bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of the inner ear efferent system across vertebrate species
Authors: Simmons Dwayne D.
Published: October 2002

Inner ear efferent neurons are part of a descending centrifugal pathway from the hindbrain known across vertebrates as the octavolateralis efferent system. This centrifugal pathway terminates on either sensory hair cells or eighth nerve ganglion cells. Most studies of efferent development have used either avian or mammalian models. Recent studies suggest that prevailing notions of the development of efferent innervation need to be revised. In birds, efferents reside in a single, diffuse nucleus, but segregate according to vestibular or cochlear projections. In mammals, the auditory and vestibular efferents are completely separate. Cochlear efferents can be divided into at least two distinct, descending medial and lateral pathways. During development, inner ear efferents appear to be a specific motor neuron phenotype, but unlike motor neurons have contralateral projections, innervate sensory targets, and, at least in mammals, also express noncholinergic neurotransmitters. Contrary to prevailing views, newer data suggest that medial efferent neurons mature early, are mostly, if not exclusively, cholinergic, and project transiently to the inner hair cell region of the cochlea before making final synapses on outer hair cells. On the other hand, lateral efferent neurons mature later, are neurochemically heterogeneous, and project mostly, but not exclusively to the inner hair cell region. The early efferent innervation to the ear may serve an important role in the maturation of afferent responses. This review summarizes recent data on the neurogenesis, pathfinding, target selection, innervation, and onset of neurotransmitter expression in cholinergic efferent neurons. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 228–250, 2002
Whole‐body nutrient composition of various ages of captive‐bred bearded dragons (Pogona vitteceps) and adult wild anoles (Anolis carolinensis)
Authors: Cosgrove Jennifer J. , Beermann Donald H. , House William A. , Toddes Barbara D. , Dierenfeld Ellen S.
Published: October 2002

Neonates, 11‐day‐old, and 17‐day‐old captive‐bred bearded dragons (Pogona vitteceps) and wild‐caught adult anoles (Anolis carolinensis) were chemically analyzed to determine the whole‐body concentrations of vitamins E and A, crude protein, and minerals. Significant differences (P<0.05) were noted between neonates and older age groups of the bearded dragons for concentrations of all the minerals except calcium (Ca) and phosphorus (P). The neonatal animals generally exhibited lower concentrations of all minerals, except for magnesium (Mg) and iron (Fe), than did the older lizards. The concentration of vitamin E was higher, and that of vitamin A was lower in neonates than in older animals. The whole‐body concentrations of protein, vitamins A and E, Ca, P, potassium (K), sodium (Na), copper (Cu), and manganese (Mn) differed significantly between the bearded dragons and anoles. Zoo Biol 21:489–497, 2002. © 2002 Wiley‐Liss, Inc.
Epidemiological study of suicide in the Republic of Croatia – comparison of war and post-war periods and areas directly and indirectly affected by war
Authors: Grubišić-Ilić Mirjana , Kozarić-Kovačić Dragica , Grubišić Frane , Kovačić Zrnka
Published: October 2002

We examined the differences in the suicide characteristics between areas directly and indirectly affected by war activities and in war and post-war periods according to the following variables: suicide rate, sex, age and method of suicide. Analysis was done on 5349 suicides committed in the period 1993–1998 (war and post-war years). The suicide rates in the Republic of Croatia oscillated in the pre-war, war and post-war periods (1985–2000) but without significant differences. In the areas directly affected by war, the suicide rate was significantly lower than in other areas during the study period 1993–1998 (chi-square = 10.3245;P= 0.0017). The number of suicides in both sexes declined in the areas directly affected by war—more in men than in women; the difference between sexes was statistically significant (chi-square = 3.6697;P= 0.055). Middle- and old-aged people were the population with high suicide risk in both areas (t= 1.76;P= 0.078). There were significant differences in the methods of suicides between war and non-war areas (chi-square = 108.8473;P= 0.001). Firearms or explosive devices were the methods used more significantly for suicides in the areas directly affected by war than in other areas, whereas hanging was more frequently used in the areas indirectly affected by war.
Life events and changes in the course of depression in young adults
Authors: Friis Robert H. , Wittchen Hans-Ulrich , Pfister Hildegard , Lieb Roselind
Published: October 2002

Background.

Few community-based studies have examined the impact of life events, life conditions and life changes on the course of depression. This paper examines associations of life events on depressive symptom onset, improvement, and stability.

Methods.

Direct interview data from the Early Developmental Stages of Psychopathology Study (EDSP), a 4–5 year prospective-longitudinal design based on a representative community sample of adolescents and young adults, aged 14–24 years at baseline, are used. Life events were measured using the Munich Event-Questionnaire (MEL) consisting of 83 explicit items from various social role areas and subscales for the assessment of life event clusters categorized according to dimensions such as positive and negative and controllable and uncontrollable. Depressive disorders were assessed with the DSM-IV version of the Munich Composite Diagnostic Interview (M-CIDI). Multiple logistic regression analyses examined the effects of 22 predictors on the course of depression (onset, improvement, stability).

Results.

Younger age, low social class, negative and stressful life events linked to the family were associated with increased risk of new onset of depression. Anxiety was a significant independent predictor of new onset of depression. Absence of stressful school and family events was related to improvement in depression. The weighted total number of life events predicted stable depression.

Conclusions.

