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Oral Treatment (oral + treatment)
Selected AbstractsA 4-trifluoromethyl derivative of salicylate, triflusal, stimulates nitric oxide production by human neutrophils: role in platelet functionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2000De Miguel Background The thrombotic process is a multicellular phenomenon in which not only platelets but also neutrophils are involved. Recent in vitro studies performed in our laboratory have demonstrated that triflusal, a 4-trifluoromethyl derivative of salicylate, reduced platelet aggregation not only by inhibiting thromboxane A2 production but also by stimulating nitric oxide (NO) generation by neutrophils. The aim of the present study was to evaluate whether oral treatment of healthy volunteers with triflusal could modify the ability of their neutrophils to produce NO and to test the role of the NO released by neutrophils in the modulation of ADP-induced platelet aggregation and ,-granule secretion. Methods The study was performed in 12 healthy volunteers who were orally treated with triflusal (600 mg day,1) for 5 days. Flow cytometric detection of platelet surface expression of P-selectin was used as a measure of the ability of platelets to release the contents of their ,-granules. Results After treatment with triflusal, there was an increase in NO production by neutrophils and an increase in endothelial nitric oxide synthase (eNOS) protein expression in neutrophils. A potentiation of the inhibition of platelet aggregation by neutrophils was reversed by incubating neutrophils with both an l -arginine antagonist, NG -nitro- l -arginine methyl ester ( l -NAME) and an NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline 1-oxyl 3-oxide (C-PTIO). A slight decrease in P-selectin surface expression on platelets was found which was not modified by the presence of neutrophils and therefore by the neutrophil-derived NO. Exogenous NO released by sodium nitroprusside dose-dependently inhibited both ADP-stimulated ,-granule secretion and platelet aggregation. Therefore, platelet aggregation showed a greater sensitivity to be inhibited by exogenous NO than P-selectin expression. Conclusion Oral treatment of healthy volunteers with triflusal stimulated NO production and eNOS protein expression in their neutrophils. After triflusal treatment, the neutrophils demonstrated a higher ability to prevent ADP-induced platelet aggregation. However, the neutrophils and the endogenous NO generated by them failed to modify P-selectin expression in ADP-activated platelets. [source] The lipid-lowering effect of trans -dehydrocrotonin, a clerodane diterpene from Croton cajucara Benth. in mice fed on high-fat dietJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2001Regilane M. Silva The clerodane diterpene trans -dehydrocrotonin extracted and isolated from the stem bark of Croton cajucara Benth. was investigated for its lipid-lowering effect in mice fed on a high-fat diet. Mice fed on a high-fat diet for a two-week period demonstrated significantly increased blood levels of total cholesterol and triglycerides, compared with normal controls. Oral treatment with trans -dehydrocrotonin at a dose of 25 or 50 mg kg,1 daily markedly suppressed the high-fat-diet associated rise in total cholesterol and triglyceride levels. The hypocholesterolaemic effect of trans -dehydrocrotonin was more prominent at the dose of 50 mg kg,1 with significant decreases in high-density lipoprotein, very-low-density lipoprotein and low-density lipoprotein cholesterol levels. The lower atherogenic index of the trans -dehydrocrotonin-treated groups suggests the hypolipidaemic potential of this plant-based drug. These results indicate that orally administered trans -dehydrocrotonin is effective in suppressing high-fat-diet-induced hyperlipidaemia in mice and suggest its likely beneficial use as anti-atherogenic agent. [source] Latest news and product developmentsPRESCRIBER, Issue 6 2007Article first published online: 8 JUN 200 Initial macrolide better for pneumonia? An observational study has suggested that initial treatment with a macrolide antibiotic (such as erythromycin) may be more effective than a fluoroquinolone (like ciprofloxacin) or tetracycline as initial treatment for community acquired pneumonia and bacteraemia (Chest 2007;131:466-73). The US review of 2209 hospital episodes found that macrolide therapy was associated with a 40 per cent lower risk of death during hospital stay or within 30 days and of hospital readmission within 30 days of discharge. By contrast, no such benefit was apparent with fluoroquinolones or tetracycline. Two-year safety data for inhaled insulin Compared with sc insulin, inhaled insulin (Exubera) is associated with a small early decrease in lung function in the first three months of therapy but no further difference for up to two years (Diabetes Care 2007;30: 579-85). The comparative trial found that FEV1 declined at a mean rate of 0.051 litres per year with inhaled insulin and 0.034 litres per year with sc insulin, but there was no significant difference in the rates of decline after three months. Inhaled insulin was associated with a higher incidence of cough (37.6 vs 13.1 per cent) but a lower incidence of severe hypoglycaemic events (2.8 vs 4.1 events per 100 subject- months) and mean weight gain was 1.25kg less. Fracture risk warning with rosiglitazone GlaxoSmithKline has warned US prescribers that rosiglitazone may be associated with an increased risk of fractures. The company says information for prescribers in Europe will follow shortly. The warning comes from the ADOPT study (N Engl J Med 2006;355:2427-43), which found a significantly higher incidence of fractures of the humerus, hand and foot among women taking rosiglitazone (9.3 per cent) than with metformin (5.1 per cent) or glibenclamide (3.5 per cent). There was no difference in fracture incidence among men. The company recommends that fracture risk should be considered for women taking or about to take rosiglitazone. Oral treatment for grass pollen allergy A new treatment for allergic rhinitis due to grass pollen allergy has been introduced by ALK-Abelló. Grazax is a sublingual tablet containing a stan-dardised dose of allergen from the pollen of timothy grass. Treatment should be initiated by a specialist four months before the onset of the allergy season and continued throughout the season. Adverse effects include oral and ear pruritus, nasopharyngitis and mouth oedema. A month's treatment at the recommended dose of one tablet daily costs £67.50. Frequent analgesics linked with hypertension Men who take analgesics regularly have an increased frequency of hypertension, a US study has shown (Arch Intern Med 2007;167:394-9). The US Health Professionals Follow-Up study evaluated the use of NSAIDs, paracetamol and aspirin in 16 031 men with normal blood pressure and followed them up for four years. Compared with those who did not report analgesic use, the risk of hypertension was increased by 38 per cent for NSAID use, 34 per cent for paracetamol and 26 per cent for aspirin, all for for six or seven days a week. Similar risks were found when anal- gesic use was determined according to the number of tablets taken. The authors acknowledge the increased risk is modest, but point out that the implications may nonetheless be important because analgesics are widely used. Multiples do most pharmacist MURs Uptake of medicines use reviews (MURs) by pharmacists was modest in 2005 and most reviews were carried out by pharmacy chains rather than independent contractors, a new study has shown (Pharm J 2007;278:218-23). The survey of PCTs and SHAs in England and Wales found that, although 38 per cent of community pharmacies claimed payments for the service, 84 per cent of MURs were carried out by pharmacy chains. Uptake was low, amounting to only 7 per cent of the maximum possible number of MURs. Patients see information needs differently There is a mismatch in the perceptions of patients and health professionals about the purpose of written information about medicines, a systematic review