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Background: In this study, the results of high dose intravenous monthly pulse CYC on patients with worsening relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) were evaluated. Methods: Fifty-six patients who presented with worsening RRMS (30) or SPMS (26) were to be treated with intravenous (IV) monthly pulse of 800 mg/m² CYC in the first year and bimonthly in the second year. We evaluated the results before treatment and after 12 and 24 months. Results: In the RRMS patients, after 2 years baseline EDSS had improved in 18, was unchanged in 5 and worse in 3. In RRMS group annual relapse rate was 0.92 at the beginning. it decreased to 0.23 in first year and to 0.23 in second year. The SPMS patients after 2 years baseline EDSS had improved in 5, was unchanged in 15 and worse in 3. In SPMS group annual relapse rate was 0.26 at the beggining. It decreased 0.13 in the first year and 0.04 in the second year. Conclusion: This study showed that high dose CYC treatment for two years was well tolerated and seemed effective for both RRMS and SPMS.

Hydatid cyst of the subcutaneous tissue is rare, and often presents as a simple soft-tissue mass. A case of primary subcutaneous hydatid disease arising in the malar region is reported. Histopathological examination revealed the characteristic findings, which are consistent with soft-tissue hydatid disease. There was no sign of echinococcal involvement of organs other than the soft tissue of the face. To the authors' knowledge, this is the first reported case of a primary subcutaneous hydatid cyst arising in the skin in the absence of internal involvement. The patient remains disease free 14 months after surgery. The authors present their clinical findings, diagnostic techniques, and treatment of the patient, and review the literature.

Background We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). Patients and methods Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. Results We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. Conclusion Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH., Italian Ministry of University and Research (MIUR)-Department of Excellence project PREMIA (PREcision MedIcine Approach: bringing biomarker research to clinic), A. Gerussi, L. Cristoferi, and P. Invernizzi acknowledge that this research was partially supported by the Italian Ministry of University and Research (MIUR)-Department of Excellence project PREMIA (PREcision MedIcine Approach: bringing biomarker research to clinic).

WOS: 000395946300003, PubMed ID: 28289585, The aim of the current study was to determine the frequency of the Mediterranean fever (MEFV) gene pathogenic variants in 60 children diagnosed with familial Mediterranean fever (FMF) and to compare the phenotype-genotype correlation. Genomic DNA was isolated by the spin-column method from peripheral blood samples (collected in vacutainers containing EDTA) and buccal smears. The MEFV gene profiles for the current FMF cohort were genotyped by pyrosequencing and direct Sanger sequencing techniques for the target pathogenic variants. The most prominent clinical symptoms were abdominal pain (53.4%), fever (23.4%) and arthritis (23.3%). Eighteen different pathogenic variants were identified and the most frequent were p. Met694Val (20.0%), p. Glu148Gln (13.3%), p. Met680 Ile (11.7%) and p. Arg202Gln (11.7%). Abdominal pain, fever and arthritis were the most common presenting clinical characteristics. Results showed that not only clinical characteristics, but also genotyping of the MEFV gene is needed to establish the correct diagnosis of FMF in children and other family members.

Edizioni Scripta Manent s.n.c., Objective: Hypercholesterolaemia promotes erectile dysfunction through increased superoxide formation and decreased nitric oxide bioactivity in cavernosal tissue. The role of nitric oxide on erectile function is well known. Statins have lipid lowering properties and can modulate endothelial nitric oxide bioavailability. Sildenafil, enhances smooth muscle relaxation in corpus cavernosum. We invastigated in-vitro effects of sildenafil and rosuvastatin on nonadrenergic, non-cholinergic and nitric oxide mediated cavernosal smooth musle relaxation in metabolic syndrome rabbits, since alterations in this pathway are recognised in diabetic and hypercholesterolemic erectile dysfunction. Methods: Ten male rabbits were fed a standart diet as control group, fourty male rabbits were fed a hypercholesterolemic diet for 12 weeks. Hypercholesterolemic group were divided for without treatment, rosuvastatin treatment, sildenafil teratment, and rosuvastatin + sildenafil treatment (N = 10 per groups). Results: Serum levels of cholesterol and glucose were significantly higher in the experimental group than in the control group (p < 0.05). After theraphy no differences were found among the groups in relaxation responses to sodium nitroprusside. The relaxation responses to carbachol and EFS were significantly reduced in metabolic syndrome group to control group (p < 0.05), but there were no differences between the other groups and control group. There was a significantly lower in-vitro relaxation response in the metabolic syndrome rabbits than in controls and the others (p < 0.05). Conclusion: Both agents improve in-vitro relaxation responses of erectile tissue from metabolic syndrome rabbits to endothelial non-adrenergic, non-cholinergic and nitric oxide. This finding supports to the results of other clinical studies with these drugs., Korgali, E.; Cumhuriyet University, School of Medicine, Department of Urology, Merkez - Sivas 58140, Turkey; email: estkorgali@hotmail.com

