scholarly journals The Role of Non-Enzymatic Degradation of Meropenem—Insights from the Bottle to the Body

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 715
Author(s):  
Uwe Liebchen ◽  
Sophie Rakete ◽  
Michael Vogeser ◽  
Florian M. Arend ◽  
Christina Kinast ◽  
...  
Keyword(s):  
Normal Saline ◽  
Degradation Rate ◽  
The Body ◽  
Population Pharmacokinetic ◽  
Open Ring ◽  
Main Degradation Product ◽  
Pharmacokinetic Approach ◽  
Poor Stability

Several studies have addressed the poor stability of meropenem in aqueous solutions, though not considering the main degradation product, the open-ring metabolite (ORM) form. In the present work, we elucidate the metabolic fate of meropenem and ORM from continuous infusion to the human bloodstream. We performed in vitro infusate stability tests at ambient temperature with 2% meropenem reconstituted in 0.9% normal saline, and body temperature warmed buffered human serum with 2, 10, and 50 mg/L meropenem, covering the therapeutic range. We also examined meropenem and ORM levels over several days in six critically ill patients receiving continuous infusions. Meropenem exhibited a constant degradation rate of 0.006/h and 0.025/h in normal saline at 22 °C and serum at 37 °C, respectively. Given that 2% meropenem remains stable for 17.5 h in normal saline (≥90% of the initial concentration), we recommend replacement of the infusate every 12 h. Our patients showed inter-individually highly variable, but intra-individually constant molar ORM/(meropenem + ORM) ratios of 0.21–0.52. Applying a population pharmacokinetic approach using the degradation rate in serum, spontaneous degradation accounted for only 6% of the total clearance.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

scholarly journals Expression of Taste Receptor 2 Subtypes in Human Testis and Sperm

2020 ◽  
Vol 9 (1) ◽  
pp. 264 ◽  
Author(s):  
Laura Governini ◽  
Bianca Semplici ◽  
Valentina Pavone ◽  
Laura Crifasi ◽  
Camilla Marrocco ◽  
...  
Keyword(s):  
Taste Receptor ◽  
Receptor Activation ◽  
Taste Buds ◽  
The Body ◽  
Semen Parameters ◽  
Human Testis ◽  
Taste Receptors ◽  
Organ Systems

Taste receptors (TASRs) are expressed not only in the oral cavity but also throughout the body, thus suggesting that they may play different roles in organ systems beyond the tongue. Recent studies showed the expression of several TASRs in mammalian testis and sperm, indicating an involvement of these receptors in male gametogenesis and fertility. This notion is supported by an impaired reproductive phenotype of mouse carrying targeted deletion of taste receptor genes, as well as by a significant correlation between human semen parameters and specific polymorphisms of taste receptor genes. To better understand the biological and thus clinical significance of these receptors for human reproduction, we analyzed the expression of several members of the TAS2Rs family of bitter receptors in human testis and in ejaculated sperm before and after in vitro selection and capacitation. Our results provide evidence for the expression of TAS2R genes, with TAS2R14 being the most expressed bitter receptor subtype in both testis tissue and sperm cells, respectively. In addition, it was observed that in vitro capacitation significantly affects both the expression and the subcellular localization of these receptors in isolated spermatozoa. Interestingly, α-gustducin and α-transducin, two Gα subunits expressed in taste buds on the tongue, are also expressed in human spermatozoa; moreover, a subcellular redistribution of both G protein α-subunits to different sub-compartments of sperm was registered upon in vitro capacitation. Finally, we shed light on the possible downstream transduction pathway initiated upon taste receptor activation in the male reproductive system. Performing ultrasensitive droplets digital PCR assays to quantify RNA copy numbers of a distinct gene, we found a significant correlation between the expression of TAS2Rs and TRPM5 (r = 0.87), the cation channel involved in bitter but also sweet and umami taste transduction in taste buds on the tongue. Even if further studies are needed to clarify the precise functional role of taste receptors for successful reproduction, the presented findings significantly extend our knowledge of the biological role of TAS2Rs for human male fertility.

scholarly journals The Role of Interleukin-18 in Serum and Follicular Fluid during In Vitro Fertilization and Intracytoplasmic Sperm Injection