has concluded (Health Technol Assess 2007;11:1-178). Some health professionals believe the main purpose of information is to promote compliance, whereas patients want information to help them make decisions about their treatment, including not taking it. In particular, patients want information on adverse effects, but health professionals have reservations about providing it. Aspirin for all women over 65? All women over 65 should take low-dose aspirin if the benefits are likely to outweigh the risk of adverse effects, according to new guidelines from the American Heart Association on preventing cardiovascular disease in women (published online 19 Feb 2007;doi: 10.1161/circulationaha.107.181546). The guidelines have moved away from the long-established Framingham model of risk assessment to categorising three levels of risk: high (heart disease or other relevant disease present), at risk (at least one risk factor) and optimal (healthy lifestyle, no risk factors). Low-dose aspirin is recommended for all women at high risk, for women aged 65 or over when reducing the risk of MI or ischaemic stroke outweighs the risk of adverse effects, and for younger women when reducing the risk of ischaemic stroke outweighs that of toxicity. Combination inhaler therapy Combining an inhaled long-acting bronchodilator with a steroid reduces COPD exacerbations but not all-cause mortality, a three-year trial has shown (N Engl J Med 2007;356:775-89). However, inhaled steroids appear to increase the risk of pneumonia. The TORCH trial randomised 6112 patients (FEV1<60 per cent predicted) to treatment with salmeterol 50µg plus fluticasone 500µg (Seretide) twice daily, salmeterol (Serevent) or fluticasone (Flixotide) as monotherapy, or placebo. All-cause mortality rates were 12.6, 13.5, 16.0 and 15.2 per cent respectively; the risk of death was 17 per cent lower with combined therapy, but the difference did not reach statistical significance. The combination reduced the incidence of exacerbations by 25 per cent and improved health status and FEV1. Use of fluticasone was not associated with more ocular or bone disorders, but there was an increased incidence of pneumonia among users (19.6 per cent with combined therapy and 18.3 per cent with fluticasone vs 12.3 per cent with placebo). Seretide is currently licensed in the UK for use in patients with FEV1 <50 per cent predicted. Tamoxifen long- term benefits Women with breast cancer who take tamoxifen for five to eight years continue to have a lower risk of recurrence for 10-20 years, long-term follow-up of two blinded trials has shown (J Nat Cancer Inst 2007; 99:258-60, 272-90). The frequency of adverse effects was markedly reduced when treatment ended, changing the balance of risk and benefit. Copyright © 2007 Wiley Interface Ltd [source] Efficacy and Tolerability of Lodenafil Carbonate for Oral Therapy in Erectile Dysfunction: A Phase II Clinical TrialTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2009Sidney Glina MD ABSTRACT Introduction., Oral treatment with phosphodiesterase type 5 inhibitor (PDE5) is considered the first-line treatment for patients with erectile dysfunction (ED). Lodenafil carbonate (LC) is a novel PDE5. Aim., This is a phase II, prospective, randomized, double-blind, and placebo controlled clinical trial of LC. Main Outcome Measures., Efficacy end points were International Index of Sexual Function (IIEF) erectile domain, IIEF questions 3 and 4, and Sexual Encounter Profile (SEP) questions 2 and 3, before and after the use of LC or placebo. Methods., Seventy-two men older than 18 years, with ED for at least 6 months with stable sexual relationship were enrolled. Patients were randomized to placebo or LC 80 mg, 40 mg, or 20 mg and followed for 4 weeks. Results., IIEF erectile domain scores before and after the use of medications were (mean ± standard deviation [SD]): placebo: 11.9 ± 3.4 and 12.6 ± 5.5; LC 20 mg: 15.8 ± 4.1 and 18.9 ± 6.6; LC 40 mg: 11.9 ± 4.4 and 15.4 ± 8.1; LC 80 mg: 14.2 ± 4.7 and 22.8 ± 6.0 (anovaP < 0.01). The SEP-2 scores before and after the use of medications were (Mean ± SD): placebo: 71.0 ± 33.1 and 51.2 ± 43.1; LC 20 mg 70.3 ± 34.2 and 75.5 ± 31.5; LC 40 mg: 48.4 ± 42.1 and 60.8 ± 42.5; LC 80 mg: 68.6 ± 33.5 and 89.6 ± 26.0. The SEP-3 scores were: placebo 23.3 ± 27.6 and 33.6 ± 42.3; LC 20 mg: 32.3 ± 38.9 and 51.2 ± 41.7; LC 40 mg: 39.7 ± 44.7 and 46.7 ± 41.1; LC 80 mg* 17.2 ± 29.5 and 74.3 ± 36.4 (*P < 0.05 for difference to placebo). Conclusions., The drug was well tolerated. Adverse reactions were mild and self-limited and included headache, rhinitis, flushing, color visual disorders, and dyspepsia. This study showed that the dosage of 80 mg of LC was significantly more efficacious than placebo and well tolerated. Glina S, Toscano I, Gomatzky C, de Góes PM, Júnior AN, de Almeida Claro JF, and Pagani E. Efficacy and tolerability of lodenafil carbonate for oral therapy in erectile dysfunction: A phase II clinical trial. J Sex Med 2009;6:553,557. [source] Oral treatment and in vitro incubation with fructose modify vascular prostanoid production in the ratAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1 2006H. A. Peredo Summary 1 In the rat, a fructose-enriched diet induces hyperglycaemia, hypertriglyceridaemia, insulin resistance and hypertension; a model which resembles the human metabolic syndrome. 2 Prostanoids, metabolites of arachidonic acid, include vasoactive substances synthesized and released from the vascular wall that have been implicated in the increase of peripheral resistance, one of the mechanisms involved in the fructose-induced hypertension. 3 The aim of the present study was to: (i) analyse the effects of the in vitro incubation with fructose on the production and release of prostanoids in rat thoracic aorta and in rat mesenteric bed and (ii) compare the effects of incubation with those of the in vivo acute and chronic treatment of rats with fructose and with the combination of both in vivo and in vitro procedures. 4 Blood pressure, glycaemia and triglyceridaemia were significantly elevated in both 4- and 22-week fructose-treated groups. Meanwhile, body and heart weight as well as insulinaemia were similar between experimental animals and controls. 5 In aortae, 4 weeks of Fructose treatment did not modify the prostanoid pattern release, but in vitro incubation decreased prostacyclin (PGI2) production. However, after 22 weeks, fructose treatment and incubation exerted the same effect. 6 In mesenteric bed, after 4 weeks, the incubation and the combination of both procedures reduced the release of the vasodilators PGI2 and PGE2, while fructose treatment only diminished the PGE2 release. On the contrary, the production of the vasoconstrictor thromboxane A2 (TXA2) was enhanced by incubation and both the procedures. After 22 weeks, fructose treatment increased PGI2 release, while it was reduced by incubation. The combination of both did not modify this peripheral resistance when compared with controls. Finally, incubation of tissues from treated rats increased the release of the vasoconstrictors, PGF2, and TXA2. 