Osteoporosis is a major public health problem associated with many factors, and it affects more than 50% of women over 50 years old. In the current study, our purpose was to investigate the effects of phosphodiestarase-5 inhibitors on osteoporosis via the nitric oxide/3′,5′-cyclic guanosine monophosphate/protein kinase G signalling pathway. A total of 50 female albino Wistar rats were separated into five groups. The first group was appointed as the healthy control group with no ovariectomy. All animals in the other groups underwent a bilateral ovariectomy. Six months after the ovariectomy, vardenafil, udenafil and tadalafil were given to the third, fourth and fifth groups, respectively, but were not administered to the positive control group (10 mg/kg per day for two months). The bone mineral density values were determined using a densitometry apparatus for all groups pre- and post-ovariectomy as well as after treatment. The levels of nitric oxide, endothelial nitric oxidesynthase, asymmetric dimethylarginine, 3′,5′-cyclic guanosine monophosphate, protein kinase G, phosphodiestarase-5, pyridinoline, deoxypyridinoline, carboxyterminal telopeptide fragments and plasma carboxy terminal propeptide of type I collagen were determined using an enzyme linked immunosorbent assay. The levels of malondialdehyde, 8-hydroxy-2-deoxy guanosine, deoxyguanosine and coenzyme Q10 were determined by a high-performance liquid chromatography assay. Additionally, the right femoral trabecular bone density and the epiphyseal plate were measured in all groups. Angiogenesis was histologically observed in the bone tissue. In addition, we determined that the inhibitors may have caused a positive impact on the increased bone mass density and reduction of bone resorption markers. We also observed the positive effects of these inhibitors on oxidative stress. In conclusion, these phosphodiestarase-5 inhibitors increase angiogenesis in bone tissue and improve the re-formation rate of bone in rats with osteoporosis. Chemical compounds studied in this article Udenafil (PubChem CID: 6918523); Tadalafil (PubChem CID: 110635); Vardanafil (PubCham CID: 110634). Impact statement The results in our study appear to establish the osteoporosis model and provide evidence of the positive effects of three separate PDE5 inhibitors (vardenafil, udenafil, and tadalafil). The positive effects of these PDE5 inhibitors are investigated and demonstrated by the bone mass density and bone resorption markers. These effects are associated with significant demonstrated antioxidant activities. Osteoporosis is a significant major public health problem especially in more aged populations. Advances in identifying and understanding new potential therapeutic modalities for this disease are significant. This study provides such an advance.

Intrahepatic cholestasis of pregnancy (ICP) is a reversible pregnancy-specific cholestatic condition characterized by pruritus, elevated liver enzymes, and increased serum bile acids. It commences usually in the late second or third trimester, and quickly resolves after delivery. The incidence is higher in South American and Scandinavian countries (9.2%-15.6% and 1.5%, respectively) than in Europe (0.1%-0.2%). The etiology is multifactorial where genetic, endocrine, and environmental factors interact. Maternal outcome is usually benign, whereas fetal complications such as preterm labor, meconium staining, fetal distress, and sudden intrauterine fetal demise not infrequently lead to considerable perinatal morbidity and mortality. Ursodeoxycholic acid is shown to be the most efficient therapeutic agent with proven safety and efficacy. Management of ICP consists of careful monitoring of maternal hepatic function tests and serum bile acid levels in addition to the assessment of fetal well-being and timely delivery after completion of fetal pulmonary maturity. This review focuses on the current concepts about ICP based on recent literature data and presents an update regarding the diagnosis and management of this challenging issue.

