Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vivo Toxicity, Pharmacokinetics, and Anti-Human Immunodeficiency Virus Activity of Stavudine-5′-(p-Bromophenyl Methoxyalaninyl Phosphate) (Stampidine) in Mice

ABSTRACT We have evaluated the clinical potential of stavudine-5′-(p-bromophenyl methoxyalaninyl phosphate(stampidine [STAMP]), a novel aryl phosphate derivative of stavudine, as a new anti-human immunodeficiency virus (anti-HIV) agent, by examining its acute, subacute, and chronic toxicity profile in mice as well as by testing its antiviral activity in a surrogate human peripheral blood lymphocyte (Hu-PBL)-SCID mouse model of human AIDS. STAMP was very well tolerated in BALB/c and CD-1 mice, without any detectable acute or subacute toxicity at single intraperitoneal or oral bolus doses as high as 500 mg/kg of body weight. Notably, daily administration of STAMP intraperitoneally or orally for up to 8 consecutive weeks was not associated with any detectable toxicity at cumulative dose levels as high as 6.4 g/kg. Micromolar concentrations of the active STAMP metabolite in plasma were rapidly achieved and maintained for more than 4 h after parenteral as well as oral administration of a nontoxic 100-mg/kg bolus dose of STAMP. In accordance with its favorable pharmacokinetic profile and in vitro potency, STAMP exhibited dose-dependent and potent in vivo anti-HIV activity in Hu-PBL-SCID mice against a genotypically and phenotypically nucleoside analog reverse transcriptase inhibitor (NRTI)-resistant clinical HIV type 1 (HIV-1) isolate (BR/92/019; D67N, L214F, T215D, K219Q) at nontoxic dose levels. The remarkable in vivo safety and potency of STAMP warrants the further development of this promising new antiretroviral agent for possible clinical use in patients harboring NRTI-resistant HIV-1.
Synthesis and investigation of antimicrobial activity and spectrophotometric and dyeing properties of some novel azo disperse dyes based on naphthalimides

A series of novel disperse dyes containing azo group were synthesized through a diazotization and coupling process. The 4‐amino‐N‐2‐aminomethylpyridine‐1,8‐naphthalimide was diazotized by nitrosylsulphuric acid and coupled with various aromatic amines such as N,N‐diethylaniline, N,N‐dihydroxyethylaniline, 8‐hydroxyquinoline, and 2‐methylindole. Chemical structures of the synthesized dyes were characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), proton nuclear magnetic resonance (1H NMR), carbon nuclear magnetic resonance (13C NMR), elemental analysis, and ultraviolet–visible (UV–visible) spectroscopy. The spectrophotometric data of all dyes were evaluated in various solvents with different polarity. Eventually, the dyes were applied on polyamide fabrics in order to investigate their dyeing properties. The fastness properties of the dyed fabrics such as wash, light, and rubbing fastness degrees were measured by standard methods. Moreover, the color gamut of the synthesized dyes was measured on polyamide fabrics. Results indicated that some of the synthesized dyes were able to dye polyamide fabrics with deep shades. They had very good wash and rubbing fastness degrees and moderate‐to‐good light fastness on polyamide fabrics. The antibacterial and antifungal activities of the synthesized dyes were evaluated in soluble state and on the dyed fabrics. The results indicated that dye 2 containing N,N‐dihydroxyethylaniline as coupler had the highest activity against all the bacteria and fungi used. © 2015 American Institute of Chemical Engineers Biotechnol. Prog. , 31:1086–1095, 2015
Association between xenobiotic gene polymorphisms and non‐Hodgkin's lymphoma risk