7 In conclusion, the mesenteric bed, a resistance vascular bed, seems to be more sensitive than the aorta, a conductance vessel, to the effects of fructose on prostanoid production. This difference could be related to a more relevant role of resistance vessels in the regulation of peripheral resistance and consequently of blood pressure. The observed effects should contribute to a shift in the balance of the release of prostanoid in favour of vasoconstrictor metabolites. This phenomenon could be related to an increase in the peripheral resistance and the mild hypertension observed in the fructose-treated rats. [source] Discovery of Selective Irreversible Inhibitors for Bruton's Tyrosine KinaseCHEMMEDCHEM, Issue 1 2007Zhengying Pan Dr. A series of highly selective irreversible inhibitors for Bruton's tyrosine kinase (Btk) was developed using a structural bioinformatics approach. Their capabilities to modulate Btk's activity were characterized both in,vitro and in,vivo. Oral treatment with once-a-day dosing of compound 4 greatly inhibited disease development in a rodent rheumatoid arthritis (RA) model. [source] Prurigo nodularis: A reviewAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 4 2005Michael R Lee SUMMARY Prurigo nodularis is a chronic condition characterized by a papulonodular pruriginous eruption of unknown aetiology. This condition is a difficult disease to treat and causes frustration to both the patient and the treating doctor. A variety of systemic conditions have been reported to be associated with prurigo nodularis. The mechanism by which these disorders may trigger prurigo nodularis is unknown. Nerve growth factor has been implicated in the pathogenesis of prurigo nodularis. Calcitonin gene-related peptide and substance P immunoreactive nerves are markedly increased in prurigo nodularis when compared with normal skin. These neuropeptides may mediate the cutaneous neurogenic inflammation and pruritus in prurigo nodularis. Topical or intralesional glucocorticoids are the treatment of choice. Other topical treatments such as topical vitamin D3, and topical capsaicin have also been reported to be effective. Oral treatments such as cyclosporin and thalidomide have been shown to improve both appearance of the skin and pruritus. We review the clinical features, associations, pathology, pathogenesis and treatment of prurigo nodularis. [source] Ascorbic acid oral treatment modifies lipolytic response and behavioural activity but not glucocorticoid metabolism in cafeteria diet-fed ratsACTA PHYSIOLOGICA, Issue 4 2009D. F. Garcia-Diaz Abstract Aim:, To analyse the effects of vitamin C (VC), a potent dietary antioxidant, oral supplementation on body weight gain, behavioural activity, lipolytic response and glucocorticoid metabolism in the early stages of diet-induced overweight in rats. Methods:, Food intake, locomotive activity and faecal corticosterone were assessed during the 14 day trial period. After 2 weeks, the animals were sacrificed and the body composition, biochemical markers and lipolytic response from isolated adipocytes from retroperitoneal white adipose tissue were examined. Results:, The intake of a high-fat diet by rats induced a significant increase in body weight, adiposity and insulin resistance markers as well as a decrease in faecal corticosterone levels compared with standard diet-fed rats. Interestingly, the animals fed on the cafeteria diet showed a significant increase in the isoproterenol-induced lipolytic response in isolated adipocytes. Furthermore, this cafeteria-fed group showed a reduced locomotive behaviour than the control rats. On the other hand, oral VC supplementation in animals receiving the high-fat diet restored the cafeteria diet effect in some of the analysed variables such as final body weight and plasma insulin to control group levels. Remarkably, increases in locomotive behaviour and a significant decrease in the lipolytic response induced by isoproterenol on isolated adipocytes from animals treated with VC were observed. Conclusion:, This work demonstrates that an oral ascorbic acid supplementation has direct effects on behavioural activity and on adipocyte lipolysis in early obesity stages in rats, which could indicate a protective short-term role of this vitamin against adiposity induced by chronic high-fat diet consumption. [source] A 4-trifluoromethyl derivative of salicylate, triflusal, stimulates nitric oxide production by human neutrophils: role in platelet functionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2000De Miguel Background The thrombotic process is a multicellular phenomenon in which not only platelets but also neutrophils are involved. Recent in vitro studies performed in our laboratory have demonstrated that triflusal, a 4-trifluoromethyl derivative of salicylate, reduced platelet aggregation not only by inhibiting thromboxane A2 production but also by stimulating nitric oxide (NO) generation by neutrophils. The aim of the present study was to evaluate whether oral treatment of healthy volunteers with triflusal could modify the ability of their neutrophils to produce NO and to test the role of the NO released by neutrophils in the modulation of ADP-induced platelet aggregation and ,-granule secretion. Methods The study was performed in 12 healthy volunteers who were orally treated with triflusal (600 mg day,1) for 5 days. Flow cytometric detection of platelet surface expression of P-selectin was used as a measure of the ability of platelets to release the contents of their ,-granules. Results After treatment with triflusal, there was an increase in NO production by neutrophils and an increase in endothelial nitric oxide synthase (eNOS) protein expression in neutrophils. A potentiation of the inhibition of platelet aggregation by neutrophils was reversed by incubating neutrophils with both an l -arginine antagonist, NG -nitro- l -arginine methyl ester ( l -NAME) and an NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline 1-oxyl 3-oxide (C-PTIO). A slight decrease in P-selectin surface expression on platelets was found which was not modified by the presence of neutrophils and therefore by the neutrophil-derived NO. Exogenous NO released by sodium nitroprusside dose-dependently inhibited both ADP-stimulated ,-granule secretion and platelet aggregation. Therefore, platelet aggregation showed a greater sensitivity to be inhibited by exogenous NO than P-selectin expression. Conclusion Oral treatment of healthy volunteers with triflusal stimulated NO production and eNOS protein expression in their neutrophils. After triflusal treatment, the neutrophils demonstrated a higher ability to prevent ADP-induced platelet aggregation. However, the neutrophils and the endogenous NO generated by them failed to modify P-selectin expression in ADP-activated platelets. [source] The role of the cutaneous cholinergic system in guttate psoriasisEXPERIMENTAL DERMATOLOGY, Issue 7 2008W. Dyck In previous studies, high levels of acetylcholine (ACh) have been reported in psoriasis lesions. In addition, patients with guttate psoriasis respond to oral treatment with atropine. We wanted to know how the cutaneous cholinergic system could be involved in this process. Since mast cells (MC) are characteristic components of the inflammatory infiltrate of guttate psoriasis, we compared ACh receptor (AChR) composition and ACh production in both epidermis and mast cells of 10 patients with guttate psoriasis in involved and uninvolved skin on protein level using immunofluorescence and in a MC line (HMC-1) using PCR. We could confirm the presence of numerous MC in guttate psoriasis lesion. Both in vivo and in vitro, MC lacked expression of cholinacetyltransferase (ChAT), vesicular acetylcholintransorter (VAChT) and cholintransporter-1 (ChT-1) but contained high levels of acetylcholinesterase (AChE). In mast cells of both involved and uninvolved skin we found both nicotinic (,3, ,5, ,7, ,9, ,10, ,2 and ,4 subunits) and muscarinic (M1, M3, M4, M5) AChR. In HMC-1 cells all AChR subunits found in skin where present on mRNA level, except ,7 and ,2. In lesional epidermis both ACh production and AChR expression was shifted from the basal to the suprabasal layers especially the nicotinic ,3, ,5, ,9, ,2 and ,4 and the muscarinic M3 and M5 AChR subunits. Our results exclude a role of the cholinergic system in the initiation of keratinocyte proliferation in the basal epidermal layer but point towards a role of epidermal AChR in suprabasal processes, most likely terminal differentiation and barrier formation as has been shown in other systems. Most importantly, mast cells are targets of paracrine and endocrine effects mediated by ACh and choline thus modulating inflammatory processes like guttate psoriasis and explaining the clinical efficacity of anticholinergic drugs like atropine. [source] Prevention of hypertension-induced cardiac hypertrophy in rats by oral treatment with the Crataegus special extract WS 1442FOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 2004E Koch [source] Dental procedures in adult patients with hereditary bleeding disorders: 10 years experience in three Italian Hemophilia