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Low Dosage (low + dosage)
Selected AbstractsLow levels of Sry transcripts cannot be the sole cause of B6-YTIR sex reversalGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 1 2001Chung-Hae Lee Abstract Summary: Sry, a single-copy gene on the Y-chromosome, triggers the fetal gonad to begin testis differentiation in mammals. On the other hand, mutation or absence of Sry results in ovary differentiation and the female phenotype. However, cases of XY sex reversal in the presence of wild-type Sry exist in mice and man. One such example is the B6-YTIR mouse, whose autosomes and X-chromosome are from the C57BL/6J mouse (an inbred strain of Mus musculus molossinus), whereas the Y-chromosome is from a Mus musculus domesticus mouse originating in Tirano, Italy. The B6-YTIR mouse never develops normal testes and instead develops ovaries or ovotestes in fetal life. It has been suggested that low levels of Sry transcription may account for the aberrant testis differentiation in the B6-YTIR mouse. In this study, however, we observed relatively low levels of Sry transcripts not only in B6-YTIR but also in B6 mice, which develop normal testes. We conclude that low dosage of Sry transcripts cannot be the sole cause of sex reversal in the B6-YTIR gonad. genesis 30:7,11, 2001. © 2001 Wiley-Liss, Inc. [source] Acute Myocardial Infarction With Sumatriptan: A Case Report and Review of the LiteratureHEADACHE, Issue 5 2009Flavio Devetag Chalaupka MD We report a case of myocardial infarction associated with the use of sumatriptan and review the literature regarding similar cases. A 54-year-old woman with a history of migraine without aura, mild arterial hypertension, depression, and no history of coronary artery disease was admitted to our hospital for acute myocardial infarction, 30 minutes after using 6 mg of subcutaneous sumatriptan. Coronary angiography performed several days later revealed a normal coronary arterial system. Although at discharge the patient was advised to permanently avoid triptans, she continued the use of oral sumatriptan at low dosage (25-50 mg) without any problems. [source] Simultaneous administration of a low-dose mixture of donor bone marrow cells and splenocytes plus adenovirus containing the CTLA4Ig gene result in stable mixed chimerism and long-term survival of cardiac allograft in ratsIMMUNOLOGY, Issue 2 2003Yongzhu Jin Summary T-cell costimulatory blockade combined with donor bone marrow transfusion may induce mixed chimerism, rendering robust tolerance in transplanted organs and cells. However, most protocols entail high doses of donor bone marrow cells (BMCs) or repeated administration of costly agents that block costimulatory pathways, thus delaying clinical development. To circumvent these shortcomings, we developed a strategy in which the dosage of donor BMCs was reduced but compensated by donor splenocytes (SPLCs). Furthermore, repeated administration of costly agents was replaced with a single injection of adenovirus expressing a gene of interest. In rat cardiac transplantation models, cardiac allografts from DA (RT-1a) rats were transplanted heterotopically into the abdomen of LEW (RT-11) recipient rats. Immediately after cardiac transplantation, an adenovirus vector (AdCTLA4Ig; 5 × 109 plaque-forming units) containing the gene for CTLA4Ig was administered to recipients (n = 6) simultaneously with a low dose of donor BMCs (1 × 108/rat) and SPLCs (5 × 107/rat) via the portal vein. The treated LEW recipient rats developed long-lasting mixed chimerism (>10% at >100 days) and exhibited long-term cardiac allografts (mean survival time of > 200 days) compared with control recipients. Moreover, recipients displaying long-lasting mixed chimerism accepted subsequent donor skin allografts while promptly rejecting third-party skin allografts. These results suggest that blockade of the CD28-B7 pathway, using adenovirus-mediated CTLA4Ig gene transfer, in concert with a low dosage of donor BMCs and SPLCs, may represent a feasible strategy to induce stable mixed chimerism and permit long-term survival of cardiac allografts. [source] Bullous variant of Sweet's syndromeINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2005Susanne Voelter-Mahlknecht MD A 69-year-old woman presented to our clinic as an emergency with erythematous, well-circumscribed plaques, which were partly vesicular, on her extremities and in her armpits, and additionally hemorrhagic blisters on both her palms and her fingers (Fig. 1a), which had developed 2 days after