4th Week Of Treatment Research Articles

Difficulties with interferon treatment in former intravenous drug users

ObjectivesIntravenous drug use accounts for most of the new hepatitis C infections worldwide. Although there is an urgent need for antiviral treatment of infected intravenous drug users (IDUs), several factors compromise their treatment including lack of treatment adherence and high dropout rate. The aim of this study was to compare antiviral treatment-related problems among former IDUs to HCV-infected patients without a history of IDU. MethodsThis was a retrospective chart review of HCV-infected IDUs who received combined antiviral therapy at the Hepatology Outpatient Clinic of Szent László Hospital between 1 January 2006 and 31 December 2008. A control group of interferon treated patients with no history of IDU matched for age and sex was selected. ResultsDropout rate was significantly higher in the IDU group (p=0.016). Treatment response at the 12th week of treatment was significantly better in the IDU group (p=0.004). Significantly more IDUs underwent antiviral treatment while in prison (p=0.008). ConclusionsIn this study higher dropout rate was found among IDUs. IDUs had a better response rate to antiviral therapy compared to controls. More attention should be paid to factors that worsen treatment adherence of IDUs - particularly lack of abstinence - in order to increase the effectiveness of antiviral therapy.

Comparison of Effects of Alpha Receptor Blockers on Endothelial Functions and Coagulation Parameters in Patients with Benign Prostatic Hyperplasia

To investigate the effects of alpha receptor blockers used in the treatment of benign prostatic hyperplasia (BPH) on endothelial functions, coagulation parameters, and arterial blood pressure. One-hundred fifteen patients admitted to the treatment protocol because of symptomatic BPH were included in this prospective study. Patients were given the following treatments: doxazosin 4 mg/d (n = 25), terazosin 5 mg/d (n = 26), alfuzosin 10 mg/d (n = 26), tamsulosin 0.4 mg/d (n = 21), and observation (n = 17). All cases were evaluated before treatment and in the 12th week of treatment, according to biochemical parameters, endothelial functions, and arterial blood pressure. Biochemical parameters were bleeding time, coagulation time, prothrombin time, activated partial thromboplastin time, total prostate-specific antigen (PSA), and free PSA. Endothelial functions were evaluated with ultrasonography of the brachial artery. When coagulation tests were evaluated, there were significant increases in bleeding and coagulation times in the groups using doxazosin and terazosin. Doxazosin and terazosin lowered arterial blood pressure significantly compared with other treatments. With regard to effects on endothelial function, there were significant differences in flow-mediated dilation rates of the brachial artery at 60 and 90 seconds before and during treatment in the alfuzosin and terazosin groups. Alpha receptor blockers can decrease the risk of cardiovascular complications by both reducing platelet aggregation and protecting endothelial functions in patients with prostatic hyperplasia. The only drug with a favorable effect in all 4 areas of interest, including BPH symptoms, blood pressure, platelet aggregation, and endothelial functions, was terazosin.

The effectiveness of manual therapy in supraspinatus tendinopathy

The aim of this randomized controlled study was to assess the efficacy of manual therapy in the treatment of patients with symptomatic supraspinatus tendinopathy. Seventy-seven patients (age range, 30 to 55 years) with supraspinatus tendinopathy, were randomly assigned to one of the three treatment groups: a supervised exercise program (Group 1), a supervised exercise program combined with joint and soft tissue mobilization (Group 2), or a home-based rehabilitation program (Group 3). All patients had rehabilitation for 12 weeks. Pain level was evaluated with a visual analogue scale (VAS) and the range of motion (ROM) was measured with a goniometer. The Modified American Shoulder and Elbow Surgery (MASES) score was used in functional assessment. Flexion, abduction, internal and external rotation strengths were measured with a manual muscle test. All patients were evaluated before, and at the 4th and 12th week of the rehabilitation. All groups experienced significant decrease in pain and an increase in shoulder muscle strength and function by both the 4th and 12th weeks of treatment (p<0.05). There was no significant difference between the groups in terms of function (p>0.05). However, the greatest improvement in functionality was found in Group 2. Supervised exercise, supervised and manual therapy, and home-based exercise are all effective and promising methods in the rehabilitation of the patients with subacromial impingement syndrome. The addition of an initial manual therapy may improve the results of the rehabilitation with exercise.

