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1.
Breast Cancer Res Treat ; 204(2): 289-297, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38155272

RESUMO

PURPOSE: Many stage III inflammatory breast cancer (IBC) patients experience a sufficient response to first-line (1L) neoadjuvant chemotherapy (NAC) to allow surgery, while some require additional NAC. We evaluated the pathologic complete response (pCR), breast cancer-free survival (BCFS) and overall survival (OS) among patients requiring 1 vs. 2-3 lines (L) of NAC prior to surgery. METHODS: Stage III IBC patients from 2 institutions who received 1L or 2-3L of NAC prior to surgery were identified. Hormone receptor and HER2 status, grade, and pCR were evaluated. BCFS and OS were evaluated by the Kaplan-Meier method. Multivariable Cox models were utilized to estimate the hazard ratio (HR). RESULTS: 808 eligible patients (1997-2020) were identified (median age 51 years, median follow-up 69 months). 733 (91%) had 1L and 75 (9%) had 2-3L of NAC. Grade III, triple-negative and HER2-positive disease were more prevalent in 2-3L patients. 178 (24%) 1L and 14 (19%) 2-3L patients had pCR. 376 1L patients and 41 2-3L patients had recurrences. The 5-year BCFS was worse for the 2-3L group (33 vs. 46%, HR = 1.37; 95% CI 0.99-1.91). However, in 192 patients with a pCR, BCFS was similar (76 vs. 83% in 1L vs. 2-3L, respectively). There were 308 deaths (276 among 1L and 32 among 2-3L patients). The 5-year OS in 1L vs. 2-3L was 60 vs. 53% (HR = 1.32, 95% CI 0.91-1.93). CONCLUSIONS: Among stage III IBC patients, pCR rates were similar, irrespective of the NAC lines number, and BCFS and OS were comparable with pCR after 1L and 2-3L.


Assuntos
Neoplasias da Mama , Neoplasias Inflamatórias Mamárias , Humanos , Pessoa de Meia-Idade , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Terapia Neoadjuvante , Neoplasias Inflamatórias Mamárias/tratamento farmacológico , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Receptor ErbB-2/genética
2.
Cancer ; 129(14): 2201-2213, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37016732

RESUMO

BACKGROUND: Selinexor (KPT-330) is a potent inhibitor of exportin 1 (XPO1), in turn inhibiting tumor growth. Selinexor enhances the antitumor efficacy of eribulin in triple-negative breast cancer (TNBC) in vitro and in vivo. Given the unmet medical need in TNBC and sarcoma, the authors explored the safety and efficacy of this combination. METHODS: The authors conducted a phase 1b trial of combined selinexor and eribulin using a 3 + 3 dose-escalation design in patients who had advanced solid tumors and in those who had TNBC in a dose-expansion cohort. RESULTS: Patients with TNBC (N = 19), sarcoma (N = 9), and other cancers (N = 3) were enrolled in the dose-escalation cohort (N = 10) and in the dose-expansion cohort (N = 21). The median number lines of prior therapy received was four (range, from one to seven prior lines). The most common treatment-related adverse events for selinexor were nausea (77%), leukopenia (77%), anemia (68%), neutropenia (68%), and fatigue (48%). One dose-limiting toxicity occurred at the first dose level with prolonged grade 3 neutropenia. The recommended phase 2 dose was 80 mg of selinexor orally once per week and 1 mg/m2 eribulin on days 1 and 8 intravenously every 3 weeks. The objective response rate (ORR) was 10% in three patients. In the dose-escalation cohort, the ORR was 10%, whereas six patients with had stable disease. In the TNBC dose-expansion cohort (n = 18), ORR was 11%, and there were two confirmed partial responses with durations of 10.8 and 19.1 months (ongoing). CONCLUSIONS: Selinexor and eribulin had an acceptable toxicity profile and modest overall efficacy with durable responses in select patients. PLAIN LANGUAGE SUMMARY: Effective therapies for advanced, triple-negative breast cancer and sarcoma represent an unmet need. Exportin 1 is associated with the transport of cancer-related proteins. Preclinical studies have demonstrated tumor growth inhibition and enhanced tumor sensitivity in patients who receive selinexor combined with eribulin. In this phase 1b study, the authors evaluated the safety profile and clinical activity of the combination of selinexor, a potent oral inhibitor of exportin 1, and eribulin in patients with advanced cancers enriched for triple-negative breast cancer or sarcoma. The combination was well tolerated; most adverse events were mild or moderate, reversible, and managed with dose modifications or growth factor support. The combination of selinexor and eribulin produced an antitumor response, particularly in some patients with triple-negative breast cancer. This work lays the foundation for prospective investigations of the role of selinexor and eribulin in the treatment of triple-negative breast cancer.


