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1.
Reprod Domest Anim ; 59(5): e14579, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38715456

RESUMO

This study evaluates factors influencing pregnancy rates per artificial insemination (P/AI) and pregnancy loss in Lohi ewes undergoing laparoscopic AI with frozen-thawed semen under sub-tropical conditions. Data from three experiments comprising ewes (n = 358) of mixed parity (nulliparous; NP and parous; P), various body condition score (BCS) and assigned to long-term (LTP, 11 days) and short-term (STP, 5 days) oestrus synchronization regimen across high breeding season (HBS) and low breeding season (LBS) were analysed. Laparoscopic insemination was conducted 54 h post-sponge removal. Pregnancy diagnosis and loss were evaluated on days 35 and 90 post-insemination via ultrasonography. Results showed parity significantly influenced P/AI, with nulliparous ewes achieving higher pregnancy ratios than parous ewes (p = .001). BCS significantly influenced P/AI (p < .05), with a quadratic relationship observed between BCS and season (BCS*BCS*Season; p = .07). Progestin treatment did not significantly influence the ratio of pregnant ewes (p = .07). Pregnancy losses were significantly higher during LBS than HBS (p < .05), irrespective of progestin treatment. In conclusion, parity and BCS significantly influenced P/AI, with BCS demonstrating a quadratic association with season. Ewes bred during LBS experienced higher pregnancy losses than HBS, irrespective of progestin treatment.


Assuntos
Criopreservação , Sincronização do Estro , Inseminação Artificial , Laparoscopia , Taxa de Gravidez , Estações do Ano , Preservação do Sêmen , Animais , Feminino , Gravidez , Inseminação Artificial/veterinária , Preservação do Sêmen/veterinária , Laparoscopia/veterinária , Masculino , Criopreservação/veterinária , Aborto Animal , Carneiro Doméstico , Paridade , Ovinos
2.
Pak J Med Sci ; 40(2ICON Suppl): S87-S90, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38328640

RESUMO

Intraabdominal cystic lesions diagnosed during antenatal period are uncommon. They are found to have varying origins, with renal tract being the most common site. Rarely, a large unilateral cystic lesion of renal origin is caused by Pelviureteric junction obstruction, crossing the midline, leading to compression of the contralateral kidney. We present a case of a neonate who was diagnosed with a large abdominal cyst in the antenatal period. The cyst persisted and crossed the midline causing hydronephrosis on the contralateral side. This is an unusual presentation of a commonly occurring condition, usually such large cyst at birth origins from alimentary tract rather renal system. It is important to understand unusual presentations of intraabdominal lesions and the associated pathology. It is mandatory to rule out renal obstruction, if there is any decompression of renal function, it is mandatory to save renal function till the time of definitive surgery.

3.
Cryobiology ; 113: 104593, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37844752

RESUMO

This study determined the individual and combined effects of extracellular adenosine triphosphate (ATP) and quercetin (QUE) on the quality of post-thawed sperm and the fertilization potential of Lohi rams. In experiment 1, semen samples from four Lohi rams were pooled and extended with different concentrations of ATP or QUE (control; no ATP or QUE, 1 or 2 mM ATP and 10 or 20 µM QUE). In experiment 2, pooled semen samples were extended with various combinations of ATP and QUE (control; no ATP and QUE, 1 mM ATP + 10 µM QUE, 1 mM ATP + 20 µM QUE, 2 mM ATP + 10 µM QUE and 2 mM ATP + 20 µM QUE). All samples in both experiments were cryopreserved and analyzed for post-thawed sperm quality. In experiment 3, the best combination of ATP and QUE from experiment 2 was to extend semen, which was then used for laparoscopic insemination in estrus-synchronized ewes (n = 83). The results of experiment 1 showed that 1 mM ATP and 20 µM QUE treatments resulted in higher total motility, progressive motility, viability, plasma membrane intactness (PMI), and motion kinetics (VCL, VSL, VAP, LIN, and STR) compared to other treatments (p < 0.05). In experiment 2, the 1 mM ATP +10 µM QUE-treated group exhibited significantly higher total and progressive motility, PMI, and motion kinetics (VSL, VCL, VAP, STR, and BCF) compared to the control group (p < 0.05). In experiment 3, the fertilizing potential of sperms treated with 1 mM ATP +10 µM QUE was greater than that of untreated controls (58.1% vs. 27.5%, respectively, p-value = 0.012). In conclusion, the quality of post-thawed ram semen is enhanced when the extender is supplemented with extracellular 1 mM ATP and 20 µM QUE, whether used separately or in combination with 1 mM ATP and 10 µM QUE. Furthermore, the inclusion of 1 mM ATP and 10 µM QUE together in the extender significantly improves in vivo fertility in Lohi ram.


