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Most S. aureus infections are multidrug resistant. S. aureus infections often occur with prolonged conditions, causing increased treatment costs and mortality rates. There is a need to understand the antibiotic susceptibility pattern to S. aureus in mothers and infants because the burden of S. aureus infection in infants is high. This study aims to determine the prevalence of nasal carriers of S. aureus in lactating mothers and their infants and their antibiotic susceptibility patterns. This cross-sectional study involved 59 pairs of breastfeeding mothers and infants aged 0 to 6 months. The research was conducted in the work area of the South Tangerang City Health Office. We take a nasal swab of the mother and the baby. We used Vitek-2 to determine antibiotic resistance against S. aureus. Overall, we found 22/59 (37%) S. aureus in infants’ noses, 18% of whom were MRSA. In mothers, we found 18/59 (30%) S. aureus isolates and 17% were MRSA. The majority of S. aureus isolates from infants were sensitive to cefoxitin (82%), gentamicin (86%), ciprofloxacin (91%), levofloxacin (95%), moxifloxacin (91%), vancomycin (100%), clindamycin (82%), erythromycin (86%), nitrofurantoin (100%), linezolid (100%) and tetracycline (77%). The majority of S. aureus isolates from mothers are sensitive to cefoxitin (83%), gentamicin (94%), ciprofloxacin (89%), levofloxacin (89%), moxifloxacin (89%), vancomycin (100%), clindamycin (89%), erythromycin (89%), nitrofurantoin (100%), linezolid (100%) and tetracycline (83%). MRSA monitoring of mothers and babies in the community needs to be done to prevent and control the spread.

None.

Multiple myeloma is a neoplastic proliferation of immunoglobulin-producing plasma cells with clinical features resulting from infiltration of plasma cells into bones and other organs. Multiple myeloma manifesting as an apical lung mass is less common and very few cases have been reported. We report the case of a 50-year-old female who presented with an apical lung mass which happened to be multiple myeloma arising from the upper ribs into the lung. At the time of diagnosis, patient had axillary lymph node metastasis with extensive bony involvement. This case report and literature review provides insight to a rare but significant presentation of multiple myeloma and highlights the need to consider multiple myeloma as a possible differential for Pancoast tumor in the appropriate clinical setting as this could potentially affect management options and patient outcome.

The inhibition of acetylcholinesterase (AChE), the key enzyme in the breakdown of acetylcholine, is presently the most common pharmacological approach available for Alzheimer’s disease (AD). Despite research on the molecular bases of AD, potent therapeutic agent against its expansion is still needed. In searching for natural cholinesterase inhibitors, the present study was focused on the isolation of three new norditerpenoid alkaloids, uncinatine B-D together with known virescenine from Delphinium uncinatum. Chemical structures for all the isolated norditerpenoids (1–4) were established using latest spectroscopic techniques. The isolated undescribed compounds along with known virescenine were testified for their acetylcholinesterase inhibitory activity supported by docking analyses. Molecular docking simulation showed that the isolated compounds (1–4) were observed to adhered in the active site of AChE with docking scores − 13.5322 (1), −11.8173 (2), −12.4240 (3) and − 8.9352 (4) respectively. Overall results demonstrated that these natural norditerpenoids compounds were found as selective inhibitors of AChE. This is the first report regarding the use of bioactive ingredients of Delphinium uncinatum in testing against Alzheimer's disease.

The conventional chemical methods of nanoparticles synthesis have been effectively replaced by nanoparticle synthesis mediated by plants. The current study describes the environmental friendly synthesis of chromium oxide nanoparticles (Cr2O3 NPs) using Erythrophleum guineense plant extract. The synthesis of Cr2O3 NPs was validated by UV/VIS spectroscopy, Energy Dispersive X-Ray (EDX), Scanning Electron Microscopy (SEM), and X-ray diffraction (XRD) studies. The appearance of the Sharpe peak at 460 nm in the UV/Vis spectrum and the colour change caused by surface plasma resonance confirmed the formation of Cr2O3 NPs. The EDX spectrum of Cr2O3 nanoparticles revealed the presence of carbon, oxygen, and chromium, while SEM analysis revealed an irregular round morphology (with a size below 400 nm). In addition, XRD studies suggested their crystalline nature by the characteristic peaks at 34° and 36° and 42° (2Ɵ), respectively. The green synthesized Cr2O3 NPs showed promise as in-vitro cholinesterase inhibitor at tested concentrations (62.5–1,000 μg/ml), with IC50 values of 120 and 100 μg/ml against Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE), respectively. The results suggested that the green synthesized Cr2O3 NPs could be used in the future to stop enzyme from working and for other biological activities.

