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Balkan Medical Journal Apr 2017Juvenile idiopathic arthritis is the most common chronic rheumatic disease of unknown aetiology in childhood and predominantly presents with peripheral arthritis. The...
Juvenile idiopathic arthritis is the most common chronic rheumatic disease of unknown aetiology in childhood and predominantly presents with peripheral arthritis. The disease is divided into several subgroups, according to demographic characteristics, clinical features, treatment modalities and disease prognosis. Systemic juvenile idiopathic arthritis, which is one of the most frequent disease subtypes, is characterized by recurrent fever and rash. Oligoarticular juvenile idiopathic arthritis, common among young female patients, is usually accompanied by anti-nuclear antibodie positivity and anterior uveitis. Seropositive polyarticular juvenile idiopathic arthritis, an analogue of adult rheumatoid arthritis, is seen in less than 10% of paediatric patients. Seronegative polyarticular juvenile idiopathic arthritis, an entity more specific for childhood, appears with widespread large- and small-joint involvement. Enthesitis-related arthritis is a separate disease subtype, characterized by enthesitis and asymmetric lower-extremity arthritis. This disease subtype represents the childhood form of adult spondyloarthropathies, with human leukocyte antigen-B27 positivity and uveitis but commonly without axial skeleton involvement. Juvenile psoriatic arthritis is characterized by a psoriatic rash, accompanied by arthritis, nail pitting and dactylitis. Disease complications can vary from growth retardation and osteoporosis secondary to treatment and disease activity, to life-threatening macrophage activation syndrome with multi-organ insufficiency. With the advent of new therapeutics over the past 15 years, there has been a marked improvement in juvenile idiopathic arthritis treatment and long-term outcome, without any sequelae. The treatment of juvenile idiopathic arthritis patients involves teamwork, including an experienced paediatric rheumatologist, an ophthalmologist, an orthopaedist, a paediatric psychiatrist and a physiotherapist. The primary goals of treatment are to eliminate active disease, to normalize joint function, to preserve normal growth and to prevent long-term joint damage. Timely and aggressive treatment is important to provide early disease control. The first-line treatment includes disease-modifying anti-rheumatic drugs (methotrexate, sulphasalazine, leflunomide) in combination with corticosteroids, used in different dosages and routes (oral, intravenous, intra-articular). Intra-articular application of steroids seems to be an effective treatment modality, especially in monoarthritis. Biological agents should be added in the treatment of unresponsive patients. Anti-tumour necrosis factor agents (etanercept, infliximab, adalimumab), anti-interleukin-1 agents (anakinra, canakinumab), anti- interleukin-6 agents (tocilizumab) and T-cell regulatory agents (abatacept) have been shown to be safe and effective in childhood patients. Recent studies reported sustained reduction in joint damage with even complete clinical improvement in paediatric patients, compared to previous data.
Topics: Adolescent; Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Juvenile; Benzimidazoles; Biological Factors; Biological Therapy; Calcium; Child; Child, Preschool; Female; Fever; Hempa; Humans; Indomethacin; Infant; Injections, Intra-Articular; Male; Vitamin D
PubMed: 28418334
DOI: 10.4274/balkanmedj.2017.0111 -
Polymers Nov 2022In this study, a novel polymeric nanomaterial was synthesized and characterized, and it its potential usability in hypertension treatment was demonstrated. For these...
Novel Polymeric Nanomaterial Based on Poly(Hydroxyethyl Methacrylate-Methacryloylamidophenylalanine) for Hypertension Treatment: Properties and Drug Release Characteristics.