The association between life events and the course of depression appears to vary according to the outcome being examined, with different clusters of life events differentially predicting onset, improvement, and stability.
Interaction of Avilamycin with Ribosomes and Resistance Caused by Mutations in 23S rRNA
Authors: Kofoed Christine B. , Vester Birte
Published: October 2002

The antibiotic growth promoter avilamycin inhibits protein synthesis by binding to bacterial ribosomes. Here the binding site is further characterized on
Escherichia coli
ribosomes. The drug interacts with domain V of 23S rRNA, giving a chemical footprint at nucleotides A2482 and A2534. Selection of avilamycin-resistant
Halobacterium halobium
cells revealed mutations in helix 89 of 23S rRNA. Furthermore, mutations in helices 89 and 91, which have previously been shown to confer resistance to evernimicin, give cross-resistance to avilamycin. These data place the binding site of avilamycin on 23S rRNA close to the elbow of A-site tRNA. It is inferred that avilamycin interacts with the ribosomes at the ribosomal A-site interfering with initiation factor IF2 and tRNA binding in a manner similar to evernimicin.
gyrA
and
gyrB
Mutations Are Implicated in Cross-Resistance to Ciprofloxacin and Moxifloxacin in
Clostridium difficile
Authors: Dridi Larbi , Tankovic Jacques , Burghoffer Béatrice , Barbut Frédéric , Petit Jean-Claude
Published: October 2002

A total of 198 nonrepetitive clinical strains of
Clostridium difficile
isolated from different French hospitals in 1991 (
n
= 100) and 1997 (
n
= 98) were screened for decreased susceptibility to fluoroquinolones by plating onto Wilkins-Chalgren agar containing 16 μg of ciprofloxacin per ml. The frequency of decreased susceptibility was 7% (14 of 198) and was identical for the years 1991 and 1997. Serogroups C, H, D, A9, and K accounted for five, four, two, one, and one of the resistant strains, respectively, one strain being nontypeable. Arbitrarily primed PCR typing showed that all resistant strains had unique patterns except two serotype C strains, which could not be clearly distinguished. All isolates with decreased susceptibility carried a mutation either in
gyrA
(eight mutations, amino acid changes Asp71→Val in one, Thr82→Ile in six, and Ala118→Thr in one) or in
gyrB
(six mutations, amino acid changes Asp426→Asn in five and Arg447→Leu in one). These changes are similar to those already described in other species except for Asp71→Val, which is novel, and Ala118→Thr, which is exceptional. Attempts to detect the topoisomerase IV
parC
gene by PCR amplification with universal
parC
primers or DNA-DNA hybridization under low-stringency conditions were unsuccessful. The susceptibilities of all resistant strains to ciprofloxacin and ethidium bromide were not affected by the addition of reserpine at 20 μg/ml. In conclusion, decreased susceptibility to fluoroquinolones in
C. difficile
is rare in France and is associated with the occurrence of a
gyrA
or
gyrB
mutation.
Dexamethasone, a Drug for Attenuation ofSchistosoma mansoniInfection Morbidity
Authors: Pyrrho Alexandre dos Santos , Ramos Juliene Antonio , Neto Roberto Moura , Silva Célia Santos da , Lenzi Henrique Leonel , Takiya Christina Maeda , Gattass Cerli Rocha
Published: October 2002

To investigate the possible use of immunomodulators as coadjuvants in the treatment of chronic schistosomiasis, the study described in the present report evaluated the effects of dexamethasone on several parameters which reflect disease severity and morbidity. Parasitological, immunological, and histological parameters were analyzed in animals treated from the first day of infection or after 35 days of infection. In both situations, dexamethasone had no effect on the parasite burden but altered the egg distribution in tissue, indicating that under the schedule used it did not interfere with the development of adult worms or oviposition. Treated mice showed a decrease in the number of eggs in hepatic tissue, reduced granuloma sizes, reduced levels of granuloma maturation, and reduced collagen contents. Dexamethasone-treated mice also had decreased gamma interferon, interleukin-12 (IL-12), and IL-4 levels in serum and increased IL-10 levels in serum. Taken together, these data suggested a decrease in the severity of murine schistosomiasis and point to dexamethasone as a convenient and promising coadjuvant agent in the therapy of this infection.
Low-Virulence
Citrobacter
Species Encode Resistance to Multiple Antimicrobials
Authors: Pepperell C. , Kus J. V. , Gardam M. A. , Humar A. , Burrows L. L.
Published: October 2002

Citrobacter
spp. are gram-negative commensal bacteria that infrequently cause serious nosocomial infections in compromised hosts. They are often resistant to cephalosporins due to overexpression of their chromosomal β-lactamase. During a recent study of multidrug-resistant
Enterobacteriaceae
(MDRE) in solid-organ transplant patients, we found that almost half of patients colonized with MDRE carried one or more cefpodoxime-resistant
Citrobacter freundii
,
Citrobacter braakii
, or
Citrobacter amalonaticus
strains. Pulsed-field gel electrophoresis showed that 36 unique strains of
Citrobacter
were present among 32 patients. Genetic and phenotypic analysis of the resistance mechanisms of these bacteria showed that the extended-spectrum β-lactamase (ESBL) SHV-5 or SHV-12 was encoded by 8 strains (26%) and expressed by 7 strains (19%). A number of strains were resistant to other drug classes, including aminoglycosides (28%), trimethoprim-sulfamethoxazole (31%), and fluoroquinolones (8%). PCR and DNA analysis of these multiresistant strains revealed the presence of class I integrons, including the first integrons reported for
C. braakii
and
C. amalonaticus
. The integrons encoded aminoglycoside resistance, trimethoprim resistance, or both. Despite the prevalence of MDR
Citrobacter
spp. in our solid-organ transplant patients, only a single infection with a colonizing strain was recorded over 18 months. Low-virulence
Citrobacter
spp., which can persist in the host for long periods, could influence pathogen evolution by accumulation of genes encoding resistance to multiple antimicrobial classes.
Stampidine Is a Potent Inhibitor of Zidovudine- and Nucleoside Analog Reverse Transcriptase Inhibitor-Resistant Primary Clinical Human Immunodeficiency Virus Type 1 Isolates with Thymidine Analog Mutations
Authors: Uckun Fatih M. , Pendergrass Sharon , Venkatachalam T. K. , Qazi Sanjive , Richman Douglas
Published: October 2002

