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1.
Braz. j. biol ; 84: e254251, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1350307

RESUMO

Abstract Blood and fecal samples of chukar partridge (Alectoris chukar), albino pheasant (Phasianus colchicus), silver pheasant (Lophura nycthemera), rose-ringed parakeet (Psittacula krameri) and turkeys (Meleagris gallopavo) were analyzed to check parasitic prevalence. To record parasites these five avian species were placed kept in separate cages at Avian Conservation and Research Center, Department of Wildlife an Ecology, University of Veterinary and Animal Sciences, Lahore, Pakistan. 100 fecal and 100 blood samples for each bird species were inspected to analyze internal parasites. During present study, 17 species of endoparasites 14 from fecal samples and three from blood were examined. Two species of ectoparasites i.e. mite Dermanyssus gallinae 42% and fowl ticks Args persicus 41%were studied. Blood parasites included Plasmodium juxtanucleare 50%, Leucoctoyzoon simond having parasitic prevalence 40%, and Aegyptinella pullorum having parasitic prevalence of 40%. Parasitic species recorded from fecal samples included 6 species of nematodes viz. Allodpa suctoria 2%. Syngamus trachea with parasitic prevalence of 60%, Capillaria annulata 37.5%, Ascardia galli 24%, Capillaria anatis 40% and Heterakis gallinarum 28.3%. Similarly, two species of trematodes viz. Prosthogonimus ovatus having parasitic prevalence of 50% and Prosthogonimus macrorchis 21% were also documented from fecal avian samples . Single cestode species Raillietina echinobothrida having parasitic prevalence of 72% and 3 protozoan species i.e. Eimeria maxima having parasitic prevalence of 21%, Giardia lamblia 41% and Histomonas meleagridis 18% were documented during corpological analysis. In our recommendation, proper sanitation, medication and vaccination of bird's enclousres are suggested to avoid parasites.


RESUMO Amostras de sangue e fezes de perdiz chukar (Alectoris chukar), faisão-albino (Phasianus colchicus), faisão-prateado (Lophura nycthemera), periquito-de-rosa (Psittacula krameri) e perus (Meleagris gallopavo) foram analisadas para verificar a prevalência de parasitas. Para registrar os parasitas, essas cinco espécies de aves foram colocadas em gaiolas separadas no Centro de Conservação e Pesquisa de Aves, Departamento de Vida Selvagem e Ecologia, Universidade de Veterinária e Ciências Animais, Lahore, Paquistão. Cem amostras fecais e 100 amostras de sangue para cada espécie de ave foram inspecionadas para analisar os parasitas internos. Durante o presente estudo, foram examinadas 17 espécies de endoparasitas, 14 de amostras fecais e 3 de sangue. Foram estudadas duas espécies de ectoparasitas, ou seja, o ácaro Dermanyssus gallinae 42% e o carrapato aviário Args persicus 41%. Os parasitas sanguíneos incluíram Plasmodium juxtanucleare 50%, Leucoctoyzoon simond com prevalência parasitária de 40% e Aegyptinella pullorum com prevalência parasitária de 40%. As espécies parasitas registradas em amostras fecais incluíram 6 espécies de nematoides viz. Allodpa suctoria 2%, Syngamus traqueia com prevalência parasitária de 60%, Capillaria annulata 37,5%, Ascardia galli 24%, Capillaria anatis 40% e Heterakis gallinarum 28,3%. Da mesma forma, duas espécies de trematódeos viz. Prosthogonimus ovatus com prevalência parasitária de 50% e Prosthogonimus macrorchis 21% também foram documentados em amostras fecais de aves. Espécies de cestoide único Raillietina echinobothrida com prevalência parasitária de 72% e 3 espécies de protozoários, isto é, Eimeria maxima com prevalência parasitária de 21%, Giardia lamblia 41% e Histomonas meleagridis 18% foram documentadas durante a análise corpológica. Em nossa recomendação, o saneamento adequado, medicação e vacinação de invólucros de pássaros são sugeridos para evitar parasitas.


Assuntos
Animais , Parasitos , Doenças das Aves/epidemiologia , Galliformes , Prevalência , Animais Selvagens
2.
Braz. j. biol ; 84: e254253, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1350308

RESUMO

Abstract During the present study, specimens were collected from selected sites of Cholistan desert and Kalabagh Game Reserve, Punjab province, Pakistan. Each captured specimen was tagged with voucher number and morphometric measurements were taken. The average snout to vent length was 172.559±1.40 mm and average weight was 92.1±1.30 g. The DNA of Uromastyx hardwickii was amplified and sequenced using 16S rRNA primer set. The obtained DNA sequence has shown reliable and clear species identification. After trimming ambiguous bases, the obtained 16S rRNA fragment was 520 bp while 16S rRNA fragments aligned with closely matched sequence from NCBI comprised of 510 bp. Closely matched sequences of genus Uromastyx were retrieved from NCBI in blast searches. Neighbour-joining tree of genus Uromastyx was constructed based on p-distance using MEGA X. The mean intraspecific variation was 0.095±0.01 while intraspecific variation was ranging from 0-1%. Similarly, interspecific variation of Uromastyx hardwikii with Saara asmussi, Uromastyx alfredschmidti, Uromastyx geyri, Uromastyx thomasi, Uromastyx alfredschmidti was 0-12%, 0-19%, 0-19%, 0-20%, 12-19% respectively. The newly produced DNA was submitted to NCBI and accession number was obtained (MW052563.1). Results of current study provided information about the molecular and morphological identification of Genus Uromastyx. In our recommendation, comprehensive molecular based identification of Pakistan's reptiles is required to report any new or subspecies from country.


