Benzocaine Research Articles

ANESTHESIA IN SURGERIES ON THE FOOT AND ANKLE (REVIEW)

Among the various anesthetic options the combination of spinal anesthesia with the implementation of regional nerve blocks of the lower extremity and local anaesthesia of area of the wound with long-acting local anesthetics is more interesting. However the recommendations for the choice of postoperative analgesia of the foot do not exist, inspite of the pain syndrome. The prospects for wider use of regional blocks include the use of electrical stimulator in conjunction with ultrasound identification of the nerve trunks, the use of infusion pumps and catheter techniques blockades.

SELECTIVE SPECTROPHOTOMETRIC DETERMINATION OF FENOTEROL BY THREE DIFFERENT METHODS.

Three simple and selective spectrophotometric methods were developed for the quantitative determination of Fenoterol in pure forms as well as in its pharmaceutical formulation. Method [A] Involves the coupling of the drug as phenolic compound with the diazonium salts of four amines, namely, Benzocaine (BZC), sulphadiazine (SDZ), sulphacetamide (SCM) and sulphanilic acid (SPA) forming red azodyes absorbed at 526, 514, 512 and 513 nm, respectively. Beer's law was obeyed in the concentration ranges of 10-70, 6-42, 4-28 and 3.5-24.5 μg ml-1 for the four reagents, respectively. Method [B] is based on reaction of Fenoterol with cobalt thiocyanate, where by a sparingly soluble blue ion-pair complex is formed. This complex is extracted by toluene and spectrophotometrically measured at 619 nm. Good linearity was obtained in the range of 10-70 μg ml-1. Method [C] is based on the reduction of iron (III) by Fenoterol in acid medium and subsequent interaction of iron (II) with ferricyanide to form Prussian blue. The product exhibits absorption maximum at 730 nm. Beer's law was obeyed in the concentration range of 1.5–10.5 μg ml-1. The reaction conditions for described methods were studied and optimized. The proposed methods were applied to the determination of Fenoterol in pharmaceutical formulation and the results demonstrate that the methods are equally accurate and precise as the reported methods found from the t and F values. The reliability of the methods was established by recovery studies using standard addition technique.

Synthetic Approaches and Biological Evaluation of Some New Sulfonate Ester-Containing Imidazolone Derivatives

Oxazolone derivative 2 was utilised as a key intermediate for the synthesis of some new imidazolone deriva- tives. Reaction of 2 with p-aminoacetophenone in the presence of acetic acid containing catalytic amount of freshly fused sodium acetate gives the corresponding imidazolone derivative 3 which on reaction with diethyl oxalate in the presence of granulated sodium metal afforded the corresponding imidazolone derivative 4. Condensation of compound 3 with some aromatic aldehydes afforded the corresponding cinnamoylphenyl derivatives 5a-c, respectively. Besides, compounds 5a-c reacted with hydrazine hydrate in boiling ethanol and yield the corresponding 4-arylidene-1- (p-(5-aryl-2- pyrazolin-3-y1) phenyl)-2-phenyl-2-imidazolin-5-ones 6a-c, respectively. Moreover, refluxing of compounds 5a-c with both ethylcyanoace- tate and/or malononitrile in ethanol and ammonium acetate afforded 7a-c and 8a-c, respectively. Claisen reaction of 3 with ethylacetate gives the corresponding imidazolone derivative 9 which on reaction with thiourea in ethanol afforded the cor- responding thienopyrimidine derivative 10. On the other hand, reaction of oxazolone 2 with both ethyl p-aminobenzoate and anthranilic acid in glacial acetic acid and freshly fused sodium acetate has been also studied. Structures of the newly synthesized compounds were established by elemental analysis and spectral data. Representative compounds of the synthe- sized products were tested and evaluated as antifungal and antimicrobial agents. Most of compounds exhibited good activi- ties, where 3, 5b, 5c, 6a, 7b, 7c, 8a, 9, 11, 13 and 14 exhibited good activities against Bacillus Thuringenesis and Klebseilla Pneumonia, while compounds 3, 4, 6a, 6b, 6c, 7c, 8a, 8c, 11, 12 and 16 exhibited good activities against Trichoderma