The increasing survival rate after discharge from the intensive care unit (ICU) has revealed long-term impairments in the cognitive, psychiatric, and physical domains among survivors. However, clinicians often fail to recognize this post-ICU syndrome (PICS) and its debilitating effects on family members (PICS-F). This study describes two cases of PICS to illustrate the different impairments that may occur in ICU survivors. The PICS risk factors for each domain and the interactions among risk factors are also described. In terms of diagnostic evaluation, limited evidence-based or validated tools are available to assist with screening for PICS. Clinicians should be aware to monitor for its symptoms on the basis of cognitive, psychiatric, and physical domains. The Montreal Cognitive Assessment is recommended to screen for cognition, as it has a high sensitivity and can evaluate executive function. Mood disorders should also be screened. For mobile patients, a 6-minute walk test should be performed. PICS can be prevented by applying the ABCDEF bundle ABCDEF bundle in ICU described in this paper. Finally, the family members of patients in the ICU should be involved in patient care and a tactful communication approach is required to reduce the risk of PICS-F.

The Sadranan tradition is a tradition that has existed for a long time since ancient times, especially in the Kecandran area. The results show the Sadranan is held once a year, usually in mid-November and June. All from various backgrounds follow this Sadranan tradition. This tradition is carried out after the month of Shuro. The purpose of Sadranan is; first, this tradition is gratitude to Allah SWT for pleasure, and the second is as a form of respect for ancestors. Third, strengthen a sense of solidarity between citizens. Fourth, preserving the traditional inter and indigenous cultures of the area. Some benefits felt by the community are that people feel closer to Allah SWT.

This study examines whether spirituality has an effect on fraud prevention with internal control as an intervening variable. This research is an associative descriptive research. The population used was all employees of the Most District Offices of Kediri Regency using the quota sampling technique determined by the researcher as many as 91 respondents. In this study using the PLS analysis method through the SEM approach and supported by SmartPLS 3.0 software. The results of the study show that Spirituality has a significant effect on internal control and fraud prevention. Furthermore, spirituality has a significant effect on fraud prevention with internal control as an intervening variable. [ABSTRACT FROM AUTHOR]

Most S. aureus infections are multidrug resistant. S. aureus infections often occur with prolonged conditions, causing increased treatment costs and mortality rates. There is a need to understand the antibiotic susceptibility pattern to S. aureus in mothers and infants because the burden of S. aureus infection in infants is high. This study aims to determine the prevalence of nasal carriers of S. aureus in lactating mothers and their infants and their antibiotic susceptibility patterns. This cross-sectional study involved 59 pairs of breastfeeding mothers and infants aged 0 to 6 months. The research was conducted in the work area of the South Tangerang City Health Office. We take a nasal swab of the mother and the baby. We used Vitek-2 to determine antibiotic resistance against S. aureus. Overall, we found 22/59 (37%) S. aureus in infants' noses, 18% of whom were MRSA. In mothers, we found 18/59 (30%) S. aureus isolates and 17% were MRSA. The majority of S. aureus isolates from infants were sensitive to cefoxitin (82%), gentamicin (86%), ciprofloxacin (91%), levofloxacin (95%), moxifloxacin (91%), vancomycin (100%), clindamycin (82%), erythromycin (86%), nitrofurantoin (100%), linezolid (100%) and tetracycline (77%). The majority of S. aureus isolates from mothers are sensitive to cefoxitin (83%), gentamicin (94%), ciprofloxacin (89%), levofloxacin (89%), moxifloxacin (89%), vancomycin (100%), clindamycin (89%), erythromycin (89%), nitrofurantoin (100%), linezolid (100%) and tetracycline (83%). MRSA monitoring of mothers and babies in the community needs to be done to prevent and control the spread. [ABSTRACT FROM AUTHOR]

This study reports the isolation of three new C20 diterpenoid alkaloids, Chitralinine A–C (1–3) from the aerial parts of Delphinium chitralense. Their structures were established on the basis of latest spectral techniques and single crystal X-rays crystallographic studies of chitralinine A described basic skeleton of these compounds. All the isolated Compounds (1–3) showed strong, competitive type inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in comparison to standard allanzanthane and galanthamine however, chitralinine-C remained the most potent with IC50 value of 11.64 ± 0.08 μM against AChE, and 24.31 ± 0.33 μM against BChE, respectively. The molecular docking reflected a binding free energy of −16.400 K Cal-mol−1 for chitralinine-C, having strong interactions with active site residues, TYR334, ASP72, SER122, and SER200. The overall findings suggest that these new diterpenoid alkaloids could serve as lead drugs against dementia-related diseases including Alzheimer’s disease.