the first appearance of the skin lesions. The rapid onset of the lesions (within a few hours) and the pain associated with them were extremely troublesome to the patient. On admission she complained of fever, tiredness and being easily fatigued. Because of a urinary tract infection 1 month prior to admission, trospiumchloride was given. On clinical examination, body temperature was found to be above 38 °C and infraclavicular lymph nodes were enlarged but not tender. Figure 1. (a) Bullae on the patient's right hand. (b) Multiple partly confluent vesicles with neutrophilic granulocytes intraepidermally and a dense interstitial perivascular infiltration of neutrophilic granulocytes and lymphomononuclear cells (H&E, ×200) Normal or negative laboratory tests included blood counts, liver and kidney parameters, electrolytes and infection screen. Laboratory examination demonstrated minor leukocytosis and absolute neutrophilia (white blood cell count 10 440 cells/µL, neutrophils 8030 cells/µL). X-ray screening, abdominal ultrasound and laboratory investigations were all normal. There was no response to antibiotics when erythromycine was given. However, there was a good response to systemic corticosteroids. The patient was treated with a low dosage of prednisolone, beginning at 50 mg/day, which was then tapered off. Skin lesions resolved within 7 days. Histology from a lesion on the patient's left forearm showed a dense interstitial inflammatory infiltration consisting predominantly of neutrophilic granulocytes from the subepidermal layer to the middle of the reticular dermis. Inflammatory cells penetrated into both blood vessels and vessel walls; vasculitis was not prominent. In the lower dermis, perivascular infiltrations of lymphomononuclear cells were found. In addition, intraepidermally multiple partly confluent vesicles, with inclusions of neutrophilic granulocytes, were found, confirming the diagnosis of this rare variant of an acute febrile neutrophilic dermatosis (Fig. 1b). [source] Inhibition of Listeria monocytogenes in chicken cold cuts by addition of sakacin P and sakacin P-producing Lactobacillus sakeiJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2002T. Katla Aims: To evaluate the potential of sakacin P and sakacin P-producing Lactobacillus sakei for the inhibition of growth of Listeria monocytogenes in chicken cold cuts, by answering the following questions. (i) Is sakacin P actually produced in food? (ii) Is sakacin P produced in situ responsible for the inhibiting effect? (iii) How stable is sakacin P in food? Methods and Results:Listeria monocytogenes, a Lact. sakei strain and/or the bacteriocin sakacin P were added to chicken cold cuts, vacuum packed and incubated at 4 or 10°C for 4 weeks. Each of two isogenic Lact. sakei strains, one producing sakacin P and the other not, had an inhibiting effect on the growth of L. monocytogenes. The effect of these two isogenic strains on the growth of L. monocytogenes was indistinguishable, even though sakacin P was produced in the product by one of the two Lact. sakei strains. The addition of purified sakacin P had an inhibiting effect on the growth of L. monocytogenes. A high dosage of sakacin P (3·5 ,g g,1) had a bacteriostatic effect throughout the storage period of 4 weeks, while a low dosage (12 ng g,1) permitted initial growth, but at a slow rate. After 4 weeks of storage, the number of L. monocytogenes in the samples with a low dosage of sakacin P was 2 logs below that in the untreated control. When using a high dosage of sakacin P, the bacteriocin was detected in samples stored for up to 6 weeks. Conclusions: (i) Sakacin P is produced by a Lact. sakei strain when growing on vacuum-packed chicken cold cuts. (ii) Inhibiting effects of Lact. sakei, other than sakacin P, are active in inhibiting the growth of L. monocytogenes growing on chicken cold cuts. (iii) Sakacin P is stable on chicken cold cuts over a period of 4 weeks. Significance and Impact of the Study: Both sakacin P and Lact. sakei were found to have potential for use in the control of L. monocytogenes in chicken cold cuts. [source] Unusual hypersensitivity to warfarin in a critically ill patientJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2004H. Konishi PhD Summary A patient was admitted to the intensive care unit because of respiratory failure, and warfarin therapy was started at 2 mg/day for the treatment of pulmonary embolism, together with other medications. Despite the low dosage of warfarin, international normalized ratio (INR) was markedly elevated from 1·15 to 