Candida dubliniensis infection, Singapore.
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Amphotericin B↗
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[Treatment of acute optic neuritis with high dose of prednisone].
OBJECTIVE: The benefit of glucocorticoid for the treatment of acute optic neuritis remains controversial. The efficacy of oral prednisone in 12 patients (14 eyes) with acute optic neuritis was reviewed. METHODS: The time of visual symptoms before treatment was 3-15 days. The visual acuities were worse than 0.1 in all patients, with positive relative afferent pupillary defect. Visual field defect and delay latency of P100 in pattern VEP were also found. The regimen of glucocorticoid therapy was oral prednisone, starting with 160 mg daily followed by reducing the dosage by 20 mg every three days until 40 mg per day was attained and then tapering the dosage at 70 mg every other day until stoppage of the drug. The treatment was 3-11 months and 9 patients were followed up more than one year. RESULTS: The visual acuities improved rapidly and stable. After 4 days, the visual acuity was 0.2 or better in 10 eyes. It was better than 0.6 in 12 eyes at 15 days. At 6 months, all had the visual acuity better than 0.7, with 85.7% equal or better than 1.0. CONCLUSIONS: The regimen of oral prednisone beginning with 160 mg followed by tapering for three months would be feasible. Pattern VEP was a sensitive and credible sign for evaluating the extent of demyelination.
Acute Disease↗
[Practicability study on a group of vigilant chemical compounds including chlorheridine diacetate].
OBJECTIVES: To test in vitro the spermatozocidine drug which can also prevent sex transmitting diseases (STD) pathogens. METHODS: Chlorheridine diacetate and other three chemical compounds were applied in vitro spermatozocidine and sperm inhibitting tests. RESULTS: The lowest concentrations of chlorheridine diacetate and p-nitrophenol which can inhibit human sperm in 20 seconds were 1.25 mg/ml. The minimal inhibitory concentration and minimal bactericidal concentration of chlorheridine diacetate and p-nitrophenol on Streptococcus albus Stemberg were 0.125 to 0.50 mg/ml and 0.25 to 1.00 mg/ml. CONCLUSIONS: Chlorheridine diacetate and p-uitrophenol have strong spermatozocidine and antibacteria effects.
Acetates↗
[Nosocomial fungal infections, analysis of 149 cases].
OBJECTIVE: To investigate the manifestation, diagnosis, antifungal therapy and outcome of nosocomial fungal infections. METHODS: The clinical data of 149 patients with nosocomial fungal infections admitted in the PUMC hospital from Dec. 1981 to Nov. 2001, 67 males and 82 females with an average age of 52.32 years, including the manifestation, diagnosis, treatment and outcome, were reviewed retrospectively. RESULTS: 134 out of the 149 patients suffered from deep mycoses. All cases had underlying conditions, including primary pulmonary diseases (n = 29), rheumatic disease (n = 20), hematological disease such as leukemia or lymphoma (n = 18), HIV infection/AIDS (n = 13), major surgery (n = 10), and intracerebral hemorrhage or cerebral infarction (n = 24). The predisposing factors or risk factors for deep mycoses included use of high dose broad-spectrum antibiotics over a long period (n = 37), steroids/cytotoxic chemotherapy (n = 29), immunosuppressant (n = 17), chemotherapy (n = 10), intravenous lines and incubation (n = 36), and tracheotomy or endotracheal intubation (n = 12). The infectious sites were lung, meninges, cerebral parenchyma, blood, etc. in the order of prevalence. Depending on infectious site and type of fungus, the clinical manifestations included fever (63.76%), respiratory symptom such as cough (37.58%), leucocytosis (39.6%), chest X-ray images (24.49%) etc. CNS fungal infection included meningitis, brain abscess, and granuloma. Meningitis due to Cryptococcus resembled that due to Mycobacterium tuberculosis. The main pathogenic fungal species were Candida albicans, C. tropicalis, C. parapsilosis, C. neoformans, and Aspergillus species. Amphotericin B, fluconazole, and flucytosine were used alone or in combination. The overall mortality rate was 29.53% (44/149). Out of the 149 patients 67 were cured, 29 made improvement. The incidence of fungal infection remarkably increased recently with 75 cases appearing in the past 5 years (50.34%). CONCLUSION: The incidence of fungal infection is increasing recently which is correlated with use of high dose broad-spectrum antibiotics over a long period, high dose steroids/cytotoxic chemotherapy, immunosuppressant, chemotherapy, and improvement of examination skills, etc. The main pathogens are still Candida albicans and non-albicans Candida species. Early diagnosis is very important.