A comparison of 48-week treatment efficacy between clevudine and entecavir in treatment-naïve patients with chronic hepatitis B

Clevudine and entecavir are currently available in Korea as antiviral drugs against chronic hepatitis B (CHB). We aimed to compare the efficacy of clevudine and entecavir therapy. Treatment-naïve CHB patients who received 30mg of clevudine or 0.5mg of entecavir a day were analyzed. Mean reduction of hepatitis B virus (HBV) DNA levels, complete virological response (cVR, undetectable HBV DNA by real-time PCR), biochemical response (recovery to normal ALT level), and hepatitis B e antigen (HBeAg) seroconversion rate at the 48th week of treatment were assessed. A number of 59 patients in clevudine group and 61 patients in entecavir group were included. Mean HBV DNA reductions from baseline were similar in the clevudine and entecavir groups, -6.4 versus -6.8 log(10) copies/mL in HBeAg-positive (p=0.417) and -6.9 versus -7.0 log(10) copies/mL in HBeAg-negative patients (p=0.640). The proportion of patients who achieved cVR was not different between the two groups, 53 versus 55% in HBeAg-positive (p=1.000) and 100 versus 95% in HBeAg-negative patients (p=0.452). Biochemical response rates and HBeAg seroconversion rates were also similar in both the groups. Two (3.4%) patients in clevudine group showed virologic breakthrough with rtM204I mutation using direct sequencing analysis. Clinical myopathy occurred in two (3.4%) patients in clevudine group. Mean reduction of viral loads was similar between clevudine and entecavir groups during 48weeks. However, virologic breakthrough and significant myopathy were noted only in clevudine-treated patients. Therefore, more attention should be paid to patients receiving clevudine.

Transient erythrocyte changes caused by infiltration of liver by plasma cell leukemia

Marked erythrocyte anisopoikilocytosis was noted in a 52-year-old man with relapsed IgD multiple myeloma. Complete blood count showed a white cell count of 14,100/mm3 with 40% circulating plasma cells. Most of the red blood cells (RBCs) were either target cells or microspherocytes, with occasional acanthocytes, stomatocytes, and knizocytes ( Images 1 and 2a). The direct antiglobulin test was negative. He had no history of a hemoglobinopathy or an RBC membrane disorder and had normal erythrocyte morphology during remission. He had renal impairment and grossly deranged liver function with elevated alanine aminotransferase of 128 u/l (normal <40 u/l), gamma glutamyltransferase of 591 u/l (normal <50 u/l) and bilirubin of 174 umol/l (normal <17 umol/l). An ultrasound scan (USS) of liver showed hepatomegaly with diffusely abnormal coarse echogenicity, consistent with infiltration by myeloma. He had hypercalcemia and hypophosphatemia at presentation, which resolved with treatment over the next 3 weeks. Severe anisopoikilocytosis with microspherocytes (solid arrows), acanthocytes (dotted arrows), and a knizocyte (dashed arrow) on the initial blood film at plasma cell leukemic relapse phase of myeloma. Two abnormal plasma cells, one binucleate and the other bilobed, are seen (×100 oil; MGG). (a) Initial blood film at relapse showing a bilobed plasma cell and widespread red cell changes including numerous target cells, microspherocytes (solid arrows), occasional acanthocytes and stomatocytes. A single knizocyte (dashed arrow) is also seen. Plasma cells constituted 40% of circulating white cells at this stage (×40; MGG). (b) Less marked red cells changes a week after initiation of treatment. Plasma cells have reduced in number, but circulating forms are still present. Most of the target cells have disappeared but microspherocytosis (solid arrows) remains conspicuous. A single nucleated RBC is seen at the bottom, most likely due to marrow infiltration by myeloma (×40; MGG). (c) Complete clearance of plasma cells from circulation during the 3rd week of treatment. Most of the red cells are now normal, though a few microspherocytes (solid arrows) persist (×40; MGG). (d) Normal blood film at 4th week of treatment (×40; MGG). He was treated with a combination of bortezomib, doxorubicin, and dexamethasone, to which he responded rapidly with clearance of plasma cells, normalization of liver function, improvement in renal function and reduction of paraprotein level. All the red cell changes disappeared serially over a period of 4 weeks ( Image 2b–d). USS of liver was repeated at this stage and showed normal size and echo pattern of liver. In retrospect, this patient had hepatic infiltration by plasma cell leukemia, which reversed completely with chemotherapy. The RBC changes were secondary to this and all abnormalities resolved with return of normal liver function. Target cells and acanthocytes are well described changes with hepatic dysfunction and are believed to be the result of net membrane accumulation of cholesterol, alteration in phospholipids and decreased lecithin cholesterol acyltransferase (LCAT) activity [1, 2]. Knizocytes are triconcave red cells with a band of hemoglobin in the center with an area of pallor on either side and are known to occur in hemolytic states or liver dysfunction. The prominent acquired microspherocytosis noted in this patient is more difficult to explain. In the absence of autoimmune hemolysis, the most likely reason for spherocytosis was the hypophosphatemia which persisted until the 3rd week of treatment. Depletion of phosphate can cause low erythrocyte adenosine triphosphate levels, which in turn can result in spherocytosis [3]. Reversible erythrocyte anisopoikilocytosis of such severity has not been reported so far in conjunction with hepatic infiltration by plasma cell leukemia.