11·28 for only 4 days, and bleeding symptoms concurrently developed. Vitamin K2 was infused along with discontinuation of warfarin. One day later, the INR was found to have decreased, and bleeding was also improved. An objective causality assessment indicated a probable relationship between clotting abnormality and warfarin administration, although the degree of elevation of the INR was unusual in the light of the daily warfarin dose and duration of its exposure. Based on the clinical status of the patient, it was suspected that several conditions contributed to the abnormal hypersensitivity to warfarin. Contributory factors probably included pharmacokinetic interactions with co-administrated drugs, vitamin K deficiency caused by decreased dietary intake, reduced gut bacterial production, impaired intestinal absorption and hepatic synthetic capacity, and increased consumption of clotting factors. In view of our experience in the present case, it should be stressed that close monitoring of coagulation capacity is necessary in critically ill patients in order to avoid fatal haemorrhage after initiating warfarin therapy regardless of the dosage. [source] The role of entecavir in preventing hepatitis B recurrence after liver transplantationJOURNAL OF DIGESTIVE DISEASES, Issue 4 2009Zhi Feng XI OBJECTIVE: Although hepatitis B recurrence after liver transplantation has been reduced to 0%,10% since the application of the combination therapy of hepatitis B immunoglobulin (HBIG) and lamivudine, the viral mutation resistance of lamivudine is still an obstacle to the outcome of liver transplantation. Here we evaluate the role of entecavir in preventing hepatitis B recurrence after liver transplantation. METHODS: Patients who received a liver transplantation for hepatitis B virus (HBV)-related end-stage liver disease in our center from March 2006 to December 2008 were enrolled in this study. All patients received entecavir (0.5 mg orally, daily) or lamivudine (100 mg orally, daily) together with a long-term low dosage of HBIG to prevent hepatitis B recurrence after transplantation. Serum viral markers (HBsAg, anti-HBs, HBeAg, anti-HBc and anti-HBe) and HBV-DNA level were determined. RESULTS: Thirty patients receiving entecavir and 90 patients receiving lamivudine were matched with the same age and sex in both groups. No reinfection of hepatitis B was detected in the entecavir group. The hepatitis B surface antigen of patients in the entecavir group became negative within one week and no patient had any adverse effect relating to entecavir. There was no difference in the cumulative survival rate between the entecavir group and the lamivudine group (P > 0.05). CONCLUSION: This study shows that entecavir combined with low dosages of HBIG is effective and safe in preventing hepatitis B recurrence after liver transplantation, but its long-term effect is still under investigation and a large-sample study will be carried out in the future. [source] Masked intervention effects: Analytic methods for addressing low dosage of interventionNEW DIRECTIONS FOR EVALUATION, Issue 110 2006John E. Lochman This chapter describes potential drawbacks of using intent-to-treat (ITT) analyses to examine intervention effects and presents several additional analytic methods as alternatives to ITT. [source] Effect of Photothermal Therapy on Breast Tumor Vascular Contents: Noninvasive Monitoring by Near-infrared Spectroscopy,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2005Yueqing Gu ABSTRACT The goal of this study was to investigate the effect of photothermal laser irradiation on rat breast tumor (DMBA-4) vascular contents. An 805-nm diode laser was used in our experiment with a power density ranging from 0.32 to 1.27 W/cm2. The dynamic changes of oxygenated hemoglobin and total hemoglobin concentrations, ,[HbO2] and ,[Hb]total, in rat tumors during photothermal irradiation were noninvasively monitored by a near-infrared spectroscopy system. A multichannel thermal detection system was also used simultaneously to record temperatures at different locations within the tumors. Our experimental results showed that: (1) photoirradiation did have the ability to induce hyperthermic effects inside the rat breast tumors in a single exponential trend; (2) the significant changes (P < 0.005) of ,[HbO2] and ,[Hb]total in response to a low dosage of laser irradiation (0.32 W/cm2) have a single exponential increasing trend, similar to that seen in the tumor interior temperature; and (3) the increase in magnitude of ,[Hb]total is nearly two times