In many different species, lactate dehydrogenase (LDH) constitutes a major checkpoint of anaerobic glycolysis, by catalyzing the reduction of pyruvate into lactate. This enzyme has recently received ...a great deal of attention since it may constitute a valid therapeutic target for diseases so different as malaria and cancer. In fact, the isoform expressed by Plasmodium falciparum (pfLDH) is a key enzyme for energy generation of malarial parasites. These species mostly depend on anaerobic glycolysis for energy production, since they lack a citric acid cycle for ATP formation. Therefore, inhibitors of pfLDH would potentially cause mortality of P. falciparum and, to this purpose, several small organic molecules have been recently designed and developed with the aim of blocking this new potential antimalarial chemotherapeutic target. Moreover, most invasive tumour phenotypes show a metabolic switch (Warburg effect) from oxidative phosphorylation to an increased anaerobic glycolysis, by promoting an upregulation of the human isoform-5 of lactate dehydrogenase (hLDH-5 or LDH-A), which is normally present in muscles and in the liver. Hence, inhibition of hLDH-5 may constitute an efficient way to interfere with tumour growth and invasiveness. This review provides an overview of the LDH inhibitors that have been developed up to now, an analysis of their possible isoform-selectivity, and their therapeutic potentials.
•HPLC–UV method to evaluate MAGL activity and test inhibitors.•The method enables measuring the PNP formation obtained from hydrolysis of 4-NPA or 4-NPDo.•The method prevents any interference ...generated in the assay readout.
Monoacylglycerol lipase (MAGL) is a membrane-associated cytosolic serine hydrolase which catalyses the hydrolysis of the endocannabinoid 2-arachidonoylglycerol into arachidonic acid and glycerol. MAGL represents the link between the endocannabinoid and the eicosanoid system indeed its inhibition enhances endocannabinoid signalling and lowers eicosanoid production. Here we present a radioactive-free, sensitive and solid HPLC–UV based method to evaluate MAGL activity by using 4-nitrophenylacetate (4-NPA) as substrate. The enzymatic activity is measured by quantifying the 4-nitrophenol (PNP) (λ=315nm) formation on a C18 stationary phase. The method was validated by calculating IC50 values of the reference inhibitors JZL184, CAY10499 and JW642 and confirming the irreversible and non-competitive mechanism of inhibition for JZL184. Furthermore in order to resemble the catalytic conditions of MAGL at cell membrane level, the surfactant Triton X-100 was added, as a micelle forming agent and 4-nitrophenyldodecanoate (4-NPDo) was used as lipophilic substrate for MAGL. The data obtained confirmed that the HPLC method is an alternative, radioactive-free approach for the screening and characterization of new MAGL inhibitors. Finally this assay prevents, in an unequivocal manner, any interference related to the intrinsic absorbance of screened compounds or metabolites generated upon enzymatic cleavage which could seriously affect the assay readout.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The effects of a collagen dressing on hard-to-heal venous leg ulcers (vlUs) were evaluated in this prospective, randomised, controlled study.
Patients with hard-to-heal vlU were included and divided ...into two groups using the block randomisation method. The first group was treated with a collagen and an alginate dressing (group A), and the second group with an alginate dressing alone (group b). both groups also had a short-stretch compression system applied at every dressing change. The dressings were changed twice a week for 12 weeks or until the ulcer was healed. Granulation tissue improvement, wound size, overall dressing performance and dressing comfort were evaluated and recorded.
A total of 40 patients completed the study evaluation period. Group A had a 65% increase in granulation tissue compared to 38% in group b. The mean ulcer area was reduced to 45% in group A compared to 20% in group b at 12 weeks. no significant side effects were detected in either group. Patients of both groups were satisfied with their treatment and healing progress.
The results of this study showed the effectiveness and safety of a collagen dressing in hard-to-heal vlUs as an adjunctive therapy with compression bandaging. These encouraging results may positively affect the quality of life of patients with chronic wounds.
Purpose
Suicidal thoughts and behaviors (STBs) remain a pressing public health problem for transgender and gender diverse (TGD) persons. The goal of this study was to apply social-ecological and ...minority stress frameworks to identify individual and interpersonal-level TGD-specific STB risk and protective factors.
Methods
This is a secondary analysis of the 2015 United States Transgender Health Survey, a comprehensive cross-sectional health assessment of a national sample of TGD adults (
N
= 27,658). Chi-square and Analysis of Variance (ANOVA) were used to identify bivariate correlates of 12-month and lifetime suicidal ideation (SI) and suicide attempt (SA). Logistic regression was employed to identify the strongest STB risk and protective factors across levels.
Results
Sexual minority identification, racial minority identification, and having a disability were lifetime STB risk factors. TGD identity, sexual minority identification, racial minority identification (SA only), lower education, lower income, military experience, having a disability, and being uninsured were 12-month STB risk factors. Psychological distress was the most robust STB risk factor. Workplace discrimination, family rejection, healthcare discrimination, and childhood bias-based victimization were lifetime STB risk factors. All forms of discrimination and victimization (with the exception of family rejection for SI) were 12-month STB risk factors. Family and coworker support were protective factors for lifetime SA (but not SI) and all 12-month STBs. Being less out about TGD identity was a protective factor for STBs (except for 12-month SI).
