FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2010
Nayrton Flávio Moura Rocha
Abstract (-)-,-Bisabolol is an unsaturated, optically active sesquiterpene alcohol obtained by the direct distillation essential oil from plants such as Vanillosmopsis erythropappa and Matricaria chamomilla. (-)-,-Bisabolol has generated considerable economic interest, since it possesses a delicate floral odor and has been shown to have anti-septic and anti-inflammatory activity. The aim of this work was to evaluate the gastroprotective action of (-)-,-bisabolol on ethanol and indomethacin-induced ulcer models in mice, and further investigate the pharmacological mechanisms involved in this action. The oral administration of (-)-,-bisabolol 100 and 200 mg/kg was able to protect the gastric mucosa from ethanol (0.2 mL/animal p.o.) and indomethacin-induced ulcer (20 mg/kg p.o.). Administration of l -NAME (10 mg/kg i.p.), glibenclamide (10 mg/kg i.p.) or indomethacin (10 mg/kg p.o.) was not able to revert the gastroprotection promoted by (-)-,-bisabolol 200 mg/kg on the ethanol-induced ulcer. Dosage of gastric reduced glutathione (GSH) levels showed that ethanol and indomethacin reduced the content of non-protein sulfhydryl (NP-SH) groups, while (-)-,-bisabolol significantly decreased the reduction of these levels on ulcer-induced mice, but not in mice without ulcer. In conclusion, gastroprotective effect on ethanol and indomethacin-induced ulcer promoted by (-)-,-bisabolol may be associated with an increase of gastric sulfydryl groups bioavailability leading to a reduction of gastric oxidative injury induced by ethanol and indomethacin. [source]

Acute hepatitis C: Dosage and compliance,

HEPATOLOGY, Issue 2 2006
Francesco De Rosa
No abstract is available for this article. [source]

Efficacy and tolerance of infliximab in children and adolescents with Crohn's disease

INFLAMMATORY BOWEL DISEASES, Issue 6 2004
Dr. Thierry Lamireau
Abstract Infliximab, a monoclonal antibody against tumor necrosis factor-alpha, has been shown to be effective for the treatment of refractory Crohn's disease in adult patients, but experience in pediatrics is limited. This retrospective study included 88 children and adolescents, 39 girls and 49 boys, with a median age of 14 years (range 3.3,17.9). Infliximab was indicated for active disease (66%) and/or fistulas (42%) that were refractory to corticosteroids (70%), and/or other immunosuppressive (82%) agents, and/or parenteral nutrition (20%). Patients received 1 to 17 infusions (median 4) of 5 mg/kg (range 3.8,7.3) of infliximab during a median time period of 4 months (1,17 months). Infusion reaction was noted in 13 patients (15%), with a total of 16 reactions in 450 infusions (4%). At Day 90 after the first infusion of infliximab, symptoms improved in 49% of patients, whereas 29% of patients were in remission and 13% of patients relapsed. From Day 0 to Day 90, Harvey,Bradshaw score decreased from 7.5 to 2.8 (P < 0.001), C-reactive protein from 36 to 16 mg/L (P < 0.01), and 1-hour erythrocyte sedimentation rate from 35 to 17 mm (P < 0.01). Dosage of corticosteroids decreased from to 0.59 to 0.17 mg/kg/d (P < 0.001); 53% of patients could be weaned of corticosteroids and 92% of parenteral nutrition. Treatment with infliximab is well tolerated and effective in most children and adolescents with Crohn's disease that is refractory to conventional immunosuppressive therapy. Nevertheless, long-term efficacy remains to be shown, and further studies are urgently needed to precisely determine the best modality of continuing treatment. [source]

Aged Mice Require Full Transcription Factor, Runx2/Cbfa1, Gene Dosage for Cancellous Bone Regeneration After Bone Marrow Ablation,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2004
Kunikazu Tsuji
Abstract Runx2 is prerequisite for the osteoblastic differentiation in vivo. To elucidate Runx2 gene functions in adult bone metabolism, we conducted bone marrow ablation in Runx2 heterozygous knockout mice and found that aged (but not young) adult Runx2 heterozygous knockout mice have reduced new bone formation capacity after bone marrow ablation. We also found that bone marrow cells from aged Runx2 heterozygous knockout mice have reduced ALP+ colony-forming potential in vitro. This indicates that full Runx2 dosage is needed for the maintenance of osteoblastic activity in adult mice. Introduction: Null mutation of the Runx2 gene results in total loss of osteoblast differentiation, and heterozygous Runx2 deficiency causes cleidocranial dysplasia in humans and mice. However, Runx2 gene functions in adult bone metabolism are not known. We therefore examined the effects of Runx2 gene function in adult mice with heterozygous loss of the Runx2 gene. Materials and Methods: Bone marrow ablation was conducted in young adult (2.5 ± 0.5 months old) or aged adult (7.5 ± 0.5 months old) Runx2 heterozygous knockout mice and wildtype (WT) littermates. Cancellous bone regeneration was evaluated by 2D ,CT. Results: Although new bone formation was observed after bone marrow ablation in the operated bone marrow cavity of WT mice, such bone formation was significantly reduced in Runx2 heterozygous knockout mice. Interestingly, this effect was observed specifically in aged but not young adult mice. Runx2 heterozygous deficiency in aged mice significantly reduced the number of alkaline phosphatase (ALP)+ cell colonies in the bone marrow cell cultures, indicating a reduction in the numbers of osteoprogenitor cells. Such effects of heterozygous Runx2 deficiency on osteoblasts in vitro was specific to the cells from aged adult mice, and it was not observed in the cultures of marrow cells from young adult mice. Conclusion: These results indicate that full gene dosage of Runx2 is required for cancellous bone formation after bone marrow ablation in adult mice. [source]