Adolescent↗
Phenylpropanosids, lignans and other constituents from Cremanthodium ellisii.
Together with twenty-six known compounds, a new phenylpropanosid, named cremanthodioside, was isolated from the whole plant of Cremanthodium ellisii Kitam. Their structures were elucidated by spectroscopic methods MS, IR, UV, NMR, including 2D NMR techniques, and by chemical methods. The anti-bacterial activity of compounds 1-6 and the anti-tumor activity of compound 1 were tested.
Acetylation↗
[Exploring relationship between traditional effects of traditional Chinese medicine and modern pharmacological activities by "co-effect compounds"].
The compound that distributes in the herbs with one common effect was named as "co-effect compound" (CEC). The CECs of three traditional Chinese medicine(TCM) effects, purgative, relieving pain and clearing heat, had been found and studied. A strong corresponding relationship was found between the pharmacological activities of CECs and the TCM effect they belong to. The study shows that it may be a feasible method to connect traditional effect of TCM with modem pharmacological activity.
Anthraquinones↗
[Generalized erythema triggered by a rapid decrease of basophils in chronic myeloid leukemia treated with imatinib].
A 57-year-old woman with chronic myeloid leukemia showing severe basophilia (WBC 17.1 X 10(9)/L, basophils 23%) was treated with 400mg imatinib in June 2003. A high basophil count (WBC 10.6 X 10(9)/L, basophils 31%) was still observed after 1 week of therapy. After 9 days of therapy, she developed generalized pruritic skin erythema, chills and high fever. After terminating imatinib treatment, prednisolone therapy was initiated. The rash quickly disappeared. Four days after withdrawal of imatinib, leukocyte count was 13.0 X 10(9)/L with 3% of basophils, suggesting the possibility that rapid decrease in basophils following imatinib therapy may induce severe cutaneous reactions.
Antineoplastic Agents↗
C-peptide and insulin secretion in diabetes mellitus treated with oral hypoglycaemic agents or diet alone. A 3 years epidemiological cohort study on the Island of Falster, Denmark.
In a 3 yr epidemiological cohort study of 273 diabetics treated with oral hypoglycaemic agents (OHA) and 60 diet-treated diabetics the predictive value of fasting plasma C-peptide levels was assessed with the attempt to discriminate between insulin dependence and non-insulin dependence. Serum insulin, blood glucose, haemoglobin AI, bicarbonate, urine for ketone bodies, height and weight were measured too. All but 8 OHA-treated patients (97%) had fasting C-peptide greater than 0.40 pmol/ml at both investigations. Six had C-peptide in the interval 0.21-0.40 pmol/ml at both investigations and 2 a C-peptide less than or equal to 0.20 pmol/ml all of which became insulin dependent during the 3 yr period. The highest fasting C-peptide concentrations were found in overweight diabetics with a blood glucose level greater than 8.5 mmol/l. Overweight diabetics had significantly elevated fasting insulin compared to the normal weights but when the IRI concentrations were corrected by the body mass index hyperinsulinaemia was positively correlated with high levels of blood glucose and haemoglobin AI, i.e. poor glycaemic control and not with overweight. The results suggest that determination of fasting plasma C-peptide can be an additional clinical help in discriminating between insulin dependence and non-dependence.
Adult↗
Between-country variation in the utilization of antihypertensive agents: Guidelines and clinical practice.
Variation in antihypertensive drug utilization and guideline preferences between six European countries (Denmark, Finland, Germany, Norway, Sweden, the Netherlands) was investigated. Our objectives were to compare between-country variability in utilization per class of antihypertensive agents and to assess guideline preferences in relation to actual use. Antihypertensive consumption data (2003) was retrieved. We classified antihypertensive agents using ATC-codes: C02CA - alpha-blockers (AB), C03A - thiazide diuretics (TD), C07AB - beta-blockers (BB), C08CA - dihydropyridine calcium antagonists (CA), C09A/C09BA/C09BB - ACE-inhibitors+combinations (AI) and C09C/C09D - angiotensin II receptor blockers+combinations (AT2). For each class, DDDs/1000 persons/day and share (%) of total antihypertensive utilization was calculated. Per class, relative standard deviations (RSD) across countries were computed. Current hypertension guidelines were requested from national medical associations. Total antihypertensive utilization varied considerably, ranging from 152.4 (Netherlands) to 246.9 (Germany) DDDs/1000 persons/day. RSD was highest for TD (106.2%) and AB (93.6%). Where guidelines advocated TDs (Norway and Netherlands), TD utilization was below (Norway) or just above (Netherlands) median TD use. Guidelines recommended TD (Norway and Netherlands), TD/BB/AI (Finland, German Physicians Association) or TD/BB/CA/AI/AT2 (Denmark, German Hypertension Society), Sweden had no recent national guideline. In conclusion, antihypertensive utilization patterns varied largely across these six countries, in absolute and relative terms. Furthermore, guidelines seem disconnected from clinical practice in some countries, and none of the guidelines discuss current utilization. Whether this reflects a need for change in prescribing or re-evaluation of guidelines warrants further research.
