeh, Hassan; Raei, Mahdi; Tafti, Razieh Fallah; Farsam, Hassan; Kebriaeezadeh, Abbas; Souri, Effat

2014-01-01

Memantine is chemically a tricyclic amine and is used for Parkinson’s disease and movement disorders. Although several HPLC methods with different derivatization reagents have been developed for the determination of memantine in biological fluids, there are some complications which limit the use of these methods in routine analysis of memantine in in vitro tests. We established a simple, sensitive, precise, and accurate HPLC method for the quantification of memantine in dosage forms. Pre-column derivatization of memantine was performed with 1-fluoro-2,4-dinitrobenzene and the reaction product was separated on a Nova-Pak C18 column. A mixture of acetonitrile and sodium dihydrogenphosphate (pH 2.5; 0.05 M) (70: 30, v/v) was used as the mobile phase. UV detection was performed at 360 nm. Forced degradation studies were performed on a powdered tablet sample of memantine hydro-chloride using acidic (0.1 M hydrochloric acid), basic (0.1 M sodium hydroxide), oxidative (10% hydrogen peroxide), thermal (105°C), photolytic, and humidity conditions. Good linearity (r2=0.999) was obtained over the range of 1–12 μg mL−1 of memantine hydrochloride with acceptable within-day and between-day precision values in the range of 0.05–0.95%. The proposed method was used for the assay determination and dissolution rate study of memantine dosage forms with excellent specificity. PMID:24959398

Development and in vitro evaluation of carboxymethyl chitosan based drug delivery system for the controlled release of propranolol hydrochloride

NASA Astrophysics Data System (ADS)

Hernawan; Nur Hayati, Septi; Nisa, Khoirun; Wheni Indrianingsih, Anastasia; Darsih, Cici; Kismurtono, Muhammad

2017-12-01

Propranolol hydrochloride is a nonselective β-adrenergic drug and has been used as angina pectoris, antihypertensive, and that of many other cardiovascular disorders. It has a relatively short plasma half-life and duration of action are considered too short in certain circumstances. Thus, it’s fascinating to elongate the action. The tablet formula was based on extended-release by a propranolol hydrochloride based carboxymethyl chitosan matrix. Here we used direct compression technique with internal wet granulation to prepare the tablets. The tablets were evaluated for physical properties (hardness, weight variation test, friability) and in vitro release studies. There was no interaction observed between propranolol hydrochloride and excipients. Dissolution profiles of each formulation were followed zero order model. In conclusion, these results strongly suggest that in appropriate proportions carboxymethyl chitosan with internal granulation is suitable for formulating propranolol hydrochloride controlled release.

Vitamin-E reduces the oxidative damage on delta-aminolevulinic dehydratase induced by lead intoxication in rat erythrocytes.

PubMed

Rendón-Ramirez, A; Cerbón-Solórzano, J; Maldonado-Vega, M; Quintanar-Escorza, M A; Calderón-Salinas, J V

2007-09-01

Lead intoxication induces oxidative damage on lipids and proteins. In the present paper we study in vivo and in vitro the antioxidant effect of vitamin-E and trolox, on the oxidative effects of lead intoxication in rat erythrocytes. Vitamin-E simultaneously administered to erythrocytes treated with lead was capable to prevent the inhibition of delta-aminolevulinic dehydratase activity and lipid oxidation. Partial but important protective effects were found when vitamin-E was administered either after or before lead exposure in rats. In vitro, the antioxidant trolox protected delta-ALA-D activity against damage induced by lead or menadione. These results indicate that vitamin-E could be useful in order to protect membrane-lipids and, notably, to prevent protein oxidation produced by lead intoxication.

Preparation and the in vitro evaluation of nanoemulsion system for the transdermal delivery of granisetron hydrochloride.

PubMed

Zheng, Wen-wu; Zhao, Ling; Wei, Yu-meng; Ye, Yun; Xiao, Shun-han

2010-08-01

The objective of this study was to develop and evaluate nanoemulsion system for transdermal delivery of granisetron hydrochloride. Pseudo-ternary phase diagram was constructed to ascertain the concentration range of components of nanoemulsion composed of isopropyl myristate (IPM) as an oil phase, tween 85 as surfactant, ethanol as cosurfactant, water as aqueous phase. The effects of the content of IPM as an oil phase and n-methyl pyrrolidone (NMP) as transdermal enhancer on rat skin permeation of granisetron hydrochloride nanoemulsion were studied in vitro. The results showed that the mean particle size of nanoemulsion ranged from 50.4+/-1.5 to 82.4+/-0.9 nm with homogeneous size distribution. The resulted optimum formulation composed of 2.5% granisetron hydrochloride, 4% IPM, 40% tween 85/ethanol (1 : 1) and 10% NMP showed that the skin permeation rate was the highest (85.39+/-2.90 microg/cm(2)/h) and enhancement of drug permeability was 4.1-fold for transdermal delivery of granisetron hydrochloridein comparison with the control group (20% of tween 85 and 20% of ethanol micelle solution containing 2.5% of granisetron hydrochloride without IPM), and cumulative permeation amount was the highest (891.8+/-2.86 microg/cm(2)) with the shortest lag time (0.11+/-0.02 h) and was stable for at least 12 months. Therefore, the nanoemulsion system developed in this study offers a promising vehicle for the transdermal delivery system of granisetron hydrochloride, which may be as effective as oral or intravenous dosage forms and avoid some difficulties associated with these dosage forms.

Formulation and in vivo evaluation of membrane-moderated transdermal therapeutic systems of nicardipine hydrochloride using carvone as a penetration enhancer.

PubMed

Krishnaiah, Y S R; Satyanarayana, V; Bhaskar, P

2003-01-01

A membrane-moderated transdermal therapeutic system (TTS) of nicardipine hydrochloride was developed using 2%w/w hydroxy propyl cellulose (HPC) gel as a reservoir system containing 8%w/w of carvone as a penetration enhancer. The permeability flux of nicardipine hydrochloride through ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38, or TACKWHITE A 4MED) on the permeability of nicardipine hydrochloride through EVA 2825 membrane (28%w/w vinyl acetate) or EVA 2825 membrane/skin composite also was studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE A 4MED/skin composite was higher than that coated with MA-31 or MA-38. Thus, a new TTS for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE A 4MED and 2%w/w HPC gel as reservoir containing 8%w/w of carvone as a penetration enhancer. The bioavailability studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady-state plasma concentration of the drug with minimal fluctuations for 23 hr with improved bioavailability in comparison with the immediate-release capsule dosage form.

Dehydration of detomidine hydrochloride monohydrate.

PubMed

Veldre, K; Actiņš, A; Jaunbergs, J

2011-10-09

The thermodynamic stability of detomidine hydrochloride monohydrate has been evaluated on the basis of phase transition kinetics in solid state. A method free of empirical models was used for the treatment of kinetic data, and compared to several known solid state kinetic data processing methods. Phase transitions were monitored by powder X-ray diffraction (PXRD) and thermal analysis. Full PXRD profiles were used for determining the phase content instead of single reflex intensity measurements, in order to minimize the influence of particle texture. We compared the applicability of isothermal and nonisothermal methods to our investigation of detomidine hydrochlorine monohydrate dehydration. Copyright © 2011 Elsevier B.V. All rights reserved.