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Veronika Günther ◽  
Ibrahim Alkatout ◽  
Corinna Fuhs ◽  
Ali Salmassi ◽  
Liselotte Mettler ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Follicular Fluid ◽  
Intracytoplasmic Sperm Injection ◽  
Ovarian Stimulation ◽  
The Body ◽  
Interleukin 18 ◽  
Vitro Fertilization ◽  
Median Level

Cytokines are key modulators of the immune system and play an important role in the ovarian cycle. IL-18 levels in serum and follicular fluid were analyzed in women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. The cohort study group consisted of 90 women, who were undergoing IVF or ICSI. The body mass index (BMI) was determined in all patients; IL-18 levels were measured in follicular fluid and serum. IL-18 levels in serum were significantly higher than those in follicular fluid. The median level in serum was 162.75 (80.21) pg/mL and that in follicular fluid, 138.24 (91.78) pg/mL. Women undergoing IVF treatment had lower IL-18 levels in serum (median, 151.19 (90.73) pg/mL) than those treated with ICSI (median, 163.57 (89.97) pg/mL). The correlation between IL-18 levels in serum and BMI was statistically significant, as well as the correlation between IL-18 levels in follicular fluid and ovarian stimulation response (p=0.003). IL-18 was correlated with the response to ovarian stimulation and was the reason for successful pregnancy after IVF or ICSI treatment. Among other cytokines, IL-18 appears to be a promising prognostic marker of success in reproductive treatment and should be evaluated as such in further prospective studies.

scholarly journals Selenium and vascular health

2011 ◽  
Vol 84 (2) ◽  
pp. 239-248 ◽  
Author(s):  
Alan A. Sneddon
Keyword(s):  
Oxidative Damage ◽  
Protective Role ◽  
The Body ◽  
Vascular Health ◽  
Vascular Cells ◽  
Optimal Health ◽  
Oxidative Challenge ◽  
Se Status

Selenium (Se) is an important dietary micronutrient required for sustaining optimal health. Se is incorporated into proteins, many of which are antioxidants that protect the body against oxidative damage. As oxidative damage may contribute to the development of chronic diseases including cardiovascular disease (CVD), Se has been proposed to provide a protective role against this disease. Studies in vitro and in animals continue to provide increasing insight into the role of Se in promoting vascular health and ameliorating CVD. Se within vascular cells limits the adhesion together of such cells, an important early step in the development of vascular disease. Organic forms of Se may also afford vascular cells greater protection against oxidative challenge compared to inorganic forms. Nevertheless, current studies in humans investigating the relationship between Se and CVD have so far proved equivocal; larger randomized trials with different Se exposures in populations spanning the broad physiological Se status are needed to determine the criteria whereby Se may influence CVD outcome within different populations. Further studies are also needed to explore the effects of different Se species and the role of different selenoprotein genotypes in modifying Se status and their resultant impact on cardiovascular function.

RATE OF THYROXINE SECRETION BY MALE AND LAYING JAPANESE QUAIL: IDENTIFICATION OF THE RADIOACTIVE THYROXINE DEGRADATION COMPONENT OF THE MULTIPHASIC 131I CURVE

1975 ◽  
Vol 65 (1) ◽  
pp. 65-71 ◽  
Author(s):  
G. A. ROBINSON ◽  
K. H. TAM
Keyword(s):  
Japanese Quail ◽  
Degradation Rate ◽  
The Body ◽  
Secretion Rate ◽  
Distribution Space ◽  
Rapid Loss ◽  
Serum Samples ◽  
Time Period

SUMMARY Counting of radioactivity in Japanese quail in vivo showed a rapid loss of 131I from the body 12–24 h after the i.v. injection of [131I]thyroxine (T4), followed by a period of slow decrease in counting rates to 96 h. From comparison of these [131I]T4 curves with curves for 131iodide-injected birds and from counts on serum and other tissues in vitro it was concluded that, for Japanese quail, the T4 secretion rate should be calculated using serum samples taken during the first 12 h. Using this time period, the parameters measured were: T4 distribution space, laying hens 45·7 and mature cocks 26·3 ml/100 g body weight; fractional degradation rate for T4, hens 5·73 and cocks 3·12/day; serum T4 concentration (Tetrasorb125 method), hens 1·20 ± 0.07 and cocks 1·34 ± 0.05 (s.e.m.)μg/100 ml (n= 16); T4 secretion rate, hens 3·14 and cocks 1·10 μg/100 g/day.