Antihypertensive Agents↗
Design, expression, purification, and application of novel recombinant miR-491 molecules to define the biogenesis and function of miR-491-3p versus -5p in posttranscriptional regulation of UDP-glucuronosyltransferase 1A1.
Interindividual variations in drug metabolism involve various factors, including posttranscriptional gene regulation mechanisms controlled by microRNAs (miRNAs or miRs) derived from the genome. The aim of this study was to use RNA bioengineering technology to produce novel recombinant human miR-491-5p, miR-491-3p, and pre-miR-491 molecules, namely BioRNA/miR-491-5p, BioRNA/miR-491-3p, and BioRNA/pre-miR-491, respectively, and define their functional difference in regulating UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and drug-metabolizing capacity. All 6 BioRNAs were heterologously overexpressed in Escherichia coli (>30% of total RNA) and isolated by fast protein liquid chromatography to high purity (>97%). As BioRNA/pre-miR-491 agents were processed to both 5p and 3p strands in Hep3B and HepG2 cells, BioRNA/miR-491-5p and -3p were selectively processed to 5p and 3p, respectively, and each accumulated to greater levels. Immunoblotting and immunofluorescence studies demonstrated the efficacy of BioRNA/miR-491-3p to suppress UGT1A1 protein levels in Hep3B and HepG2 cells, localized on the endoplasmic reticulum, exhibiting monomeric (∼55 kDa) and oligomeric (∼150 kDa) bands under different conditions, whereas BioRNA/pre-miR-491 and miR-491-5p had no effects. Using a fluorescent substrate, N-butyl-4-(4-hydroxyphenyl)-1,8-naphthalimide, lower UGT1A1 drug-metabolizing capacities were found in cells treated with BioRNA/miR-491-3p. In addition, liquid chromatography-tandem mass spectrometry analysis revealed a 45% reduction of estradiol 3-glucuronidation activity by BioRNA/miR-491-3p in Hep3B cells, whereas formation of estradiol 17-glucuronidation mediated by other UGTs was unchanged. Together, these results underline the role of miR-491-3p in regulating UGT1A1 and its impact on cellular drug-metabolizing capacity while demonstrating the applications of recombinant miRNA agents to delineating the importance of posttranscriptional gene regulation in drug metabolism. SIGNIFICANT STATEMENT: Research on posttranscriptional gene regulation mainly uses miRNA mimics chemically synthesized in vitro. This study successfully produced 6 novel recombinant miR-491 molecules through in vivo fermentation with transfer RNA scaffold and transfer RNA-fused pre-miRNA carrier-based technologies, which were further utilized to delineate the biogenesis and function of miR-491-3p versus -5p in modulating UDP-glucuronosyltransferase 1A1 protein levels and drug-metabolizing capacity. The findings demonstrate the role of miR-491-3p in regulating UDP-glucuronosyltransferase 1A1 and value of recombinant miRNA agents for studying drug metabolism.
Humans↗
Apparently high plasma angiotensin II levels in patients with essential hypertension treated by converting enzyme inhibition.
Plasma angiotensin I and II (AI and AII) were measured in 13 patients with essential hypertension before and during chronic treatment with enalapril (MK 421) and in seven subjects during an acute study. Two techniques were used for simultaneous extraction of AI and AII. Despite appropriate correction for cross-reaction of AI with the AII antibody, one of the techniques gave consistently higher AII and lower AI levels in plasma of subjects treated with enalapril. The possibility of in vitro conversion of AI into AII-immunoreactive material during the purification or the radioimmunoassay steps should be considered. The use of the alternative technique is proposed for simultaneous processing of blood samples for AI and AII.
