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1.
Reprod Domest Anim ; 59(3): e14551, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38462999

RESUMO

Cryopreservation is one of the reliable techniques for long-term storage of sperm. The success of this technique depends on the choice of cryoprotectant; therefore, a plethora of literature has reported the effects of different cryoprotective agents so far. Kappa-carrageenan (κ-carrageenan) is a hydrocolloid polysaccharide extracted from red marine seaweed. Its unique property makes it a promising option as a non-colligative cryoprotectant. The current study aims to evaluate the cryoprotective effect of k-carrageenan along with glycerol on ram sperm quality both after equilibration and freezing. Nine Kajli rams were utilized in this experiment for semen collection through an artificial vagina maintained at 42°C. Qualified samples were diluted in tris egg yolk glycerol (TEYG) extender containing different concentrations of k-carrageenan as 0 mg/mL (control), 0.2, 0.5, 0.8 and 1 mg/mL. Post-thaw assessment was done at 37°C after 24 h of storage, which showed a significant improvement (p < .05) in sperm viability, motility, membrane and acrosome integrity in an extender containing k-carrageenan at a concentration of 0.5 mg/mL compared to control. It is concluded from the current study that the combination of glycerol and 0.5 mg/mL concentration of k-carrageenan improved the sperm post-thaw quality.


Assuntos
Preservação do Sêmen , Sêmen , Masculino , Ovinos , Animais , Carragenina/farmacologia , Glicerol/farmacologia , Motilidade dos Espermatozoides , Espermatozoides , Crioprotetores/farmacologia , Criopreservação/veterinária , Criopreservação/métodos , Carneiro Doméstico , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Suplementos Nutricionais
2.
Environ Monit Assess ; 196(5): 412, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565815

RESUMO

Cadmium (Cd) is a highly toxic metal that frequently contaminates our environment. In this study, the bioflocculant-producing, cadmium-resistant Escherichia fergusonii ZSF-15 was characterized from Paharang drain, Bawa Chak, Faisalabad, Pakistan. The Cd-resistant E. fergusonii was used to determine the bioflocculant production using yeast-peptone-glycerol medium (pH 6.5) supplemented with 50 mg L-1 of Cd. The culture was incubated for 3 days at 37 °C in a rotary shaker at 120 rpm. The fermentation broth was centrifuged at 4000 g for 10 min after the incubation period. The maximum flocculating activity by isolate ZSF-15 was found to be 71.4% after 48 h of incubation. According to the Fourier transform infrared spectroscopy analysis, the bioflocculant produced by strain ZSF-15 was comprised of typical polysaccharide and protein, i.e. hydroxyl, carboxyl, and amino groups. The strain ZSF-15 exhibited bioflocculant activity at range of pH (6-8) and temperature (35-50℃). Maximum flocculation activity (i.e. 71%) was observed at 47℃, whereas 63% flocculation production was observed at pH 8. In the present study, antioxidant enzyme profile of ZSF-15 was also evaluated under cadmium stress. A significant increase in antioxidant enzymes including superoxide dismutase (118%) and ascorbate peroxidase (28%) was observed, whereas contents of catalase (86%), glutathione transferase (13%), and peroxidase (8%) were decreased as compared to control.


Assuntos
Antioxidantes , Cádmio , Escherichia , Cádmio/toxicidade , Concentração de Íons de Hidrogênio , Monitoramento Ambiental , Floculação
3.
Int J Toxicol ; 42(1): 37-49, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36472205

RESUMO

Vaccines containing mRNA with the capacity to self-amplify represent an alternative to the mRNA vaccines that came to prominence during the COVID-19 pandemic. To gain further insights on the safety profile of self-amplifying mRNA- (SAM-) vaccines, this preclinical toxicology study in rats evaluated the effect of (i) the type of delivery system (lipid nanoparticle [LNP] vs cationic nano-emulsion [CNE]); (ii) antigen-encoding sequence (rabies glycoprotein G vs SARS-CoV-2 Spike); and (iii) RNA amplification. Further analyses also evaluated gene expression in peripheral blood after vaccination, and the biodistribution of vaccine RNA. The SAM vaccines administered as two doses 2-weeks apart had acceptable safety profiles in rats, with respect to clinical signs, blood biochemistry, and macroscopic and microscopic pathology. A transient increase in ALT/AST ratio occurred only in female rats and in the absence of muscle and liver damage was dependent on RNA amplification and appeared related to the greater quantities of vaccine RNA in the muscle and livers of female rats vs male rats. The RNA and delivery-vehicle components, but not the nature of the antigen-coding sequence or the requirement for RNA amplification, affected aspects of the stimulation of innate-immune activity, which was consistent with the transient activation of type I and type II interferon signaling. The delivery vehicle, LNP, differed from CNE as vaccine RNA in CNE compositions appeared independently to stimulate innate-immune activity at 4 hours after vaccination. Our analysis supports further studies to assess whether these differences in innate-immune activity affect safety and efficacy of the SAM vaccine.