CLINICAL STUDIES ON THIOPENTONE WITH OR WITHOUT DIAZEPAM PREMEDICATION FOR GENERAL ANAESTHESIA IN DONKEYS

M.A.A. RADI; H.I. SERI and M.A.H. GHURASHI * College of Veterinary Medicine, Sudan University of Science and Technology, Sudan. ** Open University of Sudan. Corresponding author: Dr. Hisham Ismail Seri, department of Medicine and Surger, College of Veterinary Medicine, SUST. Khartoum North, P.O. Box: 204. E-mail: hishamseri@yahoo.com __________________________________________________________________________________________ ABSTRACT __________________________________________________________________________________________

Linkage and Branch Analysis of High-Mannose Oligosaccharides Using Closed-Ring Labeling of 8-Aminopyrene-1,3,6-Trisulfonate and P-Aminobenzoic Ethyl Ester and Negative Ion Trap Mass Spectrometry

A strategy based on negative ion electrospray ionization tandem mass spectrometry and closed-ring labeling with both 8-aminopyrene-1,3,6-trisulfonate (APTS) and p-aminobenzoic acid ethyl ester (ABEE) was developed for linkage and branch determination of high-mannose oligosaccharides. X-type cross-ring fragment ions obtained from APTS-labeled oligosaccharides by charge remote fragmentation provided information on linkages near the non-reducing terminus. In contrast, A-type cross-ring fragment ions observed from ABEE-labeled oligosaccharides yielded information on linkages near the reducing terminus. This complementary information provided by APTS- and ABEE-labeled oligosaccharides was utilized to delineate the structures of the high-mannose oligosaccharides. As a demonstration of this approach, the linkages and branches of high-mannose oligosaccharides Man(5)GlcNAc(2), Man(6)GlcNAc(2), Man(8)GlcNAc(2), and Man(9)GlcNAc(2) cleaved from the ribonuclease B were assigned from MS(2) spectra of ABEE- and APTS-labeled derivatives.

Preparation of hemicellulolic oligosaccharides from Chamaecyparis obtuse (Hinoki) slurry using commercial enzymes

Wood biomass is anticipated to serve as a substitute for carbon source, which has no feedstock competition with foods. Biomass is commonly used for the production of bio-ethanol by a series of processes such as pretreatment, enzymatic degradation, and fermentation. Hemicellulose, constituting 20 wt-%–40 wt-% of biomass materials, contains various kinds of saccharides known to be bioactive substrates. Practical usage of hemicellulose is generally limited to its conversion to bio-ethanol. Here, we aimed to prepare hemicellulolic oligosaccharides, more valuable products other than ethanol. Therefore, the Hinoki slurry was treated with lime at room temperature for 3 h, and then neutralized with HCl. The resulting sample was treated with 13 types of commercial enzymes, and the saccharides produced in the supernatant were evaluated. The result showed that the commercial enzyme Cellulase SS (Nagase & Co., LTD.) effectively degraded the slurry to produce disaccharides and trisaccharides. Analysis of sugar components by liquid chromatography/mass spectrography (LC/MS) after the derivation with ethyl 4-aminobenzoate (ABEE) showed that mannobiose, mannotriose, and cellobiose were the major oligosaccharides. These results indicate valuable oligosaccharides can be successfully produced from Hinoki softwood slurry.