Resumo Durante o presente estudo, os espécimes foram coletados em locais selecionados do deserto do Cholistan e da Reserva de Caça de Kalabagh, província de Punjab, Paquistão. Cada espécime capturado foi etiquetado com o número do comprovante e medidas morfométricas foram realizadas. O comprimento médio do focinho à cloaca foi de 172,559 ± 1,40 mm, e o peso médio foi de 92,1 ± 1,30 g. O DNA de Uromastyx hardwickii foi amplificado e sequenciado usando o conjunto de primer 16S rRNA. A sequência de DNA obtida mostrou identificação de espécies confiável e clara. Após o corte de bases ambíguas, o fragmento de rRNA 16S obtido tinha 520 pb, enquanto os fragmentos de rRNA 16S alinhados com a sequência próxima do NCBI composta por 510 pb. Sequências semelhantes do gênero Uromastyx foram recuperadas do NCBI em pesquisas de explosão. A árvore de união de vizinhos do gênero Uromastyx foi construída com base na distância-p usando MEGA X. A variação intraespecífica média foi de 0,095 ± 0,01, enquanto a variação intraespecífica foi de 0-1%. Da mesma forma, a variação interespecífica de Uromastyx hardwikii com Saara asmussi, Uromastyx alfredschmidti, Uromastyx geyri, Uromastyx thomasi, Uromastyx alfredschmidti foi de 0-12%, 0-19%, 0-19%, 0-20%, 12-19%, respectivamente. O DNA recém-produzido foi submetido ao NCBI e o número de acesso foi obtido (MW052563.1). Os resultados do estudo atual forneceram informações sobre a identificação molecular e morfológica do Gênero Uromastyx. Em nossa recomendação, a identificação de base molecular abrangente de répteis do Paquistão é necessária para relatar qualquer nova ou subespécie do país.


Assuntos
Animais , Lagartos , Paquistão , Filogenia , Variação Genética/genética , RNA Ribossômico 16S
3.
Front Public Health ; 10: 958021, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159302

RESUMO

The persistent rise of pandemics across the globe in recent times has led to the prescription of several collaborative preventive strategies to reduce the effect that the pandemic has on public health. Consistent monitoring and surveillance appear to be the only available approach to detecting and classifying the issues of public health threats. Global pandemic threats demand public co-operation to take preventive actions at a personal level so that the risk of infectious diseases can be contained. Said that, this study explored the influence of awareness of precaution measures (APM), concerns about coronavirus disease 2019 (COVID-19) (CAC), knowledge of COVID-19 (KOC), and perceived risk (PRK) on preventive behavior (PRB), as well as the effect of age and gender on the relationships among the studied variables. Quantitative data were collected from 551 university students across Malaysia and Vietnam through field survey and online survey, respectively. The data collection was performed from 13 March to 23 March 2020. Partial least square structural equation modeling (PLS-SEM) was employed for data analysis. The multiple group analysis (MGA) technique was applied to compare the data retrieved from the respondents based on age and gender. The results revealed that APM, CAC, KOC, and PRK on PRB significantly influenced PRB toward COVID-19. In light of the two personal factors, age and gender, significant variances were noted for age and KOC, while PRK on PRB on the PRB toward COVID-19. Based on the study outcomes, APM emerged as the most significant predictor of PRB, followed by PRK on PRB, and CAC. Since a large fraction of the world reside in rural areas and have high-level interaction with animals, the provision of education at all level can harness the attitude to adopt PRB toward COVID-19. As such, policymakers need to work with the young generation so that the latter may serve as change agents to spread the message of taking precautions and adopting effective PRB toward COVID-19.


Assuntos
COVID-19 , Ásia Sudeste , COVID-19/epidemiologia , COVID-19/prevenção & controle , Comportamentos Relacionados com a Saúde , Humanos , SARS-CoV-2 , Estudantes , Universidades
4.
Children (Basel) ; 9(8)2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-36010044

RESUMO

Consensus on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) is lacking, and comparison between studies remains difficult due to a large variety in outcome measures. We aimed to define a core outcome set (COS) for pediatric patients with an asymptomatic CPAM. An online, three-round Delphi survey was conducted in two stakeholder groups of specialized caregivers (surgeons and non-surgeons) in various European centers. Proposed outcome parameters were scored according to level of importance, and the final COS was established through consensus. A total of 55 participants (33 surgeons, 22 non-surgeons) from 28 centers in 13 European countries completed the three rounds and rated 43 outcome parameters. The final COS comprises seven outcome parameters: respiratory insufficiency, surgical complications, mass effect/mediastinal shift (at three time-points) and multifocal disease (at two time-points). The seven outcome parameters included in the final COS reflect the diversity in priorities among this large group of European participants. However, we recommend the incorporation of these outcome parameters in the design of future studies, as they describe measurable and validated outcomes as well as the accepted age at measurement.