Assuntos
COVID-19 , Vacinas , Ratos , Masculino , Feminino , Humanos , Animais , Pandemias , Distribuição Tecidual , COVID-19/prevenção & controle , SARS-CoV-2/genética , RNA Mensageiro , Vacinas Sintéticas
4.
Molecules ; 28(8)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37110702

RESUMO

As is well known, plant products have been increasingly utilized in the pharmaceutical industry in recent years. By combining conventional techniques and modern methodology, the future of phytomedicines appears promising. Pogostemon Cablin (patchouli) is an important herb used frequently in the fragrance industries and has various therapeutic benefits. Traditional medicine has long used the essential oil of patchouli (P. cablin) as a flavoring agent recognized by the FDA. This is a gold mine for battling pathogens in China and India. In recent years, this plant has seen a significant surge in use, and approximately 90% of the world's patchouli oil is produced by Indonesia. In traditional therapies, it is used for the treatment of colds, fever, vomiting, headaches, and stomachaches. Patchouli oil is used in curing many diseases and in aromatherapy to treat depression and stress, soothe nerves, regulate appetite, and enhance sexual attraction. More than 140 substances, including alcohols, terpenoids, flavonoids, organic acids, phytosterols, lignins, aldehydes, alkaloids, and glycosides, have been identified in P. cablin. Pachypodol (C18H16O7) is an important bioactive compound found in P. cablin. Pachypodol (C18H16O7) and many other biologically essential chemicals have been separated from the leaves of P. cablin and many other medicinally significant plants using repeated column chromatography on silica gel. Pachypodol's bioactive potential has been shown by a variety of assays and methodologies. It has been found to have a number of biological activities, including anti-inflammatory, antioxidant, anti-mutagenic, antimicrobial, antidepressant, anticancer, antiemetic, antiviral, and cytotoxic ones. The current study, which is based on the currently available scientific literature, intends to close the knowledge gap regarding the pharmacological effects of patchouli essential oil and pachypodol, a key bioactive molecule found in this plant.


Assuntos
Óleos Voláteis , Plantas Medicinais , Pogostemon , Quercetina , Óleos Voláteis/farmacologia , Óleos Voláteis/química
5.
HIV Med ; 23(4): 371-377, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35178848

RESUMO

OBJECTIVES: Menopause contributes to weight gain in women. We explored factors associated with obesity in women with HIV aged 45-60 years. METHODS: The present study is an analysis of cross-sectional questionnaire and clinic data from the Positive Transitions Through the Menopause (PRIME) Study. We categorized body mass index (BMI) as normal/underweight (< 25 kg/m2 ), overweight (25-29.9 kg/m2 ) and obese (> 30 kg/m2 ). We used logistic regression to explore demographic, social, lifestyle and clinical factors associated with BMI. RESULTS: We included 396 women in this analysis. Median age was 49 years [interquartile range (IQR): 47-52]. Most (83.6%) were not UK-born; the majority (69.4%) were black African (BA). Median (IQR) BMI was 28.6 (24.6-32.6) kg/m2 ; and 110 (27.8%), 127 (32.1%) and 159 (40.1%) of the women were normal/underweight, overweight and obese, respectively. Median (IQR) BMI did not differ in pre-, peri- and post-menopausal women (p = 0.90). In univariable analysis, being non-UK-born was associated with BMI > 30 kg/m2 [odds ratio (OR) = 1.94, 95% confidence interval (CI): 1.07-3.53]. Compared with BA women, women of other black ethnicities were more likely to be obese (OR = 2.37, 95% CI: 1.02-5.50) whereas white British women were less likely to be obese (OR = 0.34, 95% CI: 0.17-0.68). Current smoking and increasing number of comorbid conditions were associated with increased BMI. We found no association between obesity and socioeconomic status. On multivariable analysis, only ethnicity remained associated with obesity (compared with BA: white British, OR = 0.34, 95% CI: 0.17-0.68; other black, OR = 2.50, 95% CI: 1.07-5.82). CONCLUSIONS: Nearly two-fifths of women had BMI > 30 kg/m2 . Obesity was associated with black ethnicities but not with menopausal status. The combination of obesity and HIV may place women at increased risk of co-morbidities, requiring tailored and culturally appropriate interventions.


