bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined antipsychotics for ‘difficult-to-manage’ and forensic
patients with schizophrenia: reasons for prescribing and perceived
benefits
Authors: Haw Camilla , Stubbs Jean 
Published: December 2003

Aims and MethodWe aimed to examine reasons for initiating and continuing the
prescription of combined antipsychotics. A structured interview was
carried out with the responsible medical officers for 40
‘difficult-to-manage’ tertiary referral patients with schizophrenia who
were regularly treated with two or more antipsychotics.ResultsLack of efficacy of monotherapy was the main reason for initiating and
continuing combined antipsychotics. Other reasons for continuing combined
antipsychotics included not wishing to change medication as the patient
was reasonably well, and safety considerations. Perceived benefits of
combined antipsychotics included fewer positive symptoms and less
disturbed behaviour.Clinical Implications‘Difficult-to-manage’ and forensic treatment-resistant patients with
schizophrenia pose a particular therapeutic challenge. Use of combined
antipsychotics, although not evidence-based, is perceived by some
psychiatrists as beneficial when other options have failed.
Ethnic diversity and equality of access to specialist
therapeutic community treatment for severe personality
disorder
Authors: Geraghty Rosalind , Warren Fiona 
Published: December 2003

Aims and MethodAll mental health services are expected to aim for equality of access to
people from minority ethnic groups. Psychotherapy services typically have
a low proportion of ethnic minority clients. Specialist services such as
therapeutic communities are no exception. It is also possible that ethnic
minority residents are more likely to leave group treatments early if
they are clearly in the minority. The study examined records between
1996–2000 to ascertain whether ethnic minorities show a different pattern
of exit from the process than people from other backgrounds.ResultsJust over 9% of referrals to Henderson Hospital were from ethnic
minorities. Ethnic minority referrals were less likely to be invited to a
selection interview. However, there was no difference in length of stay
in treatment. There was a trend towards ethnic minority referrals having
more severe symptomatology and histories than those from White
backgrounds.Clinical ImplicationsEthnic background should be taken into account when considering referral
for specialist psychotherapy. Routine monitoring of the processing of
ethnic minority referrals should be conducted in all psychotherapy
services.
A standard liaison psychiatry service structure?
Authors: Ruddy Rachel , House Allan 
Published: December 2003

Aims and MethodWe surveyed all psychiatric services in the six northeast strategic health authorities to determine how the provision of liaison psychiatry services related to College recommendations and the size of the general hospital trusts served.ResultsThirty-six (100%) services provided usable data, 8% of general hospital trusts had no liaison psychiatry service, 41% of teams were not multidisciplinary with their only staff being nurses, only 38% of services had dedicated consultant psychiatry time and only a quarter met the recommended minimum standard of 0.5 whole-time equivalents. No teams contained clinical psychologists. Disorder-specific out-patient clinic provision was idiosyncratic.Clinical ImplicationsThere is a lack of rational planning of liaison psychiatry services and as a result, many services are not needs-based and do not comply with College recommendations. One indication of this is the lack of multidisciplinary teams.
Effects of the rate and composition of fluid replacement on the pharmacokinetics and pharmacodynamics of intravenous torasemide
Authors: Kim Yu Chul , Lee Myung Gull , Ko Seong-Hee , Kim So Hee 
Published: December 2003

Abstract
The effects of differences in the rate and composition of intravenous fluid replacement for urine loss on the pharmacokinetics and pharmacodynamics of torasemide were evaluated in rabbits. Each rabbit received 2-h constant intravenous infusion of 1 mg kg−1 torasemide with 0% replacement (treatment 1, n = 6), 50% replacement (treatment 2, n = 9), 100% replacement with lactated Ringer's solution (treatment 3, n = 8), and 100% replacement with 5% dextrose in water (treatment 4, n = 6). Total body (4.53, 5.72, 10.0 and 4.45 mL min−1 kg−1 for treatments 1–4, respectively) and renal clearance (1.44, 1.87, 6.78 and 1.72 mL min−1 kg−1) of torasemide, and total amount of unchanged torasemide excreted in 8-h urine (Ae 0–8 h: 694, 780, 1310 and 1040 μg) in treatment 3 were considerably faster and greater compared with treatments 1, 2 and 4. Although the difference in Ae 0–8 h between treatments 1 and 3 was only 88.8%, the diuretic and/or natriuretic effects of torasemide were markedly different among the four treatments. For example, the mean 8-h urine output was 101, 185, 808 and 589 mL for treatments 1–4, respectively, and the corresponding values for sodium excretion were 10.1, 20.6, 89.2 and 29.9 mmol, and for chloride excretion were 14.5, 27.9, 94.0 and 37.2 mmol. Although full fluid replacement was used in both treatments 3 and 4, the 8-h diuretic, natriuretic and chloruretic effects in treatment 3 were significantly greater compared with treatment 4, indicating the importance of the composition of fluid replacement. Both treatments 1 and 4 received no sodium replacement, however, the 8-h diuretic, natriuretic and chloruretic effects were significantly greater in treatment 4 compared with treatment 1, indicating the importance of rate of fluid replacement for the diuretic effects. Therefore, the 8-h diuretic, natriuretic and chloruretic effects were significantly greater in treatment 3 compared with treatments 1, 2 and 4, indicating the importance of full fluid and electrolyte replacement. Some implications for the bioequivalence evaluation of dosage forms of torasemide are discussed.
Ampicillin micronization by supercritical assisted atomization
Authors: Reverchon E , Porta G Della , Spada A 
Published: December 2003