21 CFR 520.1242 - Levamisole hydrochloride oral dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Levamisole hydrochloride oral dosage forms. 520.1242 Section 520.1242 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1242...

Differential effect of buffering agents on the crystallization of gemcitabine hydrochloride in frozen solutions.

PubMed

Patel, Mehulkumar; Munjal, Bhushan; Bansal, Arvind K

2014-08-25

The purpose of this study was to evaluate the differential effect of buffering agents on the crystallization of gemcitabine hydrochloride (GHCl) in frozen solutions. Four buffering agents, viz. citric acid (CA), malic acid (MA), succinic acid (SA) and tartaric acid (TA) were selected and their effect on GHCl crystallization was monitored using standard DSC and low temperature XRD. Onset of GHCl crystallization during heating run in DSC was measured to compare the differential effect of buffering agents. Glass transition temperature (Tg'), unfrozen water content in the freeze concentrate and crystallization propensity of the buffering agents was also determined for mechanistic understanding of the underlying effects. CA and MA inhibited while SA facilitated crystallization of GHCl even at 25 mM concentration. Increasing the concentration enhanced their effect. However, TA inhibited GHCl crystallization at concentrations <100mM and facilitated it at concentrations ≥100 mM. Lyophilization of GHCl with either SA or TA yielded elegant cakes, while CA and MA caused collapse. Tg' failed to explain the inhibitory effects of CA, MA and TA as all buffering agents lowered the Tg' of the system. Differential effect of buffering agents on GHCl crystallization could be explained by consideration of two opposing factors: (i) their own crystallization tendency and (ii) unfrozen water content in the freeze concentrate. In conclusion, it was established that API crystallization in frozen solution is affected by the type and concentration of the buffering agents. Copyright © 2014 Elsevier B.V. All rights reserved.

Preparation and controlled release of mesoporous MCM-41/propranolol hydrochloride composite drug.

PubMed

Zhai, Qing-Zhou

2013-01-01

This article used MCM-41 as a carrier for the assembly of propranolol hydrochloride by the impregnation method. By means of chemical analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy and low-temperature N(2) adsorption-desorption at 77 K, the characterization was made for the prepared materials. The propranolol hydrochloride guest assembly capacity was 316.20 ± 0.31 mg/g (drug/MCM-41). Powder XRD test results indicated that during the process of incorporation, the frameworks of the MCM-41 were not destroyed and the crystalline degrees of the host-guest nanocomposite materials prepared still remained highly ordered. Characterization by SEM and TEM showed that the composite material presented spherical particle and the average particle size of composite material was 186 nm. FT-IR spectra showed that the MCM-41 framework existed well in the (MCM-41)-propranolol hydrochloride composite. Low-temperature nitrogen adsorption-desorption results at 77 K showed that the guest partially occupied the channels of the molecular sieves. Results of the release of the prepared composite drug in simulated body fluid indicated that the drug can release up to 32 h and its maximum released amount was 99.20 ± 0.11%. In the simulated gastric juice release pattern of drug, the maximum time for the drug release was discovered to be 6 h and the maximum cumulative released amount of propranolol hydrochloride was 45.13 ± 0.23%. The drug sustained-release time was 10 h in simulated intestinal fluid and the maximum cumulative released amount was 62.05 ± 0.13%. The prepared MCM-41 is a well-controlled drug delivery carrier.

Treating Chronic Tension-type Headache Not Responding to Amitriptyline Hydrochloride With Paroxetine Hydrochloride: A Pilot Evaluation

PubMed Central

Holroyd, Kenneth A.; Labus, Jennifer S.; O'Donnell, Francis J.; Cordingley, Gary E.

2007-01-01

Context In some individuals, chronic tension-type headache fails to respond to tricyclic antidepressant medications that often serve as first-line therapy. Objective To evaluate the clinical efficacy of paroxetine hydrochloride for chronic tension-type headache not responding to amitriptyline hydrochloride. Design and Setting Open-label trial of paroxetine conducted at 2 outpatient sites in Ohio. Participants and Intervention Thirty-one adults (mean age, 37 years; 20 women) with chronic tension-type headache (mean, 25 headache days per month) who had failed to respond (less than 30% improvement) to treatment with either amitriptyline (n = 13) or matched placebo (n = 18). All participants were treated with paroxetine (up to 40 mg per day) in a 9-month protocol. Outcome Measures Monthly headache index calculated as the mean of pain ratings (0 to 10 scale) recorded by participants in a diary 4 times per day, number of days per month with at least moderate pain (pain rating of 5 or greater), and analgesic medication use. Results In patients who had not responded to amitriptyline, paroxetine failed to reduce chronic tension-type headaches or analgesic medication use. In patients who had not responded to placebo, paroxetine produced modest reductions in chronic tension-type headaches and analgesic use. Conclusions We found no evidence that chronic tension-type headaches that failed to respond to tricyclic antidepressant therapy with amitriptyline improved when subsequently treated with paroxetine. More support was found for the efficacy of paroxetine in patients with chronic tension-type headaches who had failed to respond to placebo. PMID:14511278

76 FR 11790 - Drugs for Human Use; Drug Efficacy Study Implementation; Oral Prescription Drugs Offered for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-03

... (containing promethazine hydrochloride, ipecac fluidextract, potassium guaiacolsulfonate, citric acid, sodium... promethazine hydrochloride, ipecac fluidextract, potassium guaiacolsulfonate, citric acid, sodium citrate, and... promethazine hydrochloride, ipecac fluidextract, potassium guaiacolsulfonate, citric acid, sodium citrate...

Efficacy and influence factors of icotinib hydrochloride in treating advanced non-small cell lung cancer.

PubMed

Ma, X-H; Tian, T-D; Liu, H-M; Li, Q-J; Gao, Q-L; Li, L; Shi, B

2017-01-01

To evaluate the efficacy and safety of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and discuss the influence factors on efficacy. 120 treatment-experienced patients confirmed by pathology or cytology with stage III B-IV non-small cell lung cancer took icotinib hydrochloride and erlotinib orally until the occurrence of disease progression or serious adverse reactions. Then, the efficacy of icotinib hydrochloride and the related influence factors were analyzed. In icotinib hydrochloride group, the response rate and the disease control rate were 30.00% and 65.00%, and the median progression-free survival time was 179 days (95% CI: 103.21-254.78); in erlotinib group, the response rate and the disease control rate were 25.00% and 56.70%, and the median progression-free survival time was 121 days (95% CI: 95.05-146.94). Moreover, the objective response rate and the disease control rate of second-line therapy were both superior to the third-line and above therapy. The objective response rate of patients with complete response/partial response/stable disease after the first-line therapy was higher than that of patients without response after the first-line therapy (p<0.05), and the significant differences existed in the objective response rate and the disease control rate among mutant group, wild-type group, and unknown group (p<0.05). The response rate and the disease control rate of erythra group were higher than those of non-erythra group (p<0.05). It was showed in the univariate analysis that the progression-free survival was correlated with the smoking status and the epidermal growth factor receptor gene mutations. The icotinib hydrochloride is effective and safe in treating the treatment-experienced patients with advanced NSCLC, especially for patients with sensitive mutations.