Benzocaine-Loaded Polymeric Nanocapsules: Study of the Anesthetic Activities

This paper describes a comparison of different polymeric nanocapsules (NCs) prepared with the polymers poly(D,L-lactide-co-glycolide), poly(L-lactide) (PLA), and poly(ε-caprolactone) and used as carrier systems for the local anesthetic (LA) benzocaine (BZC). The systems were characterized and their anesthetic activities investigated. The results showed particle size distributions with polydispersity indices below 0.135, average diameters up to 120 nm, zeta potentials up to -30 mV, and entrapment efficiencies around 70%. Formulations of BZC using the polymeric NCs presented slower release profiles, compared with that of free BZC. Slowest release (release constant, k = 0.0016 min(-1)) was obtained using the PLA NC system. Pharmacological evaluation showed that encapsulation of BZC in PLA NCs prolonged its anesthetic action. This new formulation could potentially be used in future applications involving the gradual release of local anesthetics (LAs).

Modification of Crystallization Behavior in Drug/Polyethylene Glycol Solid Dispersions

The crystallization kinetics of various active pharmaceutical ingredient/polyethylene glycol (API/PEG) solid dispersions has been investigated using wide-angle X-ray diffraction (XRD) and Raman spectroscopy. APIs with different physicochemical properties and crystallization tendency were employed to form solid dispersions with PEG. The crystallization rate of benzocaine (BZC) in BZC/PEG (20/80 wt %) solid dispersions was decreased substantially in comparison to that of the pure API, while the PEG matrix did not affect the crystallization behavior of haloperidol (HLP). The induction time for crystallization of ibuprofen (IBP) and fenofibrate (FNB) in a PEG matrix was decreased relative to the induction times for pure IBP and FNB. For the latter systems, it appears that crystalline PEG acted as a favorable heterogeneous nucleation site. The crystallization behavior of PEG in the API/PEG systems was also affected to different extents, depending on the API studied. These results suggest that PEG can delay, promote or have no influence on the crystallization kinetics of different APIs, and that any effects on crystallization behavior should be investigated in order to be able to produce a solid dispersion with consistent properties.

Peracetylated N-Acetylmannosamine, a Synthetic Sugar Molecule, Efficiently Rescues Muscle Phenotype and Biochemical Defects in Mouse Model of Sialic Acid-deficient Myopathy

Distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy (DMRV/hIBM), characterized by progressive muscle atrophy, weakness, and degeneration, is due to mutations in GNE, a gene encoding a bifunctional enzyme critical in sialic acid biosynthesis. In the DMRV/hIBM mouse model, which exhibits hyposialylation in various tissues in addition to muscle atrophy, weakness, and degeneration, we recently have demonstrated that the myopathic phenotype was prevented by oral administration of N-acetylneuraminic acid, N-acetylmannosamine, and sialyllactose, underscoring the crucial role of hyposialylation in the disease pathomechanism. The choice for the preferred molecule, however, was limited probably by the complex pharmacokinetics of sialic acids and the lack of biomarkers that could clearly show dose response. To address these issues, we screened several synthetic sugar compounds that could increase sialylation more remarkably and allow demonstration of measurable effects in the DMRV/hIBM mice. In this study, we found that tetra-O-acetylated N-acetylmannosamine increased cell sialylation most efficiently, and in vivo evaluation in DMRV/hIBM mice revealed a more dramatic, measurable effect and improvement in muscle phenotype, enabling us to establish analysis of protein biomarkers that can be used for assessing response to treatment. Our results provide a proof of concept in sialic acid-related molecular therapy with synthetic monosaccharides.

Double-blind comparison of two types of benzocaine lozenges for the treatment of acute pharyngitis

In a reference-controlled double-blind trial in patients with acute pharyngitis the effects of a newly developed lozenge containing 8 mg of benzocaine (p-aminobenzoic acid ethyl ester, CAS 94-09-7) were compared with those of an identically dosed commercial pastille. 246 patients were randomized to receive either the lozenges (group A, n = 123) or the pastilles (group B, n = 123). Each patient took a total of six doses within 12 h according to the double-dummy principle, with each single dose spaced by 2 h. The primary parameter was the assessment of the responder rate with = 50 % pain relief within 15 min post application. Further parameters included the relative relief of pain in the course of the study and the tolerability of the formulation. After application of the first unit the comparison of groups yielded very similar and statistically not differing results for efficacy in both groups, with responder rates of 25.2 % and 22.0 % in groups A and B, respectively. One adverse drug reaction was observed in group B (burning and tingling feeling on the tongue), which, however, did not lead to discontinuation of study participation. In all other cases tolerability was stated to be "good to very good". The application of the benzocaine lozenges was statistically non-inferior to the use of the pastilles.