Abstract
The micronization technique called supercritical assisted atomization (SAA) was used to produce ampicillin microparticles with controlled particle size and particle size distribution suitable for aerosol drug delivery. The process is based on the solubilization of supercritical CO2 in a liquid solution. The ternary mixture is then sprayed through a nozzle and, as a consequence of enhanced atomization, solid microparticles are formed. Water and organic solvents were tested with ampicillin to determine the influence of the solvent on the process mechanism. SAA process parameters were studied by testing different supercritical/liquid solvent flow ratios, ampicillin concentrations in the liquid solution and nozzle diameters. The effect of these parameters on morphology, particle size and particle size distribution of microparticles was analysed. Ampicillin particles suitable for aerosol delivery in the size range 1–5 μm were obtained using buffered water. Moreover, by varying the solute concentration, ampicillin particles in a narrower range (1–3 μm) than that usually suggested for aerosol deliverable drugs were obtained. This is an example of particle size tailoring by SAA.
Potential utility of various protease inhibitors for improving the intestinal absorption of insulin in rats
Authors: Liu Hui , Tang Ren , Pan Wei-San , Zhang Yi , Liu Hong 
Published: December 2003

Abstract
The aim of the investigation was to study the effects of protease inhibitors on the absorption of insulin in-situ from closed small and large intestinal loops in rats and to investigate the mechanism of various protease inhibitors in different intestinal loops. The intestinal absorption of insulin was evaluated by its hypoglycaemic effect and serum insulin level in the presence or absence of luminal contents. No marked hypoglycaemic effect was observed after administration of insulin alone in either region in the presence or absence of luminal contents. A significant hypoglycaemic effect of insulin was obtained in the large intestinal loop in the presence or absence of luminal contents when insulin was co-administered with bacitracin (20, 30 mM), sodium glycocholate (20, 40 mM), bestatin (29 mM), leupeptin (21 mM) and cystatin (0.8 mM). In contrast, there was no hypoglycaemic effect in the small intestinal loop in the presence of luminal contents following small intestinal co-administration of insulin with these protease inhibitors. The effectiveness of protease inhibitors was susceptible to their categories, concentrations and activity of proteolytic enzymes in different regions. The degree of improving insulin absorption in intestine was in the order of leupeptin &gt; sodium glycocholate &gt; bacitracin &gt; bestatin &gt; cystatin. At the same time, the percutaneous enhancement effect was observed in the presence of either sodium glycocholate or bacitracin. These results suggest that protease inhibitors could increase the insulin efficacy more effectively in the large intestine than in the small intestine.
The in-vivo effects of sho-saiko-to, a traditional Chinese herbal medicine, on two cytochrome P450 enzymes (1A2 and 3A) and xanthine oxidase in man
Authors: Saruwatari Junji , Nakagawa Kazuko , Shindo Junichi , Nachi Shinobu , Echizen Hirotoshi , Ishizaki Takashi 
Published: December 2003