Angiotensin I↗
Higher frequency of p53 gene mutations in diffuse large B-cell lymphoma with MALT component.
p53 gene mutation is not a frequent event in the tumorigenesis of lymphomas and the expression of p53 protein is independent of p53 gene mutations. The present study aimed to investigate mutations in the p53 gene in a series of extranodal B-cell lymphomas, and its association with p53 protein expression. A total of 52 cases were graded histologically into Grade 1, Grade 2 and Grade 3 tumors and p53 protein expression was detected using immunohistochemistry. Mutations in the p53 gene were analyzed using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and mobility shifts were confirmed by direct sequencing. The tumors comprised 26 (50%) Grade 1, 9 (17%) Grade 2 and 15 (29%) Grade 3. A high proportion of Grade 2 (25%) tumors expressed p53 protein (P = 0.051) and carried p53 gene mutation (33%) (P = 0.218). However, p53 protein expression was not associated with p53 gene mutations (P = 0.057). Transversion mutations (88%) were more frequently detected than transition mutations (12%). The present study revealed that p53 gene mutations and p53 protein expression occurred in higher frequencies in Grade 2 tumors, which may be of pathogenetic importance. The high frequency of transversion mutations may reflect the influence of an etiological agent in the tumorigenesis of mucosa-associated lymphoid tissue (MALT lymphoma).
Adolescent↗
[Structum (chondroitin sulfate)--a new agent for the treatment of osteoarthrosis].
AIM: To study efficiency and tolerance of Structum in gonarthrosis patients as well as duration of its effect after discontinuation. MATERIALS AND METHODS: 100 patients with femorotibial gonarthrosis aged 45 years and older entered an open randomised trial. They had knee joint arthrosis satisfying diagnostic criteria OA ACR at stage II-III according to Kellgren-Lawrence with pain syndrome. Walking pain intensity was > or = 30 mm by the visual analogue scale (VAS), Leken total functional index > or = 4 and < or = 11. Antiinflammatory drugs (AI) were regularly taken for 30 days for the 3 pretreatment months. 50 patients of the study group received Structum and ibuprofen (1200 mg/day) for 6 months. 50 patients of the control group received ibuprofen only. The two groups were followed up for 3 months. Clinical examination was made monthly. RESULTS: There were significant differences between the groups by the Leken's index (p < 0.005), VAS, pain, daily AI drug requirement. Structum proved more effective. Tolerance was good. Side effects were observed only in two patients (diarrhea and nausea). In the control group, side effects made 15 patients to discontinue the treatment. CONCLUSION: Structum is a new effective drug against gonarthrosis which reduces pain, improves joint function. It is well tolerated and allows to diminish the dose of AI drugs. The response to Structum persisted for 3 months after the treatment.
Aged↗
Effects of isoxazolidine or triazolidine on rat serum lipids in vivo and LDL and HDL binding and degradation in human and rodent cultured cells in vitro.
2-(3,4,5-Trimethoxybenzoyl)-4,4-diethyl-3,5-isoxazolidione (TDI) and 1-acetyl-4-phenyl-1,2,4-triazolidine-3,5-dione (APTD) are two chemically related derivatives which have demonstrated potent hypolipidemic activity in mice at 20 mg/kg/day I.P. for 16 days. The purpose of this study is to correlate in vivo effects of TDI and APTD on rat serum lipoprotein lipids and apoprotein levels as well as plasma clearance and tissue uptake with effects of the agents on tissue cultured cells' LDL and HDL receptor binding, internalization and degradation. This study also correlates in vivo effects of TDI and APTD with endogenous enzyme activities regulated by these high affinity receptors. In rats at 20 mg/kg/day orally serum cholesterol, triglyceride, and VLDL-cholesterol levels were effectively reduced while HDL cholesterol levels were significantly elevated with both agents. These compounds in human hepatocytes lowered LDL receptor binding and degradation, whereas HDL receptor binding and degradation were elevated in human hepatocytes, rat small intestinal epithelium cells, human BG fibroblasts, rat aorta cells and mouse macrophages. These drugs inhibited HMG CoA reductase and sn-glycerol-3-phosphate acyl transferase activities, findings consistent with the observed in vivo reductions in serum cholesterol and triglyceride levels. Both drugs reduced activity of acyl CoA:cholesterol acyl transferase and accelerated activity of neutral cholesterol hydrolase in liver and aorta cells. This modulation by the drugs should reduce disposition of cholesterol esters in these tissues especially aorta wall; this effect was indeed observed in vivo. In the presence of TDI and APTD, HDL uptake of intracellular cholesterol from fibroblasts was accelerated. This was consistent with results from in vivo rat studies showing that HDL clearance was faster after treatment while clearance of LDL slowed. Tissue uptake of HDL and LDL after drug treatment was reduced for the major organs; however the liver accumulation was elevated. The accelerated uptake in the liver was probably due to the observed higher levels of Apo-E and Apo-AI in HDL after drug treatment. Increased excretion of cholesterol from the liver to the bile after drug treatment indicated that the reserve cholesterol transport system by HDL was accelerated by the agents in vivo.