5.
Saudi J Biol Sci ; 29(6): 103280, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35521357

RESUMO

In human diet, poultry meat is an important component due to the presence of vitamins, proteins and minerals. But poultry meat can be contaminated by pathogenic bacteria which are responsible for food borne infections. The current study was therefore aimed at identification of Escherichia coli, a common pathogen causing food borne infections, in chicken samples (n = 400) collected from three districts of KhyberPukhtunkhwa; Peshawar, Kohat and Nowshera. The isolates were identified by Gram staining, API strips and through PCR (Universal Stress Protein). A total of 174 samples were positive for E. coli among the collected chicken samples. The isolates were resistant to TE, NOR and NA while were sensitive to MEM, TZP and FOS. The results were statistically significant having value P ≤ 0.05 in ANOVA. The isolates showed different antibiotic resistance genes; OXA-1, CTX-M15, blaTEM, QnrS, TetA, AAC, AAD, sul1 and sul2 which is the molecular explanations of their antibiotic resistance pattern. The PCR products were sequenced by Next Generation Sequencing (NGS) and the results revealed mutations in AAC gene (M120T and R197T) and CTX-M15 (A85V, N122D, A148S and G247D). To prevent and treat pathogenic diseases, the use of antimicrobial agents in animal husbandry are of utmost concern. The over-use and misuse of antimicrobial agents has made pathogenic E. coli multi drugs resistant making it a causative agent for many diseases in human beings. The results of the current study may be helpful for the physicians the better management of the diseases caused by E. coli.

6.
Braz. j. biol ; 82: e245261, 2022. tab
Artigo em Inglês | LILACS | ID: biblio-1249221

RESUMO

Abstract Present study was planned to determine variations in external and internal quality egg parameters of different avian species including ostrich Struthio camelus, ducks Anas platyrhynchos, chicken Gallus gallus, turkeys Meleagris gallopavo and grey francolin Francolinus pondicerinus. All the birds were kept under similar rearing conditions. A total of 150 eggs were collected for each species to record external features of these eggs. Statistically significant (p<0.05) variations were recorded in egg weight, egg length and egg width between ostrich, ducks, chicken, turkey and quail eggs. Significantly (p<0.05) higher egg weight, egg length and egg width was observed for ostrich eggs while the same was lowest for grey francolin eggs. Similarly, significantly (p<0.05) greater shape index and egg volume values were observed for ostrich eggs while lowest shape index values were recorded for turkey eggs and egg volume was lowest for grey francolin. Significantly, higher (p<0.05) values of egg density were noted for eggs of the quail and the same were lowest for ostrich eggs. Non-significant variations in egg density values were observed between eggs of the ducks, chicken, turkey and grey francolin. It has been concluded that the positive correlations between the internal and external egg quality traits indicated that the traits can be improved through selection.


Resumo O presente estudo foi planejado para determinar variações nos parâmetros externos e internos de qualidade dos ovos de diferentes espécies de aves, incluindo avestruz Struthio camelus, patos Anas platyrhynchos, frango Gallus gallus, perus Meleagris gallopavo e francolin cinza Francolinus pondicerinus. Todas as aves foram mantidas em condições de criação semelhantes. Um total de 150 ovos foi coletado para cada espécie para registrar as características externas desses ovos. Variações estatisticamente significativas (p < 0,05) foram registradas no peso do ovo, comprimento do ovo e largura do ovo entre os ovos de avestruz, patos, galinha, peru e codorna. Significativamente (p < 0,05) maior peso do ovo, comprimento e largura do ovo foram observados para ovos de avestruz, enquanto o mesmo foi menor para ovos de francolina cinza. Da mesma forma, significativamente (p < 0,05) maiores valores de índice de forma e volume de ovo foram observados para ovos de avestruz, enquanto os menores valores de índice de forma foram registrados para ovos de peru e o volume de ovo foi menor para francolina cinza. Significativamente, maiores (p < 0,05) valores de densidade de ovos foram observados para ovos de codorna e os mesmos foram menores para ovos de avestruz. Variações não significativas nos valores de densidade de ovos foram observadas entre os ovos de pato, frango, peru e francolina cinza. Concluiu-se que as correlações positivas entre as características internas e externas de qualidade do ovo indicaram que as características podem ser melhoradas por meio da seleção.