Summary. The last four decades have seen a significant increase in the incidence of non‐Hodgkin's lymphoma (NHL) as a possible result of increasing environmental carcinogen exposure, particularly pesticides and solvents. Based on the increasing evidence for an association between carcinogen exposure‐related cancer risk and xenobiotic gene polymorphisms, we have undertaken a case–control study of xenobiotic gene polymorphisms in individuals with a diagnosis of NHL. Polymorphisms of six xenobiotic genes (CYP1A1, GSTT1, GSTM1, PON1, NAT1, NAT2) were characterized in 169 individuals with NHL and 205 normal controls using polymerase chain reaction‐based methods. Polymorphic frequencies were compared using Fisher's exact tests, and odds ratios for NHL risk were calculated. Among the NHL group, the incidence of GSTT1 null and PON1 BB genotypes were significantly increased compared with controls, 34%vs 14%, and 24%vs 11% respectively. Adjusted odds ratios calculated from multivariate analyses demonstrated that GSTT1 null conferred a fourfold increase in NHL risk (OR = 4·27; 95% CI, 2·40–7·61, P < 0·001) and PON1 BB a 2·9‐fold increase (OR = 2·92; 95% CI, 1·49–5·72, P = 0·002). Furthermore, GSTT1 null combined with PON1 BB or GSTM1 null conferred an additional risk of NHL. This is the first time that a PON1 gene polymorphism has been shown to be associated with cancer risk. We conclude that the two polymorphisms, GSTT1 null and PON1 BB, are common genetic traits that pose low individual risk but may be important determinants of overall population NHL risk, particularly among groups exposed to NHL‐related carcinogens.
A Copper-Activated Two-Component System Interacts with Zinc and Imipenem Resistance in Pseudomonas aeruginosa

ABSTRACT The effects of copper (Cu) on trace metal and antibiotic resistance of Pseudomonas aeruginosa have been investigated. Cu treatments induced resistance not only to this metal but also, surprisingly, to zinc (Zn). Quantitative reverse transcription-PCR (qRT-PCR) revealed that after Cu treatment the transcription of the czcRS two-component system (TCS) operon was enhanced as well as that of the czcCBA operon encoding an efflux pump specific for zinc, cadmium, and cobalt. Cu treatments at the same time caused a decrease in the production of OprD porin, resulting in resistance to the carbapenem antibiotic imipenem. The CzcR regulator was known to repress oprD. However, Cu was still able to decrease the production of OprD and induce imipenem resistance in a czcRS knockout mutant. This strongly suggested that another Cu-dependent regulatory system was acting negatively on oprD expression. TCS regulator genes copR-copS have been shown to be involved in Cu tolerance in P. aeruginosa. qRT-PCR showed that overproduction of the CopR or of the CzcR regulator resulted in increased transcription of the czcC gene as well as in a decrease in oprD gene transcription, either in the wild-type strain or in the czcRS knockout mutant. Overproduction experiments suggest that a metal-dependent mechanism operates at the posttranscriptional level to control the production of the CzcCBA efflux pump. This study shows that CopR is a new negative regulator of OprD porin and that it links Zn, Cu, and imipenem resistances by interacting with the CzcRS TCS.
Microglial Activation Varies in Different Models of Creutzfeldt-Jakob Disease

ABSTRACT Progressive changes in host mRNA expression can illuminate crucial pathogenetic pathways in infectious disease. We examined general and specific approaches to mRNA expression in three rodent models of Creutzfeldt-Jakob disease (CJD). Each of these models displays distinctive neuropathology. Although mRNAs for the chemokine receptor CCR5, the lysosomal protease cathepsin S, and the pleiotropic cytokine transforming growth factor β1 (TGF-β1) were progressively upregulated in rodent CJD, the temporal patterns and peak magnitudes of each of these transcripts varied substantially among models. Cathepsin S and TGF-β1 were elevated more than 15-fold in mice and rats infected with two different CJD strains, but not in CJD-infected hamsters. In rats, an early activation of microglial transcripts preceded obvious deposits of prion protein (PrP) amyloid. However, in each of the three CJD models, the upregulation of CCR5, cathepsin S, and TGF-β1 was variable with respect to the onset of PrP pathology. These results show glial cell involvement varies as a consequence of the agent strain and species infected. Although neurons are generally assumed to be the primary sites for agent replication and abnormal PrP formation, microglia may be targeted by some agent strains. In such instances, microglia can both process PrP to become amyloid and can enhance neuronal destruction. Because microglia can participate in agent clearance, they may also act as chronic reservoirs of infectivity. Finally, the results here strongly suggest that TGF-β1 can be an essential signal for amyloid deposition.
Cytokeratin 20 as an objective marker of urothelial dysplasia.