greater than that of ,[Hb]total, suggesting that photoirradiation may enhance tumor vascular oxygenation. The last observation may be important to reveal the hidden mechanism of photoirradiation on tumors, leading to improvement of tumor treatment efficiency. [source] Facile synthesis and characterization of star-shaped polystyrene: self-condensing atom transfer radical copolymerization of N -[4-(,-bromoisobutyryloxy)phenyl]maleimide and styrenePOLYMER INTERNATIONAL, Issue 10 2008Yun Cao Abstract BACKGROUND: Generation of stars around in situ formed cores provides a facile approach to star-shaped polymers. Therefore the self-condensing atom transfer radical copolymerization (SCATRCP) of N -[4-(,-bromoisobutyryloxy)phenyl]maleimide (BiBPM) and a large excess of styrene (St) was investigated. RESULTS: BiBPM and St formed a charge transfer complex (CTC), which underwent the SCATRCP, leading to the branched core initiating the atom transfer radical polymerization of St, finally giving star-shaped polystyrene (PS). Kinetic and structural study showed that a higher dosage of BiBPM resulted in an enhanced polymerization rate, a higher degree of branching and a larger number of short PS arms. Differential scanning calorimetry suggested that the glass transition temperature of the star-shaped PS decreased with molecular weight. Melt rheometry showed that even a slightly branched architecture of the PS led to a significantly lower viscosity; both the melt flow index and the activation energy increased with the degree of branching. CONCLUSION: Due to the preferential consumption of BiBPM and formation of a CTC, even a very low dosage of BiBPM could lead to star-shaped PS, which, in comparison with linear analogues, could possess much better melt fluidity. Copyright © 2008 Society of Chemical Industry [source] A food safety control low mass-range proteomics platform for the detection of illicit treatments in veal calves by MALDI-TOF-MS serum profilingBIOTECHNOLOGY JOURNAL, Issue 11 2009Lorenza Della Donna Abstract Performance enhancing agents (PEAs) are illegally used in cattle and other meat producing species to increase food conversion and lean meat production. Due to the very short breeding cycle, veal calves represent the meat producing bovine category mostly subjected to illicit treatments. These chemical agents are difficult to detect by conventional analytical approaches due to the employment of synergistic formulations at very low dosage and given the use of uncharacterized novel compounds. Such a scenario has fostered a strong interest in the discovery of functional molecular biomarkers for the detection of growth promoting agents in meat producing species. A multivariate MALDI-TOF-MS proteomics platform has been developed using bovine serum samples. Analytical performances have been thoroughly evaluated in order to enable reproducible profiles from 10 ,L sera samples. We propose univariate and multivariate discrimination models capable to identify calves undergoing illicit treatments. In particular, we found a strong discrimination power associated with a polypeptide fragment from ,2-glycoprotein-I. We provide a fundamental proof of concept in the potential application of MALDI-TOF-MS proteomics profiling in the food safety control. [source] Homicidal ideation with intent during a manic episode triggered by antidepressant medication in a man with brain injuryBIPOLAR DISORDERS, Issue 1 2008Marie-José Dealberto Background:, Mood disorders are more frequent after brain injury and both depressive and manic episodes are associated in these patients with an increased risk of aggression. Antidepressant medications are associated with a risk of manic induction. Case report:, We describe a case of homicidal ideation with intent during the onset of a manic episode in a patient with prior brain injury on antidepressant medication at low dosage. The manic episode could have been secondary to brain injury and/or triggered by antidepressant medications. This case raises the possibility of the sensitizing role of brain injury for antidepressant-induced mania. Conclusions:, Further studies are needed to assess the role of brain injury as a risk factor for antidepressant-induced mania. Physicians should be cautious when prescribing antidepressants to patients with prior brain injury and inform them and their relatives of the possibility of a switch into mania. [source] Morphine-related apnoea in CPAP-treated preterm neonatesACTA PAEDIATRICA, Issue 9 2006Jan Enders Abstract Background: Morphine can be used to treat pain