Abstract
The Chinese herbal medicine sho-saiko-to is a mixture of seven herbal components (Bupleurum root, Pinellia tuber, Scutellaria root, Jujube fruit, Ginseng root, Glycyrrhiza root and Ginger rhizome) that is widely administered to patients with chronic hepatitis in Japan. We assessed the effects of sho-saiko-to on the activity of cytochrome P450 (CYP) 1A2, CYP3A and xanthine oxidase (XO) in man. Twenty-six healthy subjects were studied to evaluate their baseline activity of CYP1A2 and XO by the respective urinary metabolic ratios of an 8-h urine sample after an oral 150-mg dose of caffeine and of CYP3A by a urinary excretion ratio of 6β-hydroxycortisol (6β-HC) to free cortisol (FC). Thereafter, the subjects received a twice-daily 2.5-g dose of sho-saiko-to for five days, and underwent the caffeine test on day 1 and day 5. The mean activity of CYP1A2 decreased by 16% on both day 1 and day 5 compared with the baseline (P = 0.001). The mean activity of XO also significantly decreased by 25% on day 1 and 20% on day 5 (P &lt; 0.0001) compared with the baseline value. The activity of CYP3A tended to be lower on day 5 than the baseline (P = 0.146). It is concluded that sho-saiko-to reduces CYP1A2 and XO activity in man.
Effects of oxygen plasma treatment on the surface wettability and dissolution of furosemide compacts
Authors: Naseem A , Olliff C J , Martini L G , Lloyd A W 
Published: December 2003

Abstract
The plasma irradiation of furosemide (frusemide) was investigated as a possible technique for increasing the dissolution rate of this drug. Oxygen plasma was used to generate oxygen-containing functional groups on the surface of the compact to increase the wettability of the surface and the dissolution rate of the drug. Compacts of furosemide (300 mg) were produced using a stainless steel die and punch assembly, which was placed into a KBr press. The time of the plasma treatment was varied to assess the effect if any upon the dissolution rate and the wettability of the drug. Dissolution experiments of the plasma-treated and untreated compacts were carried out using the paddle apparatus method. Dissolution was carried out at 37°C using 1 L of 0.1 M HCl and phosphate buffer (pH 6). The wettability was assessed by contact angle measurements using the sessile drop technique. Untreated and plasma-treated samples were analysed by scanning electron microscopy at × 5000 magnification. Plasma treatment was found to lower the equilibrium contact angle from approximately 50 to 35° but the dissolution rate was not significantly affected. This was attributed to fusion of the surface by the plasma treatment.
Non-genomic effects of tamoxifen on the activation of membrane-bound guanylate cyclase GC-A
Authors: Chen Zi-Jiang , Vetter Michael , Chang Geen-Dong , Liu Shiguo , Ding Yaxian , Chang Chung-Ho 
Published: December 2003

Abstract
Oestrogen is known to exert both genomic and non-genomic effects on target tissues. Unlike the genomic effects, the identity of receptors mediating the non-genomic effects of oestrogen remains controversial. 17β-Estradiol has been shown to activate membrane-bound guanylate cyclase GC-A in PC12 cells in a non-genomic manner. To examine whether 17β-estradiol exerts a similar effect in other cell types, we measured the effect of 17β-estradiol and tamoxifen, an anti-oestrogen, on guanylate cyclase activity in porcine kidney proximal tubular LLC-PK1 cells. 17β-Estradiol increased cGMP levels in LLC-PK1 cells. Interestingly, addition of tamoxifen also increased cGMP levels in a concentration-dependent manner in LLC-PK1 cells. The effects of both 17β-estradiol and tamoxifen on guanylate cyclase activity were not additive, suggesting that oestrogen and tamoxifen activate the same enzyme. Similar phenomena were also observed in LLC-PK1 cell membrane preparation. LLC-PK1 cells do not express membrane-bound guanylate cyclase GC-B and express low levels of membrane-bound guanylate cyclase GC-C. Tamoxifen inhibited the activation of GC-A by atrial natriuretic factor (ANF). However, it did not affect membrane-bound guanylate cyclase GC-C stimulated by guanylin or Escherichia coli heat-stable toxin STa. These results indicate that 17β-estradiol and tamoxifen activate GC-A in LLC-PK1 cells. Thus, tamoxifen functions as an agonist rather than an antagonist for the membrane oestrogen receptor coupled to the activation of GC-A.
Long-term administration of Salvia miltiorrhiza ameliorates carbon tetrachloride-induced hepatic fibrosis in rats
Authors: Lee Tzung-Yan , Wang Guei-Jane , Chiu Jen-Hwey , Lin Han-Chieh 
Published: December 2003