Assuntos
Preservação do Sêmen , Sêmen , Ovinos , Animais , Masculino , Feminino , Quercetina/farmacologia , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Criopreservação/métodos , Espermatozoides , Fertilização , Carneiro Doméstico , Trifosfato de Adenosina , Motilidade dos Espermatozoides
4.
Biol Res ; 56(1): 3, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36658640

RESUMO

BACKGROUND: Contrary to the advantageous anticancer activities of curcumin (Cur), limited bioavailability and solubility hindered its efficacy. Here, nontoxic dendrosomal nano carrier with Cur was used to overcome these problems. Despite considerable antitumor properties of Oxaliplatin (Oxa), the limiting factors are drug resistance and adverse side-effects. The hypothesis of this study was to evaluate the possible synergism between dendrosomal nanocurcumin (DNC) and Oxa and these agents showed growth regulatory effects on SKOV3 and OVCAR3 cells. METHODS AND MATERIALS: In the present study, colony formation, wound healing motility, cell adhesion, transwell invasion and migration assay and cell cycle arrest with or without DNC, Oxa and Combination were defined. In addition to, real time PCR and Western blot were used to analyze AKT, PI3K, PKC, JNK, P38 and MMPs mRNAs and proteins expressions. Docking of MMP-2-Cur, MMP-2-DNC and MMP-2-Oxa was performed and the results of all three complexes were simulated by molecular dynamics. RESULTS: Our findings illustrated that DNC had the greatest effect on cell death as compared to the Cur alone. Moreover, the growth inhibitory effects (such as cell death correlated to apoptosis) were more intense if Oxa was added followed by DNC at 4 h interval. However, insignificant effects were observed upon simultaneous addition of these two agents in both cell lines. Besides, a combination of agents synergistically alters the relative expression of MMP-9. CONCLUSIONS: The docking results showed that His70 and Asp100 may play a key role at the MMP-2 binding site. The matrigel invasion as well as cell viability of ovarian cancer cell lines SKOV3 and OVCAR3 by DNC alone or in combination with Oxa was inhibited significantly. The inhibitory effects of these agents were due to the differential expression levels of MMP 2 and MMP 9 regulated by multiple downstream signaling cascades. From the molecular dynamic simulation studies, it was confirmed that DNC established a strong interaction with MMP-2.


Assuntos
Curcumina , Neoplasias Ovarianas , Humanos , Feminino , Oxaliplatina/farmacologia , Apoptose , Metaloproteinase 2 da Matriz/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Curcumina/farmacologia , Movimento Celular
5.
Reprod Domest Anim ; 58(1): 48-59, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36102495