We report the antiretroviral activity of stavudine-5′-(
p
-bromophenyl methoxyalaninyl phosphate) (stampidine [STAMP]), a novel aryl phosphate derivative of stavudine, against primary clinical human immunodeficiency virus type 1 (HIV-1) isolates. STAMP inhibited each one of nine clinical HIV-1 isolates of non-B envelope subtype and 20 genotypically and phenotypically nucleoside analog reverse transcriptase inhibitor-resistant HIV-1 isolates at subnanomolar to low-nanomolar concentrations.
A new approach to modelling initial dilution of a buoyancy-dominated jet in moving water
Authors: Mukhtasor  , Lye L M , Sharp J J
Published: October 2002

Initial dilution is one of the most important measures in the design of ocean outfalls. Considerable efforts have been devoted in the past to modelling initial dilution of a buoyancy-dominated jet in moving water. This paper reviews available initial dilution models and presents a new modelling approach based on a length scale analysis combined with an additive entrainment hypothesis, and nonlinear regression modelling. The proposed approach is more systematic and more justifiable than existing methods for two reasons: (1) it uses an objective measure to evaluate the model and (2) it includes the effect of ambient current in the buoyancy-dominated near field (BDNF). Using available experimental data, a new, continuous, initial dilution model is proposed and compared with presently available models. The proposed model is presented in both deterministic and probabilistic form.Key words: asymptotic solutions, buoyant jets, forced entrainment, initial dilution, ocean outfalls.
Dynamics of vitamin A in grey seal (Halichoerus grypus) mothers and pups throughout lactation
Authors: Debier C , Pomeroy P P , Van Wouwe N , Mignolet E , Baret P V , Larondelle Y
Published: October 2002

Vitamin A concentrations were measured in milk and serum of grey seal (Halichoerus grypus) mothers and in the serum of their pups sampled 26 times between parturition and weaning on the Isle of May, Scotland, in 1998 and 2000. Changes in serum vitamin A concentration were also followed in pups during the postweaning fast. During their 18-day lactation period, fasting mothers produced a milk very rich in vitamin A. Concentrations of 6.3 ± 1.6 and 10.1 ± 4.5 mg/kg (mean ± SD) were measured in colostrum (day 0) and in milk at late lactation ([Formula: see text]11 days), respectively. Surprisingly, the vitamin A concentration increased at late lactation, even when it was expressed per unit of milk lipids. The vitamin A concentration in mothers' serum was 329 ± 65 μg/L at day 0. The concentration dropped at day 3 (228 ± 21 μg/L serum), but increased to 400 ± 121 μg/L serum at late lactation. At birth, the serum vitamin A concentration of pups (111 ± 5 μg/L) was much lower than that of their mothers, revealing limited placental transfer. The vitamin A concentration in pup serum then increased throughout lactation to 499 ± 96 μg/L at the end of the nursing period. At that time, the pups' serum was more concentrated than the mothers' serum, reflecting the great vitamin A ingestion. After weaning, serum vitamin A concentrations of pups dropped over several days and then stabilized at 336 ± 45 μg/L.
THE MEAN π-FIELD SHOULD BE CALCULATED IN A RELATIVISTIC MEAN FIELD THEORY FOR NUCLEAR MATTER
Authors: GAO CHUN-YUAN , GUO HUA , ZHANG QI-REN
Published: October 2002

We extend our work on the finite value of mean π-field in the relativistic mean field theory to the derivative coupling models for nuclear matter proposed by Zimanyi and Moszkowski. We show that a finite mean π-field may lower the energy per nucleon at a not too high density for all of those models. This qualitative result seems true in general and is model independent, although the quantitative details may be different for different models.
TERNARY CONFIGURATION IN THE FRAMEWORK OF INVERSE MEAN-FIELD METHOD
Authors: KARTAVENKO V. G. , SĂNDULESCU A. , GREINER W.
Published: October 2002

A static scission configuration in cold ternary fission has been considered in the framework of mean field approach. The inverse scattering method is applied to solve single-particle Schrödinger equation, instead of constrained selfconsistent Hartree–Fock equations. It is shown, that it is possible to simulate one-dimensional three-center system via inverse scattering method in the approximation of reflectless single-particle potentials.
On local properties of compactly supported solutions of the two‐coefficient dilation equation
Authors: Morawiec Janusz
Published: October 2002