21 CFR 520.1263c - Lincomycin hydrochloride soluble powder.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Lincomycin hydrochloride soluble powder. 520.1263c Section 520.1263c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... for 7 consecutive days. Do not allow rabbits, hamsters, guinea pigs, horses, or ruminants access to...

21 CFR 520.1263c - Lincomycin hydrochloride soluble powder.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Lincomycin hydrochloride soluble powder. 520.1263c Section 520.1263c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... for 7 consecutive days. Do not allow rabbits, hamsters, guinea pigs, horses, or ruminants access to...

21 CFR 520.1263c - Lincomycin hydrochloride soluble powder.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Lincomycin hydrochloride soluble powder. 520.1263c Section 520.1263c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... for 7 consecutive days. Do not allow rabbits, hamsters, guinea pigs, horses, or ruminants access to...

A Double-Blind, Placebo-Controlled Trial of Dexmethylphenidate Hydrochloride and D,l-Threo-Methylphenidate Hydrochloride in Children with Attention-Deficit-Hyperactivity Disorder

ERIC Educational Resources Information Center

Wigal, Sharon; Swanson, James M.; Feifel, David; Sangal, R. Bart; Elia, Josephine; Casat, Charles D.; Zeldis, Jerome B.; Conners, C. Keith

2004-01-01

Objective: To evaluate the efficacy and safety of dexmethylphenidate hydrochloride (d-MPH, Focalin[TM]) for the treatment of attention-deficit/hyperactivity disorder (ADHD) and to test an a priori hypothesis that d-MPH would have a longer duration of action than d,l-threo-methylphenidate (d,l-MPH). Method: This was a randomized, double-blind study…

Vitamin D Combined with Aminolevulinate (ALA)-Mediated Photodynamic Therapy (PDT) for Human Psoriasis: A Proof-of-Principle Study

PubMed Central

Maytin, Edward V.; Honari, Golara; Khachemoune, Amor; Taylor, Charles R.; Ortel, Bernhard; Pogue, Brian W.; Sznycer-Taub, Nathaniel; Hasan, Tayyaba

2012-01-01

We previously showed that select agents (methotrexate or Vitamin D), when administered as a preconditioning regimen, are capable of promoting cellular differentiation of epithelial cancer cells while simultaneously enhancing the efficacy of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT). In solid tumors, pretreatment with Vitamin D simultaneously promotes cellular differentiation and leads to selective accumulation of target porphyrins (mainly protoporphyrin IX, PpIX) within diseased tissue. However, questions of whether or not the effects upon cellular differentiation are inexorably linked to PpIX accumulation, and whether these effects might occur in hyperproliferative noncancerous tissues, have remained unanswered. In this paper, we reasoned that psoriasis, a human skin disease in which abnormal cellular proliferation and differentiation plays a major role, could serve as a useful model to test the effects of pro-differentiating agents upon PpIX levels in a non-neoplastic setting. In particular, Vitamin D, a treatment for psoriasis that restores (increases) differentiation, might increase PpIX levels in psoriatic lesions and facilitate their responsiveness to ALA-PDT. This concept was tested in a pilot study of 7 patients with bilaterally-matched psoriatic plaques. A regimen in which calcipotriol 0.005% ointment was applied for 3 days prior to ALA-PDT with blue light, led to preferential increases in PpIX (~130%), and reductions in thickness, redness, scaling, and itching in the pretreated plaques. The results suggest that a larger clinical trial is warranted to confirm a role for combination treatments with Vitamin D and ALA-PDT for psoriasis. PMID:23264699

Determination of methadone hydrochloride in a maintenance dosage formulation.

PubMed

Hoffmann, T J; Thompson, R D

1975-07-01

A colorimetric method for direct quantitative assay of methadone hydrochloride in liquid oral dosage forms is presented. The procedure involves the formation of a dye complex with bromothymol blue buffer solution. The resultant complex is extracted with benzene and measured spectrophotometrically. Duplicate tests on the formulation showed 99.2% of the labeled amount of methadone.

Stability of midazolam hydrochloride injection 1-mg/mL solutions in polyvinyl chloride and polyolefin bags.

PubMed

Karlage, Kelly; Earhart, Zachary; Green-Boesen, Kelly; Myrdal, Paul B

2011-08-15

The stability of midazolam hydrochloride injection 1-mg/mL solutions in polyvinyl chloride (PVC) and polyolefin bags under varying conditions was evaluated. Triplicate solutions of midazolam hydrochloride 1-mg/mL were prepared in polyolefin and PVC i.v. bags by diluting midazolam hydrochloride injection 5 mg/mL with 5% dextrose injection. Bags were then stored under refrigeration (3-4 °C), exposed to light at room temperature (20-25 °C), or protected from light in amber bags at room temperature. Samples were taken immediately after preparation (day 0) and on days 1, 2, 3, 6, 13, 20, and 27 for analysis with a stability-indicating high-performance liquid chromatography assay in order to determine solution concentration. Stability was defined as retention of at least 90% of the initial drug concentration. The pH of each solution was also measured weekly. Sterility of the i.v. bags was determined at the end of the study by microbiological testing with culture in growth media. Differences in concentrations under the various storage conditions and bags used were analyzed using analysis of variance. All solutions retained over 98% of the initial midazolam hydrochloride concentration, with no statistically significant (p ≥ 0.05) change in concentration over the four-week period. Stability was not affected by temperature, exposure to light, or bag type. The pH of all solutions remained between 3.2 and 3.4 throughout the study. Sterility after 28 days was retained. Midazolam hydrochloride 1-mg/mL solutions diluted in 5% dextrose injection remained stable over 27 days in both polyolefin and PVC i.v. bags, regardless of storage condition.

Biosynthesis of vitamin B12: concerning the origin of the methine protons of the corrin nucleus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scott, A.I.; Kajiwara, M.; Santander, P.J.

1987-10-01

13C NMR spectroscopy has been used to locate six deuterium atoms incorporated biosynthetically on the periphery of the corrin nucleus of vitamin B12 (cyanocobalamin) derived from cells of Propionibacterium shermanii grown in a medium containing 50% /sup 2/H/sub 2/O and /sup 13/C-enriched delta-aminolevulinic acid. The implications of these results for the mechanism of vitamin B12 biosynthesis are discussed, and it is concluded that the same oxidation level of the intermediates is maintained throughout the biosynthetic pathway, from delta-aminolevulinic acid to corrin.

Effect of Temperature on Electrical Conductivity of Guaiacol-Guanidine Hydrochloride-Formaldehyde Copolymer Resin

NASA Astrophysics Data System (ADS)

Kukade, S. D.; Bawankar, S. V.

2018-02-01

The purpose of the present paper is to report temperature dependence of electrical conductivity on Guaiacol-guanidine hydrochloride-formaldehyde copolymer resin. By using a microwave irradiation technique, various ratios of copolymer resin were synthesized from the reacting monomers, i.e., guaiacol, guanidine hydrochloride and formaldehyde. The characterization of the copolymer resins has been fulfilled by spectral methods viz. ultraviolet visible (UV visible), infrared and proton nuclear magnetic spectroscopy (1H-NMR). The solid state direct current electrical conductivity of synthesized copolymer resins has been measured as a function of temperature. The electrical conductivity values of all the copolymers have been found in the range of a semiconductor.