Assuntos
Animais , Galinhas , Struthioniformes , Paquistão
7.
Braz J Biol ; 84: e254251, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34852138

RESUMO

Blood and fecal samples of chukar partridge (Alectoris chukar), albino pheasant (Phasianus colchicus), silver pheasant (Lophura nycthemera), rose-ringed parakeet (Psittacula krameri) and turkeys (Meleagris gallopavo) were analyzed to check parasitic prevalence. To record parasites these five avian species were placed kept in separate cages at Avian Conservation and Research Center, Department of Wildlife an Ecology, University of Veterinary and Animal Sciences, Lahore, Pakistan. 100 fecal and 100 blood samples for each bird species were inspected to analyze internal parasites. During present study, 17 species of endoparasites 14 from fecal samples and three from blood were examined. Two species of ectoparasites i.e. mite Dermanyssus gallinae 42% and fowl ticks Args persicus 41%were studied. Blood parasites included Plasmodium juxtanucleare 50%, Leucoctoyzoon simond having parasitic prevalence 40%, and Aegyptinella pullorum having parasitic prevalence of 40%. Parasitic species recorded from fecal samples included 6 species of nematodes viz. Allodpa suctoria 2%. Syngamus trachea with parasitic prevalence of 60%, Capillaria annulata 37.5%, Ascardia galli 24%, Capillaria anatis 40% and Heterakis gallinarum 28.3%. Similarly, two species of trematodes viz. Prosthogonimus ovatus having parasitic prevalence of 50% and Prosthogonimus macrorchis 21% were also documented from fecal avian samples . Single cestode species Raillietina echinobothrida having parasitic prevalence of 72% and 3 protozoan species i.e. Eimeria maxima having parasitic prevalence of 21%, Giardia lamblia 41% and Histomonas meleagridis 18% were documented during corpological analysis. In our recommendation, proper sanitation, medication and vaccination of bird's enclousres are suggested to avoid parasites.


Assuntos
Doenças das Aves , Galliformes , Parasitos , Animais , Animais Selvagens , Doenças das Aves/epidemiologia , Prevalência
8.
Wiad Lek ; 74(9 cz 2): 2340-2344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824181

RESUMO

OBJECTIVE: The aim: Facial and leg telangiectasia are usual cosmetic concern for females who have different skin phototypes and ages. Until now, the various treatments for these problem have frequently failed or led to unwanted side-effects. Based on approved pre-calculated doses, the present study highlights the clinical effects and safety of treatment after using the exact laser parameters from 1064-nm Nd: YAG laser. PATIENTS AND METHODS: Materials and methods: Twenty people with facial and leg telangiectasia underwent a single laser treatment, based on pre-calculated laser parameters for each case. RESULTS: Results: All subjects showed visible improvement, with 95-100% clearance of face telangiectasia directly after the first treatment, and 50-100% clearance of the lower extremity vessels after one to three days; with minimal side-effects. CONCLUSION: Conclusions: Treatment of facial and leg telangiectasia by using true, exact, and mathematically pre-calculated parameters of long pulse 1064 nm Nd: YAG laser was an effective and safe procedure of clearing face and leg telangiectasia.


Assuntos
Terapia a Laser , Telangiectasia , Face , Feminino , Humanos , Lasers , Perna (Membro) , Pele , Telangiectasia/cirurgia , Resultado do Tratamento
9.
Braz J Biol ; 84: e254253, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34816973

RESUMO

During the present study, specimens were collected from selected sites of Cholistan desert and Kalabagh Game Reserve, Punjab province, Pakistan. Each captured specimen was tagged with voucher number and morphometric measurements were taken. The average snout to vent length was 172.559±1.40 mm and average weight was 92.1±1.30 g. The DNA of Uromastyx hardwickii was amplified and sequenced using 16S rRNA primer set. The obtained DNA sequence has shown reliable and clear species identification. After trimming ambiguous bases, the obtained 16S rRNA fragment was 520 bp while 16S rRNA fragments aligned with closely matched sequence from NCBI comprised of 510 bp. Closely matched sequences of genus Uromastyx were retrieved from NCBI in blast searches. Neighbour-joining tree of genus Uromastyx was constructed based on p-distance using MEGA X. The mean intraspecific variation was 0.095±0.01 while intraspecific variation was ranging from 0-1%. Similarly, interspecific variation of Uromastyx hardwikii with Saara asmussi, Uromastyx alfredschmidti, Uromastyx geyri, Uromastyx thomasi, Uromastyx alfredschmidti was 0-12%, 0-19%, 0-19%, 0-20%, 12-19% respectively. The newly produced DNA was submitted to NCBI and accession number was obtained (MW052563.1). Results of current study provided information about the molecular and morphological identification of Genus Uromastyx. In our recommendation, comprehensive molecular based identification of Pakistan's reptiles is required to report any new or subspecies from country.