OBJECTIVE To investigate the dysregulation of cytokeratin 20 (CK20) expression in urothelial dysplasia and its potential as a diagnostic aid. PATIENTS AND METHODS Twenty-two patients were selected on the basis that they had undergone one or more biopsies showing dysplasia before the development of a transitional cell carcinoma (TCC): 15 of these patients also had a prior history of TCC. The dysplasia was classified as mild in 12, moderate in 14 or severe dysplasia/carcinoma in situ in 10 patients, ensuring that a spectrum of morphological appearances was represented. Control biopsies were obtained from seven children undergoing bladder reconstructions and 23 patients with recurrent urinary tract infections, haematuria or functional bladder symptoms, but no history of TCC. RESULTS The expression of CK20 was restricted to superficial 'umbrella' cells and occasional intermediate cells in the control biopsies, even in the presence of severe inflammation. In 31 of the 36 cases of dysplasia complete loss of restriction was seen at least focally with positive expression in all layers of the urothelium. CONCLUSION The abnormal expression of CK20 is a reliable, positive marker of urothelial dysplasia in the urinary bladder. Immunostaining for CK20 is therefore a useful adjunct to morphology in the diagnosis of dysplasia, of particular value in the distinction from reactive states where diagnostic difficulties are greatest.
Potential protective role of angiotensin‐converting enzyme inhibitors captopril and enalapril against adriamycin‐induced acute cardiac and hepatic toxicity in rats

Captopril and enalapril—angiotensin‐converting enzyme (ACE) inhibitors—were evaluated for their antioxidative protective action against adriamycin‐induced cardiac and hepatic toxicity. Rats were treated with either captopril (10 mg kg−1) or enalapril (2 mg kg−1) intragastrically (i.g.) daily for 7 days before single intraperitoneal (i.p.) injection with adriamycin (15 mg kg−1). The animals were killed 30 h after adriamycin administration. Adriamycin produced significant elevation in thiobarbituric acid reactive substances (TBARS), which is an indicator of lipid peroxidation, and significantly inhibited the activity of superoxide dismutase (SOD) in heart and liver tissues, with a significant rise in the serum levels of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), creatine kinase isoenzyme (CK‐MB) and lactic dehydrogenase (LDH), indicating acute cardiac toxicity. A single injection of adriamycin did not affect the cardiac or hepatic glutathione (GSH) content or cardiac catalase (CAT) activity, but hepatic CAT activity was elevated. Pretreatment with ACE inhibitors significantly reduced the TBARS concentration in both heart and liver and ameliorated the inhibition of cardiac and hepatic SOD activity. In addition, the ACE inhibitors significantly improved the serum levels of GOT, GPT, CK‐MB and LDH in adriamycin‐treated rats. Thus, these results suggest that captopril and enalapril possess antioxidative potential that may protect the heart against adriamycin‐induced acute oxidative toxicity. This protective effect might be mediated, at least in part, by the limitation of culprit free radicals and the amelioration of oxidative stress. Copyright © 2001 John Wiley & Sons, Ltd.
Attitude and practice of pregnant women regarding self-medication in Yazd, Iran.

BACKGROUND Medications, a main strategic commodity in any country, are strictly related to community health and sustainable development. Self-medication and irregular use of medications can increase their adverse effects. This study investigated the factors related to irregular and arbitrary use of medications in pregnant women admitted to health centers and clinics of Yazd, Iran, and their practice in this context. METHODS This was a descriptive- analytic cross-sectional study conducted among 180 pregnant women. Participants were selected by cluster sampling. We chose six health centers and clinics from all medical centers in Yazd by a simple random method. A questionnaire was completed by the pregnant women who were consecutively admitted to each center. Data were analyzed by ANOVA, t-test, Chi-square, and Pearson tests with SPSS-15 software. RESULTS More than 35% of the women self-medicated during pregnancy. Women with academic degrees scored higher in the knowledge section; however, this difference was not significant. The mean attitude scores for academic and nonacademic graduates were 34.92 (from 60) and 29.87, respectively while the mean practice scores were 15 (from 20) and 14.25 for academic and non-academic graduates, respectively. CONCLUSION The results of this study showed an increased prevalence of self-medication among pregnant women. Because of potential fetomaternal hazards related to medications, it is necessary to conduct educational programs to prevent this harmful habit and attitude in pregnant women.
Binding properties of liposomes containing the myelin‐associated glycoprotein MAG to neural cell cultures