WOS: 000339087300004, PubMed ID: 25023423, Background: The aim of this study is to compare the motility of Roux limb with that of normal segment. Materials and methods: Rats were divided into 3 equal groups as control, Roux-en-Y (Group A) and Roux-en-Y with vagotomy (Group B). Only midline incision and manipulations were applied in control group. Following distal gastrectomy, Roux-en-Y reconstruction was applied in Group A, while vagotomy Roux-en-Y gastrojejunostonny was applied in Group B. Rats were sacrificed 1 month later by cervical dislocations under anesthesia. The obtained jejunal segments were cut into four equal parts. The bath was 37 degrees C warm while 95 % 02 and 5 % CO2 gases were supplied in 10 ml bicarbonate Krebs' solution. Results: KCl responses were similar in all three groups. Acetylcholine contraction responses in the vagotomy and non-vagotomy Roux-en-Y groups was higher than in those in control group significantly (p < 0.05). This response in vagotomy Roux-en-Y group was also higher than that in non-vagotomy group (p < 0.05). The induced electrical field stimulation contraction response in the vagotomy + Roux-en-Y group was lower than those in control group and non-vagotomy group (p < 0.05). Conclusions: These results show that muscarinic receptor density and/or function may increase after vagotomy and non-vagotomy group operation, and vagotomy may contribute to this increase. The decrease in electrical signal response in vagotomy Roux-en-Y group may depend on the decrease in acetylcholine oscillation from the cholinergic nerve ending (Tab. 1, Fig. 5, Ref. 25). Text in PDF www.elis.sk.

An animal model was developed to elucidate the effect of chronic obstruction of the internal pudendal artery on the responsiveness of the corpus cavernosum. In male albino rabbits, the internal pudendal artery was chronically ligated unilaterally with a silk tie and the occlusion was maintained for 1 month. The control group was sham-operated. The reactivity of corpus cavernosum tissue from the ligated animals and the control animals was studied in organ chambers. Unilateral chronic ligation of the internal pudendal artery caused an impaired contractile response to α-adrenoceptor stimulation with decreased Em and pD2 values and an impaired relaxant response to electrical field stimulation but resulted in a marked increase in the endothelium-dependent relaxant response to carbachol with an increased pD2 value. However chronic obstruction of the pudendal artery had no effect on adenosine-, papaverine- and sodium nitroprusside-induced relaxant responses, and there was no change in agonist potency. These data indicate that altered penile hemodynamics have an effect on the reactivity of the corpus cavernosum and may contribute to the etiology of impotence.

WOS: 000264569100010, PubMed ID: 18823358, Many surveys worldwide have consistently demonstrated a low level of asthma control and under-utilization of preventive asthma drugs. However, these studies have been frequently criticized for using population-based samples, which include many patients with no or irregular follow-ups. Our aim, in this study, was to define the extent of asthma drug utilization, control levels, and their determinants among children with asthma attending to pediatric asthma centers in Turkey. Asthmatic children (age range: 6-18 yr) with at least 1-yr follow-up seen at 12 asthma outpatient clinics during a 1-month period with scheduled or unscheduled visits were included and were surveyed with a questionnaire-guided interview. Files from the previous year were evaluated retrospectively to document control levels and their determinants. From 618 children allocated, most were mild asthmatics (85.6%). Almost 30% and 15% of children reported current use of emergency service and hospitalization, respectively; and 51.4% and 53.1% of children with persistent and intermittent disease, respectively, were on daily preventive therapy, including inhaled corticosteroids. Disease severity [odds ratio: 12.6 (95% confidence intervals: 5.3-29.8)], hospitalization within the last year [3.4 (1.4-8.2)], no use of inhaled steroids [2.9 (1.1- 7.3)], and female gender [2.3 (1.1-5.4)] were major predictors of poor asthma control as defined by their physicians. In this national pediatric asthma study, we found a low level of disease control and discrepancies between preventive drug usage and disease severity, which shows that the expectations of guidelines have not been met even in facilitated centers, thus indicating the need to revise the severity-based approach of asthma guidelines. Efforts to implement the control-based approach of new guidelines (Global Initiative for Asthma 2006) would be worthwhile.