RESUMO

The objectives of the experiment were to determine the effect of two doses of equine chorionic gonadotropin (eCG) in a standard synchronization protocol based on a short-term progesterone (P4 ) priming on ovarian structures and haemodynamics, concentrations of steroid hormones and prolificacy rate when oestrus was induced during low-breeding season (LBS) in Beetal dairy goats. We hypothesized that inclusion of eCG in a short-term P4 priming-based synchronization protocol would increase the blood perfusion to ovarian structures leading to enhance oestrous and ovulatory responses and prolificacy rate in goats. Forty-two multiparous acyclic goats were blocked by body condition and, within block, assigned randomly to receive saline as control (CON), low eCG (L-eCG; 300 IU) or high eCG (H-eCG; 600 IU) dose. Initially, a controlled internal drug release (CIDR) device was placed in the anterior vagina on d -8, followed by removal of CIDR on d -3, concurrent with the administration of PGF2α and eCG according to their respective treatments. Goats were monitored for oestrous response. B-mode and Doppler ultrasonography was performed with 12-h interval, starting from day -3 until natural breeding (day 0), and then on days 5, 10, 15 and 20 post-breeding to monitor follicular and luteal dynamics and blood flow, respectively. Blood was sampled at 0, 12, 24, 36 and 60 h after CIDR removal to quantify plasma concentrations of estradiol-17ß (E2 ), whereas plasma concentrations of P4 were assayed at days 5, 10, 15 and 20 after breeding. Pregnancy and prolificacy rates were determined at day 30 and 150 after breeding, respectively. Data were analysed with mixed-effects models, and orthogonal contrasts were used to evaluate the effect of treatment [Con vs. (½ L-eCG + ½ H-eCG)] and dose of eCG (L-eCG vs. H-eCG). Data are presented in sequence as CON, L-eCG, H-eCG (LSM ± SEM). The oestrous intensity score (152.9 vs. 182.7 vs. 186.5 ± 15.1; p = .02) was greater in eCG-treated goats as compared to CON. Administration of eCG reduced the intervals to standing oestrus (66.2 vs. 41.8 vs. 48.9 h ± 5.5; p = .05), breeding (70.2 vs. 44.4 vs. 45.4 h ± 4.5; p = .03) and ovulation (84.5 vs. 61.2 vs. 63.4 h ± 6.2; p = .05) compared with CON goats. The mean growth rate of pre-ovulatory follicle was greater (1.11 vs. 1.49 vs. 1.45 mm ± 0.08; p = .01) in eCG-treated goats resulting in an increased diameter of pre-ovulatory follicle (6.27 vs. 7.20 vs. 7.31 mm ± 0.07; p < .01) and corpora lutea (6.75 vs. 8.26 vs. 8.07 mm ± 0.42; p = .04) than CON. The mean follicular blood flow did not differ among treatments; however, the mean luteal blood flow was greater in L-eCG-treated goats (0.81 vs. 1.61 vs. 1.07 cm2 ± 0.12; p = .001). The mean concentrations of E2 (4.03 vs. 5.21 vs. 4.78 pg/ml ± 0.42; p = .04) and P4 (4.85 vs. 6.39 vs. 6.22 ng/ml ± 0.34; p = .04) were greater in eCG-treated goats. The twinning rate did not differ between treatments; nevertheless, prolificacy rate was greater (p = .04) in L-eCG-treated goats. Collectively, our data suggest that the administration of eCG improves the induction of oestrous and ovarian dynamics. Administration of L-eCG enhances prolificacy rate, therefore, a low dose of eCG might be practically beneficial to improve reproduction during LBS in acyclic Beetal dairy goats.


Assuntos
Sincronização do Estro , Cabras , Gravidez , Feminino , Animais , Cavalos , Estações do Ano , Cabras/fisiologia , Sincronização do Estro/métodos , Progesterona , Ovulação/fisiologia , Estradiol , Hemodinâmica
6.
Sensors (Basel) ; 23(12)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37420878

RESUMO

This study presents the effectiveness of an anti-jerk predictive controller (AJPC) based on active aerodynamic surfaces to handle upcoming road maneuvers and enhance vehicle ride quality by mitigating external jerks operating on the body of the vehicle. In order to eliminate body jerk and improve ride comfort and road holding during turning, accelerating, or braking, the proposed control approach assists the vehicle in tracking the desired attitude position and achieving a realistic operation of the active aerodynamic surface. Vehicle speed and upcoming road data are used to calculate the desired attitude (roll or pitch) angles. The simulation results are performed for AJPC and predictive control strategies without jerk using MATLAB. The simulation results and comparison based on root-mean-square (rms) values show that compared to the predictive control strategy without jerk, the proposed control strategy significantly reduces the effects of vehicle body jerks transmitted to the passengers, improving ride comfort without degrading vehicle handling at the cost of slow desired angle tracking.


Assuntos
Movimento (Física) , Simulação por Computador
7.
J Environ Manage ; 329: 117109, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36571954

RESUMO

Waste separation at a household level could facilitate sustainable waste management. However, despite several efforts by the government, the adoption of household waste separation practices is still at a nascent stage. Therefore, we aim to study the factors affecting household waste separation intention (WSI). Drawing on Dual Factor Theory (DFT), two distinct sets of factors (enablers and barriers) were used to explain the WSI at the household level. This study also extended the Self Determination Theory (SDT) and Status Quo Bias (SQB) theory to broadly identify the factors and develop a conceptual model. The main study analyzed data from 494 respondents using a structural equation modeling approach. The result reveals that environmental concern, anticipated guilt, awareness of consequences, and health consciousness have a significant positive effect on WSI. In contrast, perceived inconvenience, information, and infrastructure barriers significantly negatively affect WSI. Additionally, gender and income partially moderated the studied relationships. The results offer key insights and implications for marketers and public policymakers.