Let a and b be reals. We consider the compactly supported solutions φ : ℝ → ℝ of the two‐coefficient dilation equation
φ(x) = aφ(2x) + bφ(2x − 1). In this paper, we determine sets Ba,b, Ca,b, and Za,b defined in the following way: let x ∈ [0, 1]. We say that x ∈ Ba,b (resp., x ∈ Ca,b, x ∈ Za,b) if the zero function is the only compactly supported solution of the two‐coefficient dilation equation, which is bounded in a neighbourhood of x (resp., continuous at x, vanishes in a neighbourhood of x). We also give the structure of the general compactly supported solution of the two‐coefficient dilation equation.
NOD/SCID/γcnull mouse: an excellent recipient mouse model for engraftment of human cells
Authors: Ito Mamoru , Hiramatsu Hidefumi , Kobayashi Kimio , Suzue Kazutomo , Kawahata Mariko , Hioki Kyoji , Ueyama Yoshito , Koyanagi Yoshio , Sugamura Kazuo , Tsuji Kohichiro , Heike Toshio , Nakahata Tatsutoshi
Published: October 2002

To establish a more appropriate animal recipient for xenotransplantation, NOD/SCID/γcnull mice double homozygous for the severe combined immunodeficiency (SCID) mutation and interleukin-2Rγ (IL-2Rγ) allelic mutation (γcnull) were generated by 8 backcross matings of C57BL/6J-γcnull mice and NOD/Shi-scidmice. When human CD34+ cells from umbilical cord blood were transplanted into this strain, the engraftment rate in the peripheral circulation, spleen, and bone marrow were significantly higher than that in NOD/Shi-scid mice treated with anti-asialo GM1 antibody or in the β2-microglobulin–deficient NOD/LtSz-scid (NOD/SCID/β2mnull) mice, which were as completely defective in NK cell activity as NOD/SCID/γcnull mice. The same high engraftment rate of human mature cells was observed in ascites when peripheral blood mononuclear cells were intraperitoneally transferred. In addition to the high engraftment rate, multilineage cell differentiation was also observed. Further, even 1 × 102 CD34+ cells could grow and differentiate in this strain. These results suggest that NOD/SCID/γcnull mice were superior animal recipients for xenotransplantation and were especially valuable for human stem cell assay. To elucidate the mechanisms involved in the superior engraftment rate in NOD/SCID/γcnull mice, cytokine production of spleen cells stimulated with Listeria monocytogenesantigens was compared among these 3 strains of mice. The interferon-γ production from dendritic cells from the NOD/SCID/γcnull mouse spleen was significantly suppressed in comparison with findings in 2 other strains of mice. It is suggested that multiple immunological dysfunctions, including cytokine production capability, in addition to functional incompetence of T, B, and NK cells, may lead to the high engraftment levels of xenograft in NOD/SCID/γcnull mice.
In the presence of bone marrow stromal cells human multiple myeloma cells become independent of the IL-6/gp130/STAT3 pathway
Authors: Chatterjee Manik , Hönemann Dirk , Lentzsch Suzanne , Bommert Kurt , Sers Christine , Herrmann Pia , Mathas Stephan , Dörken Bernd , Bargou Ralf C.
Published: October 2002

The interleukin 6/glycoprotein 130/signal transducer and activator of transcription 3 (IL-6/gp130/STAT3) pathway has been reported to play an important role in the pathogenesis of multiple myeloma (MM) and for survival of MM cells. However, most data concerning the role of IL-6 and IL-6–triggered signaling pathways were obtained from experiments performed with MM cell lines and without considering the bone marrow microenvironment. Thus, the precise role of IL-6 and its intracellular signaling pathways for survival of human MM cells is still unclear. Here we show that treatment of human MM cells (IL-6–dependent MM cell line INA-6 and primary MM cells) with the IL-6 receptor antagonist Sant7 or with an anti-gp130 monoclonal antibody (mAb) induced apoptosis if the cells were cultured in the absence of bone marrow stromal cells (BMSCs). In contrast, apoptosis could not be observed if the MM cells were cocultured with BMSCs. The analysis of intracellular pathways revealed that Sant7 and anti-gp130 mAb were effectively inhibiting the phosphorylation of gp130 and STAT3 in the absence and presence of BMSCs, whereas ERK1 and ERK2 (ERK1,2) phosphorylation was only slightly affected. In contrast, treatment with the farnesyl transferase inhibitor, FPT III, induced apoptosis in MM cells in the absence or presence of BMSCs and led to a complete inhibition of the Ras/mitogen-activated protein kinase pathway. These observations indicate that the IL-6/gp130/STAT3 pathway is not essential for survival of human myeloma cells if they are grown in the presence of cells from the bone marrow microenvironment. Furthermore, we provide evidence that farnesyl transferase inhibitors might be useful for the development of novel therapeutic strategies for the treatment of MM.
A new and recurrent activating length mutation in exon 20 of the FLT3 gene in acute myeloid leukemia
Authors: Spiekermann Karsten , Bagrintseva Ksenia , Schoch Claudia , Haferlach Torsten , Hiddemann Wolfgang , Schnittger Susanne
Published: October 2002