In vitro and in silico investigation of electrospun terbinafine hydrochloride-loaded buccal nanofibrous sheets.

PubMed

Szabó, Péter; Daróczi, Tünde Beáta; Tóth, Gergő; Zelkó, Romána

2016-11-30

Terbinafine hydrochloride-loaded nanofibrous buccal films were formulated with the aim to improve the solubility and dissolution behavior; thus, the local effectiveness of the antifungal agent. Poly(vinyl alcohol) and chitosan polymer composites were selected as delivery base in order to enhance the mucoadhesion of the fibrous films. The dissolution of terbinafine hydrochloride was carried out applying a stainless steel disc assembly and the terbinafine concentration was determined by HPLC-MS in selective ion monitoring mode. The prediction of the absorption behavior of the prepared fibrous samples in the human oral cavity was modeled using GastroPlus™ software. The result indicates that the fibrous films enabled fast and complete dissolution of the active agent. The drug absorption from the oral cavity could be minimized by the employment of the proper oral transit model. Because of the limited absorption of terbinafine hydrochloride from the oral mucosa the formulation can be beneficial in local administration in the case of hold and expectorate administration mode. Copyright © 2016 Elsevier B.V. All rights reserved.

Optimization of Robust HPLC Method for Quantitation of Ambroxol Hydrochloride and Roxithromycin Using a DoE Approach.

PubMed

Patel, Rashmin B; Patel, Nilay M; Patel, Mrunali R; Solanki, Ajay B

2017-03-01

The aim of this work was to develop and optimize a robust HPLC method for the separation and quantitation of ambroxol hydrochloride and roxithromycin utilizing Design of Experiment (DoE) approach. The Plackett-Burman design was used to assess the impact of independent variables (concentration of organic phase, mobile phase pH, flow rate and column temperature) on peak resolution, USP tailing and number of plates. A central composite design was utilized to evaluate the main, interaction, and quadratic effects of independent variables on the selected dependent variables. The optimized HPLC method was validated based on ICH Q2R1 guideline and was used to separate and quantify ambroxol hydrochloride and roxithromycin in tablet formulations. The findings showed that DoE approach could be effectively applied to optimize a robust HPLC method for quantification of ambroxol hydrochloride and roxithromycin in tablet formulations. Statistical comparison between results of proposed and reported HPLC method revealed no significant difference; indicating the ability of proposed HPLC method for analysis of ambroxol hydrochloride and roxithromycin in pharmaceutical formulations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Development of ligustrazine hydrochloride carboxymethyl chitosan and collagen microspheres: Formulation optimization, characterization, and vitro release

PubMed Central

Lin, Qiang; Huo, Qing; Qin, Yingzhe; Zhao, Zhuo; Tao, Fengyun

2017-01-01

ABSTRACT This study investigates the preparation of ligustrazine hydrochloride carboxymethyl chitosan and collagen microspheres. This experiment investigates effects of the ratio of carboxymethyl chitosan and collagen blend, water to oil ratio, stirring speed, and other factors on the microsphere properties. The experiment had the following conditions: a 1:2 proportion of carboxymethyl chitosan and collagen, a 1:2 proportion of drugs and materials, a 5:1 proportion of oil phase and water phase, 0.5% of span80, a 600r/min stirring speed, 3 ml of a cross-linking agent, 3 h of cross-linking curing, 1.25 ± 0.05 mm diameter LTH microcapsules, a 54.08% envelop rate, and a 14.16% carrier rate. The microspheres release rate reached 66% within 1 h, then steadily released within 5 h in vitro. The experimental results showed that the ligustrazine hydrochloride microsphere production process was stable and exhibited a good release effect compared with other ligustrazine hydrochloride tablets and pills. PMID:27689792

Effects of pilocarpine hydrochloride and cevimeline on submandibular/sublingual salivation in rat xerostomia model produced by X-ray irradiation.

PubMed

Omori, Yasuhiro; Asari, Tetsuya; Maruyama, Kazuyasu; Kusama, Hiroshi; Kojima, Masami; Shibata, Nobuo

2003-01-01

The present study was performed to assess the effects of pilocarpine hydrochloride ((3S,4R)-3-ethyl-dihydro-4-[(1-methyl-1H-imidazole-5-yl)methyl]-2(3H)-furanone monohydrochloride, CAS 54-71-7) and cevimeline ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate, CAS 153504-70-2), muscarinic receptor agonists, on salivary secretion from the submandibular/sublingual (SM/SL) glands in normal rats and in rats with xerostomia induced by X-ray (15 Gy) irradiation. To clarify their pharmacological safety profiles, the two drugs were further compared with regard to subtype selectivity for muscarinic receptors (M1, M2, and M3) and central nervous, respiratory, and cardiovascular effects. Pilocarpine hydrochloride (0.1-0.8 mg/kg i.d.) and cevimeline (3-30 mg/kg i.d.) dose-dependently increased salivary flow rate and total salivary volume in a 120-min period from SM/SL glands in both normal and irradiated rats, the minimum effective doses for their sialagogic effects being 0.2 and 10 mg/kg, respectively. Both drugs also increased protein output from SM/SL glands to a degree that depended on the increase in salivary volume in normal and irradiated rats. In a binding study using radiolabeled antagonists, neither pilocarpine hydrochloride nor cevimeline displayed subtype selectivity for muscarinic receptors, indicating non-selective muscarinic agonism. Effects on the central nervous system (CNS) were assessed by monitoring changes in body temperature in conscious normal rats. Pilocarpine hydrochloride (0.4-4 mg/kg p.o.) had no effect on body temperature, but cevimeline (30 and 100 mg/kg p.o.) caused a significant hypothermia. In terms of respiratory and cardiovascular effects in anesthetized normal rats, there was no clear difference in safety margin between pilocarpine hydrochloride and cevimeline, both drugs inducing significant changes in respiratory rate, heart rate, and blood pressure at doses close to those inducing sialagogic effects

A Clinical Study of Efficacy of 4% Articaine Hydrochloride Versus 2% Lignocaine Hydrochloride in Dentistry

PubMed Central

Darawade, Dattatraya A; Kumar, Santosh; Budhiraja, Shilpa; Mittal, Manoj; Mehta, Tanvi N

2014-01-01

Background: Articaine in an anesthetic agent, which is used less frequently in dentistry. It differs from other agents due to the presence of a thiophene ring in its molecular structure. Few groups of researchers claim that it is superior to lignocaine. Hence, the purpose of this study was to compare the efficacy of 4% articaine hydrochloride and 2% lignocaine hydrochloride in the orthodontic extraction. Materials and Methods: The study was carried out in 50 patients who needed the orthodontic extraction in the age group from 15 to 25 years. Experimental sites were injected with 0.5-1 ml of 4% articaine HCL containing 1:100000 adrenaline, incrementally in the buccal vestibule without palatal anaesthesia. Control sites were injected with 0.8-1 ml of 2% lignocaine HCL containing 1:100000 adrenaline, incrementally in the buccal vestibule. All the parameters, that is volume, duration, time of anesthesia and pain rating were noted and statistically compared. Result: When statistically compared mean volume of articaine (0.779 ± 0.1305) was less than lignocaine (1.337 ± 0.2369). Mean time of onset of articaine was 1.012 ± 0.2058 min, Whereas that of was 1.337 ± 0.2369. Pain rating showed not much difference, but in the lignocaine group palatal anesthesia was required in all the patients. Finally, the mean duration of anesthesia in articaine group was 69.08 ± 18.247, whereas in the lignocaine group was 55.66 ± 6.414. Conclusion: Articaine has proved its usefulness in all regards. Literatures have proved its usefulness. Like other anesthetic, it is safe and more effective. It surpasses the need of additional palatal anesthesia. Rapid inactivation in liver and plasma reduces the risk of the drug overdose. All the above factors make it an ideal anesthetic agent to be used in dentistry. PMID:25395799

Quantitative estimation of itopride hydrochloride and rabeprazole sodium from capsule formulation.