Alzheimer’s disease is an emerging health disorder associated with cognitive decline and memory loss. In this study, six curcumin analogs (1a–1f) were synthesized and screened for in vitro cholinesterase inhibitory potential. On the basis of promising results, they were further investigated for in vivo analysis using elevated plus maze (EPM), Y-maze, and novel object recognition (NOR) behavioral models. The binding mode of the synthesized compounds with the active sites of cholinesterases, and the involvement of the cholinergic system in brain hippocampus was determined. The synthesized curcumin analog 1d (p < 0.001, n = 6), and 1c (p < 0.01, n = 6) showed promising results by decreasing retention time in EPM, significantly increasing % SAP in Y-maze, while significantly (p < 0.001) enhancing the % discrimination index (DI) and the time exploring the novel objects in NORT mice behavioral models. A molecular docking study using MOE software was used for validation of the inhibition of cholinesterase(s). It has been indicated from the current research work that the synthesized curcumin analogs enhanced memory functions in mice models and could be used as valuable therapeutic molecules against neurodegenerative disorders. To determine their exact mechanism of action, further studies are suggested.

This paper demonstrates the design of augmented reality (AR) in-car driving simulator system architecture and its experimental design. AR in-car driving simulator is developed in order to explore its effect towards subjects' simulator sickness when operating the driving simulator. Sensory conflict theory postulates that simulator sickness is a condition where an information between vestibular input system and visual that provides orientation and movement information is misaligned. Simulator sickness is a well-known issue entangled with simulator and various past research revealed that some of the methods to avoid simulator sickness are by taking prescribed medicine, shortening the length of drives and adjusting light of driving simulation environment. Augmented reality allows a combination between real world views with computer-generated object and runs in a real-time performance. By using AR, it is possible to create an outdoor driving simulator that allows a real world view with a mixture of case study that been replicate by computer. Affording similar driving experience to driving a normal car, AR is believed to be an alternative solution to simulator sickness. Therefore, the AR driving simulator would be employed in experimental study to measure its effect on simulator sickness towards subjects.

Context: Delphinium denudatum Wall (Ranunculaceae) is a rich source of diterpenoid alkaloids and is widely used for the treatment of various neurological disorders such as epilepsy, sciatica and Alzheimer’s disease. Objective: The present study describes crystal structure determination and cholinesterase inhibitory potential of isotalatazidine hydrate isolated from the aerial part of Delphinium denudatum. Materials and methods: Phytochemical investigation of Delphinium denudatum resulted in the isolation of isotalatazidine hydrate in crystalline form. The molecular structure of the isolated compound was established by X-ray diffraction. The structural data (bond length and angles) of the compound were calculated by Density Functional Theory (DFT) using B3LYP/6-31 + G (p) basis set. The cholinesterase inhibitory potential of the isolated natural product was determined at various concentrations (62.5, 125, 250, 500 and 1000 μg/mL) followed by molecular docking to investigate the possible inhibitory mechanism of isotalatazidine hydrate. Results: The compound crystallized in hexagonal unit cell with space group P65. Some other electronic properties such as energies associated with HOMO-LUMO, band gaps, global hardness, global electrophilicity, electron affinity and ionization potential were also calculated by means of B3LYP/6-31 + G (p) basis set. The compound showed competitive type inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 12.13 μM and 21.41 μM, respectively. Discussion and conclusion: These results suggest that isotalatazidine hydrate is a potent dual cholinesterase inhibitor and can be used as a target drug in Alzheimer diseases. This is first report indicating isotalatazidine hydrate with anticholinesterase potential.

