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1.
PLoS One ; 17(9): e0274412, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36129901

RESUMO

Dietary supplements are products containing dietary elements including vitamins, minerals, amino acids, herbs, or botanicals. They can aid consumers with low dietary intake and quality, as well as those with high demands, by boosting nutritious value. A cross-sectional study was conducted among adults living in Saudi Arabia aged between 18-60 years old using online self-administered questionnaire. Information regarding sociodemographic characteristics, use and type of dietary supplements, and attitude toward and patterns of dietary supplement use was collected. The chi-square test, Pearson correlations, and the independent t-test were used. In total, 531 participants (115 men and 416 women) were included. Approximately half of the participants (51.8%, n = 275) used dietary supplements. Participants who were using dietary supplements were significantly younger (29.16 ± 9.32 years), more highly educated (85.5%, n = 235), and worked in the health sector (63.7%, n = 100). Herbal supplement use was associated with older age and female sex. Single mineral supplements were used more frequently by married, female, pregnant, or breastfeeding participants and those not working in the health sector. Fatty supplements were used more frequently by participants with a higher level of education. Regarding the attitude toward dietary supplement use, women, single participants, and health care workers showed a significant positive attitude. In-depth investigation into the amount of and reasons for dietary supplement use in the health sector is required. Additionally, educating pregnant and breastfeeding women on the importance of dietary supplements is necessary.


Assuntos
Suplementos Nutricionais , Vitaminas , Adolescente , Adulto , Aminoácidos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minerais , Gravidez , Prevalência , Arábia Saudita , Adulto Jovem
2.
Clin Appl Thromb Hemost ; 27: 10760296211047230, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34633875

RESUMO

Sickle cell anemia (SCA) is a blood condition that causes severe pain. One of the therapeutic agents used for the treatment of SCA is hydroxyurea, which reduces the episodes of pain but causes DNA damage to white blood cells. The aim of this study was to evaluate the efficacy of the combination of hydroxyurea and iron chelation therapy in relation to the extent of DNA-associated damage. Blood samples were collected from 120 subjects from five groups. Various hematological parameters of the obtained serum were analyzed. The amount of damage caused to their DNA was detected using the comet assay and fluorescent microscopy techniques. The percentage of DNA damage in the group that was subjected to the combination therapy (target group) was 1.32% ± 1.51%, which was significantly lower (P < .05) than that observed in the group treated with hydroxyurea alone (6.36% ± 2.36%). While the target group showed comparable levels of hemoglobin F and lactate dehydrogenase compared to the group that was treated with hydroxyurea alone, highly significant levels of transferrin receptors and ferritin were observed in the target group. The results of this study revealed that the administration of iron chelation drugs with hydroxyurea may help improve patients' health and prevent the DNA damage caused to white blood cells due to hydroxyurea. Further studies are needed to better understand the underlying mechanisms that are involved in this process.


Assuntos
Anemia Falciforme/tratamento farmacológico , Dano ao DNA/efeitos dos fármacos , Quelantes de Ferro/uso terapêutico , Adolescente , Adulto , Criança , Feminino , Humanos , Quelantes de Ferro/farmacologia , Masculino , Adulto Jovem
3.
Front Immunol ; 11: 1986, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983137

RESUMO

Monoclonal antibodies (mAbs) have become one of the most important classes of biopharmaceutical products, and they continue to dominate the universe of biopharmaceutical markets in terms of approval and sales. They are the most profitable single product class, where they represent six of the top ten selling drugs. At the beginning of the 1990s, an in vitro antibody selection technology known as antibody phage display was developed by John McCafferty and Sir. Gregory Winter that enabled the discovery of human antibodies for diverse applications, particularly antibody-based drugs. They created combinatorial antibody libraries on filamentous phage to be utilized for generating antigen specific antibodies in a matter of weeks. Since then, more than 70 phage-derived antibodies entered clinical studies and 14 of them have been approved. These antibodies are indicated for cancer, and non-cancer medical conditions, such as inflammatory, optical, infectious, or immunological diseases. This review will illustrate the utility of phage display as a powerful platform for therapeutic antibodies discovery and describe in detail all the approved mAbs derived from phage display.