Assuntos
Lagartos , Animais , Variação Genética/genética , Paquistão , Filogenia , RNA Ribossômico 16S
10.
Braz J Biol ; 82: e245261, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076170

RESUMO

Present study was planned to determine variations in external and internal quality egg parameters of different avian species including ostrich Struthio camelus, ducks Anas platyrhynchos, chicken Gallus gallus, turkeys Meleagris gallopavo and grey francolin Francolinus pondicerinus. All the birds were kept under similar rearing conditions. A total of 150 eggs were collected for each species to record external features of these eggs. Statistically significant (p<0.05) variations were recorded in egg weight, egg length and egg width between ostrich, ducks, chicken, turkey and quail eggs. Significantly (p<0.05) higher egg weight, egg length and egg width was observed for ostrich eggs while the same was lowest for grey francolin eggs. Similarly, significantly (p<0.05) greater shape index and egg volume values were observed for ostrich eggs while lowest shape index values were recorded for turkey eggs and egg volume was lowest for grey francolin. Significantly, higher (p<0.05) values of egg density were noted for eggs of the quail and the same were lowest for ostrich eggs. Non-significant variations in egg density values were observed between eggs of the ducks, chicken, turkey and grey francolin. It has been concluded that the positive correlations between the internal and external egg quality traits indicated that the traits can be improved through selection.


Assuntos
Galinhas , Struthioniformes , Animais , Paquistão
11.
Eur J Med Chem ; 223: 113639, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34175539

RESUMO

Nature represents a rich source of compounds used for the treatment of many diseases. Camptothecin (CPT), isolated from the bark of Camptotheca acuminata, is a cytotoxic alkaloid that attenuates cancer cell replication by inhibiting DNA topoisomerase 1. Despite its promising and wide spectrum antiproliferative activity, its use is limited due to low solubility, instability, acquired tumour cell resistance, and remarkable toxicity. This has led to the development of numerous CPT analogues with improved pharmacodynamic and pharmacokinetic profiles. Three natural product-inspired drugs, namely, topotecan, irinotecan, and belotecan, are clinically approved and prescribed drugs for the treatment of several types of cancer, whereas other derivatives are in clinical trials. In this review, which covers literature from 2015 to 2020, we aim to provide a comprehensive overview and describe efforts that led to the development of a variety of CPT analogues. These efforts have led to the discovery of potent, first-in-class chemotherapeutic agents inspired by CPT. In addition, the mechanism of action, SAR studies, and recent advances of novel CPT drug delivery systems and antibody drug conjugates are discussed.


Assuntos
Antineoplásicos Fitogênicos/química , Camptotecina/análogos & derivados , Antineoplásicos Fitogênicos/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Camptotheca/química , Camptotheca/metabolismo , Camptotecina/metabolismo , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Relação Estrutura-Atividade , Inibidores da Topoisomerase I/química , Inibidores da Topoisomerase I/metabolismo , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase I/uso terapêutico , Organização Mundial da Saúde
12.
Cancer Discov ; 11(1): 80-91, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32988960

RESUMO

Targeting the ataxia telangiectasia and RAD3-related (ATR) enzyme represents a promising anticancer strategy for tumors with DNA damage response (DDR) defects and replication stress, including inactivation of ataxia telangiectasia mutated (ATM) signaling. We report the dose-escalation portion of the phase I first-in-human trial of oral ATR inhibitor BAY 1895344 intermittently dosed 5 to 80 mg twice daily in 21 patients with advanced solid tumors. The MTD was 40 mg twice daily 3 days on/4 days off. Most common adverse events were manageable and reversible hematologic toxicities. Partial responses were achieved in 4 patients and stable disease in 8 patients. Median duration of response was 315.5 days. Responders had ATM protein loss and/or deleterious ATM mutations and received doses ≥40 mg twice daily. Overall, BAY 1895344 is well tolerated, with antitumor activity against cancers with certain DDR defects, including ATM loss. An expansion phase continues in patients with DDR deficiency. SIGNIFICANCE: Oral BAY 1895344 was tolerable, with antitumor activity in heavily pretreated patients with various advanced solid tumors, particularly those with ATM deleterious mutations and/or loss of ATM protein; pharmacodynamic results supported a mechanism of action of increased DNA damage. Further study is warranted in this patient population.See related commentary by Italiano, p. 14.This article is highlighted in the In This Issue feature, p. 1.


Assuntos
Ataxia Telangiectasia , Neoplasias , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Dano ao DNA , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Inibidores de Proteínas Quinases/efeitos adversos
13.
Br J Cancer ; 123(9): 1360-1369, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32741975

RESUMO

BACKGROUND: BAL101553 (lisavanbulin), the lysine prodrug of BAL27862 (avanbulin), exhibits broad anti-proliferative activity in human cancer models refractory to clinically relevant microtubule-targeting agents. METHODS: This two-part, open-label, phase 1/2a study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of 2-h infusion of BAL101553 in adults with advanced or recurrent solid tumours. The MTD was determined using a modified accelerated titration design in phase I. Patients received BAL101553 at the MTD and at lower doses in the phase 2a expansion to characterise safety and efficacy and to determine the recommended phase 2 dose (RP2D). RESULTS: Seventy-three patients received BAL101553 at doses of 15-80 mg/m2 (phase 1, n = 24; phase 2a, n = 49). The MTD was 60 mg/m2; DLTs observed at doses ≥60 mg/m2 were reversible Grade 2-3 gait disturbance with Grade 2 peripheral sensory neuropathy. In phase 2a, asymptomatic myocardial injury was observed at doses ≥45 mg/m2. The RP2D for 2-h intravenous infusion was 30 mg/m2. The overall disease control rate was 26.3% in the efficacy population. CONCLUSIONS: The RP2D for 2-h infusion of BAL101553 was well tolerated. Dose-limiting neurological and myocardial side effects were consistent with the agent's vascular-disrupting properties. CLINICAL TRIAL REGISTRATION: EudraCT: 2010-024237-23.