CentersHAEMOPHILIA, Issue 5 2005M. Franchini Summary., Excessive bleeding after dental procedures are one of the most frequent complications occurring in patients with hereditary bleeding disorders. In this retrospective study we collected data from 10 years of experience in the oral care of patients with congenital haemorrhagic disorders in three Italian Hemophilia Centers. Between 1993 and 2003, 247 patients with inherited bleeding disorders underwent 534 dental procedures including 133 periodontal treatments, 41 conservative dentistry procedures, 72 endodontic treatments and 288 oral surgery procedures. We recorded 10 bleeding complications (1.9%), most of which occurred in patients with severe/moderate haemophilia A undergoing multiple dental extractions. Thus, our protocol of management of patients with hereditary bleeding tendency undergoing oral treatment or surgery has been shown to be effective in preventing haemorrhagic complications. [source] A Double-Blind Comparison of OnabotulinumtoxinA (BOTOX®) and Topiramate (TOPAMAX®) for the Prophylactic Treatment of Chronic Migraine: A Pilot StudyHEADACHE, Issue 10 2009Ninan T. Mathew MD Background., There is a need for effective prophylactic therapy for chronic migraine (CM) that has minimal side effects. Objective., To compare the efficacy and safety of onabotulinumtoxinA (BOTOX®, Allergan, Inc., Irvine, CA) and topiramate (TOPAMAX®, Ortho-McNeil, Titusville, NJ) prophylactic treatment in patients with CM. Methods., In this single-center, double-blind trial, patients with CM received either onabotulinumtoxinA, maximum 200 units (U) at baseline and month 3 (100 U fixed-site and 100 U follow-the-pain), plus an oral placebo, or topiramate, 4-week titration to 100 mg/day with option for additional 4-week titration to 200 mg/day, plus placebo saline injections. OnabotulinumtoxinA or placebo saline injection was administered at baseline and month 3 only, while topiramate oral treatment or oral placebo was continued through the end of the study. The primary endpoint was treatment responder rate assessed using Physician Global Assessment 9-point scale (+4 = clearance of signs and symptoms and ,4 = very marked worsening [about 100% worse]). Secondary endpoints included the change from baseline in the number of headache (HA)/migraine days per month (HA diary), and HA disability measured using Headache Impact Test (HIT-6), HA diary, Migraine Disability Assessment (MIDAS) questionnaire, and Migraine Impact Questionnaire (MIQ). The overall study duration was approximately 10.5 months, which included a 4-week screening period and a 2-week optional final safety visit. Follow-up visits for assessments occurred at months 1, 3, 6, and 9. Adverse events (AEs) were documented. Results., Of 60 patients randomized to treatment (mean age, 36.8 ± 10.3 years; 90% female), 36 completed the study at the end of the 9 months of active treatment (onabotulinumtoxinA, 19/30 [63.3%]; topiramate, 17/30 [56.7%]). In the topiramate group, 7/29 (24.1%) discontinued study because of treatment-related AEs vs 2/26 (7.7%) in the onabotulinumtoxinA group. Between 68% and 83% of patients for both onabotulinumtoxinA and topiramate groups reported at least a slight (25%) improvement in migraine; response to treatment was assessed using Physician Global Assessment at months 1, 3, 6, and 9. Most patients in both groups reported moderate to marked improvements at all time points. No significant between-group differences were observed, except for marked improvement at month 9 (onabotulinumtoxinA, 27.3% vs topiramate, 60.9%, P = .0234, chi-square). In both groups, HA/migraine days decreased and MIDAS and HIT-6 scores improved. Patient-reported quality of life measures assessed using MIQ after treatment with onabotulinumtoxinA paralleled those seen after treatment with topiramate in most respects. At month 9, 40.9% and 42.9% of patients in the onabotulinumtoxinA and topiramate groups, respectively, reported ,50% reduction in HA/migraine days. Forty-one treatment-related AEs were reported in 18 onabotulinumtoxinA-treated patients vs 87 in 25 topiramate-treated patients, and 2.7% of patients in the onabotulinumtoxinA group and 24.1% of patients in the topiramate group reported AEs that required permanent discontinuation of study treatment. Conclusions., OnabotulinumtoxinA and topiramate demonstrated similar efficacy in the prophylactic treatment of CM. Patients receiving onabotulinumtoxinA had fewer AEs and discontinuations. [source] Intra-Arterial Milrinone for Reversible Cerebral Vasoconstriction SyndromeHEADACHE, Issue 1 2009Manon Bouchard MD Reversible cerebral vasoconstriction syndrome (RCVS) usually presents with recurrent thunderclap headaches and is characterized by multifocal and reversible vasoconstriction of cerebral arteries that can sometimes evolve to severe cerebral ischemia and stroke. We describe the case of a patient who presented with a clinically typical RCVS and developed focal neurological symptoms and signs despite oral treatment with calcium channel blockers. Within hours of neurological deterioration, she was treated with intra-arterial milrinone, a phosphodiesterase inhibitor, which resulted in a rapid and sustained neurological improvement. [source] The duration of efficacy following oral treatment with emamectin benzoate against infestations of sea lice, Lepeophtheirus salmonis (Krøyer), in Atlantic salmon Salmo salar L.JOURNAL OF FISH DISEASES, Issue 3 2000J Stone The duration of efficacy of emamectin benzoate in the oral treatment of sea lice, Lepeophtheirus salmonis, infesting Atlantic salmon, Salmo salar L., was evaluated in a tank study. One group of salmon was treated at a nominal dose of 50 ,g kg,1 biomass day,1 for 7 consecutive days and a second group was untreated. Fish were then redistributed to 16 tanks, each holding 17 control and 17 treated fish. On days 34, 41, 48, 55, 62, 69, 76 and 83, two tanks were challenged with L. salmonis copepodites. Eight to 14 days after each challenge, fish were anaesthetized and numbers of lice recorded. Treatment with emamectin benzoate prevented development of copepodites for up to 62 days from the start of treatment, and chalimus numbers remained low for 69 days. Treated fish, challenged from days 34 to 69, had significantly (P<0.01) fewer lice than control fish. Treated fish challenged at days 76 and 83 still had fewer lice than control groups, although differences were not statistically significant for both replicates. When chalimus appeared on treated fish challenged at days 69,83, survival of chalimus to adult stages was lower than on control fish. Louse egg production on treated fish challenged at days 62,83 was not reduced compared to control groups. [source] Therapy with antioxidants in human diabetic neuropathyJOURNAL OF NEUROCHEMISTRY, Issue 2003D. Ziegler Increased oxidative stress has been implicated in the pathogenesis of diabetic polyneuropathy (DPN). Antioxidant treatment with alpha-lipoic acid (ALA) has been shown to prevent or ameliorate experimental diabetic neuropathy, providing the rationale for treatment in humans. A recent meta-analysis including four controlled clinical trials provided evidence that treatment with ALA (600 mg/day i.v.) over 3 weeks is safe and significantly improves both neuropathic symptoms and deficits to a clinically meaningful degree in patients with symptomatic DPN. Moreover, oral treatment for 4,7 months tends to ameliorate neuropathic deficits and cardiac autonomic neuropathy. Clinical and postmarketing surveillance studies have revealed a highly favorable safety profile of this drug. Based on these findings, a pivotal long-term multicenter trial of oral treatment with ALA (NATHAN 1 Study) is under way aimed at slowing the progression of DPN. [source] Improvement of hyperglycaemia and metabolic syndromes in type 2 diabetic KKAy mice by oral treatment with [meso-tetrakis(4-sulfonatophenyl) porphyrinato]oxovanadium(IV)(4-) complexJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2007Tapan Kumar Saha Recently, we reported that [meso-tetrakis(4-sulfonatophenyl)porphyrinato]oxovanadium(IV)(4-), VO(tpps), shows in-vitro