Newer dynamic electrochromic nanorods of poly( o-anisidine-co-ethyl 4-aminobenzoate) synthesized by electrochemical polymerization

Electrochemical copolymerization of o-anisidine with ethyl 4-aminobenzoate was carried out in aqueous 0.1 M HClO 4 by employing cyclic voltammetry. Copolymer films were grown for different molar concentration ratios of ethyl 4-aminobenzoate. Electrochemical homopolymerizations of o-anisidine and ethyl 4-aminobenzoate were carried out independently under similar conditions. The copolymers exhibited high solubility in many polar solvents. The scan rate exerted good influence on the polymer effect on this glassy carbon electrode copolymer film, revealing electroactive film's excellent adherent properties. Spectroelectrochemical studies of the copolymer film were carried out on indium tin oxide plates. The copolymer was characterized by FTIR spectral data. The surface morphology was studied using SEM and TEM analysis. The electrical conductivity of copolymer was measured by four-probe conductivity meter.

“For Want of the Usual Manure”: Rural Civic Ethos in Ciceronian Rhetoric

This essay examines the role of rural citizens in the social fabric of ancient Italy and the redefinition of the rural by the mightiest orator of that time: Marcus Tullius Cicero. This redefinition created a novel form of ethos, a rural civic ethos, apparent in the valuing of Arpinum in The Laws and in the rural character of Sextus Roscius in Pro Sextus Roscius. Rural civic ethos is further developed through an analysis of Cicero's dual identity as rustic and urbane, trained according to the oratorical style of the city yet maintaining an allegiance to the landscapes and peoples of Arpinum.

Rapid and sensitive analyses of glycoprotein-derived oligosaccharides by liquid chromatography and laser-induced fluorometric detection capillary electrophoresis

Asparagine-type oligosaccharides are released from core proteins as N-glycosylamines in the initial step of the action of the peptide N 4-( N-acetyl-β- d-glucosaminyl)asparagine amidase F (PNGase F). The released N-glycosylamine-type oligosaccharides (which are exclusively present at least during the course of the enzyme reaction) could therefore be derivatized with amine-labeling reagents. Here we report a method using 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) as a labeling reagent for glycosylamine-type oligosaccharides. We applied the method for the sensitive analysis of some oligosaccharide mixtures derived from well-characterized glycoproteins including human transferrin, α 1-acid glycoprotein, bovine fetuin, and ribonuclease B. NBD-labeled oligosaccharides were successfully separated on an amide-bonded column or a diol-silica column. This labeling method included the release of oligosaccharides from glycoproteins and derivatization of oligosaccharides in a one-pot reaction and was completed within 3 h. The method showed approximately fivefold higher sensitivity than that involving labeling with ethyl p-aminobenzoate (ABEE) in HPLC using fluorometric detection and a one order of magnitude higher response in ESI-LC/MS. We also applied this method for the sensitive analysis of glycoprotein-derived oligosaccharides by capillary electrophoresis with laser-induced fluorometric detection (LIF-CE). The limit of detection in HPLC and LIF-CE were 100 fmol and 4 fmol, respectively.