Assuntos
Anticorpos Monoclonais , Técnicas de Visualização da Superfície Celular , Desenvolvimento de Medicamentos/métodos , Animais , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Especificidade de Anticorpos/genética , Especificidade de Anticorpos/imunologia , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Engenharia Genética , Ensaios de Triagem em Larga Escala , Humanos , Terapia de Alvo Molecular , Pesquisa Translacional Biomédica , Resultado do Tratamento
4.
Sci Rep ; 9(1): 15827, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676832

RESUMO

Spin-polarized supercurrents can be generated with magnetic inhomogeneity at a ferromagnet/spin-singlet-superconductor interface. In such systems, complex magnetic inhomogeneity makes it difficult to functionalise the spin-polarized supercurrents. However, spin-polarized supercurrents in ferromagnet/spin-triplet-superconductor junctions can be controlled by the angle between magnetization and spin of Copper pairs (d-vector), that can effectively be utilized in developing of a field of research known as superconducting spintronics. Recently, we found induction of spin-triplet correlation into a ferromagnet SrRuO3 epitaxially deposited on a spin-triplet superconductor Sr2RuO4, without any electronic spin-flip scattering. Here, we present systematic magnetic field dependence of the proximity effect in Au/SrRuO3/Sr2RuO4 junctions. It is found that induced triplet correlations exhibit strongly anisotropic field response. Such behaviour is attributed to the rotation of the d-vector of Sr2RuO4. This anisotropic behaviour is in contrast with the vortex dynamic. Our results will stimulate study of interaction between ferromagnetism and unconventional superconductivity.

5.
Poult Sci ; 97(7): 2516-2524, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29672752

RESUMO

Six hundred and eighty-four male Ross 308 broiler chicks were used to test the null hypothesis that post hatching age between day 0 and 21 does not affect utilization of energy in meat and bone meal (MBM). There were 6 replicate cages in each of 12 treatments consisting of 3 test diets (0, 40, or 80 g MBM/kg diets) at 4 feeding ages post hatching (day 0 to 7, 6 to 11, 10 to 16, or 15 to 21 post hatching) for a total of 72 cages in a randomized complete block design. Birds were assigned to the 12 treatments on day 0, fed a standard starter diet until they were switched to the test diets on day 0, 6, 10, or 15, and the number of birds per cage for day 0 to 7, 6 to 11, 10 to 16, or 15 to 21 were 12, 10, 8, or 8, respectively. Excreta were collected during the last 3 days of each feeding age post hatching and ileal digesta on the last day of each age. There was no interaction between dietary MBM level and feeding age post hatching for any of the response criteria. Weight gain and gain-to-feed ratio improved linearly (P < 0.001) with increasing dietary MBM and, expectedly, there was an increase (P < 0.001) in weight gain and a reduction (P < 0.001) in gain-to-feed ratio with bird feeding age post hatching. Ileal digestible energy (IDE), apparent metabolizable energy (AME), and nitrogen-corrected AME (AMEn) of the diet linearly increased (P < 0.001) with increasing dietary MBM. There were linear increases in dietary IDE (P < 0.05), AME (P < 0.001), and AMEn (P < 0.001) with bird feeding age post hatching. The IDE, ME, and MEn of MBM were determined by the regression procedure. During day 0 to 7, 6 to 11, 10 to 16, or 15 to 21, energy values increased (P < 0.05) with age and the respective IDE of MBM were 2.852, 2.962, 2.927, or 2.959 kcal/g DM. Corresponding ME of MBM were 2.909, 3.125, 3.083, or 3.075 kcal/g DM and those of MEn were 2.687, 2.887, 2.839, or 2.845 kcal/g DM. These results show that energy values of MBM increase with age post hatching and suggest the same energy value of MBM should not be used in formulating diets of broiler chickens during the first 3 weeks post hatching.