A Pilot Study of Epigenetic-Differentiation Therapy with Decitabine to Treat β-Thalassemia Intermedia

AbstractAbstract 2078Ineffective erythropoiesis, the hallmark of ß-thalassemia, is a result of the myriad deleterious effects of globin chain imbalance. A major translational research goal in thalassemia is to restore α/non-α globin chain balance by inducing expression of γ-globin synthesis from the intact γ-globin gene (HBG). Repression of HBG in adult erythroid cells involves DNA methylation and other epigenetic changes; one possibly useful strategy to re-induce HBG expression is to deplete DNA methyl-transferase 1 (DNMT1) in hematopoietic cells using the cytosine analogue decitabine. A dose and schedule of decitabine intended to deplete DNMT1 without causing significant cytotoxicity was examined in a pilot safety study in ß-thalassemia intermedia, a condition which, despite a lack of requirement for monthly transfusions, is often associated with significant long-term clinical complications. Six patients (≥18 years of age) with ß-thalassemia intermedia were enrolled on study to receive decitabine 0.2 mg/kg subcutaneous 2x/week on consecutive days each week for 12 weeks followed by 12 weeks of follow-up. One patient withdrew from study because of fatigue requiring transfusion after week 2. Of the five evaluable patients, two patients received 24 of the 24 planned doses of drug, one patient received 21 of 24 planned doses, and two patients received 16 of 24 planned doses. Doses were missed because of treatment-associated increases in platelet count to >1000 × 109/L which according to protocol, required interruption of therapy. The primary outcome, an increase in total hemoglobin (Hb) of ≥1.5 g/dL above that determined at baseline, was achieved in two of five evaluable patients. In the group overall, Hb increased from a baseline of (mean ± SEM) 7.88 ± 0.88 g/dL to a peak of 9.04 ± 0.77 g/dL (P = 0.004); peak values in Hb were observed from the 6th to 12th week of treatment. Absolute fetal Hb increased from a baseline of (mean ± SEM) 3.34 ± 0.97 g/dL to a peak of 4.39 ± 1.15 g/dL (P = 0.021); peak values in fetal Hb were observed in the 4th to 12th week of treatment. Reflecting decreased hemolysis and more effective erythropoiesis, indirect bilirubin declined from (mean ± SEM) 3.2 ± 1.0 mg/dL to a nadir of 2.2± 0.8 mg/dL, while reduction in serum LDH from (mean ± SEM) 479.4 ± 125.8 U/L to 362.8 ± 100.4 U/L was not significant (P =0.083). Platelet counts increased from a baseline of (mean ± SEM) 585.2 ± 90.6 (x109/L) to a peak of 940.2 ± 184.3 (x109/L) (P = 0.007); peak platelet values were observed between the 6th to 12th weeks of treatment. These increases triggered interruption of therapy in three of the five evaluable patients. In the only patient not previously splenectomized, minimal change in platelet count was observed (baseline, 233 ×109/L; peak, 296 ×109/L). No clinical events were associated with the increased platelet counts. Changes in neutrophil count, from (mean ± SEM) 6.51 ± 1.20 (x109/L) to 3.36 ± 0.63 (x109/L) were not significant (P = 0.069). The lowest neutrophil counts were observed between the 4th and 10th week of treatment. Two quantitative in vitro assays for mutagenicity, specifically enumeration of illegitimate VDJ recombination events and micronuclei within early reticulocytes, were performed at baseline, midpoint, and study exit. No significant changes were identified between baseline and 24-week values from either laboratory assay. In this first clinical study of decitabine in patients with β-thalassemia, drug dose was aimed at induction of DNMT1 depletion; the frequent but intermittent schedule of administration was intended to modify differentiation without causing prolonged cytostasis resulting in cytopenia. Consistent with a non-cytotoxic/cytostatic, differentiation-altering mechanism of action, the dose-limiting toxicity observed was not thrombocytopenia or neutropenia, but asymptomatic increases in platelet count. In conclusion, decitabine therapy was well-tolerated in thalassemia intermedia. Significant mean and individual increases in total and fetal hemoglobin concentrations observed in this study may direct the selection of patients in extended trials, to explore the potential of chromatin-relaxing therapy for β-thalassemia. Disclosures:Off Label Use: FDA approved decitabine for use in MDS, therefore, its use in thalassemia is off-label. Furthermore, the dose, schedule and route of administration used is also not on the label. Decitabine was used in a study to augment production of fetal hemoglobin in an NIH sponsored trial.