Conclusion
Findings support social-ecological and minority stress STB risk frameworks. Recommendations are provided for a comprehensive approach to TGD suicide prevention.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A growing literature on kink practitioners reveals a complex picture of elevated risk of suicidal behaviors co-occurring with reduced reports of negative mental health outcomes. A key to ...understanding this conflicting pattern may be through identifying specific risk and protective mechanisms among distinct subgroups of kink practitioners. Comparisons in the health of kink practitioners based on gender and sexual orientation are currently lacking in literature.
This paper advances understanding of the kink community by examining mental health and coping-self efficacy (CSE) variation by gender and sexual orientation.
Adult members of the National Coalition for Sexual Freedom (N = 332) completed an online cross-sectional health assessment.
The assessment included the Coping Self-Efficacy (CSE) Scale; Depression and Anxiety Stress Scale-21; and Alcohol Use Disorders Identification Test.
Transgender and non-binary persons reported consistently low coping beliefs and poor mental health. Queer sexual minority persons reported low CSE thought stopping and high anxiety. Several CSE thought stopping moderation effects on mental health were observed.
Findings may inform clinical implications, as bolstering coping-related beliefs and skills via cognitive-behavioral therapy may offer mental health benefit to kink practitioners.
Full text
Available for:
BFBNIB, DOBA, FSPLJ, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Parecoxib is the injectable prodrug of valdecoxib, a cicloxygenase-2 selective drug, currently used in human medicine. Recent studies have suggested both its excellent clinical effectiveness and wide ...safety profile. The aim of the present study was to develop and validate a new high-performance liquid chromatography (HPLC) with spectrofluorimetric detection method to quantify parecoxib and valdecoxib in canine plasma. Several parameters both in the extraction and the detection method were evaluated. The applicability of the method was determined by administering parecoxib to one dog: the protocol provided the expected pharmacokinetic results. The final mobile phase was acetonitrile: AcONH
4
(10 mM; pH 5.0) 55:45,
v
/
v
, with a flow rate of 0.4 mL min
−1
, and excitation and emission wavelengths of 265 and 375 nm, respectively. The analytical column was a reverse-phase C18 ODS2 3-μm particle size. Protein precipitation in acidic medium followed by two successive liquid–liquid steps was carried out. The best extraction solvent was cyclohexane:Et
2
O (3:2,
v
/
v
) that gave recoveries ranging from 81.1% to 89.1% and from 94.8% to 103.6% for parecoxib and valdecoxib, respectively. The limits of quantification were 25 and 10 ng mL
−1
for parecoxib and valdecoxib, respectively. The chromatographic runs were specific with no interfering peaks at the retention times of the analytes, as confirmed by HPLC–mass spectrometry experiments. The other validation parameters were in agreement with the European Medicines Evaluation Agency and International Conference on Harmonisation guidelines. In conclusion, this method (extraction, separation and applied techniques) is simple and effective. This is the first time that use of a HPLC with spectrofluorimetric detection technique to simultaneously detect parecoxib and valdecoxib in plasma has been reported. This technique may have applications for pharmacokinetic studies.
Figure 1
In vivo metabolism of the prodrug parecoxib in the active ingredient valdecoxib
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Stevia rebaudiana (Bert.) Bertoni has sporophytic self-incompatibility and this may lead to poor seed yield and quality, which are obstacles to large-scale crop establishment. This research ...investigated the influence of insect pollinators and the harvesting time on the qualitative and quantitative characteristics of the ripe seeds. A pot trial under open field conditions was established to evaluate the abundance of insect pollinators and three harvesting times on the production of ripe seeds, germination percentage, mean germination time and thousand seed weight (TSW) in 36 F1 open-pollinated genotypes. Large variability in the number of corymbs of capitula, flowering time, reproductive period and seed yield was observed among the genotypes. Genotypes with promising phenological and reproductive properties were identified. The worst germination percentage and TSW were recorded in the latest harvest. Significant linear regressions were found among the investigated parameters (insect number, germination percentage, TSW, seeds yield per plant and cycle length), confirming complex interactions on the yield and quality of stevia seeds. Results indicate that earlier flowering genotypes produced higher seed quantity, due to favourable weather conditions during the reproductive phase. Moreover, cross-pollination and the insect abundance, as Apidae and Syrphidae, play a crucial role for enhancing the stevia seed yield and quality.
Full text
Available for:
BFBNIB, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Disparities in the health services delivered to sexual and gender minority (SGM) individuals are widespread across health service disciplines. Many health service providers do not have the knowledge, ...comfort, or skills necessary to provide health services to SGM individuals. The objective of the current systematic review was to review the correlates of competency (defined as knowledge, attitude, and skill) that health service providers possess for working with SGM individuals. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was utilized to guide search and reporting strategies. PsycInfo/PsycArticles, PubMed/Medline, and Google Scholar databases were searched to find studies that addressed health service providers’ competency working with SGM individuals. There were 31 studies included in the review. Approximately half of the studies utilized the full definition of competency (knowledge, attitude, and skill). The most common competency assessed was knowledge, and the least common was skill. The majority of the studies addressed health service providers in the social sciences. Health service education needs to emphasize competency working with SGM individuals. Of particular importance is developing skill sets, as many providers reported that they did not have the skills necessary to provide culturally competent health services to SGM individuals.
Full text
Available for:
NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
PDF