Increased Dosage during Intracoronary Irradiation Due to Overlapped Source Stepping Shows No Long-Term Adverse Changes in Vessel Morphology

JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 3 2004
BONNI SYEDA M.Sc., M.D.
Purpose: The purpose of this analysis was to evaluate if overdosage during intracoronary irradiation due to overlapped source stepping may result in long-term morphologic changes in vessel anatomy. Methods: Baseline angiograms of patients with in-stent restenosis undergoing coronary reintervention followed by intracoronary irradiation with source stepping were analyzed. Overlapping was considered present for the segment with overlapped reference isodose length (RIL) (RIL = segment with ,90% of reference dose at 1 mm vessel wall depth). Baseline and 6-months follow-up volumetric intravascular ultrasound (IVUS) analysis were performed for the overlapped segment and for proximal and distal segments of equal length. Results: Overlapping was found in six patients (three patients: 32P treatment; three patients: 90Sr/Y treatment); final analysis was performed in four patients. Comparison of the baseline and follow-up IVUS volumetric parameters revealed no significant change in lumen or vessel volumes at segments of overlaps in comparison to proximal and distal reference segments. Conclusion: Increased dosage due to overlapping during source stepping is not associated with morphologic changes in vessel anatomy at follow-up. (J Interven Cardiol 2004;17:143,149) [source]

Dosage and mode of administration of methotrexate in clinical trials: Comment on the article by Genovese et al

ARTHRITIS & RHEUMATISM, Issue 3 2003
Michael Seitz MD
No abstract is available for this article. [source]

Effects of Cloned Gene Dosage on the Response of Recombinant CHO Cells to Hyperosmotic Pressure in Regard to Cell Growth and Antibody Production

BIOTECHNOLOGY PROGRESS, Issue 6 2001
Joon Soo Ryu
The effect of cloned gene dosage on growth and product formation under hyperosmotic conditions has been studied using recombinant Chinese hamster ovary (rCHO) cell lines producing chimeric antibody. Batch cultures of four rCHO cell lines carrying different numbers of antibody gene copies were carried out using the hyperosmolar medium. Depending on cloned gene dosage, hyperosmotic pressure decreased specific growth rate (,) and increased specific antibody productivity (qAb) to a different degree. The cell line with lower cloned gene dosage displayed more significant enhancement in qAb and less reduction in , at hyperosmolalities. However, the cell line with higher cloned gene dosage still yielded higher maximum antibody concentration at hyperosmolality up to 469 mOsm/kg. Northern blot analysis showed a positive relationship between immunoglobulin mRNA level per cell and qAb, indicating that transcriptional regulation was involved in the response of rCHO cells to hyperosmotic pressure. Cell cycle analysis showed that hyperosmotic pressure induced G1 -phase arrest, suggesting that the increase of cell population in G1 -phase may contribute in part to enhanced qAb at hyperosmolality. Taken together, although the cell line with lower cloned gene dosage displayed more significant enhancement in qAb at hyperosmolality, the factor that determined the maximum antibody concentration in hyperosmotic rCHO cell cultures was almost exclusively the gene dosage. [source]

Study on Decoloration of Acidic Scarlet GR by Pyrolusite Oxidation under an Acid Condition

ACTA GEOLOGICA SINICA (ENGLISH EDITION), Issue 2 2006
CHEN Gang
Abstract, Decoloration of acidic scarlet GR by pyrolusite is studied in this paper. The effects of pH in solution, dosage and granularity of pyrolusite, reaction temperature, and vibration speed on decoloration efficiency are discussed. According to experiment results, the decoloration efficiency may exceed 95% for 40 mg/L GR solution by pyrolusite. pH is most important among all factors which impact the decoloration of acidic scarlet GR. Dosage and granularity of pyrolusite, reaction temperature, and vibration speed have a little benitfit on decoloration. The high decoloration efficiency and low removal efficiency of COD as well as FT-IR spectra of products between pyrolusite and acidic scarlet GR indicate that acidic scarlet GR undergoes the redox reaction on the interface of mineral and its chromophore is oxidated and decolored, but it is not removed thoroughly by oxidation. [source]