Endocannabinoid Pro129Thr FAAH Functional Polymorphism But Not 1359G/A CNR1 Polymorphism Is Associated With Antipsychotic-Induced Weight Gain

Several candidate genes have been associated with antipsychotic-induced body weight (BW) gain. Because the endocannabinoid system is deeply involved in BW regulation, endocannabinoid genes may have a role in the antipsychotic-induced weight gain. Therefore, we investigated the 1359 G/A (rs1049353) single nucleotide polymorphisms (SNP) of the cannabinoid receptor 1 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the complementary DNA (cDNA) 385C/A (rs324420) SNP of the FAAH gene, which codes the endocannabinoid degrading enzyme, for their role in BW changes induced by antipsychotic drugs. Eighty-three white psychotic patients who underwent a naturalistic treatment with different antipsychotics (clozapine, olanzapine, risperidone, quetiapine, and haloperidol) and completed a 24-week treatment period were included into the study together with 80 age- and sex-matched white healthy controls. At the 24th week of treatment, 41 patients gained more than 7% of their baseline BW. No significant differences between patients and controls emerged in genotype and allele frequencies of both SNPs. Genotype and allele frequencies of the FAAH cDNA 385C/A SNP but not of the CNR1 1359 G/A SNP significantly differed between subjects who gained more than 7% of BW and those who did not, with both AC and AA genotypes and the A allele being significantly more frequent in patients who gained more than 7% of their baseline BW. Present findings, although obtained in a small population and in a naturalistic setting, suggest that the cDNA 385C/A SNP of the FAAH gene may predispose subjects to get a clinically meaningful weight gain after antipsychotic exposure.

Greater magnitude of turnover suppression occurs earlier after treatment initiation with risedronate than alendronate

Clinical data suggest that reductions in fractures associated with osteoporosis may occur sooner in patients treated with risedronate (RIS) compared to those treated with alendronate (ALN). This could be explained by differences in the time course of turnover suppression between these two bisphosphonates. To determine if differences in the onset of turnover suppression exist between RIS and ALN, female New Zealand white rabbits (total n=32) were treated with clinically relevant doses of RIS or ALN and then administered different fluorochrome labels weekly for four weeks in order to allow histological assessment of the time-course of turnover suppression. By the third week of treatment vertebral trabecular bone formation rate (BFR/BS) was significantly suppressed with RIS-treatment compared to both VEH and ALN. By the 4th week of treatment, turnover rates in RIS-treated animals remained significantly lower than in VEH-treated animals and were also lower than ALN; at this time-point ALN was significantly lower than VEH. There was no significant reduction in intra-cortical remodeling in the tibial mid-diaphysis at any time point for either RIS or ALN. This greater effect on turnover suppression with RIS early in treatment compared to ALN is likely the result of both risedronate's greater potency on osteoclast inhibition and its lower binding affinity. Together with studies showing more rapid return toward baseline turnover following withdrawal of RIS compared to ALN, this pre-clinical study provides evidence of the differences between bisphosphonates with respect to onset and recovery of bone turnover suppression.

Neuropsychological profiles and short-term outcome in late-onset depression

Neuropsychological impairments are common in older persons with late-onset depression. This study examined the relationship between neuropsychological profiles and short-term outcome in late-onset depression. A total of 54 non-demented Chinese elders presented with their first major depressive episode after 60 years of age participated in this study and were treated according to a standardised protocol. At entry, they were assessed on neurological signs (Parkinsonian features and neurological soft signs) and neuropsychological measures (executive function, psychomotor-speed, attention and working memory, episodic memory, conceptualisation, construction and global cognitive function). The Hamilton Depression Rating Scale (HAM-D) was administered at baseline, the sixth and 12th week of treatment. Abnormal fist-edge-palm (FEP) test, a sign reflecting impairment in motor sequencing, was more common in non-remitters (defined as HAM-D score above 7) at the 12th week of treatment. The FEP test may be included in the clinical assessment for patients with late-onset depression to identify a susceptible group who may require more intensive treatment. Further research is warranted to ascertain the link between late-onset depression, neuropsychological deficits and prognosis.