Assuntos
Eliminação de Resíduos , Gerenciamento de Resíduos , Inquéritos e Questionários , Intenção , Modelos Teóricos , Renda , Eliminação de Resíduos/métodos , Resíduos Sólidos
8.
Microb Cell Fact ; 21(1): 118, 2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35717207

RESUMO

Microbial infection and cancer are two leading causes of global mortality. Discovering and developing new therapeutics with better specificity having minimal side-effects and no drug resistance are of an immense need. In this regard, cationic antimicrobial peptides (AMP) with dual antimicrobial and anticancer activities are the ultimate choice. For better efficacy and improved stability, the AMPs available for treatment still required to be modified. There are several strategies in which AMPs can be enhanced through, for instance, nano-carrier application with high selectivity and specificity enables researchers to estimate the rate of drug delivery to a particular tissue. In this review we present the biology and modes of action of AMPs for both anticancer and antimicrobial activities as well as some modification strategies to improve the efficacy and selectivity of these AMPs.


Assuntos
Anti-Infecciosos , Nanoestruturas , Neoplasias , Antibacterianos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos , Bactérias , Nanoestruturas/química , Neoplasias/tratamento farmacológico
9.
Sensors (Basel) ; 22(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36298420

RESUMO

This paper presents a formulation of a preview optimal control strategy for a half-car model equipped with active aerodynamic surfaces. The designed control strategy consists of two parts: a feed-forward controller to deal with the future road disturbances and a feedback controller to deal with tracking error. An anti-jerk functionality is employed in the design of preview control strategy that can reliably reduce the jerk of control inputs to improve the performance of active aerodynamic surfaces and reduce vehicle body jerk to enhance the ride comfort without degrading road holding capability. The proposed control scheme determines proactive control action against oncoming potential road disturbances to mitigate the effect of deterministically known road disturbances. The performance of proposed anti-jerk optimal control strategy is compared with that of optimal control without considering jerk. Simulation results considering frequency and time domain characteristics are carried out using MATLAB to demonstrate the effectiveness of the proposed scheme. The frequency domain characteristics are discussed only for the roll inputs, while time domain characteristics are discussed for the corresponding ground velocity inputs of bump and asphalt road, respectively. The results show that using anti-jerk optimal preview control strategy improves the performance of vehicle dynamics by reducing jerk of aerodynamic surfaces and vehicle body jerk simultaneously.

10.
J Environ Manage ; 310: 114772, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35228167

RESUMO

Butyl butyrate (BB) derived from bio-renewable resources is the most promising jet fuel blend. This review highlights essential properties of jet fuel, including calorific value, kinematic viscosity, freezing point, flash point, auto-ignition temperature, and density to compare with different bio-renewable chemicals, which are compatible to be blended with the jet fuel. A detailed discussion follows on the importance of intermediate formation, reaction mechanism, and catalyst properties that are critical towards the production of bio-renewable resource-derived BB. BB is primarily produced via the esterification of butyric acid (BA) in butanol (BuOH) with or without using a catalyst. The corresponding reactions are carried out in both homogeneous and heterogeneous phases, provided it has acidic properties. Thus, a wide range of acidic catalysts such as [HSO3-pmim] HSO4 ionic liquids, heteropolyacid, methanesulfonic acid, Dowex 50 Wx8-400 resins, and sulfonated char causes up to 98%, 97.9%, 93.2%, 95.3%, and 90% of BB yield, respectively are critically reviewed. Moreover, reaction mechanism, product, and by-product formation that primarily dictate the BB yield and selectivity have been comprehensively reviewed. In addition, catalytic and mechanistic insights on BB production from other bio-renewable resources such as butyric anhydride, butyraldehyde, dibutyl ether, and methanol have been discussed in this review.


Assuntos
Biocombustíveis , Butiratos , Butanóis , Esterificação
11.
Reprod Domest Anim ; 56(11): 1369-1376, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34370879