Assuntos
Infecções por HIV , Índice de Massa Corporal , Estudos Transversais , Inglaterra/epidemiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Fatores de Risco
6.
Transfus Apher Sci ; 61(6): 103495, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35780074

RESUMO

Using 753 collections from 426 adult haematology patients, we conducted a retrospective, analysis into the effects of overnight storage and nucleated cell counts (NCC) on viable, CD34+ (vCD34+) recovery and engraftment kinetics post autologous stem cell, transplant (ASCT) with peripheral blood stem cells (PBSC). There were significant, differences in vCD34 + recovery ( P < 0.01) after cryopreservation associated with, the fresh NCC of ≥ 300 × 10 6 /mL in products stored overnight, but no association, with time to platelet or neutrophil engraftment post-ASCT was observed for these, products. There was no association of vCD34+ numbers or engraftment kinetics with cryopreserved NCC with either below or greater than the local recommended concentration of 400 × 106 /mL of product. However, there was significant difference in engraftment kinetics in relation to the viable CD34+ dose given at ASCT, in relation to the time to early engraftment and the amount of platelet support given during the engraftment period post-ASCT. We conclude the vCD34+ dose at ASCT is of great importance to early engraftment kinetics and that NCC is an important factor during overnight storage, but not for cryopreservation of PBSC. In light of our findings, we recommend that apheresis products collected in a closed system can safely be stored undiluted overnight.


Assuntos
Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Estudos Retrospectivos , Transplante Autólogo , Antígenos CD34 , Criopreservação , Contagem de Células
7.
Drug Dev Ind Pharm ; 48(9): 502-509, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36191015

RESUMO

The worldwide increase of multi-drug resistance has directed the researchers to focus on ecofriendly ways of nanoparticles synthesis with effective antivirulence properties. Here, we report the antibiofilm and quorum quenching (QQ) potential of zirconium oxide nanoparticles (ZrO2 NPs) synthesized from aqueous ginger extract against multi-drug resistant (MDR) Acinetobacter baumannii. The results indicated that ZrO2 NPs were of tetragonal shape with average diameter of 16 nm. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values for A. baumannii were 15.6 and 62.5 µg/ml, respectively, as revealed by broth microdilution assay. Exposure of bacterial cells to ZrO2 NPs resulted in reactive oxygen species (ROS) generation which in turn led to cellular membrane disruption as observed by an increase in leakage of cellular contents, such as proteins, sugars, and DNA. The antibiofilm activity was evaluated by microtiter plate assay and the results revealed that the percentage inhibition of biofilm was found to be 14.3-80.6%. ZrO2 NPs also obstructed the chemical composition of biofilms matrix by reducing the proteins and carbohydrate contents. Molecular docking studies of ZrO2 NPs with four proteins (2NAZ, 4HKG, 5D6H, and 5HM6) involved in biofilm formation of A. baumannii revealed the interaction of zirconium with target proteins. These findings suggested the in vitro efficacy of phytosynthesized ZrO2 NPs as antibiofilm and QQ agents that can be exploited in the development of alternative therapeutic options against MDR A. baumannii.


Assuntos
Acinetobacter baumannii , Nanopartículas Metálicas , Nanopartículas , Percepção de Quorum , Zircônio/farmacologia , Simulação de Acoplamento Molecular , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana , Biofilmes , Nanopartículas Metálicas/química
8.
Saudi Pharm J ; 30(5): 519-526, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35693443

RESUMO

Cisplatin (CP) is one of the most widely used antineoplastic drugs, which possesses the potential to treat a variety of malignancies. However, it displays numerous side effects as well. Male reproductive dysfunction is one of the most adverse side effects of CP. Vitexin is a naturally occurring flavonoid, which exhibits remarkable antioxidant properties. Present study was designed to evaluate the protective effects of vitexin on CP-induced damages on testes. 48 Sprague-Dawley rats were equally distributed into 4 groups: control, cisplatin (CP), cisplatin + vitexin (CP + VIT) and vitexin (VIT). After 14 days of treatment, evaluation of biochemical, spermatogenic, steroidogenical, hormonal, apoptotic and histopathological parameters was carried out. CP damaged the biochemical profile by reducing activity of CAT, SOD, GPx and GSR, while level of MDA and ROS was increased. It also decreased sperm motility, viability, number of hypo-osmotic tail swelled spermatozoa and epididymal sperm count, besides increasing the sperm morphological anomalies. Moreover, levels of LH, FSH and plasma testosterone were reduced. CP reduced the gene expression of testicular anti-apoptotic marker (Bcl-2) and steroidogenic enzymes (3ß-HSD, 17ß-HSD and StAR), but upregulated the gene expressions of apoptotic markers (Bax and Caspase-3). Besides, CP led to histopathological damages in testicular tissues. However, vitexin reversed all aforementioned damages in testes. Therefore, it is concluded that vitexin could play an effective role as a therapeutic agent against CP-prompted testicular toxicity due to its antioxidant, anti-apoptotic and androgenic potential.