Assuntos
Benzimidazóis/administração & dosagem , Neoplasias/tratamento farmacológico , Oxidiazóis/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzimidazóis/efeitos adversos , Benzimidazóis/farmacocinética , Progressão da Doença , Feminino , Humanos , Infusões Intravenosas , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/patologia , Oxidiazóis/efeitos adversos , Oxidiazóis/farmacocinética , Pró-Fármacos/administração & dosagem , Pró-Fármacos/efeitos adversos , Pró-Fármacos/farmacocinética , Fuso Acromático/efeitos dos fármacos , Reino Unido
14.
J Clin Exp Dent ; 12(4): e317-e326, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32382380

RESUMO

BACKGROUND: This in vitro study compares a novel calcium-phosphate etchant paste to conventional 37% phosphoric acid gel for bonding metal and ceramic brackets by evaluating the shear bond strength, remnant adhesive and enamel damage following water storage, acid challenge and fatigue loading. MATERIAL AND METHODS: Metal and ceramic brackets were bonded to 240 extracted human premolars using two enamel conditioning protocols: conventional 37% phosphoric acid (PA) gel (control), and an acidic calcium-phosphate (CaP) paste. The CaP paste was prepared from ß-tricalcium phosphate and monocalcium phosphate monohydrate powders mixed with 37% phosphoric acid solution, and the resulting phase was confirmed using FTIR. The bonded premolars were exposed to four artificial ageing models to examine the shear bond strength (SBS), adhesive remnant index (ARI score), with stereomicroscopic evaluation of enamel damage. RESULTS: Metal and ceramic control subgroups yielded significantly higher (p < 0.05) SBS (17.1-31.8 MPa) than the CaP subgroups (11.4-23.8 MPa) post all artificial ageing protocols, coupled with higher ARI scores and evidence of enamel damage. In contrast, the CaP subgroups survived all artificial ageing tests by maintaining adequate SBS for clinical performance, with the advantages of leaving unblemished enamel surface and bracket failures at the enamel-adhesive interface. CONCLUSIONS: Enamel conditioning with acidic CaP pastes attained adequate bond strengths with no or minimal adhesive residue and enamel damage, suggesting a suitable alternative to the conventional PA gel for orthodontic bonding. Key words:Enamel etching, calcium phosphate, bracket bond strength, adhesive residue, enamel damage.

15.
Cells ; 9(3)2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-32183164

RESUMO

Human pluripotent stem cells (hPSCs) can provide unlimited supply for mesenchymal stem cells (MSCs) and adipocytes that can be used for therapeutic applications. Here we developed a simple and highly efficient all-trans-retinoic acid (RA)-based method for generating an off-the-shelf and scalable number of human pluripotent stem cell (hPSC)-derived MSCs with enhanced adipogenic potential. We showed that short exposure of multiple hPSC lines (hESCs/hiPSCs) to 10 µM RA dramatically enhances embryoid body (EB) formation through regulation of genes activating signaling pathways associated with cell proliferation, survival and adhesion, among others. Disruption of cell adhesion induced the subsequent differentiation of the highly expanded RA-derived EB-forming cells into a pure population of multipotent MSCs (up to 1542-fold increase in comparison to RA-untreated counterparts). Interestingly, the RA-derived MSCs displayed enhanced differentiation potential into adipocytes. Thus, these findings present a novel RA-based approach for providing an unlimited source of MSCs and adipocytes that can be used for regenerative medicine, drug screening and disease modeling applications.


Assuntos
Adipócitos/citologia , Técnicas de Cultura de Células/métodos , Células-Tronco Mesenquimais/citologia , Células-Tronco Pluripotentes/citologia , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Corpos Embrioides/citologia , Corpos Embrioides/efeitos dos fármacos , Perfilação da Expressão Gênica , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Pluripotentes/efeitos dos fármacos , Tretinoína/farmacologia
16.
Reumatismo ; 71(4): 218-225, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31995961

