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Veterinary World Dec 2020Gentamicin (GM) is one of the most effective antibiotics for severe, life-threatening Gram-negative infections. Nevertheless, its clinical use has been restrained...
BACKGROUND AND AIM
Gentamicin (GM) is one of the most effective antibiotics for severe, life-threatening Gram-negative infections. Nevertheless, its clinical use has been restrained because of its nephrotoxic potential. Royal jelly (RJ) and aliskiren (ALK) can individually prevent such toxic effects. The aim of this study was to explore the protective effects of a combination treatment of RJ and ALK on GM-mediated nephrotoxicity.
MATERIALS AND METHODS
Thirty-two adult female. Wistar rats were divided equally into four groups: (I) Receiving normal saline; (II) GM (100 mg/kg, intraperitoneal [i.p.] injection); GM (100 mg/kg, i.p. injection) plus ALK (50 mg/kg, i.p. injection); and (IV) GM (100 mg/kg, i.p. injection) plus ALK (50 mg/kg, i.p. injection) in combination with RJ (150 mg/kg, orally). All treatments were administered daily for 10 days. The blood levels of creatinine, urea, uric acid, albumin, and total protein were measured. Then, the animals were sacrificed, and the kidneys were taken for histopathology.
RESULTS
Compared to normal control rats, GM-injected rats showed significantly (p<0.001) higher serum concentrations of uric acid, urea, and creatinine as well as evidently (p<0.001) lower blood levels of albumin and total protein. Moreover, GM administration was associated with significant renal histopathological changes. All these alterations were considerably (p<0.05) improved in GM-injected rats receiving ALK compared to rats receiving GM alone. However, when RJ was given in combination with ALK to GM-injected rats, it lessened the beneficial nephroprotective effects of both agents.
CONCLUSION
The combination treatment of RJ and ALK is not desirable for GM-induced nephrotoxicity. Further studies are crucial to accurately explore the precise mechanism of RJ antagonistic interaction with ALK.
PubMed: 33487984
DOI: 10.14202/vetworld.2020.2658-2662 -
Parkinsonism & Related Disorders Sep 2019Rest and re-emergent tremor (RET) in Parkinson's disease (PD) are known to be markedly variable. The aim of this study is to evaluate the effect of tremor provocation on... (Observational Study)
Observational Study
INTRODUCTION
Rest and re-emergent tremor (RET) in Parkinson's disease (PD) are known to be markedly variable. The aim of this study is to evaluate the effect of tremor provocation on RET latency and variability.
METHODS
We performed a prospective observational study in 21 PD patients with RET. Evaluations were conducted by accelerometric analysis of hand movements with and without provocation by counting out loud backwards from 100, in the OFF state. Differences in RET pause duration, tremor power at peak frequency, root mean square (RMS) and slope of return of the tremor after the pause was measured. Inter- and intra-subject variability were also calculated.
RESULTS
RET pause duration showed a 75% decrease after provocation (p < 0.001), which led to zero in 52% of cases, as compared to 9% in unprovoked measurements (p < 0.001). Provocation also led to a 2.57 time increase in tremor power (p < 0.001), 1.37 time increase in RMS (p < 0.001) and 2.47 time increase in slope (p < 0.001). A significant decrease in inter-subject variability was also observed (p = 0.001).
CONCLUSION
Tremor provocation led to RET amplitude increase, pause shortening, and variability decrease. Therefore, while provocation can be recommended for the evaluation of rest tremor in clinical practice, it might well annul its value for identifying the pause prior to re-emergent tremor.
Topics: Accelerometry; Aged; Female; Hand; Humans; Male; Middle Aged; Parkinson Disease; Prospective Studies; Tremor
PubMed: 31471122
DOI: 10.1016/j.parkreldis.2019.08.015 -
Food and Nutrition Bulletin Dec 2023Understanding seasonal patterns in nutritional status is critical for achieving and tracking global nutrition goals. However, the majority of nutrition seasonality...
BACKGROUND
Understanding seasonal patterns in nutritional status is critical for achieving and tracking global nutrition goals. However, the majority of nutrition seasonality research design draws on 2 or 3 within-year time points based on existing assumptions of seasonality, missing a more nuanced pattern.