Abstracts This study was conducted to investigate the impact of company size, audit tenure, financial distress, and audit quality on going concern audit opinions on all sectors of companies listed on the Indonesia Stock Exchange (IDX), except the financial sector in 2019–2021. The sample consisting of 153 companies was selected using purposive sampling techniques, i.e., companies were selected based on certain considerations. The sample of 153 companies was then analyzed using the logistic regression method and assisted by Eviews 10 software. The difference in this study is that company size, audit tenure, financial distress, and audit quality do not have a significant influence on going concern audit opinions. [ABSTRACT FROM AUTHOR]

The advent of web-based applications and services has created such diverse and voluminous web log data stored in web servers, proxy servers, client machines, or organizational databases. This paper attempts to investigate the effect of temporal attribute in relational rule mining for web log data. We incorporated the characteristics of time in the rule mining process and analysed the effect of various temporal parameters. The rules generated from temporal relational rule mining are then compared against the rules generated from the classical rule mining approach such as the Apriori and FP-Growth algorithms. The results showed that by incorporating the temporal attribute via time, the number of rules generated is subsequently smaller but is comparable in terms of quality.

Pharmacy students experience high levels of perceived stress. Data regarding the impact of curricular revision on students' stress level are lacking. The primary objective of this study was to compare perceived stress, academic self-concept, and coping strategies between pharmacy students prior to and following a curricular revision. Secondary objectives included determining university resources used by students to deal with stress. Students in the first, second, and third years of the pharmacy curriculum were asked to complete a survey, including the 14-item Perceived Stress Scale (PSS-14), Brief COPE, and Academic Self-Concept Scale (ASCS), and questions regarding use of university resources. Responses to the PSS-14, Brief COPE, and ASCS were compared to a student cohort prior to the curricular revision. Perceived stress was reduced to a small, statistically significant degree following a curricular revision. In both cohorts, increased stress was statistically significantly correlated with decreased academic self-concept. Students reported increased use of self-distraction, along with decreased use of active coping, substance abuse, and planning, as coping strategies when compared to the previous cohort. Approximately half of the student cohort reported no use of university resources. The most commonly used resources were financial aid and mental health services. Perceived stress decreased following the revision of a Doctor of Pharmacy curriculum. The most common coping strategies were positive and comparable with strategies reported by students in the former curriculum. The impact of curricular changes on student stress and the use of university resources in health professions students warrant further study. [ABSTRACT FROM AUTHOR]

Excessive fertilizer applications in oil palm plantations are conventionally done to increase the oil yield, but they result in high production cost and environmental pollution. There have been only separate reports on the effects of fertilizer application on soil physical, chemical characteristics, and microbial biodiversity. Therefore, this study was conducted to determine the correlation between soil characteristics and soil microbial biodiversity in oil palm plantation after long-term frequent chemical fertilizer application compared with secondary soil, using molecular methods of polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) and MiSeq. Secondary forest soil was chosen as the control. The results showed that after 25 years of fertilizer application, the total nitrogen and organic carbon contents decreased from low to very low scale, indicating soil infertility condition. Reduction of Firmicutes was related to suppression of soil borne diseases, and Bacteroidetes which is an indicator of soil health were both almost eliminated after 25 years of fertilizer application. In conclusion, long-term inorganic fertilizer application reduced the soil nitrogen, and organic carbon, altered beneficial microbes in the soil. [ABSTRACT FROM AUTHOR]

Systemic thromboembolism, along with acute multiorgan failure, should raise clinical suspicion for CAPS. Timely management, even in suspected cases, can have a significant impact on mortality. [ABSTRACT FROM AUTHOR]