9.
IUBMB Life ; 71(10): 1418-1427, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31169978

RESUMO

Altered enzymatic machineries are a substantial biochemical characteristic of tumor cell metabolism that switch metabolic profile from oxidative phosphorylation to amplified glycolysis as well as increased lactate production under hypoxia conditions. Reprogrammed metabolic profile is an emerging hallmark of cancer. Overexpression of several glycolytic enzymes and glucose transporters has been reported in 24 different types of cancers that represent approximately 70% of all the cancer cases around the globe. Thus, targeting glycolytic enzymes could serve as tempting avenue for drug design against cancer. Phosphoglycerate mutase 1 (PGAM1) is an important glycolytic enzyme that catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate. Recent investigations have revealed the overexpression of PGAM1 in several human cancers that is linked with tumor growth, survival, and invasion. The aim of this review is to update scientific research network with cancer-specific role of PGAM1 to elucidate its capability as bonafide therapeutic target for cancer therapy. Moreover, we have also summarized the reported genetic and pharmacological inhibitors of PGAM1. This study suggests that further investigations on PGAM1 should focus on the exploration of molecular mechanisms of PGAM1 overexpression in development of cancer, assessment of biosafety profiles of known inhibitors of PGAM1, and utilization of PGAM1 inhibitors in combinatorial therapies. These future studies will surely support the unbiased strategies for the development of novel PGAM1 inhibitors for cancer therapies.


Assuntos
Terapia de Alvo Molecular , Neoplasias/genética , Neoplasias/terapia , Fosfoglicerato Mutase/genética , Proliferação de Células/genética , Ácidos Glicéricos/metabolismo , Glicólise/genética , Humanos , Neoplasias/diagnóstico
10.
Cochrane Database Syst Rev ; 5: CD012342, 2018 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-29758592

RESUMO

BACKGROUND: Bone marrow disorders encompass a group of diseases characterised by reduced production of red cells, white cells, and platelets, or defects in their function, or both. The most common bone marrow disorder is myelodysplastic syndrome. Thrombocytopenia, a low platelet count, commonly occurs in people with bone marrow failure. Platetet transfusions are routinely used in people with thrombocytopenia secondary to bone marrow failure disorders to treat or prevent bleeding. Myelodysplastic syndrome is currently the most common reason for receiving a platelet transfusion in some Western countries. OBJECTIVES: To determine whether a therapeutic-only platelet transfusion policy (transfusion given when patient is bleeding) is as effective and safe as a prophylactic platelet transfusion policy (transfusion given to prevent bleeding according to a prespecified platelet threshold) in people with congenital or acquired bone marrow failure disorders. SEARCH METHODS: We searched for randomised controlled trials (RCTs), non-RCTs, and controlled before-after studies (CBAs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2017, Issue 9), Ovid MEDLINE (from 1946), Ovid Embase (from 1974), PubMed (e-publications only), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 12 October 2017. SELECTION CRITERIA: We included RCTs, non-RCTs, and CBAs that involved the transfusion of platelet concentrates (prepared either from individual units of whole blood or by apheresis any dose, frequency, or transfusion trigger) and given to treat or prevent bleeding among people with congenital or acquired bone marrow failure disorders.We excluded uncontrolled studies, cross-sectional studies, and case-control studies. We excluded cluster-RCTs, non-randomised cluster trials, and CBAs with fewer than two intervention sites and two control sites due to the risk of confounding. We included all people with long-term bone marrow failure disorders that require platelet transfusions, including neonates. We excluded studies of alternatives to platelet transfusion, or studies of people receiving intensive chemotherapy or a stem cell transplant. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures outlined by Cochrane. Due to the absence of evidence we were unable to report on any of the review outcomes. MAIN RESULTS: We identified one RCT that met the inclusion criteria for this review. The study enrolled only nine adults with MDS over a three-year study duration period. The trial was terminated due to poor recruitment rate (planned recruitment 60 participants over two years). Assessment of the risk of bias was not possible for all domains. The trial was a single-centre, single-blind trial. The clinical and demographic characteristics of the participants were never disclosed. The trial outcomes relevant to this review were bleeding assessments, mortality, quality of life, and length of hospital stay, but no data were available to report on any of these outcomes.We identified no completed non-RCTs or CBAs.We identified no ongoing RCTs, non-RCTs, or CBAs. AUTHORS' CONCLUSIONS: We found no evidence to determine the safety and efficacy of therapeutic platelet transfusion compared with prophylactic platelet transfusion for people with long-term bone marrow failure disorders. This review underscores the urgency of prioritising research in this area. People with bone marrow failure depend on long-term platelet transfusion support, but the only trial that assessed a therapeutic strategy was halted. There is a need for good-quality studies comparing a therapeutic platelet transfusion strategy with a prophylactic platelet transfusion strategy; such trials should include outcomes that are important to patients, such as quality of life, length of hospital admission, and risk of bleeding.