The myelin‐associated glycoprotein MAG is a neural cell adhesion molecule which belongs to the immunoglobulin superfamily and the carbohydrate based L2/HNK‐1 family of adhesion molecules. In this study we further characterize the adhesive properties of MAG. MAG incorporated into liposomes bound to cultured peripheral and central nervous system neurons known to be myelinated in vivo. Expression of the neuronal MAG receptor(s) on spinal cord neurons increased with time in culture and correlated with the time of active myelination of these neurons in vivo. MAG bound only poorly if at all to cerebellar neurons which are not myelinated in vivo and not to cultured oligodendrocytes or Schwann cells. A low level of MAG binding to astrocytes or fibroblast‐like cells that was MAG antibody molecules L1 and N‐CAM, two other members of the immunoglobulin superfamily, were not found to be the neuronal receptors for MAG. RGD containing peptides did not inhibit binding of MAG‐liposomes to neurons. The soluble form of MAG which contains most, if not all, of the extracellular domain of the molecule and binds to collagen, did not interfere with the binding of MAG‐liposomes to neurons. Conversely, MAG‐liposomes did not bind to collagen, suggesting the extracellular domain of the molecule.
Heterodimerization of Somatostatin and Opioid Receptors Cross-modulates Phosphorylation, Internalization, and Desensitization*

Heterodimerization has been shown to modulate the ligand binding, signaling, and trafficking properties of G protein-coupled receptors. However, to what extent heterodimerization may alter agonist-induced phosphorylation and desensitization of these receptors has not been documented. We have recently shown that heterodimerization of sst2A and sst3 somatostatin receptors results in inactivation of sst3 receptor function (Pfeiffer, M., Koch, T., Schröder, H., Klutzny, M., Kirscht, S., Kreienkamp, H. J., Höllt, V., and Schulz, S. (2001) J. Biol. Chem.276, 14027–14036). Here we examine dimerization of the sst2A somatostatin receptor and the μ-opioid receptor, members of closely related G protein-coupled receptor families. In coimmunoprecipitation studies using differentially epitope-tagged receptors, we provide direct evidence for heterodimerization of sst2A and MOR1 in human embryonic kidney 293 cells. Unlike heteromeric assembly of sst2A and sst3, sst2A-MOR1 heterodimerization did not substantially alter the ligand binding or coupling properties of these receptors. However, exposure of the sst2A-MOR1 heterodimer to the sst2A-selective ligand L-779,976 induced phosphorylation, internalization, and desensitization of sst2A as well as MOR1. Similarly, exposure of the sst2A-MOR1 heterodimer to the μ-selective ligand [d-Ala2,Me-Phe4,Gly5-ol]enkephalin induced phosphorylation and desensitization of both MOR1 and sst2A but not internalization of sst2A. Cross-phosphorylation and cross-desensitization of the sst2A-MOR1 heterodimer were selective; they were neither observed with the sst2A-sst3 heterodimer nor with the endogenously expressed lysophosphatidic acid receptor. Heterodimerization may thus represent a novel regulatory mechanism that could either restrict or enhance phosphorylation and desensitization of G protein-coupled receptors.
Pulmonary effects of welding fumes: review of worker and experimental animal studies.

BACKGROUND Approximately one million workers worldwide perform welding as part of their work duties. Electric arc welding processes produce metal fumes and gases which may be harmful to exposed workers. METHODS This review summarizes human and animals studies which have examined the effect of welding fume exposure on respiratory health. An extensive search of the scientific and occupational health literature was performed, acquiring published articles which examined the effects of welding on all aspects of worker and laboratory animal health. The databases accessed included PubMed, Ovid, NIOSHTIC, and TOXNET. RESULTS Pulmonary effects observed in full-time welders have included metal fume fever, airway irritation, lung function changes, susceptibility to pulmonary infection, and a possible increase in the incidence of lung cancer. Although limited in most cases, animal studies have tended to support the findings from epidemiologic studies. CONCLUSIONS Despite the numerous studies on welding fumes, incomplete information still exists regarding the causality and possible underlying mechanisms associated with welding fume inhalation and pulmonary disease. The use of animal models and the ability to control the welding fume exposure in toxicology studies could be utilized in an attempt to develop a better understanding of how welding fumes affect pulmonary health.
The Relationship Between Depressive Symptoms and Restless Legs Syndrome in Two Prospective Cohort Studies