Fumaric acid esters in the management of severe psoriasis

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2007
L. Brewer
Summary Background., Fumaric acid esters (FAEs) offer an effective alternative to patients with psoriasis in whom other systemic agents are contraindicated or have failed. Objective., We assessed the efficacy and side effect profile of FAEs in a group of patients with psoriasis. Methods., A retrospective study was carried out on patients treated with FAEs over 21 months. Information was gathered from patients' notes. Dosage, response and side effects were recorded. Results., In total, 31 patients were included. The mean age was 46.8 years. All patients had been treated with other modalities and 61.5% had received previous systemic treatment. There was good to excellent response in 58.6% of patients. Subjective side-effects were common (87.1%), and lymphopenia occurred in 61.3%. The drug was not tolerated by one-fifth of patients. Conclusion., The relatively low toxicity and absence of hepatotoxicity makes FAEs a reasonable first-line systemic treatment in selected patients with difficult psoriasis. [source]

Propranolol Intoxication Revealing a Brugada Syndrome

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2005
PHILIP AOUATE M.D.
This is the first report of Brugada syndrome revealed by beta-blocker intoxication. A 24-year-old healthy man ingested propranolol (2.28 g) to commit suicide. After early gastric lavage, electrolytes, cardiac enzymes, chest X-ray, and echocardiography were normal. Dosages of psychotropic drugs were negative. ECG showed a typical coved-type pattern of Brugada syndrome. Follow-up showed partial ECG normalization of the discrete saddleback-type pattern. The ajmaline- test confirmed Brugada syndrome. These ECG modifications may be explained by the stabilizing membrane effect of high concentration of propranolol and/or inhibition of ICaL. This case illustrates the possible deleterious effects of beta-blockers in patients with Brugada syndrome. [source]

Re-treatment of chronic hepatitis C patients after relapse: efficacy of peginterferon-alpha-2a (40 kDa) and ribavirin

JOURNAL OF VIRAL HEPATITIS, Issue 7 2006
C. Berg
Summary., We conducted a randomized multinational study to determine whether 48 weeks of re-treatment with peginterferon-alpha-2a (40 kDa) plus ribavirin would induce a sustained virological response (SVR) in relapsed chronic hepatitis C patients. Patients who had previously relapsed during 24 weeks of untreated follow-up, after having achieved an end-of-treatment virological response with 24 weeks of peginterferon-alpha-2a (40 kDa)/ribavirin combination therapy, within a phase III trial, were studied. Although the recommended dosage was the same as that used at the end of the initial trial, adjustments were permitted. Data on serious adverse events, or adverse events that resulted in dose reductions or discontinuations, were collected. Following re-treatment, the overall SVR rate in the 64 patients was 55%. The SVR rates in patients infected with hepatitis C virus (HCV) genotype 1 and non-1 genotypes were 51% and 63%, respectively. Early (week 12) virological responses were seen in 39 patients (61%) and were predictive of an SVR. Re-treatment was well tolerated. The most frequent adverse events recorded were fatigue (5%) and abdominal pain (3%). Dosages of peginterferon-alpha-2a (40 kDa) and/or ribavirin were modified because of adverse events in 3% and 13% of patients, and because of laboratory abnormalities in 23% and 5% of patients, respectively. Thus, a 48-week course of peginterferon-alpha-2a (40 kDa) plus ribavirin induces an SVR in 55% of patients who relapsed during follow-up after 24 weeks of combination therapy. Physicians should not hesitate to offer re-treatment to patients who relapse after an initial, 24-week course of combination therapy, or who have prematurely stopped treatment because, for example, of laboratory abnormalities. [source]

Safety and tolerability of high-dosage coenzyme Q10 in Huntington's disease and healthy subjects,

MOVEMENT DISORDERS, Issue 12 2010
Article first published online: 28 JUL 2010
Abstract Coenzyme Q10 (CoQ10), a potential neuroprotective compound, was previously investigated at a dosage of 600 mg/day in Huntington's disease (HD) patients and demonstrated a trend toward slowing disease progression. Higher CoQ10 dosages may prove beneficial. We investigated the tolerability and blood levels associated with 1,200, 2,400, and 3,600 mg/day of CoQ10 in HD and healthy subjects. Twenty-eight subjects (20 HD, 8 healthy) enrolled in a 20-week open-label trial. Subjects started on 1,200 mg/day of CoQ10, increasing every 4 weeks by 1,200 mg to a maximum dosage of 3,600 mg/day. Monthly evaluations included review of adverse events and CoQ10 blood levels. Twenty-three subjects (82%) achieved the target dosage of 3,600 mg/day. Six subjects (2 healthy, 4 HD) withdrew prematurely (gastrointestinal (GI) symptoms in 3, worsening HD in 2, and 1 because of a fall). All three serious adverse events occurred in a single subject, and were deemed unrelated to CoQ10. The most common adverse events seen were GI symptoms. Mean (± SD) CoQ10 blood levels achieved over the course of the trial were as follows: 1.26 ± 1.27 ,g/mL (baseline, n = 28), 5.59 ± 2.24 ,g/mL (1,200 mg/day, week 4, n = 26), 6.38 ± 3.25 ,g/mL (2,400 mg/day, week 8, n = 25), 7.49 ± 4.09 ,g/mL (3,600 mg/day, week 12, n = 23), and 6.78 ± 3.36,g/mL (3,600 mg/day, week 20, n = 20). CoQ10 was well tolerated with over 80% of subjects achieving the target dosage. Dosages of 2,400 mg/day may provide the best balance between tolerability and blood level achieved. Further studies examining the efficacy of 2,400 mg/day are planned. © 2010 Movement Disorder Society. [source]