RESUMO

Based on different surveys, dairy farmers are concerned about extensive use of exogenous oxytocin in buffaloes, which is being held responsible for reproductive problems including irregular oestrous cycle and delayed ovulation. For these concerns, effects of oxytocin injection on postpartum follicular dynamics, postpartum oestrous interval (PEI), oestrous length, the interval from onset of estrus to ovulation and blood progesterone (P4) were studied in Nili-Ravi buffaloes. For this purpose, 23 animals within 1 week after calving were randomly divided into three groups: without oxytocin (CON; n = 7), 10 i.u. oxytocin (LOW; n = 8), 30 i.u. oxytocin - (HIGH; n = 8) and used to record the PEI for the study period of 154 days. At subsequent estrus, three buffaloes from each group (not served) were selected randomly to monitor two cycles for 6 weeks. Transrectal ultrasonography was performed to evaluate follicular and corpus luteum (CL) development, and blood sampling was done for progesterone (P4) analysis. These results revealed that postpartum oestrous interval (PEI) decreased significantly in oxytocin-treated groups. The number of small, medium and total follicles on the left ovary was significantly higher in the HIGH group. However, an overall number of small and total follicles on both right and left ovaries was significantly higher in CON and HIGH groups. On the other hand, there was no difference in the number of follicles on the right ovary among all treatment groups. The same was true for the size of pre-ovulatory follicles, CL, P4 concentrations and oestrous cycle length. The intervals from onset of estrus to ovulation and from standing estrus to ovulation were increased considerably in the HIGH group. It is concluded that exogenous oxytocin administration resulted in the shortening of PEI but triggered a delay in ovulation. Moreover, a higher dose of oxytocin could stimulate the growth of small, medium, and total follicles in postpartum Nili-Ravi buffaloes.


Assuntos
Estro/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Ocitocina/farmacologia , Animais , Búfalos , Indústria de Laticínios/métodos , Feminino , Ovário/diagnóstico por imagem , Ocitocina/administração & dosagem , Período Pós-Parto/fisiologia , Progesterona/sangue
12.
J Appl Toxicol ; 40(10): 1410-1420, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32346888

RESUMO

Globally, more than a billion people smoke tobacco making it one of the biggest public health problems and a leading risk factor for global deaths. Nicotine, the main alkaloid in tobacco, has been shown to be associated with fertility problems in men and women. The adverse effects of tobacco/nicotine on reproduction have been attributed to deleterious effects on gametes, steroidogenic imbalance, and competitive inhibition of steroid receptors. The present study reports the sex-steroid receptor disrupting potential of nicotine and its major metabolite cotinine against the estrogen receptor-α (ERα), ERß, androgen receptor (AR), and progesterone receptor (PR). Both ligands bound in the ligand-binding pockets of ERα, ERß, AR and PR and formed important hydrophobic interactions with different amino-acid residues of receptors. Most of the residues of ERα, ERß, AR and PR interacting with nicotine and cotinine were common with those of native/bound ligands of the receptors. Interacting amino acids most important for binding of nicotine and cotinine with each receptor were identified by loss in accessible surface area. Amino acids Leucine-346, Leucine-384 and Phenylalanine-404 for ERα; Methionine-336, Phenylalanine-356 and Leucine-298 for ERß; and Leucine-704 and Leucine-718, respectively for AR and PR, were the most important residues for binding with nicotine and cotinine. Among the four receptors, based on the number of interactions, nicotine and cotinine had greater potential to interfere in the signaling of ERß. In conclusion, the results suggested that nicotine and cotinine bind and interact with sex-steroid nuclear receptors and have potential to interfere in the steroid hormone signaling resulting in reproductive dysfunction.


Assuntos
Sítios de Ligação/efeitos dos fármacos , Cotinina/toxicidade , Estrutura Molecular , Nicotina/toxicidade , Receptores de Estrogênio/efeitos dos fármacos , Receptores de Progesterona/efeitos dos fármacos , Receptores de Progesterona/metabolismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo , Nicotiana/química
13.
Pak J Pharm Sci ; 33(2(Supplementary)): 805-814, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32863255

RESUMO

Rosa brunonii L., a less investigated plant contains flavonoid glycosides and is used to treat stomach ailments, heart problems, and diabetes in folk. The crude extract of the plant possesses antioxidant activity. The current work was aimed to investigate the presence of phytochemicals, antioxidative stress and protective potential of chloroform extract of the Rosa brunonii L. fruits (RBFCE) against liver and kidney toxicity induced by anti-tuberculosis drugs, rifampicin/isoniazid (Rif/INH) in Wistar albino rats. Animals were divided into six groups, each comprising 6 rats and fed with a standard pelleted diet. Normal control group was given only a standard pelleted diet. The vehicle control group received 0.5% carboxymethylcellulose (CMC) aqueous solution (vehicle). Negative and positive control groups were given Rif/INH (50+50 mg/kg, p.o) and silymarin (SILM) (200 mg/kg, p.o) in 0.5% vehicle for 30 days, respectively. Extract treated groups received low and high doses of RBFCE (500 mg/kg, p.o and 1000 mg/kg, p.o respectively) in 0.5% vehicle for 30 days. At a higher dose, animals showed significantly reduced Rif/INH induced toxicity in liver and kidney tissues as indicated by the normalized serum biochemical markers and histopathological investigations. The present exploration reveals the presence of strong antioxidant phytochemical constituents, antioxidative stress and protective potential of RBFCE against Rif/INH induced hepatic and renal damage.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Frutas/química , Isoniazida/efeitos adversos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Rifampina/efeitos adversos , Rosa/química , Alanina Transaminase/metabolismo , Animais , Antioxidantes/metabolismo , Antituberculosos/efeitos adversos , Aspartato Aminotransferases/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Feminino , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Silimarina/efeitos adversos
14.
Pak J Pharm Sci ; 33(2): 589-595, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32276902