Assessement of Subtle Neurobehavioral Changes Induced By Potassium Nitrate In Rats And Theire Response Treatment By Ascorbic Acid

The neurobehavioral effects of continuous dosing (as food additive) with potassium nitrate were assessed in albino rats. The rats were divided into the five groups, the control group have been fed in a concentrated forage (Barley, wheat, soybean, corn, wheatbrane) where as the treatment groups were fed with the same concentrated forage with the addition of potassium nitrate in different percentages (second group added 0.1%, 3rd group added 0.1% with 0.2%ascorbic acid as antidote, 4th group added 0.2%, 5th group added 0.2%with0.4%ascorbic acid as antidote) respectively for 5 weeks. Potassium nitrate did not produce overt signs of toxicosis but significantly decreased the open-field activity and also decreased the number of rearing during the open-field activity test, they reached to minimum level at the 4th week of treatment were reported, these decrease were followed gradual elevation to reach that values of the control group level at the end of study period. Potassium nitrate significant delayed the negative geotaxis at 45° angle and retain to reach the control level in 5th week in .The treated rats also suffered from a gradual increase in the body weight in comparison with pretreatment values, where as there was no effective significant the number of fecal boluses and swimming endurance. In this study the ascorbic acid (as antidote) in group 5 (0.4% with 0.2% potassium nitrate) differed significantly with group 4 (0.2% potassium nitrate only) that means the ascorbic acid give good result when it used for treatment of nitrate poisoning in animals. The results support the notion that in the absence of overt signs of toxicosis, neurobehavioral tests could be used to detect adverse behavioral changes induced by potassium nitrate.

MOXONIDINE THERAPY, HEART AND CAROTID ARTERIES REMODELING IN HYPERTENSIVE POSTMENOPAUSAL WOMEN WITH METABOLIC SYNDROME: PP.34.442

Study Objective: To evaluate influence of moxonidine therapy on carotid wall thickness, heart structural and functional parametres in hypertensive postmenopausal women with metabolic syndrome (MS). Material and Methods: 26 hypertensive (AH grades 1–2) postmenopausal women with metabolic syndrome 45–55 years old (52,5+/−0,4 years). MS was diagnosed according to ESC-ESH (2007) criteria. Patients were treated with moxonidine (200–600 mcg/day) orally. Structure and function of the heart and the intima-media thickness of carotid arteries were reviewed by ultrasound method before therapy and on 12-th week of treatment with moxonidine. Statistical analyses were performed using SPSS 17.0 for Windows (SPSS, Inc., Chicago, IL, USA). Results: 14 (53,8%) hypertensive postmenopausal women with MS had elevated left ventricle mass index (LVMI more than 110 g/m2). 9 (34,6%) patients had LV diastolic dysfunction. We revealed correlation between LVMI, interventricular septum thickness, E/A ratio and systolic BP (r = 0,4; 0,4 and -0,4, accordingly; p = 0,02; 0,04 and 0,02 accordingly). Positive correlation was revealed between interventricular septum thickness and diastolic BP (r = 0,4; p = 0,07); left atrium diameter and diastolic BP (r = 0,4; p = 0,04). Results: Moxonidine therapy did not changed intima-media thickness of carotid arteries (0,86+/−0,03 mm vs 0,81+/−0,04 mm; p = 0,05) and LVMI (114,0+/−3,4 g/m2 and 113,9+/−3,4 g/m2, p > 0,05). LV diastolic function improved: E/A ratio increased from 1,05+/− 0,03 to 1,20+/− 0,03 (p Conclusion: Moxonidine therapy improved left ventricle diastolic function and decreased left atrium diameter and left atrium volume in hypertensive postmenopausal women with metabolic syndrome.