Postmarketing drug dosage changes of 499 FDA-approved new molecular entities, 1980,1999,

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 6 2002
James Cross MS
Abstract Purpose Risks and benefits of marketed drugs can be improved by changing their labels to optimize dosage regimens for indicated populations. Such postmarketing label changes may reflect the quality of pre-marketing development, regulatory review, and postmarketing surveillance. We documented dosage changes of FDA-approved new molecular entities (NMEs), and investigated trends over time and across therapeutic groups, on the premise that improved drug development methods have yielded fewer postmarketing label changes over time. Methods We compiled a list of NMEs approved by FDA from 1 January 1980 to 31 December 1999 using FDA's website, Freedom of Information Act request, and PhRMA (Pharmaceutical Research and Manufacturers of America) database. Original labeled dosages and indicated patient populations were tracked in labels in the Physician's Desk Reference®. Time and covariate-adjusted risks for dosage changes by 5-year epoch and therapeutic groups were estimated by survival analysis. Results Of 499 NMEs, 354 (71%) were evaluable. Dosage changes in indicated populations occurred in 73 NMEs (21%). A total of 58 (79%) were safety-motivated, net dosage decreases. Percentage of NMEs with changes by therapeutic group ranged from 27.3% for neuropharmacologic drugs to 13.6% for miscellaneous drugs. Median time to change following approval fell from 6.5 years (1980,1984) to 2.0 years (1995,1999). Contrary to our premise, 1995,1999 NMEs were 3.15 times more likely to change in comparison to 1980,1984 NMEs (p,=,0.008, Cox analysis). Conclusions Dosages of one in five NMEs changed, four in five changes were safety reductions. Increasing frequency of changes, independent of therapeutic group, may reflect intensified postmarketing surveillance and underscores the need to improve pre-marketing optimization of dosage and indicated population. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Kinetics of bone protection by recombinant osteoprotegerin therapy in Lewis rats with adjuvant arthritis

ARTHRITIS & RHEUMATISM, Issue 7 2002
Giuseppe Campagnuolo
Objective To assess the effect of different dosages and treatment schedules of osteoprotegerin (OPG) on joint preservation in an experimental model of adjuvant-induced arthritis (AIA). Methods Male Lewis rats with AIA (6,8 per group) were treated with a subcutaneous bolus of recombinant human OPG according to one of the following schedules: daily OPG (an efficacious regimen) starting at disease onset (days 9,15), early intervention (days 9,11), delayed intervention (days 13,15), and extended therapy (days 9,22). Inflammation (hind paw swelling) was quantified throughout the clinical course; osteoporosis (bone mineral density [BMD], by quantitative dual x-ray absorptiometry) and morphologic appraisals of inflammation, bone damage, intralesional osteoclasts (by semiquantitative histopathologic scoring), and integrity of the articular cartilage matrix (by retention of toluidine blue stain) were determined in histology sections of arthritic hind paws. Results OPG provided dose- and schedule-dependent preservation of BMD and periarticular bone while essentially eliminating intralesional osteoclasts. Dosages ,2.5 mg/kg/day preserved or enhanced BMD and prevented essentially all erosions. A dosage of 4 mg/kg/day protected joint integrity to a comparable degree when given for 7 (days 9,15) or 14 (days 9,22) consecutive days. At this dosage, early intervention (days 9,11) was twice as effective as delayed intervention (days 13,15) at preventing joint dissolution. Erosions and osteoclast scores were greatly decreased for 26 days (measured from the first treatment) after 7 or 14 daily doses of OPG (4 mg/kg/day). OPG treatment also prevented loss of cartilage matrix proteoglycans, an indirect consequence of protecting the subchondral bone. No OPG dosage or regimen alleviated weight loss, inflammation, or periosteal osteophyte production. Conclusion These data indicate that OPG preserves articular bone and (indirectly) articular cartilage in arthritic joints in a dose- and schedule-dependent manner, halts bone erosion when given at any point during the course of arthritis, produces sustained antierosive activity after a short course, and is most effective when initiated early in the disease. [source]

Congenital malformations in infants whose mothers reported the use of folic acid in early pregnancy in Sweden.

CONGENITAL ANOMALIES, Issue 4 2007
A prospective population study
ABSTRACT The use of folic acid prior to conception is generally recommended for the prevention of birth defects, notably neural tube defects. In a previous study from Sweden, based on interviews of women in early pregnancy, no such effect was found on the general malformation rate, but data for neural tube defects were scarce. Using data from the Swedish Medical Birth Register for the years 1995,2004, 20 891 women were identified who reported the use of folic acid in early pregnancy, but not of anticonvulsants. These women were compared to all other women who gave birth during the study period. Malformations in the infants born were identified from multiple sources. No reduction in the general malformation rate was seen among infants born to women who reported the use of folic acid (OR = 1.09, 95% CI 1.02,1.17) and no effect of neural tube defect rate was seen (RR = 1.35, 95% CI 0.82,2.22), based on 16 infants with neural tube defect whose mother reported the use of folic acid. No effect was seen on the rates of other malformations except for cardiac defects, where a statistically significant increased risk (notably for severe defects) was found (OR = 1.19, 95% CI 1.05,1.35). The effect of various deficiencies in data collection is discussed, but is unlikely to explain the lack of protective effect noticed. So far, it has not been possible to demonstrate a beneficial effect of folic acid supplementation on malformation risk in Sweden. A more complete ascertainment and detailed timing and dosage of folic acid use in a prospective study is recommended. [source]