RESUMO

This work presents a pilot method of hematological diagnosis about changes in: shape, size and rouleaux formation, cell count of leucocytes and platelet cells in the presence of different glucose [C6H12O6] and water [H2O] concentrations. The 2D microscopic images after addition of ten different glucose concentrations to normal blood (0 mM- 450 mM) revealed the lyses (disintegration) of white blood cells (WBCs). This work provides a baseline to diagnose blood disorders and complications at labs and clinical environment.


Assuntos
Plaquetas/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Solução Hipertônica de Glucose/toxicidade , Leucócitos/efeitos dos fármacos , Água/efeitos adversos , Plaquetas/metabolismo , Plaquetas/patologia , Forma Celular/fisiologia , Destilação , Relação Dose-Resposta a Droga , Solução Hipertônica de Glucose/administração & dosagem , Humanos , Hiperglicemia/sangue , Hiperglicemia/induzido quimicamente , Leucócitos/metabolismo , Leucócitos/patologia , Masculino , Água/administração & dosagem
15.
J Biol Chem ; 293(2): 484-496, 2018 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-29162720

RESUMO

As a sensitive signaling system, the mitotic checkpoint ensures faithful chromosome segregation by delaying anaphase onset even when a single kinetochore is unattached to mitotic spindle microtubules. The key signal amplification reaction for the checkpoint is the conformational conversion of "open" mitotic arrest deficient 2 (O-MAD2) into "closed" MAD2 (C-MAD2). The reaction has been suggested to be catalyzed by an unusual catalyst, a MAD1:C-MAD2 tetramer, but how the catalysis is executed and regulated remains elusive. Here, we report that in addition to the well-characterized middle region of MAD1 containing the MAD2-interaction motif (MIM), both N- and C-terminal domains (NTD and CTD) of MAD1 also contribute to mitotic checkpoint signaling. Unlike the MIM, which stably associated only with C-MAD2, the NTD and CTD in MAD1 surprisingly bound both O- and C-MAD2, suggesting that these two domains interact with both substrates and products of the O-to-C conversion. MAD1NTD and MAD1CTD also interacted with each other and with the MPS1 protein kinase, which phosphorylated both NTD and CTD. This phosphorylation decreased the NTD:CTD interaction and also CTD's interaction with MPS1. Of note, mutating the phosphorylation sites in the MAD1CTD, including Thr-716, compromised MAD2 binding and the checkpoint responses. We further noted that Ser-610 and Tyr-634 also contribute to the mitotic checkpoint signaling. Our results have uncovered that the MAD1NTD and MAD1CTD directly interact with each other and with MAD2 conformers and are regulated by MPS1 kinase, providing critical insights into mitotic checkpoint signaling.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas Mad2/metabolismo , Mitose/fisiologia , Proteínas Nucleares/metabolismo , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Humanos , Immunoblotting , Cinetocoros/metabolismo , Cinetocoros/fisiologia , Proteínas Mad2/genética , Mitose/genética , Proteínas Nucleares/genética , Fosforilação , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Fuso Acromático/metabolismo , Fuso Acromático/fisiologia
16.
Toxicol Ind Health ; 35(7): 466-481, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31364507