in preterm neonates with CPAP because of its analgetic potency; however, it is known to induce apnoea. Aim: To evaluate this risk of apnoea. Methods: We retrospectively analysed 91 preterm neonates with CPAP who received morphine intravenously. The incidence of apnoea 4 h before and after morphine administration was compared. The data were analysed for three dosage groups (<0.01, 0.01,0.03 and 0.03 mg/kg) and according to the incidence of apnoea before morphine application. Results: In the whole group (gestational age 29.1±2.9 wk, morphine dosage 0.017±0.01 mg/kg) we did not find differences in apnoea before and after morphine (0.9±1.8 vs 1.1±1.8 apnoea). The only significant increase in apnoea was seen in the subgroup of patients receiving,>,0.03 mg/kg (0.3±0.67 vs 1.5±2.5 apnoea). Interestingly, we found a significantly delayed increase in apnoea in the fourth hour. Conclusion: Morphine in preterm infants with CPAP is not widely accepted practice until further randomized studies evaluate efficacy and safety. Morphine in a low dosage (,0.03 mg/kg) did not significantly increase the apnoea rate in CPAP-treated preterm infants. For clinical work, it is very important to note that morphine-related apnoea may appear with a delay of approximately 4 h. [source] The role of entecavir in preventing hepatitis B recurrence after liver transplantationJOURNAL OF DIGESTIVE DISEASES, Issue 4 2009Zhi Feng XI OBJECTIVE: Although hepatitis B recurrence after liver transplantation has been reduced to 0%,10% since the application of the combination therapy of hepatitis B immunoglobulin (HBIG) and lamivudine, the viral mutation resistance of lamivudine is still an obstacle to the outcome of liver transplantation. Here we evaluate the role of entecavir in preventing hepatitis B recurrence after liver transplantation. METHODS: Patients who received a liver transplantation for hepatitis B virus (HBV)-related end-stage liver disease in our center from March 2006 to December 2008 were enrolled in this study. All patients received entecavir (0.5 mg orally, daily) or lamivudine (100 mg orally, daily) together with a long-term low dosage of HBIG to prevent hepatitis B recurrence after transplantation. Serum viral markers (HBsAg, anti-HBs, HBeAg, anti-HBc and anti-HBe) and HBV-DNA level were determined. RESULTS: Thirty patients receiving entecavir and 90 patients receiving lamivudine were matched with the same age and sex in both groups. No reinfection of hepatitis B was detected in the entecavir group. The hepatitis B surface antigen of patients in the entecavir group became negative within one week and no patient had any adverse effect relating to entecavir. There was no difference in the cumulative survival rate between the entecavir group and the lamivudine group (P > 0.05). CONCLUSION: This study shows that entecavir combined with low dosages of HBIG is effective and safe in preventing hepatitis B recurrence after liver transplantation, but its long-term effect is still under investigation and a large-sample study will be carried out in the future. [source] Effect of vitamin E and selenium on the tissue inhibitor of metalloproteinase-1 mRNA expression in hepatic stellate cellsJOURNAL OF DIGESTIVE DISEASES, Issue 3 2001Xuanhai Li OBJECTIVE: To investigate the effects of vitamin E and different doses of selenium on the expression of the tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA in the hepatic stellate cells (HSC) of CCl4 -induced hepato-fibrotic rats. The mechanism of these therapeutic actions is investigated at a molecular level. METHODS: Hepatic fibroses were induced by intraperitoneal injection of 40% CCl4 in olive oil and treated by dietary supplementation with vitamin E and different doses of selenium. Liver tissue sections were stained with routine hematoxylin and eosin staining and Masson trichrome staining for collagen. With ,-actin as an internal control, the reverse transcriptase,polymerase chain reaction (RT-PCR) method was applied to quantify the change of TIMP-1 mRNA in HSC. RESULTS: The expression level of TIMP-1 mRNA in HSC was significantly downregulated and collagenous fiber proliferation in the liver was also significantly reduced in the groups of rats treated with vitamin E (250 mg/kg) and low dosages of selenium (0.2 mg/kg). However, the expression of TIMP-1 mRNA was upregulated, but not significantly, in the group treated with high dosages of selenium (1.0 mg/kg). CONCLUSIONS: The expression level of TIMP-1 mRNA in HSC was significantly downregulated and collagenous fiber proliferation in