Assuntos
Galinhas/fisiologia , Digestão , Metabolismo Energético , Íleo/fisiologia , Minerais/metabolismo , Nitrogênio/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Produtos Biológicos/administração & dosagem , Produtos Biológicos/metabolismo , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Digestão/efeitos dos fármacos , Relação Dose-Resposta a Droga , Metabolismo Energético/efeitos dos fármacos , Íleo/efeitos dos fármacos , Masculino , Minerais/administração & dosagem , Distribuição Aleatória , Análise de Regressão
6.
Subst Use Misuse ; 53(1): 94-100, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-28777672

RESUMO

BACKGROUND: Khat (Catha edulis Forsk) is a natural psychoactive substance which contains two main addictive substances; Cathine and Cathinone. Khat is widely used in east Africa and southern Arabian Peninsula. Khat chewers believe that it improves work capacity and increases energy level and alertness. That is why we aimed in this study to investigate the physiological and ergogenic effects of khat extract. METHODS: This study is an experimental study conducted at the Substance Abuse Research Centre in Jazan University, Saudi Arabia. Thirty healthy young volunteers were randomly assigned into two experimental groups. The first group ingested 45 g of grounded khat leaves extract mixed with juice in the first session then placebo (juice only) in the second session. While the second group ingested the placebo in the first session and the grounded khat leaves with juice in the second session. Experiments were done between December 2012 and March 2013. We recorded the blood pressure, heart rate, grip strength, and reaction time every 15 min for 75 min after each ingestion. The study proposal was reviewed and approved by Research Ethics Committee (REC) of the Medical Research Centre in Jazan University. RESULTS: The results showed the consumption of 45 g of grounded khat leaves contributed to the increase in blood pressure (SBP & DBP) and reaction time (p < 0.05); but had no significant effect on heart rate and grip strength (p > 0.05). CONCLUSIONS: The findings of this study showed that Khat has an acute effect on some physiological parameters. These findings support the prohibition of cathinone and cathine by the World Anti-Doping Agency (WADA, 2016).


Assuntos
Catha/química , Substâncias para Melhoria do Desempenho/farmacologia , Extratos Vegetais/farmacologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Força da Mão , Voluntários Saudáveis , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Folhas de Planta/química , Tempo de Reação/efeitos dos fármacos , Adulto Jovem
7.
Sci Rep ; 7(1): 686, 2017 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-28386068

RESUMO

Salvia fruticosa (SF) Mill. is traditionally used for its antihypertensive actions. However, little is known about its pharmacologic and molecular mechanisms of action. Here we determined the effects of an ethanolic extract of SF leaves on rings of isolated thoracic aorta from Sprague-Dawley rats. Our results show that SF extract increased nitric oxide production and relaxed endothelium-intact rings in a dose-dependent (0.3 µg/ml-1 mg/ml) manner, and the maximum arterial relaxation (Rmax) was significantly reduced with endothelium denudation. Pretreatment of endothelium-intact rings with L-NAME (a non-selective inhibitor of nitric oxide synthase, 100 µM), or ODQ (an inhibitor of soluble guanylyl cyclase, 10 µM) significantly diminished SF-mediated vasorelaxation. Furthermore, SF induced Akt phosphorylation as well as increased cGMP levels in rings treated with increasing doses of SF. Prior exposure to PI3K inhibitors, wortmannin (0.1 µM) or LY294002 (10 µM), decreased cGMP accumulation and attenuated the SF-induced vasorelaxation by approximately 50% (Rmax). SF-evoked relaxation was not affected by indomethacin, verapamil, glibenclamide, tetraethylammonium, pyrilamine or atropine. Taken together, our results indicate that SF induces endothelium-dependent vasorelaxation through the PI3K/Akt/eNOS/NO/sGC/cGMP signaling pathway. Our data illustrate the health-orientated benefits of consuming SF which may act as an antihypertensive agent to reduce the burden of cardiovascular complications.