Infertility observed in female rats treated with N-acetyl-L-cysteine: Histopathological examination of ovarian follicles and recovery of fertility

CONGENITAL ANOMALIES, Issue 3 2003
Miwa Harada
ABSTRACT, We previously reported infertility in female rats that received N,acetyl-L-cysteine (NAC) intravenously at a dosage of 1000 mg/kg/day. Unfertilized oocytes and gestation day 1 and 2 embryos were assessed morphologically, and the results suggested that absence or thinning of the zona pellucida (ZP) is related to infertility. However, the morphological characteristics of oocytes before ovulation and recovery from the effects of NAC were not clarified. In the present study, the ovarian follicles were histopathologi,cally examined and the recovery of reproductive function was evaluated to investigate the effects of NAC. Female Sprague-Dawley rats at 10 weeks of age received NAC intravenously at 1000 mg/kg/day for more than 1 week. Thinning of the ZP was observed in the ovarian follicles in all stages of growth by light microscopy. Outflow of the components of the ZP between the corona radiata and disarrangement of the corona radiata were more pronounced in growing follicles than in large secondary follicles. Similar findings were observed by electron microscopy, and the effects of NAC were limited to the ZP. Infertility and thinning of the ZP were observed in the no,recovery NAC group, but not in the recovery NAC group, in which animals recovered within four estrous cycles after NAC administration. It has been reported that the ZP is expressed by oocytes or by both oocytes and granulosa cells, but no changes were noted in these cells. The present findings suggest that NAC affects the ZP directly and that reproductive function may recover from the effects of NAC. [source]

Monitoring Lung Resistivity Changes in Congestive Heart Failure Patients Using the Bioimpedance Technique

CONGESTIVE HEART FAILURE, Issue 6 2005
Sharon Zlochiver MSc
The feasibility of a novel, dedicated system for monitoring lung resistivity in congestive heart failure patients, implementing a hybrid approach of the bioimpedance technique, was assessed in this preliminary study. Thirty-three healthy volunteers and 34 congestive heart failure patients were measured with the PulmoTrace system (Cardiolnspect, Tel Aviv University, Tel Aviv, Israel) during tidal respiration, and the ability to monitor the respective lung resistivity values was assessed. Mean left and right lung resistivity values of 1205±163 and 1200±165 ,·cm for the control group and 888±193 and 943±187 ,·cm for the congestive heart failure group were found, indicating a significant (p<2·10,7) difference between the two groups. The results of long-term monitoring of two patients during medical treatment are also shown. This hybrid approach system is believed to improve diagnostic capabilities and help physicians to better adjust medication dosage on a frequent basis. [source]

A patch test study of 27 crude drugs commonly used in Chinese topical medicaments

CONTACT DERMATITIS, Issue 1 2003
Hsuan-Hsiang Chen
Chinese topical medicaments (CTMs) are commonly used in Taiwan and in Southeast Asia. However, a systematic evaluation of contact sensitization potential from CTM has not been carried out to our knowledge. This study was undertaken to investigate the incidence of contact sensitivity to the components of CTM in patients with contact dermatitis from CTM. A screening series of 27 crude drugs most commonly used in CTM as well as a modified European standard series was patch tested in 30 patients. The herbs with the most frequent positive reactions were Flos Caryophylli ( ), Radix Angelicae Pubescentis ( ), Cortex Cinnamomi ( ), Cortex Radix Acanthopanacis ( ), Caulis Impatientis ( ), Resina Draconis/Sanguis Draconis ( ), Fructus Cnidii ( ), Radix Gentiana Macrophyllae ( ), and Rhizoma Ligustici Chuanxiong ( ). Concomitant allergy to colophonium was found in most of these positive reactions. Reducing the concentration and simplifying the compositions of these components, as well as replacement with those of low allergenicity in CTM, such as Rhizoma Arisaematis ( ), Herba Lycopodii ( ), Radix Cyathulae Officinalis ( ), Rhizoma Pinelliae ( ), Radix Angelicae Dahuricae ( ), Herba Dendrobii ( ), Secretio Moschus ( ), and Stigmata Croci ( ), may be advocated. A precise labelling of the dosage of each component and the exact chemical compounds in CTM products could further improve the safety and therapeutic effects of CTM in the future. [source]