insulin-mimetic and in-vivo anti-diabetic activity in streptozotocin (STZ)-induced type 1 diabetic mice. This result prompted us to examine its ability in type 2 diabetic model KKAy mice with insulin resistance. We studied the in-vivo anti-diabetic activity of VO(tpps), compared with that of vanadium(IV) oxide sulfate, VS, as control. Both compounds were orally administered at doses of 5,10 mg (0.1-0.2 mmol) V/kg body weight to the KKAy mice for 28 days. VO(tpps) normalized the hyperglycaemia within 15 days, while VS lowered the blood glucose concentration only by a small degree. In addition, metabolic syndromes characterized by insulin and leptin resistance were significantly improved in VO(tpps)-treated KKAy mice compared with those treated with VS. The improvement in diabetes was validated by oral glucose tolerance test and decrease in HbA1c concentration. Based on these observations, VO(tpps) is proposed to be an orally active oxovanadium(IV)-porphyrin complex for treating not only type 2 diabetes but also metabolic syndromes in animals. [source] Pharmacokinetics of cimetidine in dogs after oral administration of cimetidine tabletsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009G. LE TRAON Long-term oral treatment with cimetidine is recommended to reduce vomiting in dogs with chronic gastritis. Despite this, few studies have specifically examined the plasma disposition and pharmacokinetics of cimetidine in dogs, particularly following repeated oral administration. The pharmacokinetics of cimetidine following oral administration as tablets was investigated in healthy dogs. Cimetidine was absorbed rapidly post-treatment (tmax = 0.5 h). A mean absolute bioavailability of 75% was calculated following a single oral administration of 5 mg cimetidine/kg body weight. After intravenous administration, a plasma half-life of 1.6 h was calculated. Repeated oral administration at the recommended dose rate and regime (5 mg/kg body weight three times daily) for 30 consecutive days did not lead to any accumulation of cimetidine in plasma. Food intake concomitant with oral administration of cimetidine delayed (tmax = 2.25 h) and decreased the rate and extent of absorption (AUC) by about 40%. Cimetidine was well absorbed in fasted dogs. Administration of food decreased the bioavailability of cimetidine by 40%. Cimetidine does not accumulate over time in plasma when administered long term to dogs. [source] Moxidectin and ivermectin metabolic stability in sheep ruminal and abomasal contentsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2005A. LIFSCHITZ The oral administration of macrocyclic lactones to sheep leads to poorer efficacy and shorter persistence of the antiparasitic activity compared to the subcutaneous treatment. Gastrointestinal biotransformation occurring after oral treatment to ruminant species has been considered as a possible cause of the differences observed between routes of administration. The current work was addressed to evaluate on a comparative basis the in vitro metabolism of moxidectin (MXD) and ivermectin (IVM) in sheep ruminal and abomasal contents. Both compounds were incubated under anaerobic conditions during 2, 6 and 24 h in ruminal and abomasal contents collected from untreated adult sheep. Drug concentrations were measured by high-performance liquid chromatography with fluorescence detection after sample clean up and solid phase extraction. Neither MXD nor IVM suffered metabolic conversion and/or chemical degradation after 24-h incubation in ruminal and abomasal contents collected from adult sheep. Unchanged MXD and IVM parent compounds represented between 95.5 and 100% of the total drug recovered in the ruminal and abomasal incubation mixtures compared with those measured in inactive control incubations. The partition of both molecules between the solid and fluid phases of both sheep digestive contents was assessed. MXD and IVM were extensively bound (>90%) to the solid material of both ruminal and abomasal contents collected from sheep fed on lucerne hay. The results reported here confirm the extensive degree of association to the solid digestive material and demonstrates a high chemical stability without evident metabolism and/or degradation for both MXD and IVM in ruminal and abomasal contents. [source] Early steroid withdrawal after liver transplantation: The canadian tacrolimus versus microemulsion cyclosporin a trial: 1-year follow-upLIVER TRANSPLANTATION, Issue 6 2003Paul Greig Corticosteroid therapy contributes significant toxicity to liver transplantation. The safety and efficacy of early steroid withdrawal were determined in patients treated with either tacrolimus or microemulsion cyclosporin A (micro-CsA). The primary outcome was the proportion of patients who were steroid-free 1 year posttransplantation. From the seven Canadian adult liver transplant centers, 143 patients were randomly allocated oral treatment with either tacrolimus (n = 71) or micro-CsA (n = 72), together with corticosteroids and azathioprine. Eligibility criteria for steroid withdrawal included freedom from acute rejection for a minimum of 3 months, and prednisone ,0.15 mg/kg/d. In eligible patients, the daily steroid dose was reduced by 2.5 mg each month until complete discontinuation was achieved. At 1 year after transplantation, 75% of the tacrolimus patients and 63% of the micro-CsA patients were steroid-free (P = .20). Of all of the patients who became eligible for steroid withdrawal, steroid discontinuation was achieved in over 80%. One-year patient survival was 97% with tacrolimus and 89% with micro-CsA (P = .052). Graft survival was 97% and 86%, respectively (P = .017). The overall incidence of acute rejection during the first year was 35% with tacrolimus and 43% with micro-CsA (P = .26). There was no difference in survival, acute rejection, or rate of steroid withdrawal when adjusting for hepatitis C. All acute rejection episodes experienced during steroid withdrawal were steroid-responsive. Steroid-resistant rejection occurred in 5.6% of the tacrolimus and 9.7% of the micro-CsA patients. One patient, in the micro-CsA group, experienced refractory rejection. Chronic rejection was not observed in either group. The toxicity profiles were similar. Postoperative serum creatinine levels were similar, and dialysis was required in less than 10% of patients in each group. Infectious complications were similar in both groups. Neurotoxicity was a serious adverse event in 13% and 10% of patients receiving tacrolimus and micro-CsA, respectively. Early steroid withdrawal is safe and effective after liver transplantation using either tacrolimus plus azathioprine or micro-CsA plus azathioprine immunoprophylaxis. [source] NMR-based metabonomics analysis of mouse urine and fecal extracts following oral treatment with the broad-spectrum antibiotic enrofloxacin (Baytril)MAGNETIC RESONANCE IN CHEMISTRY, Issue S1 2009Lindsey E. Romick-Rosendale Abstract The human gastrointestinal tract is home to hundreds of species of bacteria and the balance between beneficial and pathogenic bacteria plays a critical role in human health and disease. The human infant, however, is born with a sterile gut and the complex gastrointestinal host/bacterial ecosystem is only established after birth by rapid bacterial colonization. Composition of newborn gut flora depends on several factors including type of birth (Ceasarian or natural), manner of early feeding (breast milk or formula), and exposure to local, physical environment. Imbalance in normal, healthy gut flora contributes to several adult human diseases including inflammatory bowel (ulcerative colitis and Crohn's disease) and Clostridium difficile associated disease, and early childhood diseases such as necrotizing enterocolitis. As a first step towards characterization of the role of gut bacteria in human health and disease, we conducted an 850 MHz 1H nuclear magnetic resonance spectroscopy study to monitor changes in metabolic profiles of urine and fecal extracts of 15 mice following gut sterilization by the broad-spectrum antibiotic enrofloxacin (also known as Baytril). Ten metabolites