• Head and tail Pancreatic Duct stone mimically bilateral staghorn renal stone is rare. • Bilateral lumbar pain same in renal and pancreatic process due to dermatomal distribution. • Similar radiologic appearance pancreatic head and tail due to same topography of kidney. Pancreatolithiasis is an uncommon disease and the diagnosis of pancreatic duct stones is challenging. The radiological findings of pancreatic duct stones may mimic other diseases, such as renal stones. A 42-year-old male came with chief complaint of recurrent bilateral flank pain accompanied by fever which worsen 7 days before admission. The patient was diagnosed as gastritis and received analgesics in several hospitals. Ultrasonography and IVP examinations showed stones in both kidneys. CT-scan was not performed due to limitation in the hospital. Patient was diagnosed bilateral staghorn nephrolithiasis. The patient underwent bilateral bivalve nephrotomy for staghorn renal stone performed by urologist, but intraoperatively, no stones were found. The patient was then consulted intraoperatively to the digestive surgeon and get immediate median laparotomy. Intraoperatively, stones were palpated in the head and tail of the pancreas. The stones were evacuated. The symptoms were relieved, neither recurrence, nor pain, nor postoperative leakage was found. Patient was discharged uneventfully 4 days after the procedure and had no complaints in further follow-ups. The symptoms of pancreatolithiasis may overlap with nephrolithiasis and gastritis. The presented case was unique because from the history taking, clinical symptoms, USG, and IVP findings supported the diagnosis of nephrolithiasis, but intraoperative findings reveal pancreatic duct stones. For patient diagnosed with renal calculi based on sonography and IVP findings, differential diagnosis of pancreatic stone should be considered especially if no underlying cause is detected. In such circumstances relying on IVP and sonographic findings alone can be misleading. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Glioblastoma (GB) is a common brain tumor that usually presents in the cerebral hemisphere. Very rarely, these tumors can present in the cerebellum. The tumor tends to have a diffuse infiltrative growth that follows the white-matter pathway. Cerebellar GB is often difficult to diagnose on imaging and a biopsy is often needed for diagnosis. Here, we present the case of an elderly woman who presented with symptoms suggestive of acute stroke. Case Report: An 82-year-old woman presented for intermittent dizziness that started 2 weeks prior to the presentation and had been progressively worsening. She had a prior history of stroke and was noted to have decreased motor strength and sensation to touch on the left side. A cranial nerve examination was normal, as was finger-nose testing. Magnetic resonance imaging (MRI) of the brain with and without contrast showed an enhancing lesion in the left posterior cerebellum producing a mass effect in the left lateral ventricle. The differential diagnosis included cerebellitis with abscess, neoplastic process with necrosis, and, less likely, a sub-acute infarction A suboccipital craniotomy with cerebellar biopsy-diagnosed cerebellar GB. Conclusions: We report the unique presentation of cerebellar GB in an elderly woman who presented with left-sided weakness, elevated blood pressure, dizziness, vasogenic edema in the left cerebellum, and a mass effect on the fourth ventricle, mimicking acute stroke. [ABSTRACT FROM AUTHOR]

Previously, we showed vascular endothelial overexpression of human-CYP2J2 enhances coronary reactive hyperemia in Tie2-CYP2J2 Tr mice, and eNOS−/− mice had overexpression of CYP2J-epoxygenase with adenosine A2A receptor-induced enhance relaxation, but we did not see the response in CYP2J-epoxygenase knockout mice. Therefore, we hypothesized that Cyp2j5 -gene deletion affects acetylcholine- and 5'-N-ethylcarboxamidoadenosine (NECA) (adenosine)-induced relaxation and their response is partially inhibited by angiotensin-II (Ang-II) in mice. Acetylcholine (Ach)-induced response was tested with N -(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MS-PPOH, CYP-epoxygenase inhibitor; 10−5M) and Ang-II (10−6M). In Cyp2j5−/− mice, ACh-induced relaxation was different from C57Bl/6 mice, at 10−5 M (76.1 ± 3.3 vs. 58.3 ± 5.2, P < 0.05). However, ACh-induced relaxation was not blocked by MS-PPOH in Cyp2j5−/− : 58.5 ± 5.0%, P > 0.05, but blocked in C57Bl/6: 52.3 ± 7.5%, P < 0.05, and Ang-II reduces ACh-induced relaxation in both Cyp2j5−/− and C57Bl/6 mice (38.8 ± 3.9% and 45.9 ± 7.8, P < 0.05). In addition, NECA-induced response was tested with Ang-II. In Cyp2j5−/− mice, NECA-induced response was not different from C57Bl/6 mice at 10−5M (23.1 ± 2.1 vs. 21.1 ± 3.8, P > 0.05). However, NECA-induced response was reduced by Ang-II in both Cyp2j5−/− and C57Bl/6 mice (−10.8 ± 2.3% and 3.2 ± 2.7, P < 0.05). Data suggest that ACh-induced relaxation in Cyp2j5−/− mice depends on nitric oxide (NO) but not CYP-epoxygenases, and the NECA-induced different response in male vs. female Cyp2j5−/− mice when Ang-II treated. [ABSTRACT FROM AUTHOR]

