22 research outputs found

    Addressing food insecurity in San Diego by providing food to low-income patients with diabetes, educating health care providers, and increasing enrollment in CalFresh

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    In summary, consistent access to high quality food likely represents an important facet in preventing and controlling chronic disease among vulnerable populations, and this may be especially relevant for patients with diabetes. Furthermore, CalFresh has untapped potential as an effective program, and screening tools are under-utilized by healthcare providers

    Novel Group of AChE Reactivators—Synthesis, In Vitro Reactivation and Molecular Docking Study

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    The acetylcholinesterase (AChE) reactivators (e.g., obidoxime, asoxime) became an essential part of organophosphorus (OP) poisoning treatment, together with atropine and diazepam. They are referred to as a causal treatment of OP poisoning, because they are able to split the OP moiety from AChE active site and thus renew its function. In this approach, fifteen novel AChE reactivators were determined. Their molecular design originated from former K-oxime compounds K048 and K074 with remaining oxime part of the molecule and modified part with heteroarenium moiety. The novel compounds were prepared, evaluated in vitro on human AChE (HssAChE) inhibited by tabun, paraoxon, methylparaoxon or DFP and compared to commercial HssAChE reactivators (pralidoxime, methoxime, trimedoxime, obidoxime, asoxime) or previously prepared compounds (K048, K074, K075, K203). Some of presented oxime reactivators showed promising ability to reactivate HssAChE comparable or higher than the used standards. The molecular modelling study was performed with one compound that presented the ability to reactivate GA-inhibited HssAChE. The SAR features concerning the heteroarenium part of the reactivator’s molecule are described

    Účinky nabitých oximových reaktivátorů na buněčnou linii HK-2 při screeningu renální toxicity

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    Oxime cholinesterase reactivators (oximes) are used to counteract organophosphate intoxication. Charged oximes are administered via intramuscular or intravenous injection when the majority of dose is unmetabolized and is excreted as urine. In this study, the effects of selected double charged oximes were determined in the HK-2 cell line as a model for renal toxicity screening. Some effects on dehydrogenase activity were found for obidoxime, asoxime (syn. HI-6), K027, and K203. The effects of K868 and K869 were found to be unreliable due to rapid degradation of both chlorinated oximes in the assay medium, resulting for K868 in an isoxazole-pyridinium product.Oximové reaktivátory cholinesterázy (oximy) se používají k potlačení intoxikace organofosfáty. Nabité oximy se podávají intramuskulární nebo intravenózní injekcí, dokud není většina z podané dávky nemetabolizována a je vylučována močí. V této studii byly účinky vybraných oximů s dvojitým nábojem stanoveny v buněčné linii HK-2 jako modelu pro screening renální toxicity. Některé účinky na aktivitu dehydrogenázy byly zjištěny u obidoximu, asoximu (syn. HI-6), K027 a K203. Bylo zjištěno, že účinky K868 a K869 jsou nespolehlivé v důsledku rychlé degradace obou chlorovaných oximů v testovacím médiu, což má za následek pro K868 isoxazol-pyridiniový produkt

    Implementation of a food insecurity screening and referral program in student-run free clinics in San Diego, California

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    Food insecurity is associated with many poor health outcomes yet is not routinely addressed in clinical settings. The purpose of this study was to implement a food insecurity screening and referral program in Student-run Free Clinics (SRFC) and to document the prevalence of food insecurity screening in this low-income patient population. All patients seen in three SRFC sites affiliated with one institution in San Diego, California were screened for food insecurity using the 6-item United States Department of Agriculture (USDA) Food Security Survey between January and July 2015 and referred to appropriate resources. The percentage of patients who were food insecure was calculated. The screening rate was 92.5% (430/463 patients), 74.0% (318/430) were food insecure, including 30.7% (132/430) with very low food security. A food insecurity registry and referral tracking system revealed that by January 2016, 201 participants were receiving monthly boxes of food onsite, 66 used an off-site food pantry, and 64 were enrolled in the Supplemental Nutrition Assistance Program (SNAP). It is possible to implement a food insecurity screening and referral program into SRFCs. The prevalence of food insecurity in this population was remarkably high yet remained largely unknown until this program was implemented. Other health care settings, particularly those with underserved patient populations, should consider implementing food insecurity screening and referral programs

    Profiling donepezil template into multipotent hybrids with antioxidant properties

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    Alzheimer’s disease is debilitating neurodegenerative disorder in the elderly. Current therapy relies on administration of acetylcholinesterase inhibitors (AChEIs) -donepezil, rivastigmine, galantamine, and N-methyl-d-aspartate receptor antagonist memantine. However, their therapeutic effect is only short-term and stabilizes cognitive functions for up to 2 years. Given this drawback together with other pathological hallmarks of the disease taken into consideration, novel approaches have recently emerged to better cope with AD onset or its progression. One such strategy implies broadening the biological profile of AChEIs into so-called multi-target directed ligands (MTDLs). In this review article, we made comprehensive literature survey emphasising on donepezil template which was structurally converted into plethora of MTLDs preserving anti-cholinesterase effect and, at the same time, escalating the anti-oxidant potential, which was reported as a crucial role in the pathogenesis of the Alzheimer’s disease

    Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK)

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    AbstractPhosphoinositide 3-kinases (PI3K) and phosphoinositide 3-kinase-related protein kinases (PIKK) are two structurally related families of kinases that play vital roles in cell growth and DNA damage repair. Dysfunction of PIKK members and aberrant stimulation of the PI3K/AKT/mTOR signalling pathway are linked to a plethora of diseases including cancer. In recent decades, numerous inhibitors related to the PI3K/AKT/mTOR signalling have made great strides in cancer treatment, like copanlisib and sirolimus. Notably, most of the PIKK inhibitors (such as VX-970 and M3814) related to DNA damage response have also shown good efficacy in clinical trials. However, these drugs still require a suitable combination therapy to overcome drug resistance or improve antitumor activity. Based on the aforementioned facts, we summarised the efficacy of PIKK, PI3K, and AKT inhibitors in the therapy of human malignancies and the resistance mechanisms of targeted therapy, in order to provide deeper insights into cancer treatment

    Wide-antimicrobial spectrum of picolinium salts

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    Nosocomial infections, which greatly increase morbidity among hospitalized patients, together with growing antibiotic resistance still encourage many researchers to search for novel antimicrobial compounds. Picolinium salts with different lengths of alkyl chains (C12_{12}, C14_{14}, C16_{16}) were prepared by Menshutkin-like reaction and evaluated with respect to their biological activity, i.e., lipophilicity and critical micellar concentration. Picolinium salts with C14_{14} and C16_{16} side chains achieved similar or even better results when in terms of antimicrobial efficacy than benzalkoniumsnotably, their fungicidal efficiency was substantially more potent. The position of the methyl substituent on the aromatic ring does not seem to affect antimicrobial activity, in contrast to the effect of length of the N-alkyl chain. Concurrently, picolinium salts exhibited satisfactory low cytotoxicity against mammalian cells, i.e., lower than that of benzalkonium compounds, which are considered as safe
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