scholarly journals PPAR-Alpha Agonist Fenofibrate Combined with Octreotide Acetate in the Treatment of Acute Hyperlipidemia Pancreatitis

PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Wen Bao ◽  
Rui Kong ◽  
Nan Wang ◽  
Wei Han ◽  
Jie Lu

At present, there are more and more patients with acute hypertriglyceridemia pancreatitis in clinical practice. Common treatment measures include fasting and water withdrawal, fluid resuscitation, and somatostatin. In recent years, studies have pointed out that the PPARa agonist fenofibrate may help improve the condition of such patients. Therefore, through clinical research and analysis, we reported for the first time that fenofibrate combined with octreotide acetate has a more excellent effect in the treatment of patients with acute hypertriglyceridemia pancreatitis, and from the perspective of signal pathways, we revealed that the combination of the two drugs has an effect on NF-κB P65. The synergistic inhibitory effect proves that the combined treatment is beneficial to control inflammation, protect liver function, and improve the prognosis of patients. It is worthy of clinical promotion.

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Tran Thi Hong Hanh ◽  
Nguyen Hai Dang ◽  
Nguyen Tien Dat

Three bisdesmosidic saponins 3-O-[β-D-glucopyranosyl-(1→4)-β-D-glucuronopyranosyl] oleanolic acid 28-O-β-D-glucopyranosyl ester (1), polyscioside D (2), and 3-O-{β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-glucuronopyranosyl}oleanolic acid 28-O-β-D-glucopyranosyl-(1→2)-β-D-galactopyranosyl ester (3) were isolated from a methanol extract ofPolyscias fruticosa(L.) Harms leaves. Compound1was obtained as a main constituent and compound3was reported for the first time and named as polyscioside I. Saponin1inhibited porcine pancreasα-amylase and yeastα-glucosidase activities while2and3were inactive. Synergistic inhibitory effect onα-amylase was observed from the combination of low concentrations of1and acarbose. The findings suggest the use ofP. fruticosaand its major saponin1for the prevention and treatment of diabetes and its complications.


2021 ◽  
Vol 22 (18) ◽  
pp. 10029
Author(s):  
Yueh-Ming Shyu ◽  
Lawrence Yu-Min Liu ◽  
Yung-Jen Chuang

Melanoma is the most lethal form of skin cancer, which is intrinsically resistant to conventional chemotherapy. Combination therapy has been developed to overcome this challenge and show synergistic anticancer effects on melanoma. Notably, the histone deacetylase inhibitor, valproic acid (VPA), has been indicated as a potential sensitizer of chemotherapy drugs on various metastatic cancers, including advanced melanoma. In this study, we explored whether VPA could serve as an effective sensitizer of chemotherapy drug etoposide (ETO) on B16-F10 and SK-MEL-2-Luc melanoma cell lines in response to drug-induced DNA damages. Our results demonstrated that the VPA-ETO simultaneous combined treatment and ETO pretreated sequential combined treatment generated higher inhibitory effectivities than the individual treatment of each drug. We found the VPA-ETO simultaneous combined treatment contributed to the synergistic inhibitory effect by the augmented DNA double-strand breaks, accompanied by a compromised homologous recombination activity. In comparison, the ETO pretreated sequential combined treatment led to synergistic inhibitory effect via enhanced apoptosis. Surprisingly, the enhanced homologous recombination activity and G2/M phase arrest resulted in the antagonistic effect in both cells under VPA pretreated sequential combined treatment. In summary, our findings suggested that sequential order and effective dose of drug administration in VPA-ETO combination therapy could induce different cellular responses in melanoma cells. Such understanding might help potentiate the effectiveness of melanoma treatment and highlight the importance of sequential order and effective dose in combination therapy.