In this study, a novel polymeric nanomaterial was synthesized and characterized, and it its potential usability in hypertension treatment was demonstrated. For these purposes, a poly(hydroxyethyl methacrylate-methacryloylamidophenylalanine)-based polymeric nanomaterial (p(HEMPA)) was synthesized using a mini-emulsion polymerization technique. The nanomaterials were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and zeta size analysis. The synthesized p(HEMPA) nanomaterial had a diameter of about 113 nm. Amlodipine-binding studies were optimized by changing the reaction conditions. Under optimum conditions, amlodipine's maximum adsorption value (Qmax) of the p(HEMPA) nanopolymer was found to be 145.8 mg/g. In vitro controlled drug release rates of amlodipine, bound to the nanopolymer at the optimum conditions, were studied with the dialysis method in a simulated gastrointestinal system with pH values of 1.2, 6.8 and 7.4. It was found that 99.5% of amlodipine loaded on the nanomaterial was released at pH 7.4 and 72 h. Even after 72 h, no difference was observed in the release of AML. It can be said that the synthesized nanomaterial is suitable for oral amlodipine release. In conclusion, the synthesized nanomaterial was studied for the first time in the literature as a drug delivery system for use in the treatment of hypertension. In addition, AML-p(HEMPA) nanomaterials may enable less frequent drug uptake, have higher bioavailability, and allow for prolonged release with minimal side effects.
PubMed: 36433166
DOI: 10.3390/polym14225038 -
Ecotoxicology and Environmental Safety Sep 2022Bactrocera tau (Walker) is a fly pest species mainly distributed in Southeast Asia and the South Pacific; it causes substantial ecological and economic issues because of...
Bactrocera tau (Walker) is a fly pest species mainly distributed in Southeast Asia and the South Pacific; it causes substantial ecological and economic issues because of its destructiveness and rapid reproduction. Chemical sterilization technology can reduce the use of insecticides and is widely applied for insect pest control. In this study, the sterilization efficacy of varying concentrations of four chemosterilants, namely, hexamethylphosphoramide (HMPA), CSII Aqua, 5-fluorouracil (5-FU), and colchicine, on adult pumpkin flies was investigated. The results indicated that a solution of 0.03% HMPA had the highest sterilization efficacy. When the number of sterile males was equal to or exceeded 20 times that of untreated males, the hatching rate of offspring eggs was less than 10%. Chemosterilant treatment significantly altered the levels of acid phosphatase (ACP), alkaline phosphatase (AKP), and B. tau vitellogenin (BtVg); these substances have an important impact on reproductive development. The treatment also decreased the size of the reproductive organs (i.e., testes and ovaries). Our results suggest that 0.03% HMPA has unique sterilization properties and may represent a new chemical agent for the control of B. tau populations in agricultural settings.
Topics: Animals; Chemosterilants; Hempa; Insect Control; Insecta; Male; Tephritidae
PubMed: 36037635
DOI: 10.1016/j.ecoenv.2022.114028 -
PLoS Pathogens Jun 2022Vibrio cholerae is the etiologic agent of the severe human diarrheal disease cholera. To colonize mammalian hosts, this pathogen must defend against host-derived toxic...
Vibrio cholerae is the etiologic agent of the severe human diarrheal disease cholera. To colonize mammalian hosts, this pathogen must defend against host-derived toxic compounds, such as nitric oxide (NO) and NO-derived reactive nitrogen species (RNS). RNS can covalently add an NO group to a reactive cysteine thiol on target proteins, a process called protein S-nitrosylation, which may affect bacterial stress responses. To better understand how V. cholerae regulates nitrosative stress responses, we profiled V. cholerae protein S-nitrosylation during RNS exposure. We identified an S-nitrosylation of cysteine 235 of AphB, a LysR-family transcription regulator that activates the expression of tcpP, which activates downstream virulence genes. Previous studies show that AphB C235 is sensitive to O2 and reactive oxygen species (ROS). Under microaerobic conditions, AphB formed dimer and directly repressed transcription of hmpA, encoding a flavohemoglobin that is important for NO resistance of V. cholerae. We found that tight regulation of hmpA by AphB under low nitrosative stress was important for V. cholerae optimal growth. In the presence of NO, S-nitrosylation of AphB abolished AphB activity, therefore relieved hmpA expression. Indeed, non-modifiable aphBC235S mutants were sensitive to RNS in vitro and drastically reduced colonization of the RNS-rich mouse small intestine. Finally, AphB S-nitrosylation also decreased virulence gene expression via debilitation of tcpP activation, and this regulation was also important for V. cholerae RNS resistance in vitro and in the gut. These results suggest that the modulation of the activity of virulence gene activator AphB via NO-dependent protein S-nitrosylation is critical for V. cholerae RNS resistance and colonization.