Activating length mutations in the juxtamembrane (JM) domain of the FLT3 gene (FLT3-LM) and mutations in the catalytic domain (FLT3D835/836) of this receptor tyrosine kinase represent the most frequent genetic alterations in acute myeloid leukemia (AML). Here, we describe a 6-bp insertion in the activation loop of FLT3 between codons 840 and 841 of FLT3 (FLT3-840GS) in 2 unrelated patients with AML. Screening for other activating mutations of FLT3, KIT, and NRASshowed no further genetic alterations in patients carrying the FLT3-840GS. In functional analyses we could show that this mutant is hyperphosphorylated on tyrosine and confers interleukin 3–independent growth to Ba/F3 cells, which can be inhibited by a specific FLT3 protein tyrosine kinase (PTK) inhibitor. Our results show for the first time that in addition to known mutations in the JM and the catalytic domain, further activating length mutations exist in theFLT3 gene.
Clonal heterogeneity in mycosis fungoides and its relationship to clinical course
Authors: Vega Francisco , Luthra Rajyalakshmi , Medeiros L. Jeffrey , Dunmire Valerie , Lee Sang-Joon , Duvic Madeleine , Jones Dan
Published: October 2002

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma characterized by multifocal disease and protracted clinical course. The few studies that have assessed T-cell receptor (TCR) gene rearrangements (GRs) present at different anatomic sites in MF have generally reported a common clone. We used a previously validated 4-color polymerase chain reaction (PCR) assay to assess the size and V-family usage of TCR-γ GRs in 102 concurrent and/or sequential morphologically involved biopsy specimens (91 skin and 11 lymph nodes) from 39 MF patients. This assay detected TCR-γ clonal GRs in 89 samples (87%) from 36 patients (92%). In 24 patients (77%), an identical clonal GR was present in at least 2 skin samples. However, in one third of these patients, additional different clonal GRs were also noted. Four patients (13%) had clonal GRs that were distinct in different skin samples. In 3 patients (10%), no GR was detected in any sample. In a comparison of lymph node and skin samples, 8 patients had the identical clonal GRs at both sites, 2 patients had different clonal GRs, and 1 patient had no GR identified at either site. Independent of clinical stage, patients who had the same GR detected in multiple concurrent biopsy specimens at the time of diagnosis were more likely to have progressive disease than those who had different GRs (P = .04). Four-color TCR-γ PCR analysis can uncover multiple distinct clonal GRs in different samples consistent with multiclonal or oligoclonal disease in a significant proportion of MF patients. Demonstration of identical clonal GRs in multiple biopsy specimens at the time of diagnosis may provide prognostic information related to disease progression.
Preparation, characterization and taste-masking properties of polyvinylacetal diethylaminoacetate microspheres containing trimebutine
Authors: Hashimoto Yoshimi , Tanaka Masami , Kishimoto Hideyuki , Shiozawa Hiroyoshi , Hasegawa Kazumasa , Matsuyama Kenji , Uchida Takahiro
Published: October 2002

The objectives of this study were to produce acid soluble, polyvinylacetal diethylaminoacetate (AEA) microspheres containing trimebutine (as maleate), using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation method, to characterize their in-vitro release properties, and to evaluate the taste-masking potential of this formulation in human volunteers. The pH of the external aqueous phase was the critical factor in achieving a high loading efficiency for trimebutine in the microencapsulation process; nearly 90% (w/w) loading efficiency was obtained at above pH 10. Trimebutine was completely released from AEA microspheres within 10 min in a dissolution test at pH 1.2, simulating conditions in the stomach, whereas at pH 6.8, the pH in the mouth, only small quantities of trimebutine were released in the initial 1–2 min. The results of a gustatory sensation test in healthy volunteers confirmed the taste-masking effects of the AEA microspheres. Finally, an attempt was made to encapsulate the salts of other basic drugs (lidocaine, imipramine, desipramine, amitriptyline, promethazine and chlorpheniramine) into AEA microspheres using the w/o/w emulsion evaporation method. The loading efficiencies were ranked in almost inverse proportion with the solubility of the drugs in the external aqueous phase. This study demonstrated the possibility of masking the taste of salts of basic drugs by microencapsulation with AEA using a w/o/w emulsion solvent evaporation method.
The effects of iontophoresis and electroporation on transdermal delivery of buprenorphine from solutions and hydrogels
Authors: Fang Jia-You , Sung K C , Wang Jhi-Joung , Chu Chin-Chen , Chen Kuan-Ting
Published: October 2002

The in-vitro permeation of buprenorphine across skin was investigated to assess the effects of iontophoresis and electroporation on drug permeation from solutions as well as from hydrogels. Iontophoresis (0.3 mA cm−2) increased the buprenorphine permeation from solution by a factor of 14.27 as compared with passive diffusion; the application of electroporation increased the buprenorphine permeation from solutions by a factor of 8.45. The permeation experiments using cellulose membrane and stratum corneum (SC)-stripped skin as permeation barriers suggested that the enhancement with iontophoresis was primarily due to strong electrophoretic drift of buprenorphine molecules, whereas the enhancement seen with electroporation was mainly attributed to the creation of transient aqueous pores in the SC layer. Application of high-voltage pulses followed by iontophoresis resulted in a shorter permeation onset time from both solutions and hydrogels as compared with iontophoresis or electroporation alone. The charge repulsion between buprenorphine and chitosan vehicles as well as the competition effects of counter-ions for carboxymethylcellulose (CMC)-based polymers may account for the different permeation rates under electrical field. This study demonstrates the feasibility of using hydrogels for delivery of buprenorphine under the application of iontophoresis or electroporation, separately or together.
Shed king cobra and cobra skins as model membranes for in-vitro nicotine permeation studies
Authors: Pongjanyakul Thaned , Prakongpan Sompol , Panomsuk Suwannee , Puttipipatkhachorn Satit , Priprem Aroonsri
Published: October 2002

