Selective spectrofluorimetric determination of phenolic beta-lactam antibiotics through the formation of their coumarin derivatives

A simple, sensitive and selective spectrofluorimetric procedure was developed for the determination of amoxycillin, cefadroxil and cefoperazone. The method is based on the reaction between these drugs and ethyl acetoacetate, in acidic medium, to give yellow fluorescent products with excitation wavelengths ranging from 401 to 467 nm and emission wavelengths ranging from 465 to 503 nm. The reaction conditions were studied and optimized. The reaction obeyed Beer's law over the range of 10.0-20.0, 1.5-1.0 and 50.0-100.0 microg ml(-1) for amoxycillin, cefadroxil and cefoperazone, respectively. Interference's from other antibiotics, drugs and dosage forms additives, in capsules and vials dosage forms, were investigated. The proposed method was applied to the analysis of pharmaceutical formulations (capsules and vials) containing the above antibiotics, either alone or in combination with other antibiotics or drugs. The validity of the method was tested by the recovery studies of standard addition which were found to be satisfactory. The results of the proposed method demonstrated that the method is equally accurate, precise and reproducible as the official methods (USP XXIII) and those published for the non-official binary mixtures.     

Polarographic determination of N-acetyl-L-cysteine in pharmaceutical preparations.

The polarographic behaviour of N-acetyl-L-cysteine in Britton Robinson Buffer (BRB) over the whole pH range was studied. At pH 10, a well-defined anodic wave was developed. The wave was irreversible, one-electron, diffusion-controlled and partially affected by adsorption phenomenon. Adopting both direct current (DCT) and differential pulse polarographic (DPP) modes, the current concentration plot is rectilinear over the range 0.05 to 1.0 mM and 0.01 to 0.75 mM, respectively, with a minimum detection limit of 0.0005 mM using the DPP mode. The proposed method was successfully applied to the determination of N-acetyl-L-cysteine in pharmaceutical preparations. The obtained results were in a good agreement with those obtained by the official method.     

Dysequilibrium of ageing (presbyastasis)

We reviewed clinical findings in 740 patients over age 65 who consulted the Otological Medical Group, Inc., during a one-year period for dizziness. A thorough neurotologic evaluation is indicated in every such case to determine the specific cause of dizziness. In 21 per cent of these patients, a specific cause of dizziness was found. In the remaining 79 per cent, the diagnosis of primary dysequilibrium of ageing (presbyastasis) was made. We classified dysequilibrium of ageing (presbyastasis) according to the character, time course, and precipitating factors of dizziness. Two clinical types were described: constant and episodic; episodic dizziness was subdivided into orthostatic, positional, and unclassified. The histological findings in the temporal bones of four cases with dysequilibrium of ageing were reviewed. Pathological changes other than those in the peripheral vestibular system seem to be responsible for dysequilibrium of ageing. In the present series, about three-fourths of the patients had a daily dose of nicotinic acid to produce flushing of the skin. In 16 per cent, the dizziness was minor, requiring no special treatment. In the remaining 9 per cent with incapacitating vertigo, a vasodilator regimen, antivertiginous drugs, and Cawthorne's vestibular exercises were prescribed.     

A computerized data acquisition system for infusion devices--a clinical support tool, or a risk management tool?

A prototype computerized system for automatic data collection from multi-vendor infusion devices was constructed. The system was specifically designed around the needs of the critical care environment, and a survey of clinical staff was conducted to determine the functional requirements. Hardware, software and system configuration was based on the Medical Information Bus IEEE 1073 standard for medical device data communications. The infusion devices were configured into device communication controllers (DCC), which were polled at 0.25 Hz by a PC configured as a bedside communication controller (BCC). The system stores data samples after intervals of 1 ml of drug delivery and following any changes in the infusion rate. The system demonstrated significant opportunities for supporting clinical care and for the management of health care technology.     