RESUMO

Behçet's disease is a relapsing multisystemic disease. Its highest prevalence is seen along the Silk Road. While several studies reported gender disparities, others didn't. Scarce data are available about the Arabs and the gender differences detected in some ethnicities could not be applied to others. Our study aimed to detect gender differences among a cohort of adult Egyptian patients with Behçet's disease. Medical files of 255 adult patients diagnosed with Behçet's disease at the Rheumatology and Rehabilitation Department of Kasr Al-Aini Hospital, Cairo University and the Internal Medicine Department of Tanta University, between 2002 and 2018, were retrospectively reviewed. The demographic features, the cumulative clinical features, the use, if any, of an intravenous pulse of methylprednisolone and immunosuppressive/biological drugs, and the frequency of the cumulative damage to the different organ systems were described. The disease severity score was calculated as well. The study revealed a prominent male predominance; the male to female ratio was 6.7:1. Acne/pseudofolliculitis was more common in males (28.6% vs 13.2%, p=0.046); the same was observed regarding any vascular involvement and peripheral venous disease (36.3% vs 18.4%, p=0.03 and 30.4% vs 13.2%, p=0.03, respectively). On the other hand, encephalitis and cranial nerve lesions were more prevalent in females (15.8% vs 6%, p=0.03 and 10.5% vs 3.2%, p=0.04, respectively). Severe Behçet's disease equally affects Egyptian males and females. BD should not be considered a benign disease in Egyptian females. The same quality of medical care should be equally offered to both genders.


Assuntos
Síndrome de Behçet/epidemiologia , Acne Vulgar/epidemiologia , Adulto , Idade de Início , Síndrome de Behçet/tratamento farmacológico , Doenças dos Nervos Cranianos/epidemiologia , Diagnóstico Tardio/estatística & dados numéricos , Egito/epidemiologia , Encefalite/epidemiologia , Feminino , Foliculite/epidemiologia , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Distribuição por Sexo , Doenças Vasculares/epidemiologia , Adulto Jovem
17.
J Clin Exp Dent ; 12(1): e22-e30, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31976040

RESUMO

BACKGROUND: This in vitro study compares a self-etch primer (SEP) to an etch-and-rinse (EaR) for bonding sapphire brackets by evaluation of the enamel etch-pattern, shear bond strength, amount of remnant adhesive and enamel surface damage following thermal and fatigue cyclic loading. MATERIAL AND METHODS: Ceramic (sapphire) brackets were bonded to 80 extracted human premolars using two enamel etching protocols: conventional EaR using 37% phosphoric acid (PA) gel (control), and a SEP (Transbond Plus). Each group was subdivided into two subgroups (n=20 teeth) according to the time of bracket debonding: after 24 h water storage or following 5000 thermo-cycles plus 5000 cycles fatigue loading, to determine the shear bond strength (SBS), adhesive remnant index (ARI score), with scanning electron microscopy (SEM) evaluation of enamel condition. RESULTS: The control subgroups consistently exhibited significantly higher (p<0.05) SBS mean values (23.4-29.8 MPa) than the SEP subgroups (15.1-22.4 MPa) at both bracket debonding time points. However, the SEP subgroups yielded milder etch-patterns and attained SBS values above the minimum requirement range for clinical performance. In addition, the higher SBS of control subgroups was accompanied with higher ARI scores and enamel damage grades than SEP subgroups as confirmed by SEM. Thermocycling and fatigue significantly reduced the SBS of all subgroups, with a non-significant drop in the amount of adhesive residue or enamel damage. CONCLUSIONS: The use of SEP can be a suitable alternative to the conventional PA gel for sapphire bracket bonding as it maintains suitable bond strength and has the potential to produce both less remnant adhesive and enamel damage. Key words:Enamel etching, ceramic brackets, orthodontic bonding, adhesive remnants, enamel damage.

18.
Cells ; 8(8)2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31530793

RESUMO

Recent biomedical discoveries have revolutionized the concept and understanding of carcinogenesis, a complex and multistep phenomenon which involves accretion of genetic, epigenetic, biochemical, and histological changes, with special reference to MicroRNAs (miRNAs) and cancer stem cells (CSCs). miRNAs are small noncoding molecules known to regulate expression of more than 60% of the human genes, and their aberrant expression has been associated with the pathogenesis of human cancers and the regulation of stemness features of CSCs. CSCs are the small population of cells present in human malignancies well-known for cancer resistance, relapse, tumorigenesis, and poor clinical outcome which compels the development of novel and effective therapeutic protocols for better clinical outcome. Interestingly, the role of miRNAs in maintaining and regulating the functioning of CSCs through targeting various oncogenic signaling pathways, such as Notch, wingless (WNT)/ß-Catenin, janus kinases/ signal transducer and activator of transcription (JAK/STAT), phosphatidylinositol 3-kinase/ protein kinase B (PI3/AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-kB), is critical and poses a huge challenge to cancer treatment. Based on recent findings, here, we have documented the regulatory action or the underlying mechanisms of how miRNAs affect the signaling pathways attributed to stemness features of CSCs, such as self-renewal, differentiation, epithelial to mesenchymal transition (EMT), metastasis, resistance and recurrence etc., associated with the pathogenesis of various types of human malignancies including colorectal cancer, lung cancer, breast cancer, head and neck cancer, prostate cancer, liver cancer, etc. We also shed light on the fact that the targeted attenuation of deregulated functioning of miRNA related to stemness in human carcinogenesis could be a viable approach for cancer treatment.