Assuntos
Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Extratos Vegetais/farmacologia , Salvia/química , Vasodilatadores/farmacologia , Animais , Canais de Cálcio/metabolismo , GMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/química , Canais de Potássio/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Receptores Histamínicos/metabolismo , Receptores Muscarínicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vasodilatadores/química
8.
Biochem Biophys Res Commun ; 487(1): 47-53, 2017 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-28389244

RESUMO

Little is known about the role of oxytocin (OT) in colostrum during early gut colonization. We previously showed that transient OT receptor (OTR) expression on newborn rat enterocytes coincides with the milk-suckling period, and that OT activates endoplasmic reticulum stress sensors in cultured enterocytes. Here, we explored whether colostrum-OT attenuates stress in newborn villi primed and unprimed by colostrum by measuring levels of stress markers including BiP (an ER chaperone), eIF2a (translation initiation factor), and pPKR (eIF2a kinase). We also measured two inflammation-signaling proteins NF-κB and its inhibitor IκB. To test the impact of colostrum on autophagy, we measured a marker of autophagy initiation, LC3A. Colostrum increased inactive p-eIF2a, p-PKR and IκB and reduced p-IκB, BiP and LC3A. LPS increased and OT decreased p-IkB. BiP (GRP78) was higher in unprimed than primed villi. Together, these data suggest that colostrum OT attenuates the impact of inflammation on postnatal gut villi and that OT enhances autophagy to protect against amino acid insufficiency-induced stress during the interval between birth and the first feeding.


Assuntos
Colostro/metabolismo , Estresse do Retículo Endoplasmático/imunologia , Mediadores da Inflamação/imunologia , Mucosa Intestinal/imunologia , Ocitocina/administração & dosagem , Animais , Animais Recém-Nascidos , Autofagia/efeitos dos fármacos , Autofagia/imunologia , Relação Dose-Resposta a Droga , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Proteínas de Choque Térmico/imunologia , Mucosa Intestinal/efeitos dos fármacos , Masculino , Microvilosidades/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
9.
Front Pharmacol ; 7: 50, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27014064

RESUMO

Traditional medicine has a history extending back to thousands of years, and during the intervening time, man has identified the healing properties of a very broad range of plants. Globally, the use of herbal therapies to treat and manage cardiovascular disease (CVD) is on the rise. This is the second part of our comprehensive review where we discuss the mechanisms of plants and herbs used for the treatment and management of high blood pressure. Similar to the first part, PubMed and ScienceDirect databases were utilized, and the following keywords and phrases were used as inclusion criteria: hypertension, high blood pressure, herbal medicine, complementary and alternative medicine, endothelial cells, nitric oxide (NO), vascular smooth muscle cell (VSMC) proliferation, hydrogen sulfide, nuclear factor kappa-B (NF-κB), oxidative stress, and epigenetics/epigenomics. Each of the aforementioned keywords was co-joined with plant or herb in question, and where possible with its constituent molecule(s). This part deals in particular with plants that are used, albeit less frequently, for the treatment and management of hypertension. We then discuss the interplay between herbs/prescription drugs and herbs/epigenetics in the context of this disease. The review then concludes with a recommendation for more rigorous, well-developed clinical trials to concretely determine the beneficial impact of herbs and plants on hypertension and a disease-free living.