Animals↗
Treatment of severe post-kidney-transplant lung infection by integrative Chinese and Western medicine.
OBJECTIVE: To explore treatments of severe post-kidney-transplant lung infection by integrative Chinese and Western medicine (ICWM), in order to elevate the curing rate as well as to lower the death rate. METHODS: Based on conventional ways of Western medical treatments of 18 cases of severe post-kidney-transplant lung infection, such as putting the patients in single individual ward, antibiotics to prevent infection, respiratory machines, blood filtration, nutritional support, steroids, and maintaining electrolytes balance, we applied integrated Chinese medicinal treatments, like altering conventional prescription "pneumonia III", and conducted clinical observation of effectiveness, and indexes including white blood cell (WBC), neutrophilic granulocyte, blood urea nitrogen (BUN), blood creatinine (Cr), etc. RESULTS: Of the 18 cases studied, 7 were already cured, 8 proved the treatment effective, 3 died. All clinical indexes had statistically significant changes compared with those of before treatment (P < 0.01). CONCLUSION: ICWM can increase curing rate and lower death rate.
Adult↗
Mizoribine oral pulse therapy for steroid-dependent nephrotic syndrome.
There have been reports of the use of mizoribine (MZB) oral pulse therapy for the treatment of systemic lupus erythematosus. We report its efficacy in a 9-year-old girl with steroid- and cyclosporine-dependent nephrotic syndrome (NS). The patient experienced relapses of NS when prednisolone was tapered to 20 mg/day after discontinuing cyclosporine due to biopsy proven toxicity. When methylprednisolone pulse therapy combined with prednisolone therapy (40 mg/day) failed to result in a complete remission after 3 weeks, oral MZB pulse therapy (total dose of 500 mg, 10 mg/kg per day in three divided daily doses twice a week) was given. This therapy was continued for 9 months and resulted in complete remission of the NS for 6 months despite the discontinuation of prednisolone. The serum concentration of MZB was above 2.5 microg/ml for about 10 h (from 3 h after the first dose of MZB to 2 h after the final dose). Thus, our results suggest that this regimen may be effective for patients with steroid-dependent NS.
Administration, Oral↗
A novel therapeutic approach to depression via supplement with tyrosine hydroxylase.
Tyrosine hydroxylase (tyrosine 3-monooxygenase, EC 1.14.16.2, TH) is the rate-limiting enzyme in the biosynthesis of catecholamine neurotransmitters, dopamine (DA), noradrenaline (NE), and adrenaline, in the neurons. The regulated activity of TH is thought to play a critical role in modulating the functional activity of catecholaminergic neuronal systems in the brain. It is well known that the catecholaminergic neuronal systems are associated with depression. Here we showed that TH, delivered by protein transduction domain (PTD), passed through the blood-brain barrier and entered the neurons. Systemic TH treatment improved the behavioral despair in the forced swim test (FST) and the tail suspension test (TST), the two models widely used to screen the potential anti-depressant efficacy. The results indicated a novel and potential therapeutic use of TH in the depression disorder.
Animals↗
Enhanced skin permeation of cationic drug ketotifen through excised guinea pig dorsal skin by surfactants with different electric charges.
Using excised guinea pig dorsal skin, we examined the effects of three surfactants, anionic sodium dodecylsulfate (SDS), cationic n-dodecyltrimethylammonium bromide and non-ionic n-dodecyl-beta-D-maltoside, all of which commonly have an n-dodecyl group, on in vitro skin permeation of the cationic drug ketotifen. All these three surfactants increased the skin permeation of ketotifen. Among the surfactants tested, anionic SDS had the largest enhancement effects, and significantly increased the permeation at concentrations over 1 mM. The enhancement effect of the same anionic surfactant on the permeation of anionic salicylate was smaller and similar to that of cationic n-dodecyltrimethylammonium. The enhancement effects of SDS on ketotifen permeation were more marked than those of the cationic surfactant but differed from previous findings of their effects on other drugs permeation. Analysis of the retention of ketotifen in the skin suggested that SDS-induced increase in the transfer of hydrophilic ketotifen to the skin is the main reason for the marked increase in skin permeation.
Animals↗