PubMed

Pillai, S; Singhvi, I

2008-09-01

Two simple, accurate, economical and reproducible UV spectrophotometric methods and one HPLC method for simultaneous estimation of two component drug mixture of itopride hydrochloride and rabeprazole sodium from combined capsule dosage form have been developed. First developed method involves formation and solving of simultaneous equations using 265.2 nm and 290.8 nm as two wavelengths. Second method is based on two wavelength calculation, wavelengths selected for estimation of itopride hydrochloride was 278.0 nm and 298.8 nm and for rabeprazole sodium 253.6 nm and 275.2 nm. Developed HPLC method is a reverse phase chromatographic method using phenomenex C(18) column and acetonitrile: phosphate buffer (35:65 v/v) pH 7.0 as mobile phase. All developed methods obey Beer's law in concentration range employed for respective methods. Results of analysis were validated statistically and by recovery studies.

[A prospective multicenter randomized controlled clinical study on the efficacy and safety of Guaifenesin compound pseudoephedrine hydrochloride oral solution].

PubMed

Lu, Quan

2010-03-01

To evaluate efficacy and safety of Guaifenesin compound pseudoephedrine hydrochloride oral solution for the treatment of cough, expectoration, nasal congestion and runny nose in children. This was a prospective multicenter randomized single-blind, parallel-controlled clinical study. A total of 10 centers participated in this study, the actual number of cases in line with the program was 412, of whom 205 cases in trial group were treated with Guaifenesin compound pseudoephedrine hydrochloride oral solution, and 207 cases in control group with ambroxol hydrochloride oral solution, treatment of both groups persisted for 7 days. The improvement rate of each single symptom and the combined symptoms and the overall effective rate were compared between the two groups. The adverse drug reactions and compliance were assessed as well. The treatment of both groups showed efficacy. Except sputum stickiness, the improvement of all symptoms in trial group was superior to that in the control group on the 3rd day after treatment (P < 0.05) and except nasal congestion, the efficacy in all the other symptoms of trial group was better than that in the control group as well on the 7th day (P < 0.01). The improvement rate for combined symptoms of Guaifenesin compound pseudoephedrine hydrochloride oral solution was 82.9% and the overall efficacy rate was 89.3%. Guaifenesin compound Pseudoephedrine hydrochloride oral solution had higher compliance and its adverse event rate was merely 0.92%. Guaifenesin compound pseudoephedrine hydrochloride oral solution showed significant efficacy and safety in children for treatment of cough, expectoration, nasal congestion and runny nose caused by common cold or acute tracheobronchitis.

[The use of natural and synthetic hydrophilic polymers in the formulation of metformin hydrochloride tablets with different profile release].

PubMed

Kołodziejczyk, Michał Krzysztof; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

2012-01-01

Metformin hydrochloride after buformin and phenformin belongs to the group of biguanid derivatives used as oral anti-diabetic drugs. The object of the study is the technological analysis and the potential effect of biodegradable macromolecular polymers on the technological and therapeutic parameters of oral anti-diabetic medicinal products with metformin hydrochloride: Siofor, Formetic, Glucophage, Metformax in doses of 500mg and 1000mg and Glucophage XR in a dose of 500 mg of modified release. Market therapeutic products containing 500 and 1000 mg of metformin hydrochloride in a normal formulation and 500 mg of metformin hydrochloride in a formulation of modified release were analyzed. Following research methods were used: technological analysis of tablets, study of disintegration time of tablets, evaluation of pharmaceutical availability of metformin hydrochloride from tested therapeutic products, mathematical and kinetic analysis of release profiles of metformin hydrochloride, statistical analysis of mean differences of release coefficients. The percentage of excipients in the XR formulation is higher and constitutes 50.5% of a tablet mass. However, in standard formulations the percentage is lower, between 5.5% and 12.76%. On the basis of the results of disintegration time studies, the analysed therapeutic products can be divided into two groups, regardless the dose. The first one are preparations with faster (not fast!) disintegration: Glucophage i Metformax. The second group are preparations with slower disintegration, more balanced in the aspect of a high dose of the biologically active substance: Formetic and Siofor. Products with a lower content of excipients (Metformax, Glucophage) disintegrate in a faster way. The disintegration rate of the products with a higher content of excipients (Formetic, Siofor) is slower. The appearance of metformin hydrochloride concentration in the gastrointestinal contents, balanced in time, caused by a slower disintegration

Development and evaluation of a novel modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride as model drugs.

PubMed

Zeeshan, Farrukh; Bukhari, Nadeem Irfan

2010-06-01

Modified-release multiple-unit tablets of loratadine and pseudoephedrine hydrochloride with different release profiles were prepared from the immediate-release pellets comprising the above two drugs and prolonged-release pellets containing only pseudoephedrine hydrochloride. The immediate-release pellets containing pseudoephedrine hydrochloride alone or in combination with loratadine were prepared using extrusion-spheronization method. The pellets of pseudoephedrine hydrochloride were coated to prolong the drug release up to 12 h. Both immediate- and prolonged-release pellets were filled into hard gelatin capsule and also compressed into tablets using inert tabletting granules of microcrystalline cellulose Ceolus KG-801. The in vitro drug dissolution study conducted using high-performance liquid chromatography method showed that both multiple-unit capsules and multiple-unit tablets released loratadine completely within a time period of 2 h, whereas the immediate-release portion of pseudoephedrine hydrochloride was liberated completely within the first 10 min of dissolution study. On the other hand, the release of pseudoephedrine hydrochloride from the prolonged release coated pellets was prolonged up to 12 hr and followed zero-order release kinetic. The drug dissolution profiles of multiple-unit tablets and multiple-unit capsules were found to be closely similar, indicating that the integrity of pellets remained unaffected during the compression process. Moreover, the friability, hardness, and disintegration time of multiple-unit tablets were found to be within BP specifications. In conclusion, modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride was successfully developed and evaluated.

Nanosized complexation assemblies housed inside reverse micelles churn out monocytic delivery cores for bendamustine hydrochloride.