the liver was significantly reduced in the groups of rats treated with vitamin E and appropriate dosages of selenium. This did not occur in groups with high dosages of selenium. [source] Transgenerational marking of marine fish larvae: stable-isotope retention, physiological effects and health issuesJOURNAL OF FISH BIOLOGY, Issue 4 2009D. H. Williamson This study examined the toxicological and physiological responses of a commercially important coral-reef grouper, Plectropomus leopardus (Serranidae), to injection of enriched stable-isotope barium chloride (BaCl2) solution. Thirty adult P. leopardus were subject to one of two 138BaCl2 injection treatment groups (corresponding to dosage rates of 2 and 4 mg 138Ba kg,1 body mass), and a control group in which fish were injected with 0·9% sodium chloride (NaCl) solution. Fish from each group were sampled at post-injection intervals of 48 h and 1, 3, 5 and 8 weeks, at which time blood and tissue samples were removed from each fish. Residual concentrations of Ba and 138Ba:137Ba ratios were measured in muscle, gonad, liver and bone tissues of each experimental fish. Elevated Ba concentrations were detected in all treatment fish tissue samples within 48 h post injection. Residual Ba concentrations decreased throughout the remainder of the 8 week experimental period in all tissues except bone. The BaCl2 injection had no significant effects on measured whole blood variables or on the plasma concentrations of steroid hormones. Enriched Ba stable isotopes can therefore be used at low dosages to mark larvae of commercially important marine fishes, without adverse effects on the health of the fishes or on humans who may consume them. [source] PHYSIOLOGIC ABNORMALITIES AS BIOLOGIC MARKERS IN SEVERE, INTRACTABLE PAINPAIN MEDICINE, Issue 2 2002Article first published online: 4 JUL 200 Forest Tennant, MD, Dr PH; Laura Herman RN BSN FNP Veract Intractable Pain Centers, 338 S. Glendora Ave., West Covina, CA 91790 It is recognized that biologic markers of severe, intractable pain (SIP) can help distinguish degrees of pain and assist in monitoring treatment effectiveness. Fifty (50.0%) adult ambulatory SIP patients, at the time of referral described their pain as constant, excruciating, produced a bed or house-bound state, and was uncontrolled by non-opioid medications and low dosages of the weak opioids, hydrocodone or codeine. Patients were treated with a long-acting opioid preparation consisting of methadone, oxycodone, morphine, or transdermal fentanyl in addition to a short-acting opioid for breakthrough pain. These patients were screened before treatment and after three months of opioid treatment by: (1) blood pressure; (2) pulse rate; (3) morning cortisol and pregnenolone serum concentrations; and (4) erythrocyte sedimentation rate (ESR). The percentage of patients with physiologic abnormalities before and after three months of treatment were as follows: (1) hypertension above 140/90 mm/Hg; 28 (56.0%) vrs 14 (28.0%); (2) tachycardia above 84/minute; 21 (42.0%) vrs 9 (18.0%); (3) elevated serum cortisol concentration; 12 (24.0%) vrs 2 (4.0%); (4) low serum cortisol serum concentration; 7 (14.0% vrs 1 (2.0%); (5) low pregnenolone serum concentration; 18 (36.0%) vrs 3 (6.0%); and (6) elevated ESR; 10 (20.0%) vrs 3 (6.0%) (p<.05). Mean blood pressure, pulse rate, ESR, and serum concentrations of cortisol and pregnenolone in patients who demonstrated a physiologic abnormality all positively and significantly (p<.05) altered these markers toward normal. This study indicates that some physiologic abnormalities, particularly those related to pituitary-adrenal over-stimulation with excess output of catecholamines and glucocorticoids, may serve as biologic markers which can help to identify SIP and monitor treatment effectiveness. [source] Uses of Diverted Methadone and Buprenorphine by Opioid-Addicted Individuals in Baltimore, MarylandTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 5 2009Shannon Gwin Mitchell PhD This study examined the uses of diverted methadone and buprenorphine among opiate-addicted individuals recruited from new admissions to methadone programs and from out-of-treatment individuals recruited from the streets. Self-report data regarding diversion were obtained from surveys and semi-structured qualitative interviews. Approximately 16% (n = 84) of the total sample (N = 515) reported using diverted (street) methadone two,three times per week for six months or more, and for an average of 7.8 days (SD = 10.3) within the past month. The group reporting