ESTIMATING INTERVENTION EFFECTS IN VARYING RISK SETTINGS: DO POLICE RAIDS REDUCE ILLEGAL DRUG DEALING AT NUISANCE BARS?,

CRIMINOLOGY, Issue 2 2003
JACQUELINE COHEN
This paper investigates the effectiveness of police raids in reducing drug dealing in and around nuisance bars. We examine effects of both dosage (number of raids) and duration (months) of the intervention, as well as the conditioning effects of land use and population characteristics in shaping the underlying risk levels of drug dealing in the target and surrounding areas. Results indicate that the police intervention suppresses levels of drug dealing during periods of active enforcement, but the effects largely disappear when the intervention is withdrawn. Also, the effects of the intervention are mediated by risk characteristics in target and surrounding areas. Target areas characterized by higher levels of risk are more resistant to intervention effects than those with lower levels of risk. Risk factors in nearby areas are also significant. Bars with high levels of risk arising from land uses in surrounding areas are easier to treat, while bars with high levels of population-based risk in surrounding areas are harder to treat. [source]

Effects of normobaric hyperoxia on water content in different organs in rats

ACTA PHYSIOLOGICA, Issue 1 2002
L. E. B. Stuhr
ABSTRACT Pulmonary oxygen toxicity is a dose-dependent effect on alveolar epithelial and endothelial cells resulting in pulmonary oedema. Any concomitant effects on systemic capillary endothelium would be expected to result in capillary leakage and an increase in the tissues' water content. Total tissue water (TTW) in different organs was therefore studied in freely moving rats exposed to 100% O2 at normobaric pressure for 24 or 48 h, and compared to air-breathing control rats. The TTW for the following tissues was measured: Trachea, left bronchus, left lung, left and right ventricle, left kidney, skin (left paw-hindlimb), skin (back of the rat), left brain, left eye and thigh muscle left side. There was a significant increase in TTW of the lung accompanied by pleural effusion after 48 h of oxygen exposure as expected in all exposed animals. There was a small increase in TTW of the paw only, and a small decrease or no change in other tissues after 24 and 48 h of exposure. We conclude that there is no evidence of systemic capillary dysfunction as measured by tissue water content after exposure to hyperoxia in a dosage causing pulmonary oedema. [source]

10-Year trends in the treatment and outcomes of patients with first-episode schizophrenia

ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2010
J. Nielsen
Nielsen J, le Quach P, Emborg C, Foldager L, Correll CU. 10-Year trends in the treatment and outcomes of patients with first-episode schizophrenia. Objective:, The first episode of schizophrenia is a critical period for illness course and outcomes. We aimed to investigate treatments and outcomes during the first year after the diagnosis of schizophrenia. Method:, Pharmacoepidemiologic inception cohort study of all newly diagnosed patients with schizophrenia in Denmark (n = 13 600) 1996,2005. Results:, From 1996 to 2005, the mean age at first diagnosis decreased significantly (29.2,26.1 years), more patients received antipsychotics (67.2,80.7%, annual OR = 1.07, CI: 1.06,1.09, P < 0.001) and antipsychotic polypharmacy for >4 months (16.7,37.1%, OR = 1.14, CI: 1.12,1.57, P < 0.001). The antipsychotic defined daily dosage (DDD) doubled (150,332 DDD, P < 0.001), use of antidepressants (24.3,40.6%, P < 0.001). Bed days [89.9 days (CI: 81.8,98.8) to 71.8 days, CI: 63.7,80.8, P < 0.0001] decreased, whereas outpatient contacts [10.2 (CI: 9.5,11.0) to 21.4 (CI: 19.9,21.0), P < 0.0001] doubled. Conclusion:, Between 1996 and 2005, there was an earlier recognition of schizophrenia, intensified outpatient treatment, increased use and dosing of antipsychotics and antidepressants, but also more antipsychotic polypharmacy. [source]

Applications of cone-beam computed tomography in fractures of the maxillofacial complex

DENTAL TRAUMATOLOGY, Issue 4 2009
Werner H. Shintaku
Several studies support the use of conventional two-dimensional imaging for traumas involving mainly the mandible, but for more complex situations advanced imaging modalities such as computed tomography (CT) and magnetic resonance imaging have higher indication. Nowadays, besides CT, cone-beam computed tomography (CBCT) has appeared as a reasonable and reliable alternative considering radiation dosage, image quality and comfort for the patient. The purpose of this study was to review the fracture patterns involving the maxillofacial complex, provide a technical and practical comparison between CT and CBCT, and finally present the potential applications of CBCT illustrated with clinical examples. [source]

Visualized Sclerotherapy of Varicose Veins

DERMATOLOGIC SURGERY, Issue 2010
MAMORU KIKUCHI MD
BACKGROUND The spread and movement of sclerosant after injection during sclerotherapy is difficult to monitor. OBJECTIVE To develop a new visualization method that allows monitoring of sclerosant dosage and flow during sclerotherapy. METHODS We used a photodynamic eye (PDE) to perform indocyanine green (ICG) imaging. ICG produces strong fluorescence detectable using PDE and allows monitoring of sclerosant spread through blood vessels in real time. We performed visualized sclerotherapy on 50 limbs, comprising high ligation and sclerotherapy (35 limbs), stripping and sclerotherapy (10 limbs), and sclerotherapy alone (5 limbs). RESULTS In all cases, fluorescence imaging of the injected sclerosant was possible. No complications resulted from combining ICG and polidocanol in any of the patients, all of whom received follow-up evaluations at 1 week, 1 month, and 3 months after treatment. CONCLUSIONS Our new method not only avoids the risk of radiation exposure, but also allows for simple observation of sclerosant range of access, determination of the dosage for each lesion, and accurate administration of therapy to target lesions. This method will contribute to further advances in sclerotherapy, given that it allows administration of sclerosant and visual confirmation of optimal injection dosage, speed, and movement of sclerosant after injection. The authors have indicated no significant interest with commercial supporters. [source]