OBJECTIVE
We aimed to identify the intra-year variability of childhood wasting, severe wasting, and weight-for-height z-scores (WHZ) in a dryland single wet-season context and illustrate an analytical approach for improving analysis of the seasonality of nutritional status.
METHODS
To quantify the intra-year variability in nutritional status, we use data from a 23-month panel study (May 2018 to March 2020) following 231 children (6-59 months of age) in eastern Chad. We apply a mixed-effects harmonic regression with child- and village-level fixed effects on the odds of being wasted, severely wasted, and on WHZ, testing for multiple and nonsymmetrical seasonal peaks, adjusted for child sex and age. We triangulate our findings using climate data on temperature, vegetation, and precipitation.
RESULTS
We identify 2 annual peaks of wasting and severe wasting. Wasting peaks at 14.7% (confidence interval [CI], 11.8-18.2) at the end of the dry season, while the smaller peak corresponds to the start of the harvest period at 13.4% (CI, 10.7-16.6). The odds of being wasted decline during the rainy season to 11.8% (CI, 9.4-14.7), with the lowest prevalence of 8.8% (CI, 6.9-11.1) occurring during the start of the dry season. In addition, a 1°C monthly increase in temperature is significantly associated with a 5% (CI, 1.4-8.7) and 12% (CI, 3.0-20.3) increase in the odds that a child is wasted and severely wasted, respectively.
CONCLUSIONS
Intra-year variability of child wasting is far more complex and nuanced than identified by the literature, with 2 peaks, as opposed to 1, likely corresponding to different seasonal drivers, such as food insecurity, disease, water contamination, and care practices at different times of year. Better seasonality analysis can go a long way in improving the timing and content of programming with the goal of reducing child wasting.
Topics: Humans; Infant; Nutritional Status; Chad; Seasons; Prevalence
PubMed: 37850930
DOI: 10.1177/03795721231181715 -
European Journal of Pharmacology Oct 2008The plasticity hypothesis of major depression states that glucocorticoids may be detrimental to neuronal plasticity while monoamines and antidepressants may reconstitute...
The plasticity hypothesis of major depression states that glucocorticoids may be detrimental to neuronal plasticity while monoamines and antidepressants may reconstitute cellular plasticity. The aim of the present study was to investigate how dexamethasone, a synthetic glucocorticoid, and norepinephrine, both of which are involved in depression, interact to affect aspects of neuronal plasticity. Dexamethasone and norepinephrine administered separately oppositely affected differentiation of human neuroblastoma SH-SY5Y cells, observed by both morphological alterations and gene expression, at the level of mRNA and protein of the differentiation markers Gap-43, L1 and laminin. Norepinephrine increased differentiation, manifested as an increase in neurite length, neurite number, and gene expression, while dexamethasone reduced these parameters. Opposite effects were also observed in the expression of the transcription factor CREB with norepinephrine upregulating phosphorylated CREB (pCREB) levels, while dexamethasone downregulated CREB mRNA and protein levels, as well as pCREB levels. Interestingly, co-administration of dexamethasone and norepinephrine resulted in morphology more differentiated than control and similar to that induced by norepinephrine, albeit to a lesser degree. The alterations in the expression of the differentiation markers induced by norepinephrine or dexamethasone treatments were mostly annulled by the co-treatment. However, pCREB levels were robustly enhanced by co-treatment, as compared to both control and norepinephrine treated cells, providing a possible explanation for the morphological increase in differentiation. These results suggest that in order for cells to combat the deleterious effects of glucocorticoids, a hyperactivation of pCREB may be necessary to restore differentiation and plasticity.
Topics: Cell Line, Tumor; Cyclic AMP Response Element-Binding Protein; Dexamethasone; Drug Interactions; GAP-43 Protein; Glucocorticoids; Humans; Laminin; Neural Cell Adhesion Molecule L1; Neuronal Plasticity; Norepinephrine; Receptors, Glucocorticoid
PubMed: 18762182
DOI: 10.1016/j.ejphar.2008.08.006 -
IScience Sep 2021Neurons in the visual cortex quickly adapt to constant input, which should lead to perceptual fading within few tens of milliseconds. However, perceptual fading is...