WOS: 000265122700008, PubMed ID: 19246926, Background/Aims: Common bile duct ligation (CBDL) in the guinea pig is a well-defined model of acalculous cholecystitis. Nitric oxide (NO) mediates smooth muscle relaxation by stimulating the activity of soluble guanylate cyclase. The aim of this study was to determine whether the NO/cyclic guanosine monophosphate pathway plays a role in gallbladder relaxant response after CBDL. Methods: Relaxant response of gallbladder muscle strips from CBDL and sham-operated guinea pigs was studied in vitro. Animals were treated with saline, aminoguanidine or an aminoguanidine+L-arginine combination in vivo. Concentration-response curves of papaverine, diethylamine/NO, YC-1, sildenafil and amrinone were obtained and relaxations in each group were calculated as the percent of the contractions induced by carbachol (10(-6) M). Results: There was a significant decrease in the gallbladder muscle relaxant responses to these substances in CBDL and aminoguanidine groups compared with sham surgical controls. The decreased relaxant response was reversed by aminoguanidine+L -arginine but not by aminoguanidine alone. Conclusion: Decreased relaxant responses might be due to the reduced guanylate cyclase enzyme activity, but further studies are required. Copyright (C) 2009 S. Karger AG, Basel

WOS: 000258063200025, PubMed ID: 18327655, Aims Several studies have reported evidence of hormonal abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. In the present study, we examined purinergic relaxation responses in hypothyroidism in an experimental rabbit model and compared them with controls to evaluate the possible involvement of the purinergic pathway. Materials and methods The study comprised 20 male New Zealand white rabbits. The rabbits were divided into two equal groups. We tested the effects of ATP, alpha beta ATP, and adenosine precontracted with phenylephrine on the isolated corpus cavernosum preparations from control and hypothyroid rabbits. We also evaluated the effects of ATP, alpha beta ATP, and adenosine on the cGMP levels in the isolated corpus cavernosum preparations from control and hypothyroid rabbits. Results T-3, T-4, and testosterone levels were significantly lower in hypothyroid rabbits. ATP, alpha beta ATP, carbachol, and electrical field stimulation (EFS)-induced frequency-dependent relaxation responses in the isolated rabbit corpus cavernosum strips precontracted with phenylephrine reduced significantly (P < 0.05). Adenosine-induced relaxation responses did not change significantly in hypothyroid rabbits. Conclusion Reduction of relaxation response in hypothyroid rabbits corpus cavernosum can depend on a decreased release of nitric oxide (NO) from nitrergic nerves and endothelium.

Erectile dysfunction is common in men with chronic renal failure. Previously nitrergic and endothelium-dependent relaxation responses have been shown to be reduced in chronic renal failure rabbits. We have therefore investigated the efficacy of phosphodiesterase inhibitors on the corpora cavernosa obtained from uremic rabbits. Uremia was induced with 5/6 nephrectomy and 4 weeks later cavernosal tissue strips were isolated. The relaxant effect of phosphodiesterase 5 inhibitors, zaprinast (1-300 ?M) and sildenafil (0.01-300 ?M), phosphodiesterase 3 inhibitor amrinone (1-100 ?M) and non-specific phosphodiesterase inhibitor papaverine (1-300 ?M) were investigated on phenylephrine (10 ?M)-induced tone. We found a shift in the dose-response curve of only phosphodiesterase 5 inhibitors. These results suggest that the decreased production or availability of endogenous nitric oxide in chronic renal failure animals leads to decreased efficacy of phosphodiesterase 5 inhibitors to induce relaxation. © 2003 Elsevier Science B.V. All rights reserved.

Haemangioma localised in the wrist originating from the sheath of the fifth deep flexor tendon and obstructing the movement of the tendon through the carpal tunnel as an unusual cause of trigger wrist is presented. Tumoural masses around the wrist can cause triggering by obstructing the movement of tendons through the carpal tunnel and the clinician should consider other causes of triggering for surgical treatment.