Abstract
Carbon tetrachloride (CCl4) is metabolized by cytochrome P450 to form a reactive trichloromethyl radical that triggers a chain of lipid peroxidation. These changes lead to cell injury, and chronic liver injury leads to excessive deposition of collagen in liver, resulting in liver fibrosis. The aim of this study was to evaluate the effects of long-term Salvia miltiorrhiza administration in CCl4-induced hepatic injury in rats. Salvia miltiorrhiza (10, 25 or 50 mg kg−1 twice a day) was given for 9 weeks, beginning at the same time as the injections of CCl4. Rats receiving CCl4 alone showed a decreased hepatic glutathione level and an increased glutathione-S-transferase content. The hepatic thiobarbituratic acid-reactive substance levels were increased. CCl4 also caused a prominent collagen deposition in liver histology that was further supported by the increased hepatic mRNA expression of transforming growth factor-β1, tissue inhibitor of metallproteinase-1 and procollagen I. Salvia miltiorrhiza administration led to a dose-dependent increase in hepatic glutathione levels and a decrease in peroxidation products. Additionally, it reduced the mRNA expression of markers for hepatic fibrogenesis. In conclusion, long-term administration of Salvia miltiorrhiza in rats ameliorated the CCl4-induced hepatic injury that probably related to a reduced oxidant stress and degree of hepatic fibrosis.
Evaluation of the bitterness of antibiotics using a taste sensor
Authors: Uchida Takahiro , Tanigake Atsu , Miyanaga Yohko , Matsuyama Kenji , Kunitomo Masaru , Kobayashi Yoshikazu , Ikezaki Hidekazu , Taniguchi Akira 
Published: December 2003

Abstract
The bitterness of nine commercial antibiotics (clarithromycin, erythromycin, cefdinil, doxycycline, vancomycin, tetracycline, minocycline, oxytetracycline and bacampicillin) was evaluated in human gustatory sensation tests with nine volunteers. The bitterness of 0.1–0.3 mM solutions (or suspensions in the case of clarithromycin) of the antibiotics was then measured using an artificial multichannel taste sensor. In the sensor measurements, three variables were used to predict estimated bitterness in single and multiple regression analysis and principal component analysis: sensor output as relative value (R), the change of membrane potential caused by adsorption (C) and C/R. Particularly good correlation was obtained between obtained bitterness scores and predicted scores using C from channel 2 of the sensor (r2 = 0.870, P &lt; 0.005) and C/R values for channels 2 and 3 (r2 = 0.947, P &lt; 0.005). The taste sensor was also successful in assessing the bitterness intensity of clarithromycin powder suspensions of various concentrations. Clarithromycin has a low aqueous solubility but is the most bitter of the nine antibiotics. Sensory data from channel 3 of the sensor predicted the bitterness of clarithromycin powder suspensions and their filtered solutions well. Finally, the bitterness intensity of a commercial clarithromycin dry syrup product (Clarith dry syrup, Taisho Pharmaceutical Co. Ltd, Tokyo, Japan) was evaluated in gustatory sensation tests and using the taste sensor. In Clarith dry syrup the drug is coated with aminoalkyl methacrylate polymer using a spray congealing method. The taste sensor results confirmed that the polymer was successful in almost completely masking the bitter taste of the dry syrup product.
Persistent reversal of P-glycoprotein-mediated daunorubicin resistance by tetrandrine in multidrug-resistant human T lymphoblastoid leukemia MOLT-4 cells
Authors: Liu Zhen-Li , Hirano Toshihiko , Tanaka Sachiko , Onda Kenji , Oka Kitaro 
Published: December 2003

Abstract
Multidrug resistance (MDR) represents a major problem in cancer chemotherapy. P-glycoprotein (P-gp), the drug efflux pump that mediates this resistance, can be inhibited by compounds with a variety of pharmacological functions, thus circumventing the MDR phenotype. The present study was performed to evaluate a unique MDR-reversal feature of a bisbenzylisoquinoline alkaloid tetrandrine (TET) in a P-gp expressing MOLT-4 MDR line (MOLT-4/DNR) established in our laboratory. Cell viability was determined by an MTT assay. P-gp function was characterized by determining the Rh123 accumulation/efflux capacity. P-gp overexpression in resistant MOLT-4/DNR cells was confirmed by flow cytometry analysis after staining with phycoerythrin-conjugated anti-P-gp monoclonal antibody 17F9. Compared to ciclosporin A (CsA), TET exhibited stronger activity to reverse drug resistance to daunorubicin (DNR), vinblastine (VLB) and doxorubicin (DOX) in MOLT-4/DNR cells. TET showed no cytotoxic effects on parental MOLT-4 cells lacking P-gp expression or on the resistant MOLT-4/DNR cells. TET modulated DNR cytotoxicity even after it was washed with the medium for 24 h, while CsA almost completely lost its reversal capability 24 h after washing. TET and CsA similarly increased the accumulation of Rh123 in resistant MOLT-4/DNR cells. However, TET inhibited Rh123 efflux from resistant cells even after washing with the medium, while CsA rapidly lost its ability to inhibit Rh123 efflux after washing. The current study suggests that TET enhances the cytotoxicity of anticancer drugs in the P-gp expressing MDR cell line by modulating P-gp in a different manner to the well-known P-gp inhibitor CsA.
Repetitive administration of Shaoyao-Gancao-tang to rats restores the bioavailability of glycyrrhizin reduced by antibiotic treatment
Authors: He Ju-Xiu , Akao Teruaki , Tani Tadato 
Published: December 2003