Assuntos
Síndromes Mielodisplásicas/terapia , Transfusão de Plaquetas/métodos , Adulto , Humanos , Síndromes Mielodisplásicas/congênito
11.
Drug Chem Toxicol ; 41(2): 213-220, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28721745

RESUMO

To control agricultural pests and meet the increasing food demands, pesticides use has been increased substantially over time. Although pesticides are relatively specific to their targets, they can affect non-target organisms and are hazardous for the population around the application areas particularly to the individuals engaged in different types of agricultural activities. This situation is worse in developing and under-developed countries where personal protective equipment is merely used and regulatory guidelines are hardly practiced. In the present study, DNA damage in women exposed to pesticides while picking cotton with bare hands was assessed using single cell gel electrophoresis assay or comet assay. The presence of pesticides in blood serum of exposed individuals was also analyzed using high-performance liquid chromatography. Blood samples were collected from 138 (69 exposed and 69 control) randomly selected females from a major cotton growing area (Bahawalpur District) of the Punjab province of Pakistan. DNA damage, as determined by the mean comet tail length, was significantly higher (p < 0.001) in the exposed group compared to the unexposed. A positive correlation of DNA damage with age and exposure time was also observed. Residues of three pesticides, cyhalothrin, endosulfan, and deltamethrin found significantly higher (p < 0.001) in the serum samples of the exposed group compared to the unexposed. It was observed that the groups with higher mean comet tail length also had a higher concentration of pesticides in their serum samples indicating a positive association of DNA damage and pesticide exposure. The present study suggests that exposure to pesticides leads to DNA damage.


Assuntos
Produtos Agrícolas , Dano ao DNA , Fazendeiros , Gossypium , Mutagênicos/efeitos adversos , Exposição Ocupacional/efeitos adversos , Resíduos de Praguicidas/efeitos adversos , Sementes , Adulto , Idoso , Estudos de Casos e Controles , Ensaio Cometa , Endossulfano/efeitos adversos , Endossulfano/sangue , Monitoramento Ambiental/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Nitrilas/sangue , Paquistão , Resíduos de Praguicidas/sangue , Piretrinas/efeitos adversos , Piretrinas/sangue , Medição de Risco , Fatores Sexuais , Adulto Jovem
12.
Pak J Pharm Sci ; 31(6 (Supplementary): 2645-2654, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30587474

RESUMO

Microwave and conventional techniques were employed to synthesize a novel array of compounds 7a-g with 1,2,4-triazole and piperidine rings having great biological importance. The microwave assisted method has a better operational scope with respect to time and yield comparative to the conventional method. 1H-NMR, 13C-NMR and IR techniques were employed to justify the structure of synthesized compounds. The antioxidant, butyrylcholinesterase inhibition and urease inhibition potential of every synthesized compound was evaluated. Every member of the synthesized series was found potent against mentioned activities. Compound 7g was the most active anti-urease agent having IC50 (µM) value 16.5±0.09 even better than the thiourea with an IC50(µM) value of 24.3±0.24. The better urease inhibition potential of 7g was also elaborated and explained by docking and bovine serum albumin (BSA) binding studies.


Assuntos
Simulação por Computador , Micro-Ondas , Simulação de Acoplamento Molecular/métodos , Soroalbumina Bovina/metabolismo , Triazóis/metabolismo , Animais , Bovinos , Ligação Proteica/fisiologia , Estrutura Terciária de Proteína , Soroalbumina Bovina/síntese química , Relação Estrutura-Atividade , Triazóis/síntese química
13.
Pak J Pharm Sci ; 31(2(Suppl.)): 611-616, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29625932

RESUMO

Drug-drug interactions are most commonly occurring phenomenon in clinical practice. Many physicians are afraid of being involved in an allegation of malpractices due to the occurrence of any severe interaction. These interactions not only occur between drugs but also between any kind of food, tobacco smoke, caffeine and alcohol etc. Therefore, the present study was directed to inspect the effect of caffeine on the anticoagulation activity of warfarin in healthy adult male albino rabbits. Blank blood samples were collected from each rabbit. Rabbits were given warfarin (0.5mg kg-1) orally via stomach tube and blood samples were collected in PT/INR vials at various intervals. After a washout period of 14 days, warfarin was orally administrated at same dose rate along with caffeine (5 mg kg-1 every twelve hours for three days) and same sampling schedule was repeated. Prothrombin time (PT) and the international normalized ratio (INR) of blood samples were determined to estimate changes in the anticoagulation activity of warfarin after its concurrent administration with caffeine. The PT data revealed that Rmax and AUC increased significantly (P<0.05) from 1991.6 and 60.5 to 2124.8 and 67.5, respectively, before and after co-administration. Similarly, a significant (P<0.05) increase was observed in Rmax and AUC of INR from 6.42 and 153.7 to 7.4 and 167.5, respectively, alone and along with caffeine. However, no change was observed in Tmax associated with PT and INR either the drug was administered alone or in combination with caffeine. It was concluded that caffeine has the capacity to inhibit the metabolism of warfarin and enhance its plasma concentration and hence anticoagulant effects. Thus, patients should be advised to limit the frequent use of caffeine-rich products i.e. tea and coffee during warfarin therapy.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Cafeína/farmacologia , Sinergismo Farmacológico , Varfarina/farmacologia , Animais , Anticoagulantes/farmacologia , Coeficiente Internacional Normatizado , Masculino , Tempo de Protrombina , Coelhos
14.
J Gen Virol ; 98(8): 2143-2155, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28758637

