Pharmacological profiles of opioid ligands at Kappa opioid receptors

BACKGROUND: The aim of the present study was to describe the activity of a set of opioid drugs, including partial agonists, in a human embryonic kidney cell system stably expressing only the mouse κ-opioid receptors. Receptor activation was assessed by measuring the inhibition of cyclic adenosine mono phosphate (cAMP) production stimulated by 5 μM forskolin. Intrinsic activities and potencies of these ligands were determined relative to the endogenous ligand dynorphin and the κ agonist with the highest intrinsic activity that was identified in this study, fentanyl. RESULTS: Among the ligands studied naltrexone, WIN 44,441 and dezocine, were classified as antagonists, while the remaining ligands were agonists. Intrinsic activity of agonists was assessed by determining the extent of inhibition of forskolin-stimulated cAMP production. The absolute levels of inhibition of cAMP production by each ligand was used to describe the rank order of intrinsic activity of the agonists; fentanyl = lofentanil ≥ hydromorphone = morphine = nalorphine ≥ etorphine ≥ xorphanol ≥ metazocine ≥ SKF 10047 = cyclazocine ≥ butorphanol > nalbuphine. The rank order of affinity of these ligands was; cyclazocine > naltrexone ≥ SKF 10047 ≥ xorphanol ≥ WIN 44,441 > nalorphine > butorphanol > nalbuphine ≥ lofentanil > dezocine ≥ metazocine ≥ morphine > hydromorphone > fentanyl. CONCLUSION: These results elucidate the relative activities of a set of opioid ligands at κ-opioid receptor and can serve as the initial step in a systematic study leading to understanding of the mode of action of these opioid ligands at this receptor

Delay in Diagnosis of Two Siblings with Severe Ocular Problems and Autoimmune Polyglandular Syndrome

Autoimmune polyendocrine syndrome type 1 (APS1) is a scarce polyendocrinopathy with autosomal recessive inheritance results from defects in the human autoimmune regulatory (AIRE) gene. In addition to three major manifestations of APS1 including mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease, ophthalmic problems such as keratoconjunctivitis, dry eye, iridocyclitis, and cataract can be seen in these patients. In this article, we introduced two siblings presented with nail dystrophia, severe photophobia, and keratitis since early childhood which genetic examination revealed single nucleotide T>C translocation in their 2nd exon and heterozygous deletion mutation in their 12th exon

Conventional and extended intramammary therapy of persistent subclinical mastitis using nafcillin-penicillin- dihydrostreptomycin in lactating dairy cattle

Summary The objective of the present study was to compare the efficacy of conventional and extended intramammary (IMM) therapy of persistent subclinical mastitis in lactating dairy cattle using nafcillinpenicillin-dihydrostreptomycin combination (NPD). Sixty-five dairy cows with 126 infected quarters were enrolled in the study. Infected cows were allocated randomly to 1 of 3 different treatment regimens: (1) conventional group: NPD administered IMM 3 times at 24-h intervals (20 infected cows, 43 intramammary infections [IMI]), (2) extended group: NPD administered IMM 6 times at 24-h intervals (23 cows, 43 IMI), and (3) untreated control group (22 cows, 40 IMI). The overall bacteriological cure (BC) rates for subclinical IMI were 86.04%, 100%, and 20% for the conventional, extended and the control groups, respectively; indicating a higher BC rate (P<0.0001) for the treated groups than the control group. Significant difference (P=0.029) concerning the BC rate was also observed between the extended and the conventional groups. Significant difference (P=0.0021) in somatic cell count (SCC) was detected between the extended and the control group. Fat percentage increased in the conventional (P=0.029) and in the extended (P<0.0001) groups, and protein percentage increased only in the extended group (P=0.0016). There was no significant difference in posttreatment milk production between the groups (P>0.05). Results of this study indicate that NPD therapy was effective in eliminating subclinical IMI in lactating dairy cows, and that extended therapy enhanced BC rate and reduced SCC

Gender similarity in low agreement between written and video ISAAC asthma questionnaires

Background and Aim. The prevalence of childhood asthma varies among different nations and appears to have increased in recent years. It has been difficult to determine this prevalence precisely and compare the communities due to the lack of a standardized method. The International Studies of Asthma and Allergies in Childhood (ISAAC) has developed a written and video questionnaire to measure asthma prevalence and overcome these difficulties. This study was carried out to determine the prevalence of childhood asthma in Kashan, the central area of Iran, and to assess the agreement between the ISAAC written and video questionnaires and its gender relationship. Methods. Between December 2002 and June 2003, 2533 school children, aged 13-14 years, in Kashan secondary schools completed sequentially the ISAAC written and video questionnaires. The agreement between responses to the two questionnaires for reported “ever wheeze”, “exercise wheeze”, “night wheeze” and “night cough” was determined, using kappa coefficient and concordance. Results. The prevalence of asthma symptoms were significantly lower in the responses to the video questionnaire compared with the written questionnaire. Kappa coefficient showed only poor to fair agreement (κ = 0.13- 0.24) between video and written questionnaires, although the concordance between them always exceeded 60%. Conclusions. This study showed that reported asthma symptoms based on video questionnaires were significantly lower than the written questionnaire, and that there is low agreement between the two questionnaires which requires further investigation to explain the findings. In addition, this investigation revealed no significant difference between the genders for this low agreement