PubMed

Singh, Yuvraj; Chandrashekhar, Anumandla; Meher, Jaya Gopal; Durga Rao Viswanadham, K K; Pawar, Vivek K; Raval, Kavit; Sharma, Komal; Singh, Pankaj K; Kumar, Animesh; Chourasia, Manish K

2017-04-01

We explore a plausible method of targeting bendamustine hydrochloride (BM) to circulatory monocytes by exploiting their intrinsic endocytic/phagocytic capability. We do so by complexation of sodium alginate and chitosan inside dioctyl sulfo succinate sodium (AOT) reverse micelles to form bendamustine hydrochloride loaded nanoparticles (CANPs). Dynamic light scattering, electrophoretic mobility and UV spectroscopy were used to detail intra-micellar complexation dynamics and to prove that drug was co-captured during interaction of carbohydrate polymers. A fluorescent conjugate of drug (RBM) was used to trace its intracellular fate after its loading into nanoparticles. CANPs were sized below 150nm, had 75% drug entrapment and negative zeta potential (-30mV). Confocal microscopy demonstrated that developed chitosan alginate nanoparticles had the unique capability to carry BM specifically to its site of action. Quantitative and mechanism based cell uptake studies revealed that monocytes had voracious capacity to internalize CANPs via simultaneous scavenger receptor based endocytic and phagocytic mechanism. Comparative in vitro pharmacokinetic studies revealed obtainment of significantly greater intracellular drug levels when cells were treated with CANPs. This caused reduction in IC 50 (22.5±2.1μg/mL), enhancement in G 2 M cell cycle arrest, greater intracellular reactive oxygen species generation, and increased apopotic potential of bendamustine hydrochloride in THP-1 cells. Selective monocytic targeting of bendamustine hydrochloride using carbohydrate constructs can prove advantageous in case of leukemic disorders displaying overabundance of such cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Health and environmental effects profile for 4-chloro-2-methylaniline and 4-chloro-2-methylaniline hydrochloride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1986-12-01

The Health and Environmental Effects Profile for 4-chloro-2-methylaniline and 4-chloro-2-methylaniline hydrochloride was prepared to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and information obtained from Agency program office files were evaluated as they pertained to potential human-health, aquatic-life and environmental effects of hazardous-waste constituents. The human carcinogen potency factors (q1*) for 4-chloro-2-methylaniline and 4-chloro-2-methylaniline hydrochloride are 0.58 and 0.46/(mg/kg/day), respectively,more » for oral exposure. The Reportable Quantity (RQ) value for 4-chloro-2-methylaniline and 4-chloro-2-methylaniline hydrochloride is 5000.« less

Formulation and Evaluation of Tramadol hydrochloride Rectal Suppositories.

PubMed

Saleem, M A; Taher, M; Sanaullah, S; Najmuddin, M; Ali, Javed; Humaira, S; Roshan, S

2008-09-01

Rectal suppositories of tramadol hydrochloride were prepared using different bases and polymers like PEG, cocoa butter, agar and the effect of different additives on in vitro release of tramadol hydrochloride was studied. The agar-based suppositories were non-disintegrating/non-dissolving, whereas PEGs were disintegrating/dissolving and cocoa butter were melting suppositories. All the prepared suppositories were evaluated for various physical parameters like weight variation, drug content and hardness. The PEG and cocoa butter suppositories were evaluated for macromelting range, disintegration and liquefaction time. In vitro release study was performed by USP type I apparatus. The prepared suppositories were within the permissible range of all physical parameters. In vitro drug release was in the order of PEG>Agar>cocoa butter. Addition of PVP, HPMC in agar suppositories retards the release. The mechanism of drug release was diffusion controlled and follows first order kinetics. The results suggested that blends of PEG of low molecular weight (1000) with high molecular weight (4000 and 6000) in different percentage and agar in 10% w/w as base used to formulate rapid release suppositories. The sustained release suppositories can be prepared by addition of PVP, HPMC in agar-based suppositories and by use of cocoa butter as base.

[Clinical effect of atomoxetine hydrochloride in 66 children with narcolepsy].

PubMed

Zhang, Shen; Ding, Changhong; Wu, Husheng; Fang, Fang; Wang, Xiaohui; Ren, Xiaotun

2015-10-01

To observe the efficacy and safety of atomoxetine hydrochloride in children with narcolepsy. Totally 66 patients with narcolepsy who were conformed international classification of sleep disturbances (ICSD-2) diagnostic criteria treated with atomoxetine hydrochloride seen from November 2010 to December 2014 were enrolled into this study, 42 of them were male and 24 female, mean age of onset was 7.5 years (3.75-13.00 years), mean duration before diagnosis was 1.75 years (0.25-5.00 years). Complete blood count, liver and kidney function, multiple sleep latency test (MSLT), polysomnography (PGS), neuroimaging and electroencephalography (EEG) were performed for each patient. For some of the children HLA-DR2 gene and serum markers of infection were tested. The 66 cases were followed up from 2 to 49 months (average 18 months) to observe the clinical efficacy and adverse reactions. In 62 cases excessive daytime sleepiness was improved, in 11 cases (16.7%) it was controlled (16.7%), in 29 cases (43.9%) the treatment was obviously effective and in 22 (33.3%) it was effective; cataplexy occurred in 54 cases, in 18 (33.3%) it was controlled, in 19 (35.2%) the treatment was obviously effective and in 10 (18.5%) effective; night sleep disorders existed in 55 cases, in 47 cases it was improved, in 14 (25.5%) it was controlled, in 20 (36.4%) the treatment was obviously effective and in 13 (23.6%) effective; hypnagogic or hypnopompic hallucination was present in 13 cases, in only 4 these symptoms were controlled. Sleep paralysis existed in 4 cases, it was controlled in only 1 case. In 18 cases attention and learning efficiency improved.Anorexia occurred in 18 cases, mood disorder in 5 cases, depression in 2 cases, nocturia, muscle tremors, involuntary tongue movement each occurred in 1 case. P-R interval prolongation and atrial premature contraction were found in 1 case. Atomoxetine hydrochloride showed good effects in patients with narcolepsy on excessive daytime sleepiness

Pharmacokinetics of hydromorphone hydrochloride after intravenous and intramuscular administration of a single dose to American kestrels (Falco sparverius)

USGS Publications Warehouse

Guzman, David Sanchez-Migallon; KuKanich, Butch; Drazenovich, Tracy L.; Olsen, Glenn H.; Paul-Murphy, Joanne R.

2014-01-01

Results indicated hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with a short terminal half-life, rapid plasma clearance, and large volume of distribution in American kestrels. Further studies regarding the effects of other doses, other administration routes, constantrate infusions, and slow release formulations on the pharmacokinetics of hydromorphone hydrochloride and its metabolites in American kestrels may be indicated.

The effect of phenformin on insulin-stimulated isoaminobutyric acid (AIB) transport by isolated hepatocytes.

PubMed Central

Woods, R. J.; Dandona, P.

1984-01-01

Hepatocytes isolated from adult rat livers by collagenase perfusion were used to investigate the effect of phenformin on amino acid transport by measuring the uptake of aminoisobutyric acid (AIB). At concentrations between 0.01 and 100 micrograms/ml, phenformin hydrochloride did not affect AIB uptake, but concentrations of 500 and 1000 micrograms/ml were inhibitory. Incubating hepatocytes with insulin increased their accumulation of AIB. Inclusion of up to 100 micrograms/ml, phenformin hydrochloride during maximal and submaximal stimulation by insulin did not affect AIB uptake, but inhibition occurred with 500 and 1000 micrograms/ml. The continued presence of phenformin after addition of AIB was not required in order to produce inhibition. Furthermore, increasing the duration of exposure of hepatocytes to phenformin increased the degree of inhibition, suggesting that it is a non-competitive inhibitor. We conclude that phenformin does not enhance the sensitivity of hepatocytes to insulin and that at higher concentrations it may exert an inhibitory effect on basal and insulin stimulated aminoacid transport. PMID:6370292

Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application.