Adverse effects of serotonin depletion in developing zebrafish

In this study, p-chlorophenylalanine (pCPA), an inhibitor of tryptophan hydroxylase (the rate limiting enzyme of serotonin synthesis), was used to reduce serotonin (5HT) levels during early development in zebrafish embryos. One day old dechorionated embryos were treated with 25μM pCPA for 24h and subsequently rescued. Immunohistological studies using a 5HT antibody confirmed that 5HT neurons in the brain and spinal cord were depleted of transmitter by 2days post fertilization (dpf). Twenty four hours after pCPA exposure embryos were unable to burst swim and were nearly paralyzed. Movement began to improve at 4dpf, and by 7dpf, larvae exhibited swimming activity. Rescued larvae continued to grow in rostrocaudal length over 5days post-rescue, but their length was always 16–21% below controls. Surprisingly, both groups displayed the same number of myotomes. To examine whether hypertonicity of myotomes in treated embryos played a role in their shorter rostrocaudal lengths, 1dpf embryos were exposed to a combination of 25μM pCPA and 0.6mM of the sodium channel blocker ethyl 3-aminobenzoate methanesulfonate (MS-222). After a 24hour exposure, the embryos exhibited the same rostrocaudal length as control embryos suggesting that myotome hypertonicity plays a major role in the decreased axial length of the treated larvae. In addition, pCPA treated 2dpf embryos exhibited abnormal notochordal morphology that persisted throughout recovery. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the relative levels of the serotonin 1A receptor (5HT1A) transcript and the serotonin transporter (SERT) transcript in the brain and spinal cord of control and treated embryos. Transcripts were present in both brain and spinal cord as early as 1dpf and reached maximal concentrations by 3dpf. Embryos treated with pCPA demonstrated a decrease in the concentration of 5HT1A transcript in both brain and spinal cord. While SERT transcript levels remained unaffected in brain, they were decreased in spinal cord. Five days subsequent to pCPA rescue, 5HT1A transcript concentrations remained decreased in brain while SERT transcript levels were elevated in both regions. These findings suggest that reduction of 5HT during early zebrafish development may have an adverse effect on body length, notochordal morphology, locomotor behavior, and serotonin message-related expression.

Endo-β-1,3-galactanase from Winter Mushroom Flammulina velutipes

Arabinogalactan proteins are proteoglycans found on the cell surface and in the cell walls of higher plants. The carbohydrate moieties of most arabinogalactan proteins are composed of β-1,3-galactan main chains and β-1,6-galactan side chains, to which other auxiliary sugars are attached. For the present study, an endo-β-1,3-galactanase, designated FvEn3GAL, was first purified and cloned from winter mushroom Flammulina velutipes. The enzyme specifically hydrolyzed β-1,3-galactan, but did not act on β-1,3-glucan, β-1,3:1,4-glucan, xyloglucan, and agarose. It released various β-1,3-galactooligosaccharides together with Gal from β-1,3-galactohexaose in the early phase of the reaction, demonstrating that it acts on β-1,3-galactan in an endo-fashion. Phylogenetic analysis revealed that FvEn3GAL is member of a novel subgroup distinct from known glycoside hydrolases such as endo-β-1,3-glucanase and endo-β-1,3:1,4-glucanase in glycoside hydrolase family 16. Point mutations replacing the putative catalytic Glu residues conserved for enzymes in this family with Asp abolished activity. These results indicate that FvEn3GAL is a highly specific glycoside hydrolase 16 endo-β-1,3-galactanase.

Electrochemically synthesized nano size copolymer, poly (aniline-co-ethyl 4-aminobenzoate) and its spectroelectrochemical studies

Electroactive conducting copolymers of aniline (ANI) and ethyl 4-aminobenzoate (EAB) were prepared electrochemically. Cyclic voltammetric studies were carried out with different feed concentration of EAB on glassy carbon electrode surface. The voltammograms exhibited different behavior for different concentrations of EAB. The copolymers exhibited high solubility in many polar solvents. The scan rate exerted good influence on the polymer effect on this GCE copolymer film, revealing electroactive film’s excellent adherent properties. The effect of pH on the copolymer film showed that the polymer was electrochemically active up to pH 7.0. Spectroelectrochemical analysis of the copolymer film, carried out on an indium tin oxide (ITO) plate, showed multicolor electrochromic behavior when the applied potential was changed. The color of the copolymer was changed from neutral yellow (422 nm) to green (760 nm) and to blue (600 nm) at the concentration of 0.1 M aniline and 0.1 M EAB in 0.1 M H 2SO 4 medium. The copolymer was characterized by FT-IR spectral data. The surface morphology were studied using SEM and TEM analysis. The grain size of the copolymer was measured using XRD studies and was found to be 80 nm. The electrical conductivity of the copolymer was 3.21 × 10 −2 S cm −1, as determined using a four-probe conductivity meter.