RESUMO

The present study was conducted to investigate the antioxidant, histomorphometric, histochemical, immunohistochemical, biochemical, and cytological effects of coenzyme Q10 (CoQ10) against bisphenol-A (BPA)-induced testicular toxicity in rats. A total of 40 adult male Wistar rats were divided into five equal groups. The control group remained untreated. The vehicle control group was administered corn oil (2 ml/kg/day), the BPA group was given BPA (100 mg/kg/day), the CoQ10 group was supplemented with CoQ10 (10 mg/kg/day), and the rats in the CoQ10-BPA group received CoQ10 (10 mg/kg/day) followed by BPA (100 mg/kg/day) 1 h later. The treatments were administered by oral gavage for 14 days. Results showed that the seminiferous tubule diameters (STDs) and seminiferous epithelium heights (SEHs) at stages VII-VIII and XII-XIV, number of undifferentiated embryonic cell transcription factor-1 (UTF-1) positive cells per tubule, UTF-1 positive tubules (%), plasma glutathione (GSH), and serum superoxide dismutase activities, testicular GSH activity and sperm viability (%) decreased whereas the number of terminal dUTP nick end labeling (TUNEL) positive cells per tubule, TUNEL positive tubules (%), testicular and serum malondialdehyde (MDA) levels, and the rate of mid-piece sperm abnormality increased in the BPA administered group. However, while the STDs at stages VII-VIII and XII-XIV, SEHs at stages VII-VIII, plasma GSH, and serum SOD activities increased, serum MDA level decreased in the CoQ10-BPA group. In conclusion, these results suggest a protective effect of CoQ10 against BPA-induced testicular toxicity in rats.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Fenóis/efeitos adversos , Testículo/efeitos dos fármacos , Testículo/patologia , Ubiquinona/análogos & derivados , Animais , Glutationa/metabolismo , Masculino , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fatores de Transcrição/biossíntese , Ubiquinona/administração & dosagem , Ubiquinona/farmacologia
17.
Cryobiology ; 75: 15-20, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28279680

RESUMO

This study was performed to evaluate the effectiveness of quercetin as a non-enzymatic antioxidant in combination with glycerol or Dimethylacetamide (DMA), on freezability of goat semen. Ejaculates from four healthy mature Mahabadi goats were collected using an artificial vagina. After primary processing, semen was pooled and extended by egg yolk based extender supplemented with different concentrations of quercetin (10 or 20 µM) along with 5% glycerol or DMA. The extended semen was frozen and sperm motility parameters, viability, abnormality, membrane integrity and lipid peroxidation were assessed after thawing. Results showed that sperm viability, total motility, progressive motility, straightness (STR) and linearity (LIN) were higher (P < 0.05), and abnormality percentage and MDA concentration were lower (P < 0.05) in extender containing DMA. Similarly, higher (P < 0.05) total motility, progressive motility, viability and membrane integrity along with lower (P < 0.05) MDA level were noted in Q10 group. The lowest (P < 0.05) MDA level was observed in DMA extender containing moderate level of quercetin (Q10D). Also the STR was higher (P < 0.05) in Q10D compared to Q10G and Q20G groups. In conclusion, supplementation of extender with 10 µM quercetin in combination with DMA improves the goat sperm motion kinetics and suppresses lipid peroxidation after freezing and thawing. Furthermore, DMA is more effective cryoprotectant for the freezing of goat sperm.


Assuntos
Antioxidantes/farmacologia , Criopreservação/métodos , Quercetina/farmacologia , Preservação do Sêmen/métodos , Sêmen , Acetamidas/farmacologia , Animais , Criopreservação/veterinária , Crioprotetores/farmacologia , Gema de Ovo , Congelamento , Glicerol/farmacologia , Cabras , Masculino , Preservação do Sêmen/veterinária , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos
18.
Ecotoxicol Environ Saf ; 135: 284-291, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27750096

RESUMO

Environmental contamination has been one of the major drawbacks of the industrial revolution. Several man-made chemicals are constantly released into the environment during the manufacturing process and by leaching from the industrial products. As a result, human and animal populations are exposed to these synthetic chemicals on a regular basis. Many of these chemicals have adverse effects on the physiological functions, particularly on the hormone systems in human and animals and are called endocrine disrupting chemicals (EDCs). Bisphenol A (BPA), 4-tert-octylphenol (OP), and 4-nonylphenol (NP) are three high volume production EDCs that are widely used for industrial purposes and are present ubiquitously in the environment. Bisphenol A is metabolized in the human body to a more potent compound (MBP: 4-Methyl-2, 4-bis (4-hydroxyphenyl) pent-1-ene). Epidemiological and experimental studies have shown the three EDCs to be associated with adverse effects on reproductive system in human and animals. Sex hormone-binding globulin (SHBG) is a circulatory protein that binds sex steroids and is a potential target for endocrine disruptors in the human body. The current study was done in order to understand the binding mechanism of OP, BPA, NP, and MBP with human SHBG using in silico approaches. All four compounds showed high binding affinity with SHBG, however, the binding affinity values were higher (more negative) for MBP and NP than for OP and BPA. The four ligands interacted with 19-23 residues of SHBG and a consistent overlapping of the interacting residues for the four ligands with the residues for the natural ligand, dihydrotestosterone (DHT; 82-91% commonality) was shown. The overlapping SHBG interacting residues among DHT and the four endocrine disruptors suggested that these compounds have potential for interference and disruption in the steroid binding function.