lifetime use of diverted methadone as compared to the group that did not report such use was less likely to use heroin and cocaine in the 30 days prior to admission (ps < .01) and had lower ASI Drug Composite scores (p < .05). Participants in our qualitative sub-sample (n = 22) indicated that street methadone was more widely used than street buprenorphine and that both drugs were largely used as self-medication for detoxification and withdrawal symptoms. Participants reported using low dosages and no injection of either medication was reported. [source] Neural and orofacial defects in Folbp1 knockout mice ,BIRTH DEFECTS RESEARCH, Issue 4 2003Louisa S. Tang Abstract BACKGROUND Folic acid is essential for the development of the nervous system and other associated structures. Mice deficient in the folic acid-binding protein one (Folbp1) gene display multiple developmental abnormalities, including neural and craniofacial defects. To better understand potential interactions between Folbp1 gene and selected genes involved in neural and craniofacial morphogenesis, we evaluated the expression patterns of a panel of crucial differentiation markers (Pax-3, En-2, Hox-a1, Shh, Bmp-4, Wnt-1, and Pax-1). METHODS Folbp1 mice were supplemented with low dosages of folinic acid to rescue nullizygotes from dying in utero before gestational day 10. The gene marker analyses were carried out by in situ hybridization. RESULTS In nullizygote embryos with open cranial neural tube defects, the downregulation of Pax-3 and En-2 in the impaired midbrain, along with an observed upregulation of the ventralizing marker Shh in the expanded floor plate, suggested an important regulatory interaction among these three genes. Moreover, the nullizygotes also exhibit craniofacial abnormalities, such as cleft lip and palate. Pax-3 signals in the impaired medial nasal primordia were significantly increased, whereas Pax-1 showed no expression in the undeveloped lateral nasal processes. Although Shh was downregulated, Bmp-4 was strongly expressed in the medial and lateral nasal processes, highlighting the antagonistic activities of these molecules. CONCLUSIONS Impairment of Folbp1 gene function adversely impacts the expression of several critical signaling molecules. Mis-expression of these molecules, perhaps mediated by Shh, may potentially contribute to the observed failure of neural tube closure and the development of craniofacial defects in the mutant mice. Birth Defects Research (Part A) 67:209,218, 2003. © 2003 Wiley-Liss, Inc. [source] Role of valproate across the ages.ACTA NEUROLOGICA SCANDINAVICA, Issue 2006Treatment of epilepsy in the elderly In June 2005, a team of experts participated in a workshop with the objective of reaching agreement on several important aspects of valproate in the treatment of elderly patients with epilepsy. Epilepsy in the elderly is relatively common and its incidence increases for each decade after age 60. The aetiology and manifestations of epilepsies in the elderly are complex because of comorbidity and other underlying risk factors. A consensus was reached that elderly patients who present with a seizure disorder should be referred rapidly to a specialist and that diagnosis should be improved by using a multidisciplinary team of cardiologists, neurologists and epilepsy experts (syncope, falls and seizure specialists). This is especially important to avoid mistreatment with antiepileptic drugs (AEDs). There was consensus that the elderly are generally more susceptible to the adverse effects of AEDs than younger adults. For these reasons, in older persons AEDs should be started at low dosages, and titrated slowly according to clinical response. Some of the most troublesome side effects of AEDs in the elderly include sedation and cognitive side effects, as well as osteoporosis. Drug,drug interactions should be given special consideration. There was consensus that the pharmacokinetics of all AEDs are altered in the elderly, and that the most significant change common to all AEDs is a moderate reduction in renal and metabolic clearance. Predicting pharmacokinetic changes in the individual, however, can be very difficult because multiple factors contribute to a high inter-patient variability. There was agreement on the advantages and disadvantages of the use of valproate in the elderly, and consensus that valproate is a useful option in this population. There was no consensus, however, on whether valproate should be considered among the preferred first-line treatments in the elderly. [source] | ||||||||||||||||