Development, Characterization, and In Vitro and In Vivo Evaluation of Benzocaine- and Lidocaine-Loaded Nanostructrured Lipid Carriers

The present study concerns the in vitro and in vivo evaluation of benzocaine (BENZO) and lidocaine (LIDO) topical delivery from nanostructured lipid carriers (NLCs). Morphology and dimensional distribution of NLCs have been, respectively, characterized by differential scanning calorimetry (DSC) and photon correlation spectroscopy. The release pattern of BENZO and LIDO from NLCs was evaluated in vitro determining drug percutaneous absorption through excised human skin. Radiant heat tail-flick test was carried out in mice to determine the antinociceptive effect of BENZO and LIDO from NLC. DSC studies revealed that the inner oil phase of NLC plays a significant role in stabilizing the particle architecture and increasing the drug solubility. In vitro evidences show that BENZO and LIDO, when incorporated in viscosized NLC dispersions, exhibited a lower flux with respect to formulations containing the free drugs in the aqueous phase. In vivo study enabled to demonstrate that BENZO and LIDO can be released in a prolonged fashion when incorporated into lipid carriers. The results obtained pointed out NLC capability to act as an effective drug reservoir, thus prolonging the anesthetic effect of BENZO and LIDO.

A comparative study of monosaccharide composition analysis as a carbohydrate test for biopharmaceuticals

The various monosaccharide composition analysis methods were evaluated as monosaccharide test for glycoprotein-based pharmaceuticals. Neutral and amino sugars were released by hydrolysis with 4–7 N trifluoroacetic acid. The monosaccharides were N-acetylated if necessary, and analyzed by high-performance liquid chromatography (HPLC) with fluorometric or UV detection after derivatization with 2-aminopyridine, ethyl 4-aminobenzoate, 2-aminobenzoic acid or 1-phenyl-3-methyl-5-pyrazolone, or high pH anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Sialic acids were released by mild acid hydrolysis or sialidase digestion, and analyzed by HPLC with fluorometric detection after derivatization with 1,2-diamino-4,5-methylenedioxybenzene, or HPAEC-PAD. These methods were verified for resolution, linearity, repeatability, and accuracy using a monosaccharide standard solution, a mixture of epoetin alfa and beta, and alteplase as models. It was confirmed that those methods were useful for ensuring the consistency of glycosylation. It is considered essential that the analytical conditions including desalting, selection of internal standards, release of monosaccharides, and gradient time course should be determined carefully to eliminate interference of sample matrix. Various HPLC-based monosaccharide analysis methods were evaluated as a carbohydrate test for glycoprotein pharmaceuticals by an inter-laboratory study.

The modifying effects of a cationic surfactant on the rates of base catalysed hydrolysis of esters of different structures.

Abstract The effect of a cationic surfactant, cetyltrimethylammonium bromide (CTAB), on the hydrolysis rates of four esters of different structure has been investigated. The esters used were ethyl p-aminobenzoate (EPAB), p-nitrophenyl acetate (PNPA), ethyl p-nitrobenzoate (EPNB) and p-aminophenyl acetate (PAPA). Association between the esters and the CTAB occurs so that above its cmc the surfactant modifies the rates of hydrolysis, increasing those of EPNB and PNPA and decreasing those of EPAB and PAPA. It thus appears that the type of group on the p-position of the aromatic ring plays a major role in determining the kind of effect brought about by the CTAB. Possible reasons to explain the two different effects that CTAB has on ester hydrolysis are put forward.

The sorption of benzocaine by nylon 6 (polycaprolactam).

The sorption of benzocaine by nylon 6 (polycaprolactam).