10.
Front Pharmacol ; 6: 323, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26834637

RESUMO

The use of herbal therapies for treatment and management of cardiovascular diseases (CVDs) is increasing. Plants contain a bounty of phytochemicals that have proven to be protective by reducing the risk of various ailments and diseases. Indeed, accumulating literature provides the scientific evidence and hence reason d'etre for the application of herbal therapy in relation to CVDs. Slowly, but absolutely, herbal remedies are being entrenched into evidence-based medical practice. This is partly due to the supporting clinical trials and epidemiological studies. The rationale for this expanding interest and use of plant based treatments being that a significant proportion of hypertensive patients do not respond to Modern therapeutic medication. Other elements to this equation are the cost of medication, side-effects, accessibility, and availability of drugs. Therefore, we believe it is pertinent to review the literature on the beneficial effects of herbs and their isolated compounds as medication for treatment of hypertension, a prevalent risk factor for CVDs. Our search utilized the PubMed and ScienceDirect databases, and the criterion for inclusion was based on the following keywords and phrases: hypertension, high blood pressure, herbal medicine, complementary and alternative medicine (CAM), nitric oxide, vascular smooth muscle cell (VSMC) proliferation, hydrogen sulfide, nuclear factor kappa-B, oxidative stress, and epigenetics/epigenomics. Each of the aforementioned keywords was co-joined with herb in question, and where possible with its constituent molecule(s). In this first of a two-part review, we provide a brief introduction of hypertension, followed by a discussion of the molecular and cellular mechanisms. We then present and discuss the plants that are most commonly used in the treatment and management of hypertension.

11.
Curr Opin Support Palliat Care ; 8(3): 235-40, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25004179

RESUMO

PURPOSE OF REVIEW: To better understand the mechanism of radiation-induced hemorrhagic cystitis and the advantages and disadvantages of available treatment options for bladder hemorrhage as well as preventive measures. RECENT FINDINGS: There have been several attempts recently to manage hemorrhagic cystitis with hyperbaric oxygen therapy, transurethral coagulation using Greenlight potassium-titanyl-phosphate laser and other different treatment modalities, but we still need more investigation on larger cohort studies. SUMMARY: Hemorrhagic cystitis is an uncommon urological problem. It is most often caused by radiation therapy and cyclophosphamide, but can be associated with other contributing factors. Technological advances in radiation therapy have resulted in greater treatment efficacy, with significant reduction in side-effects such as hemorrhagic cystitis. Higher dose radiation treatment, however, is more often associated with problematic hemorrhagic cystitis. Treatment of hemorrhagic cystitis is multifactorial and can range from simple bladder irrigation to cystectomy with urinary diversion.


Assuntos
Cistite/terapia , Hemorragia , Lesões por Radiação/terapia , Antineoplásicos Alquilantes/efeitos adversos , Ciclofosfamida/efeitos adversos , Cistectomia , Cistite/prevenção & controle , Eletrocoagulação/métodos , Humanos , Oxigenoterapia Hiperbárica/métodos , Lesões por Radiação/prevenção & controle , Fatores de Risco , Irrigação Terapêutica/métodos
12.
Public Health ; 126(6): 507-17, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22579325

RESUMO

INTRODUCTION: This narrative review was carried out to collate the work of researchers on health-seeking behaviour in Pakistan, to discuss the methods used, highlight the emerging themes and identify areas that have yet to be studied. STUDY DESIGN: Review. METHODS: An overview of studies on health-seeking behaviour in Pakistan, found via searches on scholarly databases intended to locate material of medical and anthropological relevance. RESULTS: In total, 29 articles were reviewed with a range of different methodologies. A retrospective approach was the most common. A variety of medical conditions have been studied in terms of health-seeking behaviour of people experiencing such conditions. However, a wide range of chronic illnesses have yet to be studied. Nevertheless, some studies highlighting unusual issues such as snake bites and health-seeking behaviour of street children were also found. In terms of geographical area, the majority of studies reviewed were performed in the provinces of Sind and Punjab, with little research targeting the people from the two other provinces (Balochistan and Khyber Pakhtunkhwa) of Pakistan. Predominant utilization of private healthcare facilities, self-medication, involvement of traditional healers in the healthcare system, women's autonomy, and superstitions and fallacies associated with health-seeking behaviour were found to be the themes that repeatedly emerged in the literature reviewed. CONCLUSIONS: The sociocultural and religious background of Pakistan means that health-seeking behaviour resembles a mosaic. There is a need to improve the quality of service provided by the public healthcare sector and the recruitment of female staff. Traditional healers should be trained and integrated into the mainstream to provide adequate healthcare. Serious efforts are required to increase the awareness and educational level of the public, especially women in rural areas, in order to fight against myths and superstitions associated with health-seeking behaviour.