PubMed

Mahmood, Syed; Taher, Muhammad; Mandal, Uttam Kumar

2014-01-01

Raloxifene hydrochloride, a highly effective drug for the treatment of invasive breast cancer and osteoporosis in post-menopausal women, shows poor oral bioavailability of 2%. The aim of this study was to develop, statistically optimize, and characterize raloxifene hydrochloride-loaded transfersomes for transdermal delivery, in order to overcome the poor bioavailability issue with the drug. A response surface methodology experimental design was applied for the optimization of transfersomes, using Box-Behnken experimental design. Phospholipon(®) 90G, sodium deoxycholate, and sonication time, each at three levels, were selected as independent variables, while entrapment efficiency, vesicle size, and transdermal flux were identified as dependent variables. The formulation was characterized by surface morphology and shape, particle size, and zeta potential. Ex vivo transdermal flux was determined using a Hanson diffusion cell assembly, with rat skin as a barrier medium. Transfersomes from the optimized formulation were found to have spherical, unilamellar structures, with a homogeneous distribution and low polydispersity index (0.08). They had a particle size of 134±9 nM, with an entrapment efficiency of 91.00%±4.90%, and transdermal flux of 6.5±1.1 μg/cm(2)/hour. Raloxifene hydrochloride-loaded transfersomes proved significantly superior in terms of amount of drug permeated and deposited in the skin, with enhancement ratios of 6.25±1.50 and 9.25±2.40, respectively, when compared with drug-loaded conventional liposomes, and an ethanolic phosphate buffer saline. Differential scanning calorimetry study revealed a greater change in skin structure, compared with a control sample, during the ex vivo drug diffusion study. Further, confocal laser scanning microscopy proved an enhanced permeation of coumarin-6-loaded transfersomes, to a depth of approximately160 μM, as compared with rigid liposomes. These ex vivo findings proved that a raloxifene hydrochloride

Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application

PubMed Central

Mahmood, Syed; Taher, Muhammad; Mandal, Uttam Kumar

2014-01-01

Raloxifene hydrochloride, a highly effective drug for the treatment of invasive breast cancer and osteoporosis in post-menopausal women, shows poor oral bioavailability of 2%. The aim of this study was to develop, statistically optimize, and characterize raloxifene hydrochloride-loaded transfersomes for transdermal delivery, in order to overcome the poor bioavailability issue with the drug. A response surface methodology experimental design was applied for the optimization of transfersomes, using Box-Behnken experimental design. Phospholipon® 90G, sodium deoxycholate, and sonication time, each at three levels, were selected as independent variables, while entrapment efficiency, vesicle size, and transdermal flux were identified as dependent variables. The formulation was characterized by surface morphology and shape, particle size, and zeta potential. Ex vivo transdermal flux was determined using a Hanson diffusion cell assembly, with rat skin as a barrier medium. Transfersomes from the optimized formulation were found to have spherical, unilamellar structures, with a homogeneous distribution and low polydispersity index (0.08). They had a particle size of 134±9 nM, with an entrapment efficiency of 91.00%±4.90%, and transdermal flux of 6.5±1.1 μg/cm2/hour. Raloxifene hydrochloride-loaded transfersomes proved significantly superior in terms of amount of drug permeated and deposited in the skin, with enhancement ratios of 6.25±1.50 and 9.25±2.40, respectively, when compared with drug-loaded conventional liposomes, and an ethanolic phosphate buffer saline. Differential scanning calorimetry study revealed a greater change in skin structure, compared with a control sample, during the ex vivo drug diffusion study. Further, confocal laser scanning microscopy proved an enhanced permeation of coumarin-6-loaded transfersomes, to a depth of approximately160 μM, as compared with rigid liposomes. These ex vivo findings proved that a raloxifene hydrochloride

Neuroleptic malignant syndrome possibly caused by molindone hydrochloride.

PubMed

Gradon, J D

1991-10-01

The case of a patient who developed neuroleptic malignant syndrome (NMS) on three separate occasions is presented. Her third bout of this syndrome possibly was caused by molindone hydrochloride. This medication has been reported only once previously to cause NMS. The pharmacology of molindone is reviewed and a complicating factor in this case--the recent onset of hypothyroidism--is discussed together with its implication in the development of the clinical manifestations of this syndrome.

Silicone adhesive matrix of verapamil hydrochloride to provide pH-independent sustained release.

PubMed

Tolia, Gaurav; Li, S Kevin

2014-02-01

Providing pH-independent oral release of weakly basic drugs with conventional matrix tablets can be challenging because of the pH-dependent solubility characteristics of the drugs and the changing pH environment along the gastrointestinal tract. The aim of the present study was to use a hydrophobic polymer to overcome the issue of pH-dependent release of weakly basic model drug verapamil hydrochloride from matrix tablets without the use of organic buffers in the matrix formulations. Silicone pressure-sensitive adhesive (PSA) polymer was evaluated because of its unique properties of low surface energy, hydrophobicity, low glass transition temperature, high electrical resistance, and barrier to hydrogen ion diffusion. Drug release, hydrogen ion diffusion, tablet contact angle, and internal tablet microenvironment pH with matrix tablets prepared using PSA were compared with those using water-insoluble ethyl cellulose (EC). Silicone PSA films showed higher resistance to hydrogen ion diffusion compared with EC films. Verapamil hydrochloride tablets prepared using silicone PSA showed higher hydrophobicity and lower water uptake than EC tablets. Silicone PSA tablets also showed pH-independent release of verapamil and decreased in dimensions during drug dissolution. By contrast, verapamil hydrochloride tablets prepared using EC did not achieve pH-independent release.

Development of Novel Potentiometric Sensors for Determination of Lidocaine Hydrochloride in Pharmaceutical Preparations, Serum and Urine Samples

PubMed Central

Ali, Tamer Awad; Mohamed, Gehad Genidy; Yahya, Ghada A.

2017-01-01

This article is focused on the determination of lidocaine hydrochloride as a local anaesthetic drug. A potentiometric method based on modified screen-printed and modified carbon paste ion-selective electrodes was described for the determination of lidocaine hydrochloride in different pharmaceutical preparations and biological fluids (urine and serum). It was based on potentiometric titration of lidocaine hydrochloride using modified screen-printed and carbon paste electrodes as end point indicator sensors. The influences of the paste composition, different conditioning parameters and foreign ions on the electrodes performance were investigated and response times of the electrodes were studied. The electrodes showed Nernstian response of 58.9 and 57.5 mV decade-1 in the concentration range of 1×10-7–1×10-2 and 6.2×10-7–1×10-2 mol L-1 for modified screen-printed and carbon paste electrodes, respectively. The electrodes were found to be usable within the pH range of 2.0–8.0 and 2.0-7.5, exhibited a fast response time (about 6 and 4) low detection limit (1×10-7 and 6.2×10-7 mol L-1), long lifetime (6 and 4 months) and good stability for modified screen-printed (Electrode VII) and carbon paste electrodes (Electrode III), respectively. The electrodes were successfully applied for the determination of lidocaine hydrochloride in pure solutions, pharmaceutical preparation and biological fluids (urine and serum) samples. The results obtained applying these potentiometric electrodes were comparable with British pharmacopeia. The method validation parameters were optimized and the method can be applied for routine analysis of lidocaine hydrochloride drug. PMID:28979305

Development of Novel Potentiometric Sensors for Determination of Lidocaine Hydrochloride in Pharmaceutical Preparations, Serum and Urine Samples.