Antibiotic susceptibility profile of bifidobacteria as affected by oxgall, acid, and hydrogen peroxide stress

The effects of acid, oxgall, and H(2)O(2) on susceptibilities to antibiotics and nisin were examined for 13 strains of bifidobacteria. Susceptibilities to ampicillin, cloxacillin, penicillin, vancomycin, kanamycin, neomycin, paramomycin, streptomycin, chloramphenicol, erythromycin, tetracycline, and nisin A were assayed by a microdilution broth method. Acid-, oxgall- and H(2)O(2)-stressed variants were produced and assayed. Exposure to a pH of 2.0 for 60 min reduced susceptibilities to cloxacillin and nisin A but increased susceptibilities to ampicillin, vancomycin, aminoglycosides, chloramphenicol, and erythromycin in a strain-dependent manner. Exposure to oxgall (0.3%) for 90 min increased susceptibilities to cell wall-directed antibiotics and aminoglycosides but increased resistances to tetracycline and nisin A. Oxidative stress increased the susceptibilities of 70% of the strains to ampicillin and chloramphenicol, of 50% of the strains to cloxacillin and tetracycline, and of 40% of the strains to erythromycin but did not affect susceptibilities to vancomycin, kanamycin, and nisin A. This study shows that exposure of bifidobacteria to stressful conditions resembling those in the gastrointestinal tract may substantially modify their susceptibilities to antibiotics and may thus affect their probiotic capacities, especially when they are used for the management of intestinal infections and antibiotic-associated diarrhea.     

In vivo requirement of TGF-β/GDNF cooperativity in mouse development: focus on the neurotrophic hypothesis

Neurotrophic factors are well-recognized extracellular signaling molecules that regulate neuron development including neurite growth, survival and maturation of neuronal phenotypes in the central and peripheral nervous system. Previous studies have suggested that TGF-β plays a key role in the regulation of neuron survival and death and potentiates the neurotrophic activity of several neurotrophic factors, most strikingly of GDNF. To test the physiological relevance of this finding, TGF-β2/GDNF double mutant (d-ko) mice were generated. Double mutant mice die at birth like single mutants due to kidney agenesis (GDNF−/−) and congential cyanosis (TGF-β2−/−), respectively. To test for the in vivo relevance of TGF-β2/GDNF cooperativity to regulate neuron survival, mesencephalic dopaminergic neurons, lumbar motoneurons, as well as neurons of the lumbar dorsal root ganglion and the superior cervical ganglion were investigated. No loss of mesencephalic dopaminergic neurons was observed in double mutant mice at E18.5. A partial reduction in neuron numbers was observed in lumbar motoneurons, sensory and sympathetic neurons in GDNF single mutants, which was further reduced in TGF-β2/GDNF double mutant mice at E18.5. However, TGF-β2 single mutant mice showed no loss of neurons. These data point towards a cooperative role of TGF-β2 and GDNF with regard to promotion of survival within the peripheral motor and sensory systems investigated.     

Tunisian hereditary spastic paraplegias: clinical variability supported by genetic heterogeneity

Hereditary spastic paraplegias (HSP) constitute a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by slowly progressive spasticity of the lower extremities. We performed the first clinical, epidemiological and genetic study of HSP in Southern Tunisia. We investigated 88 patients belonging to 38 unrelated Tunisian HSP families. We could establish the minimal prevalence of HSP in the district of Sfax at 5.75/100,000. Thirty‐one percent of the families had a pure HSP, whereas 69% had a complicated form. The mode of inheritance was almost exclusively compatible with an autosomal recessive trait (97%, 37/38). Taking into account previously published results and new data generated in this work, genetic studies revealed significant or putative linkage to known HSP loci in 13 families (34.2%) to either SPG11 (7/38, 18.4%), SPG15 (4/38, 10.5%) or to SPG4 and SPG5 in one family each. The linkage results could be validated through the identification of two recurrent truncating mutations (R2034X and M245VfsX246) in the SPG11 gene, three different mutations (Q493X, F683LfsX685 and the novel S2004T/r.?) in the SPG15 gene, the recurrent R499C mutation in the SPG4 gene as well as the new R112X mutation in the SPG5 gene. SPG11 and SPG15 are the major responsible HSP genes in Tunisia.