A retrospective evaluation of the impact of total smoking cessation on psychiatric inpatients taking clozapine

ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2010
I. Cormac
Cormac I, Brown A, Creasey S, Ferriter M, Huckstep B. A retrospective evaluation of the impact of total smoking cessation on psychiatric inpatients taking clozapine. Objective:, To investigate the effect of a complete smoking ban on a group of psychiatric inpatients maintained on the antipsychotic medication clozapine. Method:, Retrospective data on clozapine dose and plasma levels were collected from a three month period before and a six month period after the introduction of the smoking ban. Results:, Before the ban only 4.2% of patients who smoked had a plasma clozapine level ,1000 ,g/l but after the ban this increased to 41.7% of the sample within the six month period following the ban despite dose reductions. Conclusion:, Abrupt cessation of smoking is associated with a potentially serious risk of toxicity in patients taking clozapine. Plasma clozapine levels must be monitored closely and adjustments made in dosage, if necessary, for at least six months after cessation. [source]

Human and pig SRY 5, flanking sequences can direct reporter transgene expression to the genital ridge and to migrating neural crest cells

DEVELOPMENTAL DYNAMICS, Issue 3 2006
Alexandre Boyer
Abstract Mechanisms for sex determination vary greatly between animal groups, and include chromosome dosage and haploid,diploid mechanisms as seen in insects, temperature and environmental cues as seen in fish and reptiles, and gene-based mechanisms as seen in birds and mammals. In eutherian mammals, sex determination is genetic, and SRY is the Y chromosome located gene representing the dominant testes determining factor. How SRY took over this function from ancestral mechanisms is not known, nor is it known what those ancestral mechanisms were. What is known is that SRY is haploid and thus poorly protected from mutations, and consequently is poorly conserved between mammalian species. To functionally compare SRY promoter sequences, we have generated transgenic mice with fluorescent reporter genes under the control of various lengths of human and pig SRY 5, flanking sequences. Human SRY 5, flanking sequences (5 Kb) supported reporter transgene expression within the genital ridge of male embryos at the time of sex determination and also supported expression within migrating truncal neural crest cells of both male and female embryos. The 4.6 Kb of pig SRY 5, flanking sequences supported reporter transgene expression within the male genital ridge but not within the neural crest; however, 2.6 Kb and 1.6 Kb of pig SRY 5, flanking sequences retained male genital ridge expression and now supported extensive expression within cells of the neural crest in embryos of both sexes. When 2 Kb of mouse SRY 5, flanking sequences (,3 to ,1 Kb) were placed in front of the 1.6 Kb of pig SRY 5, flanking sequences and this transgene was introduced into mice, reporter transgene expression within the male genital ridge was retained but neural crest expression was lost. These observations suggest that SRY 5, flanking sequences from at least two mammalian species contain elements that can support transgene expression within cells of the migrating neural crest and that additional SRY 5, flanking sequences can extinguish this expression. Developmental Dynamics 235:623,632, 2006. © 2006 Wiley-Liss, Inc. [source]

Phenotypic analyses of mouse embryos with ubiquitous expression of Oct4: Effects on mid,hindbrain patterning and gene expression

DEVELOPMENTAL DYNAMICS, Issue 1 2005
Verónica Ramos-Mejía
Abstract Oct4 is a transcription factor that has been associated with pluripotency and fate determination in the initial cell lineages of mammals. On the other hand, Pou2, the ortholog of Oct4 in zebrafish, serves additional later functions during brain development acting as a differentiation switch. In mice, Oct4 is expressed throughout the neural plate of embryos until embryonic day (E) 8.0. In this study, we produced transgenic mouse embryos that ubiquitously express Oct4 and analyzed the consequences during development. We show that, at E8.0, a higher dosage of Oct4 in the neuroectoderm is sufficient to transiently alter mid,hindbrain patterning and produced a strong up-regulation of Pax2, indicating that Oct4 can regulate this gene in vivo. After E9.5, ectopic Oct4 in this region produced cell death and affected the development of the forebrain, suggesting that, at these later stages, Oct4 down-regulation is necessary for normal development to proceed. The phenotype of the transgenic embryos was also accompanied with an increase of Fgf8 expression in several of its endogenous domains, suggesting the possibility that Oct4 can participate in the regulation of expression of this ligand. Our observations support the hypothesis that Oct4, like zebrafish Pou2, has a conserved function during early brain patterning in mouse. Developmental Dynamics 232:180,190, 2005. © 2004 Wiley-Liss, Inc. [source]

Seizures and paroxysmal events: symptoms pointing to the diagnosis of pyridoxine-dependent epilepsy and pyridoxine phosphate oxidase deficiency