Shed king cobra skin (SKCS) and shed cobra skin (SCS) were investigated for use as barrier membranes, including some pre-hydration factors, for in-vitro nicotine permeation. Inter-specimen variations in nicotine fluxes using shed snake skin were compared with those using human epidermis. Nicotine in the form of 1% w/v aqueous buffer solution at pH 5 and transdermal patches (dose 14 mg day−1) were used. The nicotine fluxes across the shed snake skin were not significantly affected (P > 0.05) by temperature and duration of hydration pre-treatment. Scanning electron micrographs of SKCS and SCS revealed a remarkable difference in surface morphology, but the nicotine fluxes using both shed skins were not significantly different (P > 0.05). When compared with the results obtained using human epidermis, there were similarities in fluxes and permeation profiles of nicotine. Using nicotine solution, the nicotine permeation profiles of all membranes followed zero order kinetics. The amount of nicotine permeated provided good linearity with the square root of time over 24 h (R2 > 0.98) when using nicotine patches. The nicotine fluxes using SKCS and SCS had less inter-specimen variation than those using human epidermis. The results suggest a potential use for SKCS or SCS as barrier membranes for in-vitro nicotine permeation studies.
Inhibition of proteolysis in luminal extracts from the intestine of the brushtail possum
Authors: Wen J-Y , Ledger R , Butt A G , McLeod B J , Davies N M , Tucker I G
Published: October 2002

The proteolytic activity of luminal extracts from five regions (duodenum, jejunum, ileum, caecum and colon) of the brushtail possum intestine towards bovine serum albumin (BSA) and human luteinizing hormone releasing hormone (LHRH) was investigated. There were no significant differences in degradation rates between fresh and previously frozen extracts from any region of the possum intestine. The inhibition of degradation of BSA by luminal extracts from two regions (jejunum and ileum) and of LHRH from four regions (jejunum, ileum, caecum and colon) was evaluated. Soybean trypsin-chymotrypsin inhibitor (SBTI), sodium deoxycholate, Carbopol 934P, bacitracin and bestatin significantly inhibited the degradation of both LHRH and BSA (P < 0.05). SBTI almost totally inhibited the proteolysis of BSA and the peptidolysis of LHRH in extracts from the small intestine. This finding suggests that serine proteases such as chymotrypsin are responsible for the protein and peptide degradation in luminal extracts. It is concluded that including serine protease inhibitors in a formulation may enhance oral delivery of bioactive peptides and proteins to possums.
Ketoprofen-induced intestinal permeability changes studied in side-by-side diffusion cells
Authors: Legen Igor , Kristl Albin
Published: October 2002

It is known that non-steroidal anti-inflammatory drugs (NSAIDs) increase intestinal permeability. Increased intestinal permeability is believed to result from the opening of tight junctions because of NSAID-induced reduction of prostaglandin synthesis and/or energy-depletion. In this study, ketoprofen-induced changes in intestinal permeability were evaluated by measuring tissue electrical parameters, namely tissue electrical resistance (TER), short circuit current (Isc) and transepithelial potential difference (PD), and the transport of a paracellular marker, fluorescein, across rat jejunum in-vitro. Ketoprofen, added to the mucosal side of the tissue, decreased TER and increased fluorescein transport in a concentration-dependent manner. Isc values and the active transport of D-glucose were not affected at ketoprofen concentrations of less than 5 mM. Higher ketoprofen concentrations decreased Isc values and diminished active transport of D-glucose, while transport of fluorescein increased markedly. Similar effects on intestinal properties were observed when the metabolic inhibitor sodium azide was added to the incubation medium. The results of this study suggest that the increased intestinal permeability observed at lower ketoprofen concentrations (< 5 mM) is most probably a consequence of reduced prostaglandin tight junction control, whereas at higher concentrations, ATP depletion caused by ketoprofen seems to be the major mechanism for increased intestinal permeability.
Retine revisited
Authors: Douglas D E
Published: October 2002

Retine, so named by Albert Szent-Györgyi, an inhibitor of the growth of transplanted malignant tumours in animals, is present in all mammalian tissues and in urine. Its inhibitory activity was extensively investigated by Szent-Györgyi, but its exact chemical identity was not determined. Details of the reported physical and chemical properties of retine and its ubiquitous occurrence identify it as being identical to a complex mixture of lipid 2,4-diketones of similar ubiquitous occurrence. This lipid mixture has been extensively studied, and individual members have been synthesized.
Sonolytic Control of Rate of Gold(III) Reduction and Size of Formed Gold Nanoparticles: Relation between Reduction Rates and Sizes of Formed Nanoparticles
Authors: Okitsu Kenji , Yue Akihiko , Tanabe Shuji , Matsumoto Hiroshige , Yobiko Yoshihiro , Yoo Youngeok
Published: October 2002