scholarly journals Understanding Inter-Individual Variability in Monoclonal Antibody Disposition

Antibodies ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 56 ◽  
Author(s):  
Veena A. Thomas ◽  
Joseph P. Balthasar
Keyword(s):  
Individual Variability ◽  
Population Pharmacokinetic ◽  
Population Pharmacokinetic Modeling ◽  
Dominant Class ◽  
Physiological Relevance ◽  
Underlying Mechanisms ◽  
Preclinical And Clinical Studies ◽  
Subject Differences

Monoclonal antibodies (mAbs) are currently the largest and most dominant class of therapeutic proteins. Inter-individual variability has been observed for several mAbs; however, an understanding of the underlying mechanisms and factors contributing to inter-subject differences in mAb disposition is still lacking. In this review, we analyze the mechanisms of antibody disposition and the putative mechanistic determinants of inter-individual variability. Results from in vitro, preclinical, and clinical studies were reviewed evaluate the role of the neonatal Fc receptor and Fc gamma receptors (expression and polymorphism), target properties (expression, shedding, turnover, internalization, heterogeneity, polymorphism), and the influence of anti-drug antibodies. Particular attention is given to the influence of co-administered drugs and disease, and to the physiological relevance of covariates identified by population pharmacokinetic modeling, as determinants of variability in mAb pharmacokinetics.

scholarly journals Integrated Bioinformatics Data Analysis and Experimental Studies Reveals Prognostic Significance of ALDH Family in Endometria Cancer

2021 ◽  
Author(s):  
Zhou-Tong Dai ◽  
Yuan Xiang ◽  
Xing-Hua Liao
Keyword(s):  
Cell Lines ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Experimental Studies ◽  
Female Reproductive Tract ◽  
The Body ◽  
Mouse Tumor ◽  
The Impact

Abstract Background Uterine Corpus Endometrial Cancer (UCEC) is one of the three common malignant tumors of the female reproductive tract. According to reports, the cure rate of early UCEC can reach 95%. Therefore, the development of prognostic markers will help UCEC patients to find the disease earlier and develop treatment earlier. The ALDH family was first discovered to be the essential gene of the ethanol metabolism pathway in the body. Recent studies have shown that ALDH can participate in the regulation of cancer. Methods We used the gene profile data of 33 cancers in the TCGA database to analyze the expression and survival of the ALDH family. GO, KEGG, PPI multiple functional analysis was used to predict the regulatory role of ALDH family in cancer. In addition, using CCK-8, colony formation, nude mouse tumor formation and other methods, the in vitro function of UCEC cancer cell lines was tested to further confirm the key role of ALDH2 expression in the proliferation of UCEC cell lines. Finally, Lasso and Cox regression methods were used to establish an overall survival prognosis model based on ALDH2 expression. Result In our research, we explored the expression of ALDH family in 33 cancers. It was found that ALDH2 was abnormally expressed in UCEC. Besides, in vivo and in vitro experiments were conducted to explore the effect of ALDH2 expression on the proliferation of UCEC cell lines. Meanwhile, the change of its expression is not due to gene mutations, but is regulated by miR-135-3p. At the same time, the impact of ALDH2 changes on the survival of UCEC patients is deeply discussed. Finally, a nomogram for predicting survival was constructed, with a C-index of 0.798 and AUC of 0.764. Conclusion This study suggests that ALDH2 may play a crucial role in UCEC progression and has the potential as a prognostic biomarker of UCEC.