changed in urine following enrofloxacin treatment including decreased acetate due to loss of microbial catabolism of sugars and polysaccharides, decreased trimethylamine- N -oxide due to loss of microbial catabolism of choline, and increased creatine and creatinine due to loss of microbial enzyme degradation. Eight metabolites changed in fecal extracts of mice treated with enrofloxacin including depletion of amino acids produced by microbial proteases, reduction in metabolites generated by lactate-utilizing bacteria, and increased urea caused by loss of microbial ureases. Copyright © 2009 John Wiley & Sons, Ltd. [source] Potential effects of tyramine on the transition to reproductive workers in honeybees (Apis mellifera L.)PHYSIOLOGICAL ENTOMOLOGY, Issue 2 2007KEN SASAKI Abstract To explore the role of brain tyramine in reproductive worker honeybees, its effects after injection and oral treatment on brain dopamine levels and ovarian development in queenless worker honeybees are determined. Both tyramine injection and oral treatment in 10-day-old queenless bees leads to tyramine transportation into the brain and significantly elevates brain dopamine levels as a function of the tyramine concentration. Ovarian diameters are significantly larger in 10-day-old queenless bees treated with tyramine compared with queenless bees of the same age without tyramine treatment. Results on yolk formation in the ovary support the finding of increased ovarian diameter, suggesting that oral tyramine treatment accelerates ovarian development through dopamine effects and/or direct effects of tyramine on the ovary in queenless bees. Thus, tyramine has potential effects on the enhancement of brain dopamine levels and the acceleration of ovarian development for the transition of normal workers to reproductive worker honeybees. [source] Anthelminthic and antiallergic activities of Mangifera indica L. stem bark components Vimang and mangiferinPHYTOTHERAPY RESEARCH, Issue 10 2003D. García Abstract This study investigated the antiallergic and anthelmintic properties of Vimang (an aqueous extract of Mangifera indica family stem bark) and mangiferin (the major polyphenol present in Vimang) administered orally to mice experimentally infected with the nematode, Trichinella spiralis. Treatment with Vimang or mangiferin (500 or 50 mg per kg body weight per day, respectively) throughout the parasite life cycle led to a signi,cant decline in the number of parasite larvae encysted in the musculature; however, neither treatment was effective against adults in the gut. Treatment with Vimang or mangiferin likewise led to a signi,cant decline in serum levels of speci,c anti- Trichinella IgE, throughout the parasite life cycle. Finally, oral treatment of rats with Vimang or mangiferin, daily for 50 days, inhibited mast cell degranulation as evaluated by the passive cutaneous anaphylaxis test (sensitization with infected mouse serum with a high IgE titre, then stimulation with the cytosolic fraction of T. spiralis muscle larvae). Since IgE plays a key role in the pathogenesis of allergic diseases, these results suggest that Vimang and mangiferin may be useful in the treatment of diseases of this type. Copyright © 2003 John Wiley & Sons, Ltd. [source] Protein kinase C inhibition in diabetic retinopathy and microvascular diseasePRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 5 2007Dr C Walton FRCP Abstract Protein kinase C (PKC) activation by hyperglycaemia may play an important role in the evolution of diabetic retinopathy and other microvascular complications. The PKC-, inhibitor ruboxistaurin belongs to a new class of drugs and has been studied in several clinical trials in microvascular disease, the outcomes of which are described in this review. Ruboxistaurin exhibits promise as the first oral treatment shown to reduce visual loss and the need for laser treatment for macular oedema in patients with moderate to severe non-proliferative diabetic retinopathy. Copyright © 2007 John Wiley & Sons. [source] Latest news and product developmentsPRESCRIBER, Issue 8 2008Article first published online: 12 MAY 200 Glargine preferred to lispro as type 2 add-on Basal insulin glargine (Lantus) and insulin lispro (Humalog) at mealtimes improved glycaemic control equally well in patients with type 2 diabetes poorly controlled by oral agents, but patient satisfaction was greater with basal insulin (Lancet 2008;371:1073-84). The 44-week APOLLO trial, funded by Sanofi Aventis, was a nonblinded randomised comparison of basal and prandial insulin regimens added to oral treatment in 418 patients. It found similar reductions in HbA1C (,1.7 vs ,1.9 per cent respectively). Fasting and nocturnal glucose levels were lower with insulin glargine and postprandial levels were lower with insulin lispro. The basal regimen was associated with fewer hypoglycaemic events (5.2 vs 24 per patient per year), less weight gain (3.01 vs 3.54kg) and greater improvement in patient satisfaction scores. Treating hypertension cuts mortality in over-80s Treating hypertension in the over-80s reduces all-cause mortality by 21 per cent, the HYVET study has shown (N Engl J Med online: 31 March 2008; doi: 10.1056/NEJMoa 0801369). Compared with placebo, treatment with indapamide alone or with perindopril for an average of 1.8 years also reduced the incidence of fatal stroke by 39 per cent, cardiovascular death by 23 per cent and heart failure by 64 per cent. The incidence of stroke was reduced by 30 per cent but this was of borderline statistical significance. Fewer serious adverse events were reported with treatment than with placebo. New work for NICE The DoH has announced the 18th work programme for NICE. Seven public health interventions include preventing skin cancer, smoking by children and excess weight gain during pregnancy. Public health guidance will include the provision of contraceptive services for socially disadvantaged young people. Two new clinical guidelines are sedation in young people and management of fractured neck of femur. New technology appraisals may include eight therapies for cancer, two new monoclonal antibodies for psoriasis and rheumatoid arthritis, an oral retinoid for severe chronic hand eczema and methylnaltrexone for opioid-induced bowel dysfunction. Combinations no better against CV disease Taking ezetimibe and simvastatin (Inegy) does not appear to slow the progression of atherosclerosis more than high-dose simvastatin alone, say researchers from The Netherlands (N Engl J Med 2008;358: 1431-43). In patients with hypercholesterolaemia, there was no difference in regression or progression of atherosclerosis after two years' treatment with simvastatin 80mg per day alone or combined with ezetimibe 10mg per day. Adverse event rates were similar. In patients with vascular disease or high-risk diabetes, there was no difference between the ACE inhibitor ramipril 10mg per day or the ARB telmisartan (Micardis) 80mg per day as monotherapy, or their combination, in the risk of a composite outcome of cardiovascular death, MI, stroke and admission for heart failure (N Engl J Med 2008;358:1547-59). Combined treatment was associated with higher risks of hypotensive symptoms, syncope and renal dysfunction. Twice-daily celecoxib increases CV risk Taking celecoxib (Celebrex) twice daily carries a higher risk of cardiovascular events than the same total dose taken once daily, a metaanalysis suggests (Circulation 2008; doi: 10.1161/ CIRCULATIONAHA.108. 