Objective Cross-sectional studies suggest a strong association between depression and restless legs syndrome (RLS); however, the temporal relationship between the two disorders remains unknown. We tested whether the presence of clinically relevant depressive symptoms (CRDS) is a risk factor for subsequent RLS in the general population. The relationship between prevalent RLS and incident CRDS was also examined. Methods Two independent, prospective cohort studies with representative, age-stratified random samples, the Dortmund Health Study (DHS; n = 1312/1122 [baseline/follow-up], median follow-up time = 2.1 years) and the Study of Health in Pomerania (SHIP; n = 4308/3300, median follow-up time = 5.0 years) were analyzed. RLS was assessed in both studies according to the RLS minimal criteria, at baseline and at follow-up. CRDS were assessed by the Center for Epidemiologic Studies–Depression scale (a score of ≥16) in DHS only at baseline and by the Munich-Composite International Diagnostic-Screener in SHIP at baseline and at follow-up. Results Clinically relevant depressive symptoms at baseline were associated new-onset RLS in both studies (DHS: odds ratio [OR] = 1.94, 95% confidence interval [CI] = 1.09–3.44; SHIP: OR = 2.37, 95% CI = 1.65–3.40) after adjustment for age, sex, education, body mass index, smoking, physical activity, and the presence of various comorbidities. RLS at baseline was an independent risk factor of incident CRDS in SHIP (OR = 1.82, 95% CI = 1.10–3.00). Conclusions The presence of CRDS may be a risk factor for subsequent RLS. The relationship between the two disorders might be bidirectional because RLS also predicts incident depressive symptoms.
Anti-inflammatory actions of flavonoids and structural requirements for new design.

Flavonoids are low molecular weight compounds rich in seeds, citrus fruits, olive oil, tea and red wine, with potent antioxidant, cytoprotective and antiinflammatory activities. Flavonoids are composed of a three-ring structure (A,B and C) with various substitutions; they can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3 or a hydroxyl group in position 3 of the C (middle) ring. Particular hydroxylation patterns of the B ring of the flavones permit them to inhibit histamine, tryptase, interleukin-6 and interleukin-8 release from human umbilical-cord derived cultured mast cells, as well as from macrophages. The catechol (o-dihydroxy) group in the B ring as in quercetin confers potent inhibitory ability, while a pyrogallol (trihydroxy) group, as in myricetin, produces even higher activity. However, addition of one hydroxyl group on position 2′ of the B ring, as in the flavonol morin, renders this compound inactive. The C2-C3 double bond of the C ring appears to increase scavenger activity because it confers stability to the phenoxy-radicals produced, while the 4-oxo (keto double bond at position 4 of the C ring) increases free radical scavenger activity by delocalizing electrons from the B ring. The 3-OH group on the C ring appears tobe critical for anti-inflammatory activity. Inhibition of mast cell secretion was shown to be mediated by a 78-kD phosphoprotein which has been cloned and serves as a bridge between the cell surface and the cytoskeleton. Phosphorylation at particular sites in the C-terminus unfolds the three dimensional structure of this protein making actin binding sites accessible; crosslinking with actin in the cytoskeleton prevents secretion of inflammatory mediators. These properties present unique opportunities for the synthesis of new compounds for the treatment of inflammatory and possibly proliferative disorders.
Calcium status in premenopausal and postmenopausal women.

BACKGROUND In postmenopausal women, the two major causes of bone loss are oestrogen deficiency after menopause and age related processes. Bone turnover increases to high levels and oestrogen deficiency may induce calcium loss by indirect effects on extra skeletal calcium homeostasis. Objective of this study was to evaluate calcium status in pre-menopausal and postmenopausal women. METHODS This cross sectional study was carried out in 34 premenopausal women and 33 postmenopausal women, in Department of Physiology, Services Institute of Medical Sciences, Lahore. Height and weight of each woman were taken to find out the body mass index (BMI). Serum calcium, parathyroid hormone and calcitonin levels of each subject were determined. RESULTS Premenopausal women were obese (BMI>30 Kg/m2) while postmenopausal women were overweight (BMI>25 Kg/m2). Serum calcium levels were significantly lower in postmenopausal women than in pre-menopausal women, while serum parathyroid hormone levels were significantly higher in postmenopausal woman. Serum calcitonin level was not significantly different in the two groups. CONCLUSION Postmenopausal women are calcium deficient and have increased bone turnover as indicated by increased serum parathyroid hormone levels.