Neurons in the visual cortex quickly adapt to constant input, which should lead to perceptual fading within few tens of milliseconds. However, perceptual fading is rarely observed in everyday perception, possibly because eye movements refresh retinal input. Recently, it has been suggested that amplitudes of large saccadic eye movements are scaled to maximally decorrelate presaccadic and postsaccadic inputs and thus to annul perceptual fading. However, this argument builds on the assumption that adaptation within naturally brief fixation durations is strong enough to survive any visually disruptive saccade and affect perception. We tested this assumption by measuring the effect of luminance adaptation on postsaccadic contrast perception. We found that postsaccadic contrast perception was affected by presaccadic luminance adaptation during brief periods of fixation. This adaptation effect emerges within 100 milliseconds and persists over seconds. These results indicate that adaptation during natural fixation periods can affect perception even after visually disruptive saccades.
PubMed: 34485868
DOI: 10.1016/j.isci.2021.102986 -
Bioorganic & Medicinal Chemistry Mar 2002Recently we have over-expressed the enzyme alpha 1,6-fucosyltransferase from Rhizobium sp. in Escherichia coli. In this heterologous system the enzyme was mainly...
Recently we have over-expressed the enzyme alpha 1,6-fucosyltransferase from Rhizobium sp. in Escherichia coli. In this heterologous system the enzyme was mainly expressed as inclusion bodies and the one that was expressed soluble showed a short-lasting activity in solution due to precipitation of the protein. A structural analysis of the sequence using the TMpred program predicted a highly hydrophobic region of 19 aa close to the C-terminal of the protein. In order to investigate the influence of this region on the formation of inclusion bodies and the precipitation from solution, we cloned a truncated version of the protein where a C-terminal fragment of 65 aa, including the predicted transmembrane-like region, was removed. The resulting protein was expressed in a soluble form without formation of inclusion bodies. The truncated protein catalyzed the transfer of a fucopyranosyl moiety from GDP-beta-L-Fucose to chitobiose. Comparison of the acceptor specificity between the truncated alpha 1,6-fucosyltransferase and the wild-type enzyme, showed a similar behavior for both enzymes. Our results indicate that the active center is not located in the C-terminal extreme of the protein in contrast to the case of the mammalian glycosyltransferases. Also, these results indicate that the alpha-6-motif III is not directly involved in the catalytic activity of the enzyme.
Topics: Amino Acid Sequence; Catalytic Domain; Cloning, Molecular; Disaccharides; Fucosyltransferases; Guanosine Diphosphate Fucose; Inclusion Bodies; Molecular Sequence Data; Rhizobium; Sequence Deletion; Solubility; Structure-Activity Relationship
PubMed: 11814863
DOI: 10.1016/s0968-0896(01)00327-3 -
Frontiers in Bioengineering and... 2020Organ-on-chip (OOC) systems recapitulate key biological processes and responses exhibited by cells, tissues, and organs . Accordingly, these models of both health and... (Review)
Review
Organ-on-chip (OOC) systems recapitulate key biological processes and responses exhibited by cells, tissues, and organs . Accordingly, these models of both health and disease hold great promise for improving fundamental research, drug development, personalized medicine, and testing of pharmaceuticals, food substances, pollutants etc. Cells within the body are exposed to biomechanical stimuli, the nature of which is tissue specific and may change with disease or injury. These biomechanical stimuli regulate cell behavior and can amplify, annul, or even reverse the response to a given biochemical cue or drug candidate. As such, the application of an appropriate physiological or pathological biomechanical environment is essential for the successful recapitulation of behavior in OOC models. Here we review the current range of commercially available OOC platforms which incorporate active biomechanical stimulation. We highlight recent findings demonstrating the importance of including mechanical stimuli in models used for drug development and outline emerging factors which regulate the cellular response to the biomechanical environment. We explore the incorporation of mechanical stimuli in different organ models and identify areas where further research and development is required. Challenges associated with the integration of mechanics alongside other OOC requirements including scaling to increase throughput and diagnostic imaging are discussed. In summary, compelling evidence demonstrates that the incorporation of biomechanical stimuli in these OOC or microphysiological systems is key to fully replicating physiology in health and disease.