Investigation of the Effect of GaAs Laser Therapy on Lateral Epicondylitis

There are conflicting reports regarding the efficacy of low energy laser therapy in treatment of lateral epicondylitis (LE). Contradictory results are considered to be due to different joint treatment protocols regarding variables such as dose, duration, and frequency. The aim of this study was to investigate the efficacy of gallium-arsenide (GaAs) laser therapy, which was performed with the dose regimen recommended by the World Association for Laser Therapy, in relieving pain and improving functional activities in patients with LE. Forty-nine patients (50 elbows) evaluated in our outpatient clinic were included in the study. Elbows were randomized into two groups: laser (n = 25) and placebo laser (n = 25). Either laser or placebo laser therapy was applied to patients for 15 sessions (5 d per week for 3 weeks). Main outcome measures were visual analog scale, tenderness, Disability of the Arm Shoulder and Hand (DASH) questionnaire, the Patient-Related Lateral Epicondylitis Evaluation (PRTEE) test, pain-free grip strength, and the Nottingham Health Profile (NHP) questionnaire. Evaluations were performed before treatment, at the end of 3 weeks of treatment, and after the 12th week of treatment ended. Upon post-treatment evaluation, a significant improvement in all parameters was observed for both groups (p < 0.05). No significant difference was found when the laser and placebo groups were compared. At the 12 week evaluation, a significant sustained improvement in all parameters was observed. On intergroup evaluation, a significant improvement was observed in favor of the active treatment group regarding pain with resisted extension of the wrist, tenderness with pressure, and for both the total and subgroup scores of the DASH questionnaire and PRTEE test, as well as for the pain subgroup of the NHP questionnaire (p < 0.05). Although low energy laser therapy had no advantage compared to placebo in patients with LE for the short term, a significant improvement, particularly in functional parameters, was achieved in the long term. Laser, which has relatively no side effects, might be included among long-term treatment options for LE.

External Qigong for Chronic Pain

External qigong as a pharmacotherapy adjunct was investigated in 50 subjects with chronic pain (pain lasting > 3 months with pain score of > or = 3 on 0-10 numeric analog scale) who presented to a qigong healing center. Participants were randomized to receive either external qigong treatment (EQT) or equivalent attention time (EAT) in weekly 30-min sessions for four consecutive weeks. Outcomes were assessed before and after sessions. The primary outcome measure was intensity of pain by a 10-cm visual analog scale used to rate all pain severity measurements. At 8-week follow-up, participants were contacted by telephone and mailed a questionnaire. Most had experienced pain for > 5 years (66%); the rest, for > 3 to 5 years (8%), 1 to 3 years (10%), or < 1 year but > 3 months (10%). The most frequent concomitant diagnoses were multifactorial (26%), osteoarthritis (18%), and low back pain (12%). Most patients were also receiving other treatments (74%); none previously had EQT. Participants were randomly assigned to EQT (n = 26) or EAT (n = 24). These groups had no significant differences at baseline except for prior awareness of qigong (EQT 31% vs. EAT 63%; p = 0.025). Compared to the EAT group, EQT participants had a significant decrease in pain intensity in the 2nd (p = 0.003), 3rd (p < 0.001), and 4th weeks of treatment (p = 0.003). At week 8, these differences in overall decreased pain intensity persisted but were not statistically significant.

An oral nutraceutical containing antioxidants, minerals and glycosaminoglycans improves skin roughness and fine wrinkles

Various nutraceuticals (dietary supplements) are claimed to have cutaneous antiageing properties, however, there are a limited number of research studies supporting these claims. The objective of this research was to study the effectiveness of an oral nutraceutical containing antioxidants, minerals and glycosaminoglycans on cutaneous ageing. In this double-blind, placebo-controlled trial, 60 women aged 35-60 years were randomized to receive oral dietary supplement (n = 30) or placebo (n = 30), once daily for 12 weeks. The depth of skin roughness and fine wrinkles were measured using surface evaluation of skin parameters for living skin (Visioscan) at baseline, and at the 4, 8 and 12 weeks of treatment. Surface evaluation using a replica film (Visiometer) at baseline and at the 12th week of treatment was also carried out. Statistical differences in objective skin improvement were assessed by the independent t-test. The volunteers' satisfaction was tested using the chi-squared test. The baseline depth of skin roughness and fine wrinkles in the treatment group and the placebo group were 100.5 and 100 mum, respectively. At the end of the study, the depth of skin roughness and fine wrinkles in the treatment group showed a 21.2% improvement, whereas improvement in the control group was 1.7%. This difference was statistically significant (P < 0.001). With regard to the volunteers' satisfaction, there was no statistically significant decrease in the homogenization of skin colour, however, a statistically significant reduction in pore size and depth of skin roughness and fine wrinkles were observed (P < 0.05). No side effects were noted throughout the study. The oral dietary supplement containing antioxidants, minerals and glycosaminoglycans improved skin roughness and fine wrinkles but did not affect skin colour change in female volunteers.