RESUMO

The partial success of the RV144 trial underscores the importance of envelope-specific antibody responses for an effective HIV-1 vaccine. Oligomeric HIV-1 envelope proteins delivered with a potent adjuvant are expected to elicit strong antibody responses with broad neutralization specificity. To test this hypothesis, two SIV envelope proteins were formulated with delta inulin-based adjuvant (Advax) and used to immunize nonhuman primates. Oligomeric gp140-gp145 from SIVmac251 and SIVsmE660 was purified to homogeneity. Oligomers showed high-affinity interaction with CD4 and were highly immunogenic in rabbits, inducing Tier 2 SIV-neutralizing antibodies. The immunogenicity of an oligomeric Env DNA prime and protein boost together with Advax was evaluated in Chinese rhesus macaques. DNA administration elicited antibodies to both envelopes, and titres were markedly enhanced following homologous protein boosts via intranasal and intramuscular routes. Strong antibody responses were detected against the V1 and V2 domains of gp120. During peak immune responses, a low to moderate level of neutralizing activity was detected against Tier 1A/1B SIV isolates, with a moderate level noted against a Tier 2 isolate. Increased serum antibody affinity to SIVmac251 gp140 and generation of Env-specific memory B cells were observed in the immunized macaques. Animals were subjected to low-dose intravaginal challenge with SIVmac251 one week after the last protein boost. One out of three immunized animals was protected from infection. Although performed with a small number of macaques, this study demonstrates the utility of oligomeric envelopes formulated with Advax in eliciting broad antibody responses with the potential to provide protection against SIV transmission.


Assuntos
Anticorpos Antivirais/imunologia , DNA Viral/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , Vacinas contra a SAIDS/imunologia , Vírus da Imunodeficiência Símia/imunologia , Vacinas contra a AIDS , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Neutralizantes/imunologia , DNA Viral/administração & dosagem , DNA Viral/genética , Anticorpos Anti-HIV/imunologia , Proteína gp120 do Envelope de HIV/administração & dosagem , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , HIV-1/genética , HIV-1/imunologia , Humanos , Imunidade Humoral , Imunização Secundária , Inulina/administração & dosagem , Macaca mulatta , Coelhos , Vacinas contra a SAIDS/administração & dosagem , Vacinas contra a SAIDS/genética , Vírus da Imunodeficiência Símia/genética , Vacinação
15.
Intern Med J ; 47(1): 104-109, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27800661

RESUMO

BACKGROUND: Anthracyclines are commonly used chemotherapeutic medications. AIM: In the current analysis, we evaluated all-cause mortality and incidence, timing and response to medical therapy of anthracycline cardiotoxicity. METHODS: Left ventricular ejection fraction (LVEF) was serially assessed using gated heart pool scan/echocardiography in patients receiving anthracycline-based chemotherapy from January 2009 to December 2014. RESULTS: A total of 1204 patients was administered anthracyclines during the study period. During a median follow up of 32 (interquartile range: 15-58) months, all-cause mortality was 38% (n = 463), with the incidence of cardiotoxicity 10.2% (n = 123). Only 15.4% (n = 19) patients required heart failure hospitalisation, with 48% (n = 59) of patients commenced on beta blockade therapy and/or angiotensin-converting enzyme inhibitors. The majority of patients (73.2%, n = 90) experienced cardiotoxicity within 1 year of anthracycline initiation. The proportion of patients with complete, partial and no LVEF recovery were 16.3% (n = 20), 29.3% (n = 36) and 54.4% (n = 67) respectively. Mortality was higher in the cardiotoxicity group (49% vs 37%, P < 0.01). History of coronary artery disease, leukaemia, idarubicin use and high cumulative anthracycline dose were predictors of cardiotoxicity. CONCLUSIONS: Cardiotoxicity after anthracycline use predictably occurs within the first year of therapy and is dose-related, with variable degrees of recovery. While the need for hospitalisation for heart failure was uncommon, medical therapy appears underutilised, suggesting there may be a role for improved surveillance and early initiation of treatment.