PubMed: 33363131
DOI: 10.3389/fbioe.2020.602646 -
Journal of Biosciences Apr 2003The complement system is a potent innate immune mechanism consisting of cascades of proteins which are designed to fight against and annul intrusion of all the foreign... (Review)
Review
The complement system is a potent innate immune mechanism consisting of cascades of proteins which are designed to fight against and annul intrusion of all the foreign pathogens. Although viruses are smaller in size and have relatively simple structure, they are not immune to complement attack. Thus, activation of the complement system can lead to neutralization of cell-free viruses, phagocytosis of C3b-coated viral particles, lysis of virus-infected cells, and generation of inflammatory and specific immune responses. However, to combat host responses and succeed as pathogens, viruses not only have developed/adopted mechanisms to control complement, but also have turned these interactions to their own advantage. Important examples include poxviruses, herpesviruses, retroviruses, paramyxoviruses and picornaviruses. In this review, we provide information on the various complement evasion strategies that viruses have developed to thwart the complement attack of the host. A special emphasis is given on the interactions between the viral proteins that are involved in molecular mimicry and the complement system.
Topics: Animals; CD59 Antigens; Complement System Proteins; Humans; Immune System; Molecular Mimicry; Viral Proteins; Virus Physiological Phenomena
PubMed: 12734404
DOI: 10.1007/BF02970145 -
Journal of Neuroimmunology Sep 2000Prolactin (PRL) enhances inflammatory and antitumor responses in vitro and thus exhibits Th1-type cytokine-like effects. Evidence from experimental models indicates that... (Review)
Review
Prolactin (PRL) enhances inflammatory and antitumor responses in vitro and thus exhibits Th1-type cytokine-like effects. Evidence from experimental models indicates that inhibition of PRL release by bromocriptine downregulates immune reactions and ameliorates autoimmune diseases in which Th1 responses are predominant. A direct effect of locally produced PRL in some Th1 diseases, such as rheumatoid arthritis, supports this concept. Paradoxically, however, hyperprolactinemia can also be associated with conditions such as pregnancy, where remission of Th1-mediated diseases is known to occur in the context of a Th2-dominated milieu. This reversal of the Th1-promoting effect of PRL may be due to major changes in the levels of other hormones that can annul and/or override the PRL-mediated proinflammatory state. Nevertheless, PRL, as an immunopotentiating agent, may have a powerful therapeutic role in cancer and other immunocompromised patients.
Topics: Autoimmune Diseases; Autoimmunity; Cytokines; Humans; Neoplasms; Neurosecretory Systems; Prolactin; Th1 Cells; Th2 Cells
PubMed: 10969181
DOI: 10.1016/s0165-5728(00)00302-7 -
Stress Biology Aug 2023Vesicle trafficking is an essential cellular process upon which many physiological processes of eukaryotic cells rely. It is usually the 'language' of communication... (Review)
Review
Vesicle trafficking is an essential cellular process upon which many physiological processes of eukaryotic cells rely. It is usually the 'language' of communication among the components of the endomembrane system within a cell, between cells and between a cell and its external environment. Generally, cells have the potential to internalize membrane-bound vesicles from external sources by endocytosis. Plants constantly interact with both mutualistic and pathogenic microbes. A large part of this interaction involves the exchange of transport vesicles between the plant cells and the microbes. Usually, in a pathogenic interaction, the pathogen releases vesicles containing bioactive molecules that can modulate the host immunity when absorbed by the host cells. In response to this attack, the host cells similarly mobilize some vesicles containing pathogenesis-related compounds to the pathogen infection site to destroy the pathogen, prevent it from penetrating the host cell or annul its influence. In fact, vesicle trafficking is involved in nearly all the strategies of phytopathogen attack subsequent plant immune responses. However, this field of plant-pathogen interaction is still at its infancy when narrowed down to plant-fungal pathogen interaction in relation to exchange of transport vesicles. Herein, we summarized some recent and novel findings unveiling the involvement of transport vesicles as a crosstalk in plant-fungal phytopathogen interaction, discussed their significance and identified some knowledge gaps to direct future research in the field. The roles of vesicles trafficking in the development of both organisms are also established.
PubMed: 37676627
DOI: 10.1007/s44154-023-00114-0