Molecular and physiological study of the artificial maturation process in European eel males: From brain to testis

European eel males can be artificially matured (1.5 IU hCG/g fish), but the regulatory mechanisms of their reproductive development are practically unknown. Spermatogenic stages (S1–S6), biometric characters [eye index (EI), gonadosomatic index (GSI), hepatosomatic index (HSI)] and sperm quality parameters (motility, viability and head spermatozoa morphometry) were analysed. Moreover, the present study evaluated the expression of GnRHs (mammal and chicken II Gonadotropin Release Hormone I) and gonadotrophins (FSHβ and LHβ) during hormonal treatment, as well as 11-ketotestosterone (11-KT) and 17,20β-dihydroxy-4-pregnen-3-one (17,20β-P) plasma levels. One week was enough to observe the S2 of gonad development, but it was necessary to reach the 7th week of treatment to obtain animals that presented the most advanced stage of development (S6). Differential regulation of the two GnRH expressions was found, supporting the main role of mGnRH in the control of gonadotrophin release. One hCG injection was enough to dramatically decrease the FSHβ expression, being close to zero during the rest of the treatment. LHβ expression and 17,20β-P registered a significant increase in the same stage of development, S3/4, confirming the role of this gonadotrophin in the last steps of maturation and 17,20β-P in the spermatozoa maturation. The 11-KT increased with GSI, and the highest 11-KT values coincided with the advanced steps of spermatogenesis prior to spermiation. Being consistent with the known role of the steroid in these processes. Furthermore, this study supports a role for 11-KT in stimulating eye growth, presenting high values when EI increased. Sperm production was obtained from the 4th week of treatment, but it was in the 8th week when a significant increase was observed in sperm quality [viability, high motility (>75%)].

Homeostatic Role of Transforming Growth Factor-β in the Oral Cavity and Esophagus of Mice and Its Expression by Mast Cells in These Tissues

Transforming growth factor-beta (TGF-beta) is a pleiotropic growth factor; its overexpression has been implicated in many diseases, making it a desirable target for therapeutic neutralization. In initial safety studies, mice were chronically treated (three times per week) with high doses (50 mg/kg) of a murine, pan-neutralizing, anti-TGF-beta antibody. Nine weeks after the initiation of treatment, a subset of mice exhibited weight loss that was concurrent with decreased food intake. Histopathology revealed a unique, nonneoplastic cystic epithelial hyperplasia and tongue inflammation, as well as dental dysplasia and epithelial hyperplasia and inflammation of both the gingiva and esophagus. In an effort to determine the cause of this site-specific pathology, we examined TGF-beta expression in these tissues and saliva under normal conditions. By immunostaining, we found higher expression levels of active TGF-beta1 and TGF-beta3 in normal tongue and esophageal submucosa compared with gut mucosal tissues, as well as detectable TGF-beta1 in normal saliva by Western blot analysis. Interestingly, mast cells within the tongue, esophagus, and skin co-localized predominantly with the TGF-beta1 expressed in these tissues. Our findings demonstrate a novel and restricted pathology in oral and esophageal tissues of mice chronically treated with anti-TGF-beta that is associated with basal TGF-beta expression in saliva and by mast cells within these tissues. These studies illustrate a previously unappreciated biological role of TGF-beta in maintaining homeostasis within both oral and esophageal tissues.

Evaluation of controller medication efficiency in patients with moderate and severe uncontrolled asthma

Evaluation of efficiency of controller medication (combination of fluticasone propionate and Salmeterol) in 40 patients (age from 18 to 65 years) with moderate (n = 15) and severe (phenotype brittle n = 10, asthma with fixed obstruction n = 15) uncontrolled asthma was evaluated in open prospective trial. It was observed, that all patients with moderate asthma achieved control criteria (GINA, 2006) to 12th week of treatment with combination of fluticasone propionate and Salmeterol. Improvement of clinical-functional indexes was observed in patients with severe asthma to 24th week of therapy. 5 patients with brittle asthma achieved controlled and partly controlled asthma to 24th week therapy. Controlled asthma was not reach through the patients with fixed obstruction asthma, whereas increase of clinical-functional parameters was observed, usage of inhaled combined therapy allowed us to reduce oral steroids dose in 4 patients of this group.