Assuntos
Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Cardiotoxicidade/mortalidade , Insuficiência Cardíaca/mortalidade , Neoplasias/tratamento farmacológico , Adulto , Idoso , Antraciclinas/administração & dosagem , Antineoplásicos/administração & dosagem , Austrália , Cardiotoxicidade/etiologia , Ecocardiografia , Feminino , Insuficiência Cardíaca/induzido quimicamente , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Prospectivos , Volume Sistólico , Função Ventricular Esquerda
16.
Pak J Pharm Sci ; 30(2(Suppl.)): 567-572, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28650322

RESUMO

Newcastle disease is highly infectious viral disease causing huge economic losses worldwide. These losses can be prevented by control of viral diseases. Medicinal plants have been traditionally used for treatment of different diseases since long. In this study the effect of extracts from Glycyrrhiza glabra leaves are investigated against Newcastle disease virus (NDV) by an in-vivo assay. Seven groups of nine-day-old embryonated chicken eggs were inoculated with various treatments of different plant extracts. All the groups except uninoculated negative control group were inoculated with velogenic NDV strain; five groups received different concentrations of the three extracts. Daily observe the rate of embryo survival. Allantoic fluid from treated eggs was collected for hem agglutination test. Results showed that embryo survival rate was higher 300µg/mL treated group as all the extracts showed antiviral activity. Similarly, the plant extracts effectively control virus as no viruses were identified in the allantoic fluids of all groups treated with low doses of plant. The current results have clearly verified that all the extracts especially that of methanol 300µg/mL from leaves of Glycyrrhiza glabra have strong antiviral activity against NDV in vivo.


Assuntos
Inibidores Enzimáticos/farmacologia , Glycyrrhiza/química , Vírus da Doença de Newcastle/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Galinhas , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Testes de Hemaglutinação , Óvulo/virologia , Extratos Vegetais/química , Folhas de Planta/química , Taxa de Sobrevida
17.
Med J Aust ; 205(3): 121-5, 2016 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-27465767

RESUMO

OBJECTIVE: The system of care in the Hunter New England Local Health District for patients with ST-segment elevation myocardial infarction (STEMI) foresees pre-hospital thrombolysis (PHT) administered by paramedics to patients more than 60 minutes from the cardiac catheterisation laboratory (CCL), and primary percutaneous coronary intervention (PCI) at the CCL for others. We assessed the safety and effectiveness of the pre-hospital diagnosis strategy, which allocates patients to PHT or primary PCI according to travel time to the CCL. DESIGN, SETTING AND PARTICIPANTS: Prospective, non-randomised, consecutive, single-centre case series of STEMI patients diagnosed on the basis of a pre-hospital electrocardiogram (ECG), from August 2008 to August 2013. All patients were treated at the tertiary referral hospital (John Hunter Hospital, Newcastle). MAIN OUTCOME MEASURES: The primary efficacy endpoint was all-cause mortality at 12 months; the primary safety endpoint was bleeding. RESULTS: STEMI was diagnosed in 484 patients on the basis of pre-hospital ECG; 150 were administered PHT and 334 underwent primary PCI. The median time from first medical contact (FMC) to PHT was 35 minutes (IQR, 28-43 min) and to balloon inflation 130 minutes (IQR, 100-150 min). In the PHT group, 37 patients (27%) needed rescue PCI (median time, 4 h; IQR, 3-5 h). The 12-month all-cause mortality rate was 7.0% (PHT, 6.7%; PCI, 7.2%). The incidence of major bleeding (TIMI criteria) in the PHT group was 1.3%; no patients in the primary PCI group experienced major bleeding. CONCLUSION: PHT can be delivered safely by paramedical staff in regional and rural Australia with good clinical outcomes.


Assuntos
Serviço Hospitalar de Emergência , Infarto do Miocárdio/terapia , Terapia Trombolítica/métodos , Tempo para o Tratamento , Austrália , Eletrocardiografia , Serviços Médicos de Emergência , Feminino , Fibrinolíticos/administração & dosagem , Humanos , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Estudos Prospectivos , Resultado do Tratamento
18.
Cochrane Database Syst Rev ; 2016(9)2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27660553

RESUMO

This is the protocol for a review and there is no abstract. The objectives are as follows: To compare a therapeutic-only versus prophylactic platelet transfusion policy for people with myelodysplasia, inherited or acquired aplastic anaemia, and other congenital bone marrow failure disorders.