Assuntos
Características Culturais , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Classe Social , Instalações de Saúde/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Medicina Tradicional/estatística & dados numéricos , Paquistão , Religião
13.
Exp Parasitol ; 128(2): 104-10, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21354144

RESUMO

Present paper reports the effects of aqueous and ethanolic extracts of sugar cane (Saccharum officinarum L.) juice and bagasse, respectively on protective immune responses in industrial broiler chickens against coccidiosis. Immunotherapeutic efficacies of the extracts were measured by evaluating their effect on body weight gain, oocyst shedding, lesion score, anti-coccidial indices, per cent protection and elicited serum antibody responses against coccidiosis. Results revealed a significantly lower (P<0.05) oocyst shedding and mortality in chickens administered with sugar cane extracts as compared to control. Further, significantly higher (P<0.05) body weight gains and antibody responses were detected in chickens administered with sugar cane extracts as compared to chickens of control group. Moreover, ethanolic extract showed higher anti-coccidia index (227.61) as compared to aqueous extract (192.32). The organ body weight ratio of the lymphoid organs of experimental and control groups were statistically non-significant (P>0.01). These results demonstrated that both ethanolic and aqueous extracts of sugar cane possess immune enhancing properties and their administration in chickens augments the protective immunity against coccidiosis.


Assuntos
Galinhas/parasitologia , Coccidiose/veterinária , Eimeria/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Doenças das Aves Domésticas/tratamento farmacológico , Saccharum/química , Animais , Anticorpos Antiprotozoários/biossíntese , Anticorpos Antiprotozoários/sangue , Coccidiose/tratamento farmacológico , Coccidiose/parasitologia , Eimeria/classificação , Eimeria/imunologia , Imunoterapia/métodos , Tecido Linfoide/efeitos dos fármacos , Tecido Linfoide/crescimento & desenvolvimento , Oocistos/classificação , Oocistos/efeitos dos fármacos , Oocistos/imunologia , Extratos Vegetais/farmacologia , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/parasitologia
14.
Clin Cancer Res ; 15(1): 382-9, 2009 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19118069

RESUMO

PURPOSE: Pemetrexed is approved as monotherapy and in combination with cisplatin. The established combination dose was identified before the addition of folic acid and vitamin B(12) to the treatment regimen. We evaluated the toxicity and pharmacokinetics (PK) of higher pemetrexed doses with cisplatin and vitamin supplementation. EXPERIMENTAL DESIGN: Patients with malignant pleural mesothelioma or non-small cell lung cancer received pemetrexed doses from 500 to 900 mg/m(2) + 75 mg/m(2) cisplatin once every 21 days. Folic acid and vitamin B(12) were administered per label recommendations. RESULTS: Twenty-one patients received a combined total of 84 cycles. The maximum tolerated dose was 900 mg/m(2) pemetrexed + 75 mg/m(2) cisplatin. Dose-limiting toxicities at this dose included grade 3 anemia, bronchopneumonia, and neutropenia, and 1 death from sepsis secondary to grade 4 febrile neutropenia, considered possibly related to study drugs. The recommended dose was 800 mg/m(2) pemetrexed + 75 mg/m(2) cisplatin. Pemetrexed PK were consistent across doses; pemetrexed did not seem to affect total or free platinum PK. CONCLUSIONS: Pemetrexed with vitamin supplementation was safe and well tolerated at higher doses than the currently established 500 mg/m(2) + 75 mg/m(2) cisplatin. Based on this study, the recommended dose would be 800 mg/m(2) pemetrexed + 75 mg/m(2) cisplatin. However, recent studies showed a lack of improved efficacy for 900 or 1,000 mg/m(2) single-agent pemetrexed versus 500 mg/m(2) and a lack of PK/pharmacodynamic exposure-response relationship for the pemetrexed/cisplatin combination across pemetrexed exposures corresponding to this dose range. Based on currently available evidence, we recommend retaining the established dose.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Glutamatos/administração & dosagem , Glutamatos/farmacocinética , Guanina/análogos & derivados , Mesotelioma/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/secundário , Suplementos Nutricionais , Esquema de Medicação , Feminino , Glutamatos/efeitos adversos , Guanina/administração & dosagem , Guanina/efeitos adversos , Guanina/farmacocinética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Dose Máxima Tolerável , Mesotelioma/secundário , Pessoa de Meia-Idade , Pemetrexede , Platina/sangue , Vitaminas/administração & dosagem
15.
Reprod Domest Anim ; 43(6): 672-7, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18673331