The sonochemical reduction of gold(III) [tetrachloroaurate(III)] was carried out under various irradiation conditions in an aqueous solution containing only a small amount of 1-propanol. Identical starting materials and the same initial concentrations were used in each preparation. The rates of gold(III) reduction were strongly dependent on the atmosphere, the temperature of the bulk solution, the intensity of the ultrasound, and the distance of the reaction vessel from the oscillator. For example, the rates of reduction under several atmospheres were in the order of CH4 = CO2 < N2 < Ne < He < Ar < Kr, where no reduction proceeded under the CH4 and CO2 atmospheres. It was clearly found that the rates of reduction were influenced by the cavitation phenomenon. Upon irradiation, colloidal gold particles having a surface plasmon absorption were formed, although in the absence of any stabilizers for the gold particles. It was found by TEM observations that the average size of the formed gold particles changed from 30 to 120 nm by selecting the irradiation parameters. The size of the gold particles was closely correlated to the initial rate of gold(III) reduction; the higher the rate of reduction, the smaller the particles. This relationship suggested that the rate of reduction would affect the initial gold nucleation processes. In a 200 kHz standing wave system used in the present study, the strength of the generated shock waves as well as the mechanical effects could be regarded as relatively weak.
Troponin T: role in altering patient management and enabling earlier discharge from a district general hospital
Authors: Owen Avril , Khan Waqas , Griffiths Keith D
Published: October 2002

The use of troponin T to facilitate early patient discharge was investigated in a prospective study in a district general hospital. Troponin T was measured in 91 patients admitted over a period of 6 months with chest pain but without evidence of myocardial infarction. The main outcome measure was length of hospital stay. A negative troponin T was found in 70 patients. Fifty of these were discharged within 24h of the troponin result being available and they had a significantly shorter hospital stay than a case-control group and a historical control group from the previous 6 months. Troponin T measurement has a role in altering patient management by enabling early discharge, resulting in significant cost savings and increasing bed availability.
Fragile X syndrome in Calcutta, India
Authors: Saha Sharmila , Karmakar Parimal , Chatterjee Chandrahas , Banerjee Dalia , Das Shyamal , Dasgupta Uma B
Published: October 2002

Fragile-X-linked mental retardation usually results from amplification of the CGG repeat in the 5' untranslated region of the FMR1 gene. To assess the extent of variation of the CGG repeat in the population from the eastern region of India we studied 98 mentally retarded individuals living in and around Calcutta and identified 21 distinct alleles ranging in size from 8 to 44 CGG repeats. A repeat size of 28 was the most frequent; this value is different from the most frequent repeat size found in other studies, indicating a racial or ethnic variation. Patients with the clinical features of the syndrome have been found to carry expanded CGG repeats. Thus, it can be inferred that the expansion of CGG repeats may be a frequent cause of the syndrome in our population.
Multiple sclerosis: use of light-chain typing to assist diagnosis
Authors: Jenkins Margaret A , Cheng Louisa , Ratnaike Sujiva
Published: October 2002

Although the presence of oligoclonal IgG with abnormal ratio in multiple sclerosis (MS) has been known for many years, this finding has not been put to diagnostic use in most routine clinical laboratories. In a retrospective study we report differences in the oligoclonal banding patterns between multiple sclerosis and non-MS patients. We had sufficient cerebrospinal fluid (CSF) on 36 from 71 patients with oligoclonal bands for immunofixation for κ and λ light chains, and for free κ and free λ. Thirteen out of 14 patients with clinically confirmed MS had predominantly IgG (κ) banding. In contrast, in seven out of eight patients with diagnoses other than MS the IgG was linked to both κ and λ light chains in approximately equal proportions. Nine out of 14 patients with probable/possible/ suspected MS showed predominantly IgG (κ) banding; five others in this group had both IgG (κ) and IgG (λ) and free λ light chains. The finding of IgG (κ) bands in CSF samples with oligoclonal bands supports a diagnosis of MS.
A falling HbA1c is not necessarily an indicator of improving diabetes control
Authors: Wiener K
Published: October 2002

The finding of a very low haemoglobin A1c(HbA1c)(1·4%) in a diabetic patient with fairly high plasma glucose levels prompted haematological investigations, which revealed auto-immune haemolysis and a Hb concentration of 7·7g/L. Following treatment, both Hb and HbA1c concentrations increased roughly in parallel until, 4 months later, Hb was 13·8g/L, HbA1c 5·2% and plasma glucose was 6·8mmol/L. This case illustrates that a falling HbA1c cannot always be attributed to improving glucose control in diabetic patients.
Herbal remedy poisoning presenting with acute abdomen and raised urine porphyrins
Authors: Anderson N R , Gama R , Kapadia S
Published: October 2002

We describe a case of lead poisoning due to herbal remedies, presenting with an acute abdomen, raised porphyrins and increased liver enzyme activities. We suggest that lead poisoning should be considered in the differential diagnosis of the 'acute abdomen', and that the presence of liver dysfunction points to the possibility of Asian herbal remedies as the source of the lead poisoning.
Determination of D-sorbitol in human erythrocytes by an enzymatic fluorometric method with an improved deproteinization procedure
Authors: Umeda Mamoru , Otsuka Yoko , Li Toshihiro , Matsuura Tsuneaki , Shibati Hideaki , Ota Hatsunori , Sakurabayashi Ikunosuke
Published: October 2002

We developed an improved enzymatic assay of D-sorbitol in human erythrocytes by employing highly specific D-sorbitol dehydrogenase from Pseudomonas sp. (EC 1.1.1.14) and replacing perchloric acid (HClO 4) and potassium carbonate (K2CO3), generally used for deproteinization, with sodium hydroxide (NaOH) and zinc sulphate (ZnSO4). In this assay, erythrocytes were separated from plasma by centrifugation and washed once with physiological saline. Subsequently, the erythrocytes were lysed with distilled water and proteins precipitated with NaOH and ZnSO4. After centrifugation, the resulting colourless supernatant was mixed with a glycine buffer (pH 9·0) containing NAD+ and D-sorbitol dehydrogenase. After incubation for 30 min at 37°C, the NADH produced was measured fluorimetrically. The fluorescence intensities were corrected for sample blanks, and the values of D-sorbitol were normalized for haemoglobin content.