BACKGROUND: A series of fluorescence indices (anthocyanin, flavonol, chlorophyll and nitrogen balance) were deployed to detect the pigments and colourless flavonoids in cacao pods of three commercial cacao (Theobroma cacao L.) genotypes (QH1003, KKM22 and MCBC1) using a fast and non‐destructive multiparametric fluorescence sensor. The aim was to determine optimum harvest periods (either 4 or 5 months after pod emergence) of commercial cacao based on fluorescence indices of cacao development and bean quality. RESULTS: As pod developed, cacao exhibited a rise with the peak of flavonol occurring at months 4 and 5 after pod maturity was initiated while nitrogen balance showed a decreasing trend during maturity. Cacao pods contained high chlorophyll as they developed but chlorophyll content declined significantly on pods that ripened at month 5. CONCLUSION: Cacao pods harvested at months 4 and 5 can be considered as commercially‐ready as the beans have developed good quality and comply with the Malaysian standard on cacao bean specification. Thus, cacao pods can be harvested earlier when they reach maturity at month 4 after pod emergence to avoid germinated beans and over fermentation in ripe pods harvested at month 5. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

This research was conducted to investigate the compaction performance and mechanical strength of compacted urea fertilizer in unlubricated and lubricated die systems. The ground urea 46% N fertilizer was compacted in a 13 mm flat-face cylindrical die set in both unlubricated and lubricated die systems with vegetable fatty acids and magnesium stearate as lubricants at various compaction stresses to produce urea fertilizer tablets. In conclusion, a lubricated die system reduces the frictional effects during the production of urea fertilizer tablets and also produces a mechanically stronger urea fertilizer tablet than those produced in an unlubricated die system. In addition, the vegetable fatty acids and magnesium stearate lubricants are found to improve the compaction performance of urea fertilizer tablet as well as its mechanical strength. [ABSTRACT FROM AUTHOR]

Coronary reactive hyperemia (CRH) protects the heart against ischemia. Adenosine A 2A AR–deficient (A 2A AR −/− ) mice have increased expression of soluble epoxide hydrolase (sEH); the enzyme responsible for breaking down the cardioprotective epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs). sEH–inhibition enhances CRH, increases EETs, and modulates oxylipin profiles. We investigated the changes of oxylipins and their impact on CRH in A 2A AR −/− and wild type (WT) mice. We hypothesized that the attenuated CRH in A 2A AR −/− mice is mediated by changes in oxylipin profiles, and that it can be reversed by either sEH- or ω-hydroxylases–inhibition. Compared to WT mice, A 2A AR −/− mice had attenuated CRH and changed oxylipin profiles, which were consistent between plasma and heart perfusate samples, including decreased EET/DHET ratios, and increased hydroxyeicosatetraenoic acids (HETEs). Plasma oxylipns in A 2A AR −/− mice indicated an increased proinflammatory state including increased ω-terminal HETEs, decreased epoxyoctadecaenoic/dihydroxyoctadecaenoic acids (EpOMEs/DiHOMEs) ratios, increased 9-hydroxyoctadecadienoic acid, and increased prostanoids. Inhibition of either sEH or ω-hydroxylases reversed the reduced CRH in A 2A AR −/− mice. In WT and sEH −/− mice, blocking A 2A AR decreased CRH. These data demonstrate that A 2A AR–deletion was associated with changes in oxylipin profiles, which may contribute to the attenuated CRH. Also, inhibition of sEH and ω-hydroxylases reversed the reduction in CRH. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases remain the number one diseases affecting patients' morbidity and mortality. The adenosine receptors are G-protein coupled receptors which have been of interest for drugs target for the treatment of multiple diseases ranging from cardiovascular to neurological. Adenosine receptors have been connected to several biological pathways affecting the physiology and pathology of the cardiovascular system. In this review, we will cover the different adenosine receptor ligands that have been identified to interact with adenosine receptors and affect the vascular system. These ligands will be evaluated from clinical as well as medicinal chemistry perspectives with more emphasis on how structural changes in structure translate into ligand potency and efficacy. Adenosine receptors represent a novel therapeutic target for development of treatment options treating a wide variety of diseases, including vascular disease and obesity. [ABSTRACT FROM AUTHOR]

Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by cytochrome (CYP) P450 epoxygenases, and to ω-terminal hydroxyeicosatetraenoic acids (HETEs) by ω-hydroxylases. EETs and HETEs often have opposite biologic effects; EETs are vasodilatory and protect against ischemia/reperfusion injury, while ω-terminal HETEs are vasoconstrictive and cause vascular dysfunction. Other oxylipins, such as epoxyoctadecaenoic acids (EpOMEs), hydroxyoctadecadienoic acids (HODEs), and prostanoids also have varied vascular effects. Post-ischemic vasodilation in the heart, known as coronary reactive hyperemia (CRH), protects against potential damage to the heart muscle caused by ischemia. The relationship among CRH response to ischemia, in mice with altered levels of CYP2J epoxygenases has not yet been investigated. Therefore, we evaluated the effect of endothelial overexpression of the human cytochrome P450 epoxygenase CYP2J2 in mice (Tie2-CYP2J2 Tr) on oxylipin profiles and CRH. Additionally, we evaluated the effect of pharmacologic inhibition of CYP-epoxygenases and inhibition of ω-hydroxylases on CRH. We hypothesized that CRH would be enhanced in isolated mouse hearts with vascular endothelial overexpression of human CYP2J2 through modulation of oxylipin profiles. Similarly, we expected that inhibition of CYP-epoxygenases would reduce CRH, whereas inhibition of ω-hydroxylases would enhance CRH. Compared to WT mice, Tie2-CYP2J2 Tr mice had enhanced CRH, including repayment volume, repayment duration, and repayment/debt ratio (P < 0.05). Similarly, inhibition of ω-hydroxylases increased repayment volume and repayment duration, in Tie2-CYP2J2 Tr compared to WT mice (P < 0.05). Endothelial overexpression of CYP2J2 significantly changed oxylipin profiles, including increased EETs (P < 0.05), increased EpOMEs (P < 0.05), and decreased 8-iso-PGF2α (P < 0.05). Inhibition of CYP epoxygenases with MS-PPOH attenuated CRH (P < 0.05). Ischemia caused a decrease in mid-chain HETEs (5-, 11-, 12-, 15-HETEs P < 0.05) and HODEs (P < 0.05). These data demonstrate that vascular endothelial overexpression of CYP2J2, through changing the oxylipin profiles, enhances CRH. Inhibition of CYP epoxygenases decreases CRH, whereas inhibition of ω-hydroxylases enhances CRH. [ABSTRACT FROM AUTHOR]

Cytochromes P450 metabolize arachidonic acid (AA) into two vasoactive oxylipins with opposing biologic effects: epoxyeicosatrienoic acids (EETs) and omega-(ω)-terminal hydroxyeicosatetraenoic acids (HETEs). EETs have numerous beneficial physiological effects, including vasodilation and protection against ischemia/reperfusion injury, whereas ω-terminal HETEs induce vasoconstriction and vascular dysfunction. We evaluated the effect of these oxylipins on post-ischemic vasodilation known as coronary reactive hyperemia (CRH). CRH prevents the potential harm associated with transient ischemia. The beneficial effects of EETs are reduced after their hydrolysis to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). ω-terminal HETEs are formed by ω-hydroxylase family members. The relationship among endothelial over-expression of sEH (Tie2-sEH Tr), the changes in oxylipins it may produce, the pharmacologic inhibition of ω-hydroxylases, activation of PPARγ, and CRH response to a brief ischemia is not known. We hypothesized that CRH is attenuated in isolated mouse hearts with endothelial sEH over-expression through modulation of oxylipin profiles, whereas both inhibition of ω-hydroxylases and activation of PPARγ enhance CRH. Compared to WT mice, Tie2-sEH Tr mice had decreased CRH, including repayment volume, repayment duration, and repayment/debt ratio (P < 0.05), whereas inhibition of ω-hydroxylases increased these same CRH parameters in Tie2-sEH Tr mice. Inhibition of sEH with t-AUCB reversed the decreased CRH in Tie2-sEH Tr mice. Endothelial over-expression of sEH significantly changed oxylipin profiles, including decreases in DHETs, mid-chain HETEs, and prostaglandins (P < 0.05). Treatment with rosiglitazone, PPARγ-agonist, enhanced CRH (P < 0.05) in both Tie2-sEH Tr and wild type (WT) mice. These data demonstrate that endothelial over-expression of sEH (through changing the oxylipin profiles) attenuates CRH, whereas inhibition of ω-hydroxylases and activation of PPARγ enhance it. [ABSTRACT FROM AUTHOR]