Topics: Animals; Bacterial Proteins; Cysteine; Gene Expression Regulation, Bacterial; Hempa; Mammals; Mice; Promoter Regions, Genetic; Trans-Activators; Vibrio cholerae; Virulence
PubMed: 35714156
DOI: 10.1371/journal.ppat.1010581 -
Report on Carcinogens : Carcinogen... 2011
Topics: Animals; Carcinogens; Chemosterilants; Dimethylamines; Government Regulation; Hempa; Humans; Occupational Exposure; Solvents; United States
PubMed: 21852847
DOI: No ID Found -
Bulletin of the World Health... 1969Many aziridinyl compounds are known to induce high sterility in Culex pipiens fatigans Wiedemann, but as the practical application of these chemosterilants is quite...
Many aziridinyl compounds are known to induce high sterility in Culex pipiens fatigans Wiedemann, but as the practical application of these chemosterilants is quite hazardous, compounds such as phosphoramides and s-triazines have been tried against this species. These compounds are relatively less reactive, thermally more stable and less toxic to mammals. The phosphoramides included hempa, N,N,N',N'-tetramethyl-P-piperidino-phosphonic diamide (ENT-51007) and a compound, ENT-60210, whose structure is not known to the authors. The s-triazines employed were hemel, 2,4-diamino-6-morpholino-s-triazine hydrochloride (ENT-51143), 2-amino-4,6-bis (dimethylamino)-s-triazine hydrochloride (ENT-51146), and a compound ENT-60433, whose structure is not known to the authors.The triazines were more toxic than the phosphoramides in both larval and pupal treatments. Among the phosphoramides, hempa and ENT-51007 were quite promising for larval treatment and resulted in 80% and 83% control of reproduction respectively at non-toxic doses. Hempa at a toxic dose induced complete sterility. ENT-60210 was least toxic and least effective. Among the triazines, hexa-substituted hemel was better than tetra-substituted ENT-51146 and cyclic-substituted ENT-51143 in inducing sterility. ENT-51143 was most toxic and least effective. For larval treatment, hempa was better than hemel in inducing sterility while for pupal treatment the latter was better than hempa. Both the compounds produced more sterility in treated females than in treated males. Oviposition was significantly lowered in treated females.
Topics: Amides; Animals; Chemosterilants; Culex; Female; Infertility; Male; Metamorphosis, Biological; Mosquito Control; Phosphoric Acids; Triazines
PubMed: 5309537
DOI: No ID Found -
International Journal of Molecular... Nov 2023Gene therapy is extensively studied as a realistic and promising therapeutic approach for treating inherited and acquired diseases by repairing defective genes through... (Review)
Review
Gene therapy is extensively studied as a realistic and promising therapeutic approach for treating inherited and acquired diseases by repairing defective genes through introducing (transfection) the "healthy" genetic material in the diseased cells. To succeed, the proper DNA or RNA fragments need efficient vectors, and viruses are endowed with excellent transfection efficiency and have been extensively exploited. Due to several drawbacks related to their use, nonviral cationic materials, including lipidic, polymeric, and dendrimer vectors capable of electrostatically interacting with anionic phosphate groups of genetic material, represent appealing alternative options to viral carriers. Particularly, dendrimers are highly branched, nanosized synthetic polymers characterized by a globular structure, low polydispersity index, presence of internal cavities, and a large number of peripheral functional groups exploitable to bind cationic moieties. Dendrimers are successful in several biomedical applications and are currently extensively studied for nonviral gene delivery. Among dendrimers, those derived by 2,2-bis(hydroxymethyl)propanoic acid (b-HMPA), having, unlike PAMAMs, a neutral polyester-based scaffold, could be particularly good-looking due to their degradability in vivo. Here, an overview of gene therapy, its objectives and challenges, and the main cationic materials studied for transporting and delivering genetic materials have been reported. Subsequently, due to their high potential for application in vivo, we have focused on the biodegradable dendrimer scaffolds, telling the history of the birth and development of b-HMPA-derived dendrimers. Finally, thanks to a personal experience in the synthesis of b-HMPA-based dendrimers, our contribution to this field has been described. In particular, we have enriched this work by reporting about the b-HMPA-based derivatives peripherally functionalized with amino acids prepared by us in recent years, thus rendering this paper original and different from the existing reviews.