764530). The analysis of six placebo-controlled trials involving a total of 7950 patients taking celecoxib for indications other than rheumatoid arthritis found that the combined risk of cardiovascular death, myocardial infarction, stroke, heart failure or thromboembolic event increased with dose over the range 400-800mg per day. The risk was significantly greater with 200mg twice daily (HR 1.8) than 400mg once daily (HR 1.1). Patients at greatest baseline risk were at disproportionately increased risk from celecoxib. Long-term etanercept effective in AS An open-label study suggests that etanercept (Enbrel) remains effective in the treatment of ankylosing spondylitis in the long term (Ann Rheum Dis 2008;67:346-52). Of 257 patients who completed six months' treatment with etanercept and who entered the nonblinded extension study, 126 completed a total of 168-192 weeks' treatment. The commonest adverse events were injection-site reactions (22 per cent), headache (20 per cent) and diarrhoea (17.5 per cent). The annual rate of serious infections was 0.02 per person. Response and partial remission rates after 192 weeks were similar to those reported after 96 weeks. Metformin reduces risk Metformin reduces the risk of developing diabetes in individuals at increased risk, a meta-analysis suggests (Am J Med 2008;121:149-57.e2). The study included 31 mostly small, randomised, controlled trials involving a total of 4570 participants and lasting at least eight weeks (8267 patient-years of treatment). Metformin was associated with reductions in body mass (,5.3 per cent), fasting glucose (,4.5 per cent) and insulin resistance (,22.6 per cent); lipid profiles also improved. The odds of developing diabetes were reduced by 40 per cent,an absolute risk reduction of 6 per cent over 1.8 years. MHRA clarifies cough and colds advice Press reports mistakenly suggested that the MHRA had banned some cough and cold remedies when it issued new guidance on treating young children, the MHRA says. The Agency's advice followed a review of over-thecounter cough and cold medicines for children by the Commission on Human Medicines. Children under two are at increased risk of adverse reactions and should no longer be treated with products containing antihistamine (chlorphenamine, brompheniramine, diphenhydramine), antitussives (dextromethorphan, pholcodine), expectorants (guaifenesin, ipecacuanha) and decongestants (phenylephrine, pseudoephedrine, ephedrine, oxymetazoline and xylometazoline). The MHRA said these products, which are classified as general sale medicines, should be removed from open shelves until available in new packaging that complies with the advice. They may still be supplied by a pharmacist for the treatment of older children. Coughs and colds should be treated with paracetamol or ibuprofen for fever, a simple glycerol, honey or lemon syrup for cough, and vapour rubs and inhalant decongestants for stuffy nose. Saline drops can be used to thin and clear nasal secretions in young babies. Parents are being urged not to use more than one product at a time to avoid inadvertently administering the same constituent drug twice. Perindopril brand switch Servier Laboratories is replacing its current formulations of perindopril (Coversyl, Coversyl Plus) with a new product that is not bioequivalent. The current Coversyl brand contains perindopril erbumine (also known as tert -butylamine). The new formulation contains perindopril arginine; it will be distinguished by new brand names (Coversyl Arginine, Coversyl Arginine Plus) and new packaging. Coversyl 2, 4 and 8mg tablets are equivalent to Coversyl Arginine 2.5, 5 and 10mg. Servier says the change is part of the simplification and harmonisation of global manufacturing; the arginine salt is already used in other countries and offers greater stability and a longer shelf-life. Both Coversyl and Coversyl Arginine will be in the supply chain for the next few weeks. Generic perindopril will continue to be the erbumine salt and prescriptions for generic perindopril are not affected. New from NICE Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Clinical Guidance No. 63, March 2008 This clinical guideline focuses on additional aspects of care for women with gestational diabetes (88 per cent of cases) or pre-existing diabetes (of which about 40 per cent is type 2 diabetes) and their babies. To date, insulin aspart (NovoRapid) is the only drug in the guideline specifically licensed for use in pregnancy and NICE advises obtaining informed consent to implement its recommendations for using other insulins and oral hypoglycaemic agents. As with other guidelines, NICE begins by stressing the importance of patient-centred care and involving women in decisions about their treatment. The guideline is divided into six sections, dealing with consecutive periods of pregnancy. Preconceptual planning should include empowering women to help them reduce risks, optimising glycaemic control (after retinal assessment) and increasing monitoring intensity, and providing information about the effects of pregnancy on diabetes. Metformin may be recommended as an adjunct or alternative to insulin, but other oral hypoglycaemic agents should be replaced with insulin, although glibenclamide is an option during pregnancy. Isophane insulin is the preferred long-acting insulin; lispro (Humalog) and aspart are considered safe to use. ACE inhibitors and angiotensin-II receptor blockers should be replaced with other antihypertensive agents and statins should be discontinued. Recommendations for screening and treatment of gestational diabetes build on previous guidance (CG62). Drug treatment will be needed by 10-20 per cent , this includes insulin (soluble, aspart or lispro) and/or metformin or glibenclamide, tailored to individual need. Antenatal care includes optimising glycaemic control. Insulin lispro or aspart should be considered in preference to soluble insulin. If glycaemic control cannot be achieved with insulin injections, an insulin pump may be indicated. The guideline includes a timetable for appointments and the care that should offered after each interval. Recommendations for intrapartum care, which supplement those in CG55, include frequent monitoring of blood glucose. Neonatal care includes recommendations for monitoring and screening the infant and the management of hypoglycaemia. Postnatal care (supplementing CG37) involves adjusting maternal treatment to avoid hypoglycaemia and recommendations for returning to community care. Metformin and glibenclamide are the only oral agents suitable for breastfeeding women. Women with gestational diabetes need advice about glycaemic control and planning for future pregnancies. Lifestyle advice and measurement of annual fasting plasma glucose should be offered. Inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over. Technology Appraisal No. 138, March 2008 The latest technology appraisal of asthma treatments covers inhaled steroids for adults and children over 12 with chronic asthma. It makes only two recommendations. First, the cheapest appropriate option is recommended. Second, when a steroid and a long-acting beta2-agonist are indicated, the decision to prescribe a combined inhaler or separate devices should take into account therapeutic need and likely adherence. Combined inhalers are currently less expensive than separate devices, though they may not remain so. When a combined inhaler is chosen it should be the cheapest. NICE concludes that, at equivalent doses, there is little difference in the effectiveness or adverse event profile of the available steroids or the fixed-dose combinations. According to specialist advice, choosing the best device for an individual remains the overriding concern. Continuous positive airway pressure for the treatment of obstructive sleep apnoea/hypopnoea syndrome. Technology Appraisal No. 139, March 2008 NICE recommends continuous positive airway pressure (CPAP) for adults with moderate or severe obstructive sleep apnoea, and for those with a milder disorder if quality of life and functioning are impaired and alternative strategies such as lifestyle change have failed. Diagnosis and treatment is the responsibility of a specialist team. A CPAP device costs £250-£550 and lasts for seven years. Copyright © 2008 Wiley Interface Ltd [source] Comparison of Selected Endocrine Parameters During Luteal Phase and Pregnancy in German Shepherd Dogs and BeaglesREPRODUCTION IN DOMESTIC ANIMALS, Issue 2009AR Günzel-Apel Contents Concentrations of progesterone, prolactin and relaxin in serum at predetermined intervals after ovulation (day 0) in non-pregnant and pregnant normocyclic Beagles were assayed and results compared with those observed in German Shepherd dogs (GSD) in a previous study. The goal was to determine