1982 ◽  
Vol 92 (1) ◽  
pp. 37-42 ◽  
Author(s):  
H. M. A. MEIJS-ROELOFS ◽  
P. KRAMER ◽  
L. GRIBLING-HEGGE

A possible role of 5α-androstane-3α,17β-diol (3α-androstanediol) in the control of FSH secretion was studied at various ages in ovariectomized rats. In the rat strain used, vaginal opening, coincident with first ovulation, generally occurs between 37 and 42 days of age. If 3α-androstanediol alone was given as an ovarian substitute, an inhibitory effect on FSH release was evident with all three doses tested (50, 100, 300 μg/100 g body wt) between 13 and 30 days of age; at 33–35 days of age only the 300 μg dose caused some inhibition of FSH release. Results were more complex if 3α-androstanediol was given in combined treatment with oestradiol and progesterone. Given with progesterone, 3α-androstanediol showed a synergistic inhibitory action on FSH release between 20 and 30 days of age. However, when 3α-androstanediol was combined with oestradiol a clear decrease in effect, as compared to the effect of oestradiol alone, was found between 20 and 30 days of age. Also the effect of combined oestradiol and progesterone treatment was greater than the effect of combined treatment with oestradiol, progesterone and 3α-androstanediol. At all ages after day 20 none of the steroid combinations tested was capable of maintaining FSH levels in ovariectomized rats similar to those in intact rats. It is concluded that 3α-androstanediol might play a role in the control of FSH secretion in the immature rat, but after day 20 the potentially inhibitory action of 3α-androstanediol on FSH secretion is limited in the presence of oestradiol.


Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1311
Author(s):  
Magdalena Chmur ◽  
Andrzej Bajguz

Brassinolide (BL) represents brassinosteroids (BRs)—a group of phytohormones that are essential for plant growth and development. Brassinazole (Brz) is as a synthetic inhibitor of BRs’ biosynthesis. In the present study, the responses of Wolffia arrhiza to the treatment with BL, Brz, and the combination of BL with Brz were analyzed. The analysis of BRs and Brz was performed using LC-MS/MS. The photosynthetic pigments (chlorophylls, carotenes, and xanthophylls) levels were determined using HPLC, but protein and monosaccharides level using spectrophotometric methods. The obtained results indicated that BL and Brz influence W. arrhiza cultures in a concentration-dependent manner. The most stimulatory effects on the growth, level of BRs (BL, 24-epibrassinolide, 28-homobrassinolide, 28-norbrassinolide, catasterone, castasterone, 24-epicastasterone, typhasterol, and 6-deoxytyphasterol), and the content of pigments, protein, and monosaccharides, were observed in plants treated with 0.1 µM BL. Whereas the application of 1 µM and 10 µM Brz caused a significant decrease in duckweed weight and level of targeted compounds. Application of BL caused the mitigation of the Brz inhibitory effect and enhanced the BR level in duckweed treated with Brz. The level of BRs was reported for the first time in duckweed treated with BL and/or Brz.


2015 ◽  
Vol 26 (3) ◽  
pp. 495-505 ◽  
Author(s):  
Meredith O. Sweeney ◽  
Agnieszka Collins ◽  
Shae B. Padrick ◽  
Bruce L. Goode

Branched actin filament networks in cells are assembled through the combined activities of Arp2/3 complex and different WASP/WAVE proteins. Here we used TIRF and electron microscopy to directly compare for the first time the assembly kinetics and architectures of actin filament networks produced by Arp2/3 complex and dimerized VCA regions of WAVE1, WAVE2, or N-WASP. WAVE1 produced strikingly different networks from WAVE2 or N-WASP, which comprised unexpectedly short filaments. Further analysis showed that the WAVE1-specific activity stemmed from an inhibitory effect on filament elongation both in the presence and absence of Arp2/3 complex, which was observed even at low stoichiometries of WAVE1 to actin monomers, precluding an effect from monomer sequestration. Using a series of VCA chimeras, we mapped the elongation inhibitory effects of WAVE1 to its WH2 (“V”) domain. Further, mutating a single conserved lysine residue potently disrupted WAVE1's inhibitory effects. Taken together, our results show that WAVE1 has unique activities independent of Arp2/3 complex that can govern both the growth rates and architectures of actin filament networks. Such activities may underlie previously observed differences between the cellular functions of WAVE1 and WAVE2.