Topics: Dendrimers; Propionates; Hempa; Transfection; Gene Transfer Techniques; Genetic Therapy
PubMed: 37958989
DOI: 10.3390/ijms242116006 -
Scientific Reports Dec 20233-(4-hydroxy-3-methoxyphenyl) propionic acid (HMPA) is a metabolite produced by the gut microbiota through the conversion of 4-hydroxy-3-methoxycinnamic acid (HMCA),...
3-(4-hydroxy-3-methoxyphenyl) propionic acid (HMPA) is a metabolite produced by the gut microbiota through the conversion of 4-hydroxy-3-methoxycinnamic acid (HMCA), which is a widely distributed hydroxycinnamic acid-derived metabolite found abundantly in plants. Several beneficial effects of HMPA have been suggested, such as antidiabetic properties, anticancer activities, and cognitive function improvement, in animal models and human studies. However, the intricate molecular mechanisms underlying the bioaccessibility and bioavailability profile following HMPA intake and the substantial modulation of metabolic homeostasis by HMPA require further elucidation. In this study, we effectively identified and characterized HMPA-specific GPR41 receptor, with greater affinity than HMCA. The activation of this receptor plays a crucial role in the anti-obesity effects and improvement of hepatic steatosis by stimulating the lipid catabolism pathway. For the improvement of metabolic disorders, our results provide insights into the development of functional foods, including HMPA, and preventive pharmaceuticals targeting GPR41.
Topics: Animals; Humans; Lipid Metabolism; Hempa; Liver; Propionates
PubMed: 38040866
DOI: 10.1038/s41598-023-48525-3 -
Journal of the American Chemical Society Dec 2022Camphorsultam-based lithium enolates referred to colloquially as Oppolzer enolates are examined spectroscopically, crystallographically, kinetically, and computationally...
Camphorsultam-based lithium enolates referred to colloquially as Oppolzer enolates are examined spectroscopically, crystallographically, kinetically, and computationally to ascertain the mechanism of alkylation and the origin of the stereoselectivity. Solvent- and substrate-dependent structures include tetramers for alkyl-substituted enolates in toluene, unsymmetric dimers for aryl-substituted enolates in toluene, substrate-independent symmetric dimers in THF and THF/toluene mixtures, HMPA-bridged trisolvated dimers at low HMPA concentrations, and disolvated monomers for the aryl-substituted enolates at elevated HMPA concentrations. Extensive analyses of the stereochemistry of aggregation are included. Rate studies for reaction with allyl bromide implicate an HMPA-solvated ion pair with a Li(HMPA) counterion. Dependencies on toluene and THF are attributed to exclusively secondary-shell (medium) effects. Aided by density functional theory (DFT) computations, a stereochemical model is presented in which neither chelates nor the lithium gegenion serves roles. The stereoselectivity stems from the chirality within the sultam ring and not the camphor skeletal core.
Topics: Molecular Structure; Lithium; Hempa; Toluene; Alkylation
PubMed: 36534055
DOI: 10.1021/jacs.2c09341 -
IARC Monographs on the Evaluation of... 1999
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Hempa; Humans; Mutagenicity Tests; Mutagens; Neoplasms, Experimental; Salmonella typhimurium
PubMed: 10476429
DOI: No ID Found