Assuntos
Compostos Benzidrílicos/farmacologia , Disruptores Endócrinos/farmacologia , Poluentes Ambientais/farmacologia , Simulação de Acoplamento Molecular , Fenóis/farmacologia , Globulina de Ligação a Hormônio Sexual/efeitos dos fármacos , Sítios de Ligação/efeitos dos fármacos , Di-Hidrotestosterona/metabolismo , Estrogênios/farmacologia , Humanos , Ligantes , Globulina de Ligação a Hormônio Sexual/metabolismo
19.
J Pak Med Assoc ; 67(8): 1157-1160, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28839297

RESUMO

OBJECTIVE: To determine the impact of using colistin for multidrug-resistant organisms in neonates. METHODS: This retrospective study was conducted at the Shifa International Hospital, Islamabad, Pakistan, and comprised microbiological data of babies from January 2010 to October 2012.The data was reviewed to identify the babies infected with multidrug-resistant organisms and who had received colistin therapy. SPSS 16 was used for data analysis. RESULTS: Of the 30 neonates, 24(80%) were males and 6(20%) were females. Besides, 16(53.3%) neonates were preterm babies (< 37 weeks gestation). Two or more risk factors for multidrug-resistant organisms were present in 13(44%) babies. Mechanical ventilation was found in 26(87%) neonates and prior prolonged use of antibiotics in 7(23%). The commonest pathogen isolated was Acinetobacter, in 22(73%) cases. All isolates were susceptible to colistin but pan-resistant to multiple antibiotics, including cephalosporins, amikacin, meropenem and piperacillin/tazobactam. Colistin therapy was used for bacteraemia in 2(7%) cases, clinical sepsis 18(60%), pneumonia 2(7%) and tracheitis 8(26.7%). Moreover, 15(50%) neonates received both intravenous and aerosolised colistin while 9(30%) received aerosolised therapy alone. CONCLUSIONS: Colistin therapy was well tolerated in neonates for the treatment of multidrug-resistant organisms.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Colistina/uso terapêutico , Sepse Neonatal/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Traqueíte/tratamento farmacológico , Infecções por Acinetobacter/complicações , Administração por Inalação , Administração Intravenosa , Asfixia Neonatal/complicações , Bacteriemia/complicações , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Pneumonia Bacteriana/complicações , Respiração Artificial , Síndrome do Desconforto Respiratório do Recém-Nascido/complicações , Estudos Retrospectivos , Traqueíte/complicações
20.
BMC Genomics ; 17(Suppl 9): 759, 2016 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-27766960

RESUMO

BACKGROUND: Preterm birth (PTB), birth at <37 weeks of gestation, is a significant global public health problem. World-wide, about 15 million babies are born preterm each year resulting in more than a million deaths of children. Preterm neonates are more prone to problems and need intensive care hospitalization. Health issues may persist through early adulthood and even be carried on to the next generation. Majority (70 %) of PTBs are spontaneous with about a half without any apparent cause and the other half associated with a number of risk factors. Genetic factors are one of the significant risks for PTB. The focus of this review is on single nucleotide gene polymorphisms (SNPs) that are reported to be associated with PTB. RESULTS: A comprehensive evaluation of studies on SNPs known to confer potential risk of PTB was done by performing a targeted PubMed search for the years 2007-2015 and systematically reviewing all relevant studies. Evaluation of 92 studies identified 119 candidate genes with SNPs that had potential association with PTB. The genes were associated with functions of a wide spectrum of tissue and cell types such as endocrine, tissue remodeling, vascular, metabolic, and immune and inflammatory systems. CONCLUSIONS: A number of potential functional candidate gene variants have been reported that predispose women for PTB. Understanding the complex genomic landscape of PTB needs high-throughput genome sequencing methods such as whole-exome sequencing and whole-genome sequencing approaches that will significantly enhance the understanding of PTB. Identification of high risk women, avoidance of possible risk factors, and provision of personalized health care are important to manage PTB.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/genética , Adulto , Suscetibilidade a Doenças , Feminino , Saúde Global , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Morbidade , Gravidez , Fatores de Risco
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