Functional Role of Peptidergic Anterior Lobe Neurons in Male Sexual Behavior of the Snail Lymnaea stagnalis

1997 ◽  
Vol 78 (6) ◽  
pp. 2823-2833 ◽  
Author(s):  
Pamela A.C.M. De Boer ◽  
Andries Ter Maat ◽  
Anton W. Pieneman ◽  
Roger P. Croll ◽  
Makoto Kurokawa ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Functional Role ◽  
Lymnaea Stagnalis ◽  
Anterior Lobe ◽  
The Body ◽  
Specific Element ◽  
Male Sexual Behavior ◽  
Implanted Electrodes

De Boer, Pamela A.C.M., Andries Ter Maat, Anton W. Pieneman, Roger P. Croll, Makoto Kurokawa, and René F. Jansen. Functional role of peptidergic anterior lobe neurons in male sexual behavior of the snail Lymnaea stagnalis. J. Neurophysiol. 78: 2823–2833, 1997. A morphologically defined group of peptidergic neurons in the CNS of the hermaphroditic snail, Lymnaea stagnalis, is concerned with the control of a very specific element of male sexual behavior. These neurons are located in the anterior lobe of the right cerebral ganglion (rAL). By using chronically implanted electrodes, we show that the rAL neurons are selectively active during eversion of the penis-carrying structure, the preputium. The preputium is normally contained inside the body cavity and is everted during copulation in the male role. Electrical stimulation of the rAL neurons through the implanted electrodes, induced eversion of the preputium in vivo. Injection of APGWamide (Ala-Pro-Gly-Try-NH2), a small neuropeptide that is present in all rAL neurons, induced eversion of the preputium. Application of APGWamide to in vitro preparations of the preputium caused relaxation of this organ. In contrast, injection of the neuropeptide conopressin, which is co-localized with APGWamide in 60% of the rAL neurons, did not induce any behavior associated with male sexual activities. These results show that the neurons of the rAL can induce an eversion of the preputium as occurs during male copulation by release of APGWamide during a period of electrical activity.

scholarly journals THE ROLE OF A NATURAL ANTIBODY IN THE REJECTION OF MOUSE TUMOR CELLS BY THE CHICK EMBRYO

1957 ◽  
Vol 106 (1) ◽  
pp. 111-126 ◽  
Author(s):  
Howard Green ◽  
Allan L. Lorincz
Keyword(s):  
Chick Embryo ◽  
Tumor Cells ◽  
The Body ◽  
Mouse Tumor ◽  
Internal Organs ◽  
Tissue Sections ◽  
Viable Cells ◽  
Viable Tumor

Cells of the Krebs ascites tumor of mice grow well in the body of the chick embryo until about the 17th day of incubation, when degeneration of the tumor can be seen in tissue sections and viable tumor cells begin to disappear from the internal organs of the embryo. This death of tumor cells follows the appearance in the chick embryo of serum gamma globulins. Among these are antibodies which can agglutinate the tumor cells in vitro, and destroy their viability. These antibodies occur in the blood without the introduction of any foreign antigen. Their possible origin is discussed. Small numbers of mouse tumor cells growing in the chick embryo are completely eliminated shortly after the time when antibodies ordinarily become detectable. When the number of cells present is larger, viable cells persist longer, and at still higher cell numbers, the embryo or chick is unable to eliminate the tumor, and is itself killed by it. Gamma globulins of older birds injected into young chick embryos bearing growing tumor clear the embryonic organs of viable tumor cells.

scholarly journals Role of Human Mesenchymal Stem Cells in Regenerative Therapy

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 54
Author(s):  
Jayavardini Vasanthan ◽  
Narasimman Gurusamy ◽  
Sheeja Rajasingh ◽  
Vinoth Sigamani ◽  
Shivaani Kirankumar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
The Body ◽  
The Past ◽  
Multipotent Cells ◽  
Mitochondrial Transfer ◽  
Quality Control Parameters

Mesenchymal stem cells (MSCs) are multipotent cells which can proliferate and replace dead cells in the body. MSCs also secrete immunomodulatory molecules, creating a regenerative microenvironment that has an excellent potential for tissue regeneration. MSCs can be easily isolated and grown in vitro for various applications. For the past two decades, MSCs have been used in research, and many assays and tests have been developed proving that MSCs are an excellent cell source for therapy. This review focusses on quality control parameters required for applications of MSCs including colony formation, surface markers, differentiation potentials, and telomere length. Further, the specific mechanisms of action of MSCs under various conditions such as trans-differentiation, cell fusion, mitochondrial transfer, and secretion of extracellular vesicles are discussed. This review aims to underline the applications and benefits of MSCs in regenerative medicine and tissue engineering.

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