Treatment of hypocalcemia caused by hypoparathyroidism or pseudohypoparathyroidism with domestic-made calcitriol: a prospective and self-controlled clinical trial

Background Parathyroid hormone deficiency or resistance may cause hypocalcemia with related symptoms and signs. Lifelong treatment of calcium combined with vitamin D or its metabolites is always necessary for these patients. Here we reported a prospective and open-label trial to investigate the efficacy and safety of domestic-made calcitriol in treatment of hypocalcemia caused by hypoparathyroidism or pseudohypoparathyroidism. Methods Twenty-four patients with confirmed hypoparathyroidism or pseudohypoparathyroidism aged (36.5±11.0) years old were studied. Among them, 16 patients had idiopathic hypoparathyroidism, 2 had pseudohypoparathyroidism and 6 had hypoparathyroidism secondary to cervical surgery. Serum calcium levels were lower than 1.88 mmol/L. Oral calcitriol was administered twice or three times with elemental calcium 1.2 g per day. All patients were followed every 4 weeks throughout the 12-week period. Dose adjustments of calcitriol were based on serum and urinary calcium levels and symptoms of hypocalcemia. Results Twenty patients were included by the end of this study. Muscular weakness, cramps, extremity paresthesia, Chovestek's sign and Trousseau's sign were relieved in 76.9%, 100%, 94.4%, 93.3% and 78.9% of patients, respectively. Serum calcium, plasma ionized calcium and serum phosphorus levels were (1.54±0.25) mmol/L, (0.64±0.10) mmol/L and (2.00±0.46) mmol/L at baseline, and reached (2.20±0.20) mmol/L, (0.95±0.06) mmol/L and (1.68±0.25) mmol/L (P &lt;0.01) at the 12th week of treatment, respectively. Eighty percent of patients were assessed as effective and 20% as partly effective. Three, four and eight patients had hypercalciuria at the 4th, 8th and 12th week of treatment, respectively, which were reduced by thiazide diuretics. The final dose of calcitriol was (1.09±0.50) μg/d. Conclusions Calcitriol combined with calcium can be used in treatment of hypocalcemia caused by hypoparathyroidism or pseudohypoparathyroidism effectively and safely. Serum and urinary calcium levels should be monitored during the course of the therapy.

Subcutaneous histamine versus botulinum toxin type A in migraine prophylaxis: a randomized, double‐blind study

To compare the efficacy and tolerability of the subcutaneous administration of histamine and botulinum toxin type A (BoNTA) in migraine prophylaxis. Histamine has a selective affinity for H3 receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. One hundred patients with migraine were selected in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week) n = 50, compared with administration of 50 U of BoNTA (one injection cycle) n = 50. The data collected during the 4th week of treatment revealed a significant decrease in all parameters studied, in histamine and BoNTA (P < 0.001). After 4 weeks of treatment, but one injection cycle of 50 U BoNTA had only a 40-day period of efficacy. This randomized study demonstrated that both histamine and BoNTA are similarly effective and well tolerated in reducing or eliminating headache in migraine prophylaxis. Low doses of histamine applied subcutaneously may represent a novel and effective therapeutic alternative in migraine patients and lay the clinical and pharmacological groundwork for the use of H3 agonist in migraine prophylaxis.

The effects of pioglitazone and metformin on plasma visfatin levels in patients with treatment naive type 2 diabetes mellitus

Aims Circulating visfatin levels are altered in insulin resistant states. We evaluated the effects of two insulin-sensitizing hypoglycemic agents on plasma visfatin and adiponectin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus (T2DM). Methods Forty-four patients with T2DM were randomized to treatment either with pioglitazone (15–45 mg/day) or metformin (1000–2000 mg/day). Plasma visfatin and adiponectin levels and homeostasis model assessment of insulin resistance (HOMA-IR) scores were determined at baseline and at 12th week of treatment. Results By the end of the 12th week, fasting plasma glucose, HbA1c, HOMA-IR scores and waist circumferences improved equally in both treatment arms. HDL cholesterol and adiponectin levels increased only in the pioglitazone group ( p = 0.01 and p = 0.003, respectively). On the other hand, metformin treatment had additional regulatory effects on BMI, blood pressure and total and LDL-cholesterol levels ( p = 0.002, p = 0.01, p = 0.004, p = 0.001 and p < 0.001, respectively). Neither pioglitazone nor metformin displayed a significant effect on circulating visfatin concentration. Conclusions Despite improvements in insulin sensitivity and glycemic regulation, either pioglitazone or metformin treatment did not result in any effect on blood visfatin levels in patients with treatment naïve T2DM.