Assuntos
Carcinogênese/metabolismo , MicroRNAs/fisiologia , Neoplasias , Células-Tronco Neoplásicas/patologia , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Transdução de Sinais
19.
Biomolecules ; 9(4)2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934922

RESUMO

Greensporone A is a fungal secondary metabolite that has exhibited potential in vitro for anti-proliferative activity in vitro. We studied the anticancer activity of greensporone A in a panel of leukemic cell lines. Greensporone A-mediated inhibition of proliferation is found to be associated with the induction of apoptotic cell death. Greensporone A treatment of leukemic cells causes inactivation of constitutively activated AKT and its downstream targets, including members GSK3 and FOXO1, and causes downregulation of antiapoptotic genes such as Inhibitor of Apoptosis (IAPs) and Bcl-2. Furthermore, Bax, a proapoptotic member of the Bcl-2 family, was found to be upregulated in leukemic cell lines treated with greensporone A. Interestingly, gene silencing of AKT using AKT specific siRNA suppressed the expression of Bcl-2 with enhanced expression of Bax. Greensporone A-mediated increase in Bax/Bcl-2 ratio causes permeabilization of the mitochondrial membrane leading to the accumulation of cytochrome c in the cytoplasm. Greensporone A-induced cytochrome c accumulation causes the activation of caspase cascade and cleavage of its effector, poly(ADP-ribose) polymerase (PARP), leading to apoptosis. Greensporone A-mediated apoptosis in leukemic cells occurs through the generation of reactive oxygen species (ROS) due to depletion of glutathione (GSH) levels. Finally, greensporone A potentiated the anticancer activity of imatinib in leukemic cells. In summary, our study showed that greensporone A suppressed the growth of leukemic cells via induction of apoptotic cell death. The apoptotic cell death occurs by inhibition of AKT signaling and activation of the intrinsic apoptotic/caspase pathways. These results raise the possibility that greensporone A could be developed as a therapeutic agent for the treatment of leukemia and other hematological malignancies.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ascomicetos/química , Macrolídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Ascomicetos/metabolismo , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Macrolídeos/química , Macrolídeos/isolamento & purificação , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estrutura Molecular , Proteínas Proto-Oncogênicas c-akt , Espécies Reativas de Oxigênio/análise , Metabolismo Secundário , Relação Estrutura-Atividade , Células Tumorais Cultivadas
20.
Lupus ; 27(6): 1039-1044, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29460702

RESUMO

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease that occurs worldwide in both children and adults, with different disease manifestations, activity and severity between them. Objectives To analyse the difference in disease onset patterns and activity in Egyptian children and adults with SLE. Methods A retrospective cohort study conducted on 298 Egyptian SLE patients, 215 adults (a-SLE) (>18 years) and 83 children (j-SLE) (≤18 years). Disease onset, clinical manifestations and laboratory investigations were recorded. The systemic lupus erythematosus disease activity index (SLEDAI) was used to assess disease onset activity; renal biopsy was performed for all cases affected with renal symptoms. Results A total of 215 a-SLE (F/M: 14.4/1), mean age 29.65 ± 10.235 years, and 83 j-SLE (F/M: 5.4/1), mean age at diagnosis 12.63 ± 3.112 years. The most frequent initial a-SLE symptoms were constitutional (88.8%), mucocutaneous (71.2%), haematological (64.2%), articular (62.3%), renal (43.7%), vascular (15.3%), serositis (14.4%) and finally central nervous system (11.6%). There were no significant differences between a-SLE and j-SLE with regard to constitutional, mucocutaneous, renal, vascular and serositis manifestations, which were 92.8%, 74.7%, 53%, 16.9% and 10.8%, respectively, but the j-SLE haematological (88%) and central nervous system (30.1%) manifestations were significantly higher than a-SLE and articular manifestations were significantly lower in j-SLE (14.5%) than a-SLE. Antinuclear antibodies were positive for 95.3% of a-SLE and 97.6% of j-SLE. Anti-dsDNA was positive for 84.7% a-SLE and was significantly higher in j-SLE (92.8%). The SLEDAI score was 12.23 ± 4.966 in a-SLE and was significantly higher in j-SLE (27.13 ± 19.968). International Society of Nephrology lupus nephritis classes III and IV (42.4%) were the commonest findings in a-SLE; however, classes I and III (57.9%) were the commonest in j-SLE. Conclusions SLE had a wide variety of clinical and immunological manifestations, with some similarity and differences between a-SLE and j-SLE; juvenile onset lupus had a higher SLEDAI with more aggressive initial manifestations than a-SLE.


Assuntos
Lúpus Eritematoso Sistêmico/epidemiologia , Adolescente , Adulto , Idade de Início , Autoanticorpos/sangue , Biomarcadores/sangue , Criança , Egito/epidemiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
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