Abstract
Shaoyao-Gancao-tang (SGT), a traditional Chinese formulation, is often used together with antibiotics such as amoxicillin and metronidazole (AMPC-MET) for the treatment of peptic ulcers in Japan. However, the bioavailability of glycyrrhizin (GL) in SGT is severely reduced by a single administration of AMPC-MET, and the reducing effect continues for 12 days. GL is one of the major pharmacologically important glycosides in SGT and is transformed into the active metabolite 18β-glycyrrhetic acid (GA) by intestinal bacteria in the gut, followed by absorption of the latter into the blood. In order to reduce the negative effect of AMPC-MET on the bioavailability of GL, the optimum scheduling of the medications was examined. We found that the reduction in the plasma GA concentration and the GL-metabolizing activity in faeces caused by a single dose of AMPC-MET could be sharply attenuated by the repetitive administration of SGT for 4 days. The GA concentration and the GL-metabolizing activity were strongly enhanced by further continuous administration of SGT. These findings suggest that repetitive administration of SGT starting 1 or 2 days after the administration of AMPC-MET speeds the recovery of the bioavailability of GL in SGT. Similar strategies for administering medications may also be useful for combination therapy of antibiotics with other traditional Chinese formulations containing bioactive glycosides.
Magnetic resonance imaging study of the transport phenomena of solvent into the gel layer of hypromellose matrices containing tetracycline hydrochloride
Authors: Tritt-Goc Jadwiga , Kowalczuk Joanna , Pislewski Narcyz 
Published: December 2003

Abstract
Magnetic resonance imaging was used to study the diffusion of a water solution of hydrochloric acid into hypromellose (hydroxypropylmethylcellulose) matrices. Spatially resolved information was obtained about the self-diffusion coefficient and spin–spin relaxation time of solvent protons in the gel layer of hypromellose matrices loaded with different amounts of tetracycline hydrochloride. The data showed the influence of the drug concentration on the diffusion and spin–spin relaxation. Higher drug concentrations in the hypromellose matrix led to greater swelling of the matrix and faster diffusion of the water molecules inside the gel layer of the polymer. The observed differences between the radial and axial diffusion were interpreted in terms of the stresses imposed in the axial direction during the compression of the samples. The spin–spin and diffusion profiles indicated that the diffusion of a water solution of hydrochloric acid into hypromellose, pure and loaded with different amounts of tetracycline hydrochloride, was characterized as a Case II mechanism.
Significance of measured elevation of skin temperature induced by calcitonin gene-related peptide in anaesthetized rats
Authors: Noguchi Masamichi , Ikarashi Yasushi , Yuzurihara Mitsutoshi , Kase Yoshio , Takeda Shuichi , Aburada Masaki 
Published: December 2003

Abstract
To assess whether peripheral changes related to skin temperature rise were induced by ovarian hormone deficiency, we investigated the effects of anaesthesia on calcitonin gene-related peptide (CGRP)- or luteinizing hormone-releasing hormone (LH-RH)-induced elevation of skin temperature in female rats. CGRP was used as an inducer of peripherally-mediated elevation of skin temperature, whereas LH-RH was used as an inducer of centrally-mediated elevation of skin temperature. Intravenous (i.v.) but not intracerebroventricular injection of CGRP (10 μg kg−1) or intracerebroventricular but not intravenous injection of LH-RH (10 μg/rat) elevated the skin temperature of unanaesthetized rats restrained in a Ballman's cage. The elevation with LH-RH was completely inhibited by urethane anaesthesia, whereas the elevation with CGRP was not. These results suggested that changes in skin temperature measured under anaesthesia reflected a peripherally rather than a centrally mediated mechanism. The CGRP (1.0–30 μg kg−1, i.v.)-induced elevation of skin temperature was potentiated in ovariectomized rats and inhibited by pretreatment with a CGRP receptor antagonist CGRP8–37 (1000 μg kg−1, i.v.), suggesting that the potentiation may participate in peripheral factors such as a postsynaptic hypersensitivity to CGRP following ovarian hormone deficiency. Thus, measurement of skin temperature in the anaesthetized rat was a useful procedure to seek the peripheral mechanism of potentiation of skin temperature induced by CGRP, thought to be closely related to menopausal hot flashes.