1989 ◽  
Vol 262 (1) ◽  
pp. 83-89 ◽  
Author(s):  
K J Föhr ◽  
J Scott ◽  
G Ahnert-Hilger ◽  
M Gratzl

The inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ compartment of endocrine cells was studied with alpha-toxin- and digitonin-permeabilized rat insulinoma (RINA2) and rat pheochromocytoma (PC12) cells. The Ca2+ uptake was ATP-dependent, and submicromolar concentrations of IP3 specifically released the stored Ca2+. Half-maximal Ca2+ release was observed with 0.25-0.5 mumol of IP3/l, and the amount of Ca2+ released due to IP3 could be enhanced by additional loading of the Ca2+ compartment. Consecutive additions of the same concentration of IP3 for 1-2 h always released the same amount of Ca2+ without desensitization, providing an ideal basis to further characterize the IP3-induced Ca2+ release. Here we describe for the first time a reversible inhibitory effect of decavanadate on the IP3-induced Ca2+ release. Among the vanadium species tested (decavanadate, oligovanadate and monovanadate), only decavanadate was inhibitory, with a half-maximal effect at 5 mumol/l in both cell types. The effect of decavanadate could be overcome by increasing the amount of sequestered Ca2+ or added IP3. Decavanadate did not affect the ATP-driven Ca2+ uptake but oligovanadate was inhibitory on Ca2+ uptake. p-Hydroxymercuribenzoate (pHMB) at concentrations between 10 and 30 mumol/l also inhibited the Ca2+ release due to IP3. Thiol compounds such as dithiothreitol (DTT; 1 mmol/l) added before pHMB removed all its inhibitory effect on the IP3-induced Ca2+ release, whereas the inhibition caused by decavanadate was unaffected by DTT. Thus, the decavanadate-dependent inhibition functions by a distinctly different mechanism than pHMB and could serve as a specific tool to analyse various aspects of the IP3-induced Ca2+ release within endocrine cells.


2019 ◽  
Author(s):  
MG Onyango ◽  
AF Payne ◽  
J Stout ◽  
C Dieme ◽  
L Kuo ◽  
...  

AbstractElizabethkingia anophelis has been the cause of four outbreaks with significant morbidity and mortality. Its transmission routes remain unknown and no point source of infection has been identified. Here we show that E. anophelis can be found in the saliva of Aedes mosquitoes, suggesting the novel possibility of vector-borne transmission of this bacterium. We additionally characterized diverse microbial communities in Aedes midguts, salivary glands and saliva. To the best of our knowledge, this represents the first description of the microbiome of Aedes saliva. Further, we demonstrate that increased abundance of E. anophelis is associated with decreased susceptibility and replication of Zika virus (ZIKV) in the midgut of Aedes mosquitoes, suggesting a novel transmission barrier for arboviruses transmitted by Aedes mosquitoes. Together, these results demonstrate the complex relationships between the mosquito, the midgut microbial community and arboviruses and offer insights into the epidemiology and control of emerging bacterial and viral pathogens.Author SummaryElizabethkingia anophelis has in the recent past caused outbreaks different parts of the world resulting both in morbidity and mortality. Until now, to the best of our knowledge, no study has been able to demonstrate that this bacterium can be transmitted by mosquitoes. We have demonstrated for the first time that Elizabethkingia anophelis is present in the saliva of both infected and non-infected Aedes mosquitoes. Further, we have shown that it confers an inhibitory effect on Zika virus establishment in the midguts of Aedes mosquitoes. Together, these results potentially display the potential for vector borne transmission of E. anophelis as well as a novel transmission barrier of ZIKV. Lastly, we have for the first time characterized salivary microbes of Aedes mosquitoes necessitating the investigation of the impact of salivary microbes in severity of disease in vertebrate hosts.


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