possible reproductive hormone specificities related to the GSD breed. Furthermore, the effects of medroxyprogesterone acetate (MPA)-treatment in non-pregnant Beagles and of progesterone supplementation in pregnant Beagles on the hormone concentrations were examined. Mean concentrations of progesterone and prolactin were not different in the non-pregnant Beagles compared with those seen in non-pregnant GSD, except at days 50,60, when progesterone concentrations were found to be higher in Beagles (p < 0.05). Mean progesterone concentrations in pregnant Beagles at days 50,60 after ovulation (day 0) were higher (p < 0.05) than in GSD at that time, but not at earlier time periods. Prolactin concentrations were higher (p < 0.05) in Beagles throughout pregnancy compared with those in the GSD. Mean relaxin concentrations were numerically but not significantly lower in GSD than in Beagles throughout pregnancy. A 10-day oral MPA treatment did not affect progesterone or prolactin secretion in normocyclic non-pregnant Beagles. Medroxyprogesterone acetate serum concentrations were approximately 3.9 ng/ml during treatment and decreased to 0.42 and 0.021 ng/ml within 5 and 15 days after end of treatment, respectively. Intramuscular progesterone supplementation from days 30 to 40 in pregnant Beagles resulted in higher concentrations of progesterone in the 36- to 45-day time periods; prolactin and relaxin concentrations were not significantly affected during or after treatment compared with administration of placebo. The results suggest a tendency towards deficient luteal function in the short-cycle GSD bitches previously studied, which in pregnancy may reflect the observed decreased prolactin concentrations; the possibility that GSD relaxin secretion is deficiency required needs further study. As oral treatment with MPA did not affect progesterone and prolactin release, it may be useful for studying luteal function in pregnant bitches with suspected hypoluteoidism. [source] Effect of the proteolytic enzyme serrapeptase in patients with chronic airway diseaseRESPIROLOGY, Issue 3 2003Seiichi NAKAMURA Objectives: The proteolytic enzyme serrapeptase (SER) is widely used in clinical practice in Japan. We investigated the effect of SER on sputum properties and symptoms in patients with chronic airway diseases. Methods: This study was an open-labelled trial with a non-treatment control group. Patients were randomly assigned to oral treatment with (n = 15) and without (n = 14) SER 30 mg/day for 4 weeks. Patients collected sputum samples for about 4 h in the morning on the day the trial began and 4 weeks later. We measured the amount of sputum by weighing. Part of each sputum sample was weighed and then completely dried and reweighed. The percentage solid component, viscosity and elasticity of the sputum were measured. Mucociliary transportability index was measured using ciliated bovine trachea ex vivo. Sputum smears were also prepared to count sputum neutrophils. Patients' symptoms were assessed by a questionnaire that used a visual analogue scale. Results: After 4 weeks of SER treatment, sputum weight in the morning, percentage solid component, viscosity and elasticity of sputum, sputum neutrophil count, frequency of coughing and frequency of expectoration significantly decreased. The mean mucociliary transportability index increased from 13.3 ± 1.8 to 24.4 ± 2.5 (P = 0.0103). Conclusions: SER may exert a beneficial effect on mucus clearance by reducing neutrophil numbers and altering the viscoelasticity of sputum in patients with chronic airway diseases. [source] Superior Prevention of Acute Rejection by Tacrolimus vs.AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2006A Large European Trial, Cyclosporine in Heart Transplant Recipients We compared efficacy and safety of tacrolimus (Tac)-based vs. cyclosporine (CyA) microemulsion-based immunosuppression in combination with azathioprine (Aza) and corticosteroids in heart transplant recipients. During antibody induction, patients were randomized (1:1) to oral treatment with Tac or CyA. Episodes of acute rejection were assessed by protocol biopsies, which underwent local and blinded central evaluation. The full analysis set comprised 157 patients per group. Patient/graft survival was 92.9% for Tac and 89.8% for CyA at 18 months. The primary end point, incidence of first biopsy proven acute rejection (BPAR) of grade , 1B at month 6, was 54.0% for Tac vs. 66.4% for CyA (p = 0.029) according to central assessment. Also, incidence of first BPAR of grade , 3A at month 6 was significantly lower for Tac vs. CyA; 28.0% vs. 42.0%, respectively (p = 0.013). Significant differences (p < 0.05) emerged between groups for these clinically relevant adverse events: new-onset diabetes mellitus (20.3% vs. 10.5%); post-transplant arterial hypertension (65.6% vs. 77.7%); and dyslipidemia (28.7% vs. 40.1%) for Tac vs. CyA, respectively. Incidence and pattern of infections over 18 months were comparable between groups, as was renal function. Primary use of Tac during antibody induction resulted in superior prevention of acute rejection without an associated increase in infections. [source] Minocycline and doxycycline are not beneficial in a model of Huntington's diseaseANNALS OF NEUROLOGY, Issue 2 2003Donna L. Smith BSc Huntington's Disease (HD) is an inherited neurological disorder causing movement impairment, personality changes, dementia, and premature death, for which there is currently no effective therapy. The modified tetracycline antibiotic, minocycline, has been reported to ameliorate the disease phenotype in the R6/2 mouse model of HD. Because the tetracyclines have also been reported to inhibit aggregation in other amyloid disorders, we have investigated their ability to inhibit huntingtin aggregation and further explored their efficacy in preclinical mouse trials. We show that tetracyclines are potent inhibitors of huntingtin aggregation in a hippocampal slice culture model of HD at an effective concentration of 30,M. However, despite achieving tissue levels approaching this concentration by oral treatment of R6/2 mice with minocycline, we observed no clear difference in their behavioral abnormalities, or in aggregate load postmortem. In the light of these new data, we would advise that caution be exercised in proceeding into human clinical trials of minocycline. Ann Neurol 2003 [source] Morphological sex change upon treatment by endocrine modulators in meiogynogenetic tench (Tinca tinca L.)AQUACULTURE RESEARCH, Issue 2 2010Martin Hulak Abstract Exogenous steroids alter sex differentiation in fish substantially. In the present study we have evaluated the effects of 17,-methyltestosterone (MT) and oestrogen receptor antagonist Tamoxifen (TA) on gonadal development and skewness of the sex ratio in all-female tench juveniles. In the first two experiments, sexually undifferentiated juveniles were orally treated with three doses of MT and TA (50, 100 and 150 mg kg,1). Both the treatments resulted in a moderate dose-dependent masculinization, with neomale production ranging from 17% (50 mg kg,1) to 26% (150 mg kg,1) for the MT only treatment, and from 0% (50 mg kg,1) to 27% (100 mg kg,1) only for the TA treatment respectively. In the third experiment treatment of sexually differentiated tench females with single steroid treatments or combinations of the two resulted in populations composed of females and intersex individuals. The significantly highest occurrence of intersex individuals (45.5%) was found in the group subjected to combine treatment of MT+TA (150+200 mg kg,1). No masculinization effect of the single or the combined treatment occurred. It can be concluded that oral treatment with MT or TA only slightly modifies the normal process of sex differentiation in gynogenetic tench juvenile, but treatment with the above-mentioned combinations has a highly significant potential to skew the sex ratio in sexually differentiated tench females. However, from an applied point of view, the treatment procedure will need optimization before use at a commercial level. [source] | |||||||||||||||||||||||||||||||||||||