19.
Pak J Pharm Sci ; 29(6 Suppl): 2321-2326, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28167473

RESUMO

Glimepiride and atorvastatin in combination are commonly employed for treating the hyperglycemia and dyslipidemia, respectively, in patients of type 2 diabetes. The present study was designed to find out the influence of atorvastatin on urinary excretion and renal clearance of Glimepiride in healthy adult male volunteers. In each experimental subject, Glimepiride 2mg was given orally after an overnight fasting. Samples of blood and urine were taken at different specific time intervals. After a washout period of ten days, Glimepiride 2mg was co-administered with atorvastatin 20mg orally. Post-medication, blood and urine samples were collected following the same sampling schedule as for Glimepiride alone. The samples were analyzed for Glimepiride and creatinine concentration by HPLC-UV and Spectrophotometer, respectively. Mean (±SE) values for blood pH 7.445±0.05 and 7.382±0.05, urine pH 4.972±0.08 and 5.08±0.10, diuresis 0.0207±0.00 and 0.0237±0.00ml/min/kg, endogenous creatinine in plasma 9.048±0.33 and 8.613±0.024µg/ml, endogenous creatinine in urine 512.34±18.20 and 556.72±4.60µg/ml, Glimepiride plasma concentration 0.16069±0.00 and 0.3227±0.01µg/ml, Glimepiride urine concentration 1.5994±0.03 and 0.8665±0.04µg/ml, renal clearance of creatinine 1.224±0.09 and 1.550±0.09ml/min/kg, renal clearance of Glimepiride 0.2064±0.01 and 0.0641±0.00ml/min/kg and clearance ratio 0.1791±0.01 and 0.0414±0.00 were observed for Glimepiride alone and its concurrent administration with atorvastatin, respectively. Atorvastatin decreased the urinary excretion and renal clearance of Glimepiride due to which chances of hypoglycemia provokes and renal handling of Glimepiride involves back diffusion besides glomerular filtration and no influence of atorvastatin was seen on these mechanisms.


Assuntos
Atorvastatina/administração & dosagem , Inibidores do Citocromo P-450 CYP2C9/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipoglicemiantes/urina , Rim/efeitos dos fármacos , Eliminação Renal/efeitos dos fármacos , Compostos de Sulfonilureia/urina , Adulto , Atorvastatina/efeitos adversos , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP2C9/metabolismo , Inibidores do Citocromo P-450 CYP2C9/efeitos adversos , Interações Medicamentosas , Voluntários Saudáveis , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Rim/metabolismo , Masculino , Espectrofotometria Ultravioleta , Compostos de Sulfonilureia/administração & dosagem , Compostos de Sulfonilureia/farmacocinética
20.
Int J Ment Health Syst ; 18(1): 24, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909254

RESUMO

BACKGROUND: Depression among young people is a global health problem due to its rising prevalence and negative physical and social outcomes. The prevalence of depression and the treatment gap among young people in Sub-Saharan Africa (SSA) is higher than global estimates. Most psychosocial interventions for adolescent and youth depression were developed in high-income countries and less is known about their effectiveness in SSA. Due to contextual differences, findings from High-Income Countries (HICs) are less applicable to SSA. Yet, no systematic review of psychosocial interventions for depression among young people in SSA has been conducted. METHODS: A systematic literature search of four databases (Medline, Web of Science, PsycInfo, and Cochrane library) was conducted. Experimental studies published before May 2024 that evaluated the effect of psychosocial interventions on depressive symptoms among young people (aged 10-24 years) in SSA were included in the systematic review. Effect sizes (Hedge's g (g)) indicating differences between intervention and control groups were calculated using a random effects model. RESULTS: Twenty-two eligible studies were identified for the systematic review, of which eighteen randomized control trials (RCTs) involving 2338 participants were included in the meta-analysis. The findings revealed that psychosocial interventions significantly reduced depressive symptoms (g = -1.55, 95% CI -2.48, -0.63), although heterogeneity was high (I2 = 98.8%). Subgroup analysis revealed that efficacy differed significantly by intervention type, with Cognitive Behavioural Therapy (9 studies) showing the strongest effect (g = -2.84, 95% CI -4.29; -1.38). While Wise Interventions (a form of positive psychology interventions; 2 studies) had a moderate effect (g = -0.46, 95% C.I -0.53, -0.39), Interpersonal Psychotherapy (2 studies; g = -0.08, 95% CI -1.05, 0.88) and Creative Psychological Interventions (3 studies; g = -0.29, 95% CI -1.38, 0.79) showed smaller, non-significant effects. Sensitivity analysis excluding studies at high risk of bias strengthened the effect size. Few studies assessed factors affecting intervention efficacy and showed mixed effects of age, gender, and adherence levels. CONCLUSION: Psychosocial interventions, particularly CBT, significantly reduced depressive symptoms among young people in SSA. However, it is crucial to acknowledge the high heterogeneity which likely stems from variations in study populations and intervention delivery modalities. This highlights the need for further research to identify the specific intervention components and delivery methods that work best for distinct subpopulations. Future research should also explore how long intervention effects are maintained and factors affecting efficacy.

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