Pulmonary complications in primary hypogammaglobulinemia: a survey by high resolution CT scan

Background. Primary hypogammaglobulinemia disorders are a group of heterogeneous immunodeficiency syndromes with an increased susceptibility to pulmonary complications. Methods. The aim of this study was to evaluate the extent of lung abnormalities in primary hypogammaglobulinaemic patients by high resolution computed tomography (HRCT) scan and pulmonary function test (PFT). HRCT and PFT were performed in 22 Iranian patients with primary hypogammaglobulinemia. Results. Pathological bronchial findings were observed in thirteen patients: three patients showed only peribronchial thickening and the remaining ten patients suffered from both bronchiectasis and peribronchial wall thickening. Mild type of bronchiectasis and peribronchial wall thickening were the most common type, predominantly observed in the right middle and both right and left lower lobe segments of lungs. Although bullae were not found, emphysema, air-trapping, and collapse/consolidation were observed in two patients. Bronchial involvement was mostly limited to 1 up to 5 bronchopulmonary segments; only one HRCT indicated bronchial involvement in more than nine bronchopulmonary segments. Pathological bronchial findings mostly observed in the proximal bronchi; meanwhile the involvement of the distal bronchi was less common. Decreasing FEV1 and FVC were observed in 65% and 55% of patients, respectively. There was a significant correlation between the HRCT score and the predicted values by PFT. The delay of diagnosis in patients with bronchiectasis was significantly higher than those without bronchiectasis. Conclusions. It seems that the majority of hypogammaglobulinaemic patients suffer from the mild type of bronchiectasis, which is mostly observed in the proximal bronchi of the lower lobe segments. The delay of diagnosis plays an important role in the occurrence of this complication in these patients

Influence of calcination temperature on structural and magnetic properties of nanocomposites formed by Co-ferrite dispersed in sol-gel silica matrix using tetrakis(2-hydroxyethyl) orthosilicate as precursor

Effects of calcination temperatures varying from 400 to 1000°C on structural and magnetic properties of nanocomposites formed by Co-ferrite dispersed in the sol-gel silica matrix using tetrakis(2-hydroxyethyl) orthosilicate (THEOS) as water-soluble silica precursor have been investigated. Studies carried out using XRD, FT-IR, TEM, STA (TG-DTG-DTA) and VSM techniques. Results indicated that magnetic properties of samples such as superparamagnetism and ferromagnetism showed great dependence on the variation of the crystallinity and particle size caused by the calcination temperature. The crystallization, saturation magnetization Ms and remenant magnetization Mr increased as the calcination temperature increased. But the variation of coercivity Hc was not in accordance with that of Ms and Mr, indicating that Hc is not determined only by the crystallinity and size of CoFe2O4 nanoparticles. TEM images showed spherical nanoparticles dispersed in the silica network with sizes of 10-30 nm. Results showed that the well-established silica network provided nucleation locations for CoFe2O4 nanoparticles to confinement the coarsening and aggregation of nanoparticles. THEOS as silica matrix network provides an ideal nucleation environment to disperse CoFe2O4 nanoparticles and thus to confine them to aggregate and coarsen. By using THEOS as water-soluble silica precursor over the currently used TEOS and TMOS, the organic solvents are not needed owing to the complete solubility of THEOS in water. Synthesized nanocomposites with adjustable particle sizes and controllable magnetic properties make the applicability of Co-ferrite even more versatile

Primary antibody deficiency in a tertiary referral hospital: A 30-year experiment

Background: Primary antibody deficiency (PAD) is the most common group of primary immunodeficiency disorders (PID), with a broad spectrum of clinical features ranging from severe and recurrent infections to asymptomatic disease. Objectives: The current study was performed to evaluate and compare demographic and clinical data in the most common types of PAD. Materials and Methods: We performed a retrospective review of the medical records of all PAD patients with a confirmed diagnosis of common variable immunodeficiency (CVID), hyper IgM syndrome (HIgM), selective IgA deficiency (SIgAD), and X-linked agammaglobulinemia (XLA) who were diagnosed during the last 30 years at the Children�s Medical Center, Tehran, Iran. Results: A total number of 280 cases of PAD (125 CVID, 32 HIgM, 63 SIgAD, and 60 XLA) were enrolled in the study. The median (range) age at the onset of disease in CVID, HIgM, SIgAD, and XLA was 2 (0-46), 0.91 (0-9), 1 (0-26), and 1 (0-10) years, respectively. Gastrointestinal infections were more prevalent in CVID patients, as were central nervous system infections in XLA patients. Autoimmune complications were more prevalent in HIgM patients, malignancies in CVID patients, and allergies in SIgAD patients. The mortality rate for CVID, HIgM, and XLA was 27.2, 28.1, and 25, respectively. No deaths were reported in SIgAD patients. Conclusions: SIgAD patients had the best prognosis. While all PAD patients should be monitored for infectious complications, special attention should be paid to the finding of malignancy and autoimmune disorders in CVID and HIgM patients, respectively. © 2015 Esmon Publicidad