The method had an analytical range of 1-180 µmol/L. The intra- and inter-assay precisions were < 3·3% and < 5·8%, respectively. The detection limit was 0·65 µmol/L. In terms of the linearity, precision and sensitivity, the improved method using NaOH and ZnSO4 was superior to the conventional method using HClO4 and K2CO23.
Audit of investigation of subclinical hypothyroidism in Scottish laboratories
Authors: Berry Peter
Published: October 2002

Background An audit of thyroid function testing in the investigation of subclinical hypothyroidism in Scotland was performed. Methods The audit looked at the tests used and the strategies employed by 18 out of a total of 25 Scottish laboratories and found significant differences between them. It also looked at the comments and advice given by 59 clinical scientists and chemical pathologists in the interpretation of results from patients with subclinical hypothyroidism. These comments were compared with standards derived from guidelines in current literature. Results The advice given was generally accurate and helpful but the audit showed a marked variation in interpretative comments. Conclusions This variation may reflect the lack of emphasis that has been placed on standardizing the interpretive function of laboratories and underlines the need for liaison both within and between laboratories to achieve better agreement on the interpretation of laboratory tests. The audit also showed that the importance of thyroid peroxidase antibody estimation in subclinical hypothyroidism needs to be emphasized.
Is a 0900-h serum cortisol useful prior to a short Synacthen test in outpatient assessment?
Authors: le Roux CW , Meeran K , Alaghband-Zadeh J
Published: October 2002

Background: The short synacthen test (SST) is the gold standard investigation for the evaluation of adrenal insufficiency and is also frequently used for the evaluation of the hypothalamic-pituitary-adrenal (HPA) axis. The 0900-h serum cortisol concentration has also been evaluated as an indication of cortisol reserve, and a result >450 nmol/L is highly suggestive of a normal serum cortisol response to the insulin tolerance test, while no patient with a 0900-h serum cortisol <100nmol/L had a sufficient response. The aim of this study was to determine if the number of inappropriate SSTs could be reduced if a 0900-h serum total cortisol was done prior to the dynamic function test. Method: Two hundred and ten SSTs were performed at 0900 h and the response at 30 min evaluated. Results: Of the 210 SST, 151 (71%) demonstrated a maximum response at 30 min of serum cortisol >550 nmol/L. All the patients with a 0900-h serum cortisol >500 nmol/L had an adequate response (>550 nmol/L), while no patient with a 0900-h serum cortisol of <100 nmol/L had an adequate SST response. Twenty one per cent of patients were shown to have had an unnecessary invasive procedure. Conclusion: We conclude that the SST is of little added value in patients with a 0900-h serum cortisol of less than 100 nmol/L or more than 500 nmol/L and it should be included in the appropriate protocols for endocrine investigation.
Cardiovascular disease and osteoporosis: is there a link between lipids and bone?
Authors: Burnett John R , Vasikaran Samuel D
Published: October 2002

Atherosclerotic heart disease and osteoporosis are both diseases of old age. Evidence is accumulating for a link between vascular and bone disease. Calcification is a common feature of atherosclerotic plaques, and osteoporosis is associated with both atherosclerosis and vascular calcification. However, the relationship of vascular calcification to the pathogenesis of atherosclerosis remains incompletely understood. Hormone replacement therapy has beneficial effects in the prevention of both atherosclerosis and osteoporosis. Bisphosphonates inhibit bone resorption and are used in the treatment of osteoporosis, whereas the statins inhibit cholesterol biosynthesis and are used for the treatment of atherosclerosis. We have reviewed recent advances in the knowledge of the actions of bisphosphonates and statins at the cellular, molecular and end-organ levels in order to examine the relationship between cardiovascular disease and osteoporosis and to explore the link between lipids and bones. These studies suggest that the mechanism of actions of these two classes of drugs at the cellular level may not be mutually exclusive. There are some early clinical data to complement these findings, suggesting that statins increase bone density and bisphosphonates may have a beneficial effect in vivo on plasma lipid levels and on the atherosclerotic process. Properly designed prospective studies that examine the effect of statins on bone density and fractures, as well as the effects of bisphosphonates on lipid profiles, atherosclerotic progression and cardiovascular morbidity and mortality are needed to define clearly the clinical effects and potential new roles for these agents.
Analysis of serum angiotensin-converting enzyme
Authors: Muller BR
Published: October 2002

Serum angiotensin-converting enzyme (SACE) levels are influenced by genetic polymorphism. Interpretation of serum levels with the appropriate genotypic reference range improves the diagnostic sensitivity of the assay for sarcoidosis. SACE assays are performed by a large number of routine clinical laboratories. However, there is no external quality assessment (EQA) for SACE other than an informal regional scheme. This showed analytical performance of SACE assays to be poor, with a diversity of reference ranges, leading to widely disparate clinical classification of EQA samples. Genetic polymorphism combined with poor analytical performance suggest that perhaps SACE assays should revert to being the province of specialized laboratories.