PubMed

Ali, Tamer Awad; Mohamed, Gehad Genidy; Yahya, Ghada A

2017-01-01

This article is focused on the determination of lidocaine hydrochloride as a local anaesthetic drug. A potentiometric method based on modified screen-printed and modified carbon paste ion-selective electrodes was described for the determination of lidocaine hydrochloride in different pharmaceutical preparations and biological fluids (urine and serum). It was based on potentiometric titration of lidocaine hydrochloride using modified screen-printed and carbon paste electrodes as end point indicator sensors. The influences of the paste composition, different conditioning parameters and foreign ions on the electrodes performance were investigated and response times of the electrodes were studied. The electrodes showed Nernstian response of 58.9 and 57.5 mV decade -1 in the concentration range of 1×10 -7 -1×10 -2 and 6.2×10 -7 -1×10 -2 mol L -1 for modified screen-printed and carbon paste electrodes, respectively. The electrodes were found to be usable within the pH range of 2.0-8.0 and 2.0-7.5, exhibited a fast response time (about 6 and 4) low detection limit (1×10 -7 and 6.2×10 -7 mol L -1 ), long lifetime (6 and 4 months) and good stability for modified screen-printed (Electrode VII) and carbon paste electrodes (Electrode III), respectively. The electrodes were successfully applied for the determination of lidocaine hydrochloride in pure solutions, pharmaceutical preparation and biological fluids (urine and serum) samples. The results obtained applying these potentiometric electrodes were comparable with British pharmacopeia. The method validation parameters were optimized and the method can be applied for routine analysis of lidocaine hydrochloride drug.

Bioavailability of paracetamol, phenylephrine hydrochloride and guaifenesin in a fixed-combination syrup versus an oral reference product.

PubMed

Janin, Annick; Monnet, Joelle

2014-04-01

The primary objective of this study was to compare the bioavailability of paracetamol, phenylephrine hydrochloride and guaifenesin in a new oral syrup with an established oral reference product. The secondary objective was to compare the safety of the new syrup and the reference product. This was a single-centre, open-label, randomized, reference-replicated, crossover study. Healthy adult volunteers received one dose of syrup and two separate doses of a reference oral liquid formulation in a randomized sequence over three study periods, with a washout interval of ≥ 7 days between study periods. Blood samples were taken regularly postdose and analysed for paracetamol, phenylephrine hydrochloride and guaifenesin concentrations; adverse events were recorded. This study enrolled 45 subjects. For paracetamol and guaifenesin, the syrup and reference product were considered to be bioequivalent. Bioequivalence was not shown for phenylephrine hydrochloride. All adverse events were mild or moderate, most of which were considered formulation related. The syrup did not reach bioequivalence with the reference product, as bioequivalence could not be shown for phenylephrine hydrochloride. This may be due to differences in the excipients between the two products. Both the syrup and the reference product had a good safety profile and were well tolerated.

Quantitative Estimation of Itopride Hydrochloride and Rabeprazole Sodium from Capsule Formulation

PubMed Central

Pillai, S.; Singhvi, I.

2008-01-01

Two simple, accurate, economical and reproducible UV spectrophotometric methods and one HPLC method for simultaneous estimation of two component drug mixture of itopride hydrochloride and rabeprazole sodium from combined capsule dosage form have been developed. First developed method involves formation and solving of simultaneous equations using 265.2 nm and 290.8 nm as two wavelengths. Second method is based on two wavelength calculation, wavelengths selected for estimation of itopride hydrochloride was 278.0 nm and 298.8 nm and for rabeprazole sodium 253.6 nm and 275.2 nm. Developed HPLC method is a reverse phase chromatographic method using phenomenex C18 column and acetonitrile: phosphate buffer (35:65 v/v) pH 7.0 as mobile phase. All developed methods obey Beer's law in concentration range employed for respective methods. Results of analysis were validated statistically and by recovery studies. PMID:21394269

Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride.

PubMed

Ahmed, Sayed M; Ahmed Ali, Adel; Ali, Ahmed Ma; Hassan, Omiya A

2016-01-01

The aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form. Sustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F 10 composed of 28.5% Eudragit RSPM, 3% NaHCO 3 , and 7% citric acid provided sustained drug release. In vitro results showed sustained release of F 10 where the drug release percentage was 96.51%±1.75% after 24 hours ( P =0.031). The pharmacokinetic results indicated that the area under the curve (AUC 0-∞ ) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton ® ) and the relative bioavailability of the sustained-release formulation F 10 increased to 187.80% ( P =0.022). The prepared floating tablets of ITO HCl (F 10 ) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

Positive response of a recurrent keloid scar to topical methyl aminolevulinate-photodynamic therapy.

PubMed

Nie, Zhuxiang; Bayat, Ardeshir; Behzad, Farhad; Rhodes, Lesley E

2010-12-01

A 36-year-old Caucasian female of Iranian origin presented with a persistently raised dermal lesion under her chin, confirmed histologically to be a keloid scar. There was a 4-year history of a negative response to a range of conventional treatments including topical silicone gel sheets, steroid creams, steroid injections and surgical excision. In view of treatment failure and an in vitro study indicating a positive effect of photodynamic therapy (PDT)on keloid fibroblasts, we treated our patient's lesion with five sessions of methyl aminolevulinate photodynamic therapy (MAL-PDT) over a period of 5 months. Following this treatment regime, her keloid scar had considerably reduced in size and become flattened.The surface of the keloid also became smooth, with attenuation in erythema at the margin as well as an improvement in the colour of the scar, which was better matched to the surrounding skin. There was no recurrence at 1-year follow-up and this treatment resulted in an overall acceptable cosmetic outcome. This case report presents PDT as a potential treatment option for persistent keloid lesions unresponsive to conventional scar modulation therapies and suggests a need for further research in this area.

Propranolol hydrochloride enhancement of tumor perfusion and uptake of gallium-67 in a mouse sarcoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bomber, P.; McCready, R.; Hammersley, P.

1986-02-01

The effect of propranolol hydrochloride on the blood perfusion of a mouse sarcoma and other tissues has been studied using /sup 86/Rb. The maximum increase in relative tumor perfusion (2x controls) occurred 15 min after an i.v. administration of 10 mg per kg propranolol hydrochloride. To study the effect of this drug on the uptake of /sup 67/Ga, it was injected at a concentration of 10 mg/kg 10 min before administering 3 microCi (110 kBq) (/sup 67/Ga)citrate. Tissue uptakes were measured 4 hr later. The tumor: blood ratio increased from 1.16 +/- 0.17 to 3.41 +/- 2.27 (s.d.) and tumor:more » liver ratio increased from 2.39 +/- 0.30 to 7.13 +/- 3.52 (s.d.). The results showed that propranolol hydrochloride can improve the relative tumor blood flow and radiopharmaceutical concentration in an animal model. It is hoped that this and other agents will yield similar results in the human situation.« less