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 7 2010
BERNHARD SCHMITT
Aim, We report on seizures, paroxysmal events, and electroencephalogram (EEG) findings in four female infants with pyridoxine-dependent epilepsy (PDE) and in one female with pyridoxine phosphate oxidase deficiency (PNPO). Method, Videos and EEGs were analysed and compared with videos of seizures and paroxysmal events archived from 140 neonates. PDE and PNPO were proven by complete control of seizures once pyridoxine or pyridoxal 5,-phosphate was administered and by recurrence when withdrawn. Mutations in the antiquitin gene were found in three patients and in the PNPO gene in one child. Results, Seizures began within 48 hours after birth in four newborns and at age 3 weeks in one. Frequent multifocal and generalized myoclonic jerks, often intermixed with tonic symptoms, abnormal eye movement, grimacing, or irritability, were observed in all infants with PDE and PNPO, but rarely in the other archived videos of neonates. EEGs were inconstant and frequently no discernable ictal changes were recorded during the seizures and the paroxysmal events. In addition, interictal EEGs were inconclusive, with normal and abnormal recordings. In older children tonic,clonic seizures, abnormal behaviour, inconsolable crying, frightened facial expression, sleep disturbance, loss of consciousness, paraesthesia, or intermittent visual symptoms were described during controlled and uncontrolled withdrawal or insufficient dosage. Interpretation, PDE or PNPO should be considered in infants with prolonged episodes of mixed multifocal myoclonic tonic symptoms, notably when associated with grimacing and abnormal eye movements. [source]

Effects and serum levels of glibenclamide and its active metabolites in patients with type 2 diabetes

DIABETES OBESITY & METABOLISM, Issue 6 2001
A. Jönsson
SUMMARY Objective To study the effects and serum levels of glibenclamide (Gb) and its active metabolites in patients on chronic Gb medication on different daily doses. Material and methods Fifty patients with type 2 diabetes on regular Gb therapy (1.75,14.0 mg daily). Blood samples were taken immediately before and 90 min after regular Gb intake. A standardized breakfast was served 30 min after drug intake. Serum insulin and proinsulin levels were determined by ELISA methods without cross-reactivities. Serum drug levels were determined by HPLC. Fischer's R to Z -test (correlation coefficients) and paired Student t -tests were used when comparing values within the entire group and unpaired non-parametric Mann,Whitney tests were used when comparing high and low dose levels. A p-value <,0.05 was considered significant. Results There were significant correlations between daily Gb dose, on the one hand, and, on the other, HbAlc (r = 0.55), ,-insulin (r = , 0.59) and ,-proinsulin (r = , 0.52) levels. Significant correlations between Gb therapy duration and insulin (r = , 0.40) and proinsulin (r = , 0.34) secretion and between Gb dose and ratio proinsulin/insulin (RPI) at both time points (r = 0.32 and 0.30) were also found. The RPI was lower after Gb intake. In patients on , 10.5 mg steady state serum metabolite levels (Ml and Ml + M2) were higher (29(0,120) and 33 (0,120) ng/ml) than those of Gb itself (18(0,64) ng/ml). A great inter-subject variability in Gb levels at both time points was seen. Conclusions Our results indicate that, in patients on chronic medication, Gb is capable of stimulating both insulin and proinsulin secretion; the effect on insulin release is relatively greater. The effect was more pronounced in patients on a low Gb dose, either because of less impaired ,-cells in those receiving low doses, or due to reduced sulphonylurea sensitivity in those on high dosage (down-regulation). In patients on a daily dose of 10.5 mg or more, serum metabolite levels of clinical relevance were demonstrated; the metabolites may contribute to hypoglycaemic events. [source]

Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan

DIABETIC MEDICINE, Issue 3 2010
V. Bravis
Diabet. Med. 27, 327,331 (2010) Abstract Background and Aims, During Ramadan, Muslims fast from dawn to dusk for one lunar month. The majority of Muslim diabetic patients are unaware of complications such as hypoglycaemia during fasting. The safety of fasting has not been assessed in the UK Muslim population with diabetes. The aim of this study was to determine the impact of Ramadan-focused education on weight and hypoglycaemic episodes during Ramadan in a Type 2 diabetic Muslim population taking oral glucose-lowering agents. Methods, We retrospectively analysed two groups. Group A attended a structured education programme about physical activity, meal planning, glucose monitoring, hypoglycaemia, dosage and timing of medications. Group B did not. Hypoglycaemia was defined as home blood glucose < 3.5 mmol/l. Results, There was a mean weight loss of 0.7 kg after Ramadan in group A, compared with a 0.6-kg mean weight gain in group B (P < 0.001). The weight changes observed were independent of the class of glucose-lowering agents used. There was a significant decrease in the total number of hypoglycaemic events in group A, from nine to five, compared with an increase in group B from nine to 36 (P < 0.001). The majority were in patients treated with short-acting sulphonylureas (group A,100%, group B,94%). At 12 months after attending the programme, glycated haemoglobin (HbA1c) reduction were sustained in group A. Conclusions, Ramadan-focused education in diabetes can empower patients to change their lifestyle during Ramadan. It minimizes the risk of hypoglycaemic events and prevents weight gain during this festive period for Muslims, which potentially benefits metabolic control. [source]