RESUMO

In the present study, the effect of heat stress, which is commonly observed in the animals of Upper Egypt area in summer, as well as the effect of antioxidant treatment as a thermo-protective was examined. In this study, the animals (n = 120) were divided into winter group (n = 40, bred during winter) and summer group (n = 80, bred during summer) as well as, animals in the summer group were divided into first subgroup animals (n = 40) and injected with Viteselen intramuscularly (15 ml) twice weekly for 10 weeks and second subgroup animals (n = 40) were not treated (as control). Serum levels of progesterone (P4), oestradiol (E2), cortisol, superoxide dismutase (SOD), lipid peroxidase (LPO) and nitric oxide (NO) were measured. The pregnancy rate of all animals was detected rectally. The levels of oestradiol and the activity of the antioxidant SOD were decreased in serum of animals in behavioural oestrus during summer as compared with those in winter. During the same time period the levels of oxidants such as LPO and NO were increased in the serum of animals again in the phase of oestrus. In another group of animals treated by intramuscular injection with 15 ml viteselen (antioxidant) twice weekly for 6 weeks during hot months, the activities of serum SOD showed an increase and the levels of oxidants and cortisol decreased. Moreover, the levels of oestradiol were increased during the oestrous behaviour. The pregnancy rate was decreased in animals under heat stress and the pregnancy rate was enhanced dramatically when these animals received antioxidants during the heat stress. This means that the heat-stress in Upper Egypt may affect the fertility of animals and pregnancy rate and this effect may be through an increased production of free radicals and decreased production of antioxidants as well as increased levels of cortisol. Treatment of animals or supplementation with antioxidants before the beginning of months of heat-stress and also during the stress period may correct the infertility due to heat-stress through the decrease in cortisol secretion and a decrease in the oxidative stress. These results resulted in an increase in pregnancy rate in treated animals.


Assuntos
Antioxidantes/farmacologia , Búfalos/metabolismo , Estro/metabolismo , Transtornos de Estresse por Calor/veterinária , Hidrocortisona/sangue , Animais , Antioxidantes/metabolismo , Búfalos/sangue , Búfalos/fisiologia , Estradiol/sangue , Feminino , Transtornos de Estresse por Calor/sangue , Transtornos de Estresse por Calor/prevenção & controle , Injeções Intramusculares/veterinária , Peroxidação de Lipídeos/efeitos dos fármacos , Óxido Nítrico/sangue , Óxido Nítrico/metabolismo , Oxirredução , Gravidez , Taxa de Gravidez , Progesterona/sangue , Estações do Ano , Superóxido Dismutase/sangue , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo
16.
Forensic Sci Int ; 179(2-3): e31-6, 2008 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-18602779

RESUMO

The study presents a case of fatal poisoning with oleander leaves in an adult diabetic male. After repeated vomiting, and gastrointestinal distress the patient was admitted at the hospital with cardiac symptoms 1h after the ingestion. Urine samples were assayed immunochemically and by GC-MS for drugs of abuse and for general toxicological screen. Blood was analyzed for alcohol and volatiles by static head space GC-MS. Blood and oleander leaves were analyzed by LC-MS/MS for oleandrin and related compounds, the main cardiac glycosides of Nerium oleander. Oleandrin was detected by LC-MS/MS in the blood sample at a concentration of approximately 10 ng/ml. Another cardiac glycoside with pseudo-molecular ion of m/z 577, a likely structural isomer of oleandrin, was also detected in the blood and oleander leaves. However, by using the response as a function of concentration for oleandrin, this cardiac glycoside was roughly estimated at a concentration of approximately 10 ng/ml in the deceased blood. This would give a total fatal blood concentration of cardiac glycosides of about approximately 20 ng/ml in the deceased blood.


Assuntos
Cardenolídeos/intoxicação , Fitoterapia/efeitos adversos , Cardenolídeos/sangue , Diabetes Mellitus/tratamento farmacológico , Toxicologia Forense , Cromatografia Gasosa-Espectrometria de Massas , Parada Cardíaca/induzido quimicamente , Bloqueio Cardíaco/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Folhas de Planta/intoxicação , Fibrilação Ventricular/induzido quimicamente
18.
Oncology ; 73(1-2): 9-20, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18334829

RESUMO

BACKGROUND: This multicenter, randomized trial compared overall response rate between pemetrexed plus irinotecan (ALIRI) and leucovorin-modulated 5-fluorouracil plus irinotecan (FOLFIRI) in patients with advanced colorectal cancer. Secondary objectives included overall and progression-free survival, duration of response, toxicities, and biomarkers. PATIENTS AND METHODS: ALIRI patients received pemetrexed 500 mg/m(2) and irinotecan 350 mg/m(2) with vitamin supplementation on day 1 of each 21-day cycle. FOLFIRI patients received irinotecan 180 mg/m(2) on days 1, 15, 29; on days 1, 2, 15, 16, 29, 30, patients received leucovorin 200 mg/m(2), bolus 5-fluorouracil 400 mg/m(2), and 5-fluorouracil 600 mg/m(2) as 22-hour infusion. RESULTS: Of 132 patients randomly assigned, 130 patients (64 = ALIRI, 66 = FOLFIRI) received > or =1 dose of treatment. Response rates (ALIRI = 20.0%, FOLFIRI = 33.3%) were not significantly different between arms (p = 0.095). Progression-free survival was 5.7 months for ALIRI and 7.7 months for FOLFIRI (p < 0.001). Neutropenia, fatigue, diarrhea, nausea, and vomiting were the major toxicities. There were 5 drug-related deaths (ALIRI = 4, FOLFIRI = 1). Biomarker analysis failed to reveal that any of the 18 preselected genes were clearly associated with tumor response. CONCLUSIONS: Neither efficacy nor safety improved on the ALIRI arm compared to the FOLFIRI arm. Progression-free survival on FOLFIRI was significantly longer compared to ALIRI. Potential biomarkers capable of predicting response to either regimen in advanced or metastatic colorectal carcinoma need further characterization.


Assuntos
Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Adenocarcinoma/secundário , Adenocarcinoma Mucinoso/secundário , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/genética , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/metabolismo , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Regulação Neoplásica da Expressão Gênica , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Irinotecano , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pemetrexede , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sequências de Repetição em Tandem , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/metabolismo , gama-Glutamil Hidrolase/metabolismo
20.
Gut ; 55 Suppl 1: i36-58, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16481630

RESUMO

This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease.


Assuntos
Doença de Crohn/cirurgia , Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite/diagnóstico , Artrite/etiologia , Artrite/terapia , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/terapia , Terapias Complementares , Doença de Crohn/diagnóstico , Doença de Crohn/psicologia , Resistência a Medicamentos , Feminino , Humanos , Fístula Intestinal/diagnóstico , Fístula Intestinal/terapia , Mesalamina/uso terapêutico , Relações Médico-Paciente , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/psicologia , Complicações na Gravidez/terapia , Resultado da Gravidez , Psicoterapia/métodos , Qualidade de Vida , Fatores de Risco , Prevenção Secundária , Dermatopatias/diagnóstico , Dermatopatias/etiologia , Dermatopatias/terapia
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