Assuntos
Neutropenia , Sarcoma , Neoplasias de Tecidos Moles , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Estudos Prospectivos , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
3.
Pak J Pharm Sci ; 35(2(Special)): 671-678, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35668569

RESUMO

Cadmium is a potent neurotoxin and induces adverse impact on brain function. Protective effects of monoterpenes on the CNS have been reported previously. The present study was designed to investigate the beneficial effect of thymol on cadmium-induced neurotoxicity. Rats were initially divided into 2 groups, vehicle control and thymol. Thymol (40mg/kg) was given orally for 14 days. Each group was subdivided into two groups (Vehicle control and Cadmium, Thymol and Thymol+Cadmium). Cadmium Chloride (5mg/kg) was given for last 3 days only to the groups assigned as Cadmium and Thymol+Cadmium. Behavioral parameters were assessed after 24h of last dose of cadmium. Brain sample were collected and BDNF was measured in hippocampus. The present study suggests that pre-administration of thymol provides a protective therapy against cadmium-induced intoxication by enhancing the brain BDNF levels and plasticity. Results further suggest that thymol not only ameliorates cadmium-induced learning and memory impairment but also reduced anxiety, motor incoordination and depression assessed by various behavioral tests. The study may provide a better apprehension of the neuroprotective role of thymol and highlighting its significance in the diet for human health particularly in cadmium intoxication.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Timol , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cádmio/toxicidade , Cognição , Hipocampo , Ratos , Timol/farmacologia
4.
Invest New Drugs ; 39(2): 509-515, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32984932

RESUMO

Folate receptor alpha (FRα) has been reported to be expressed in up to 80% of triple-negative breast cancers (TNBC) with limited expression in normal tissues, making it a promising therapeutic target. Mirvetuximab soravtansine (mirvetuximab-s) is an antibody drug conjugate which has shown promise in the treatment of FRα-positive solid tumors in early phase clinical trials. Herein, are the results of the first prospective phase II trial evaluating mirvetuximab-s in metastatic TNBC. Patients with advanced, FRα-positive TNBC were enrolled on this study. Mirvetuximab-s was administered at a dose of 6.0 mg/kg every 3 weeks. 96 patients with advanced TNBC consented for screening. FRα staining was performed on tumor tissue obtained from 80 patients. The rate of FRα positivity by immunohistochemistry was 10.0% (8/80). Two patients were treated on study, with best overall responses of stable disease in one and progressive disease in the other. Adverse events were consistent with earlier studies. The study was terminated early due to the low rate of FRα positivity in the screened patient population and lack of disease response in the two patients treated. The observed rate of FRα positivity was considerably lower than previously reported and none of the patients had a partial or complete response. Treatment with mirvetuximab-s should only be further explored in TNBC if an alternate biomarker strategy is developed for patient selection on the basis of additional preclinical data.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunoconjugados/uso terapêutico , Maitansina/análogos & derivados , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Receptor 1 de Folato/biossíntese , Humanos , Imunoconjugados/efeitos adversos , Maitansina/efeitos adversos , Maitansina/uso terapêutico , Estudos Prospectivos , Neoplasias de Mama Triplo Negativas/patologia
5.
J Community Health ; 46(3): 476-486, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32661860

RESUMO

Exceptional precautionary measures have been adopted to stop the transmission and control of COVID-19 through the world and Pakistan is facing lockdown in this scenario. Public loyalty to precautionary measures is affected by their knowledge, attitude, risk factors and practices (KAP) towards COVID-19. The present study was conducted among the Pakistani residents to observe the knowledge, attitude, practices and risk factors towards COVID-19 outbreak in Pakistan. A questionnaire was designed, and a cross-sectional survey was conducted among participants of the study area. Participants were asked the questions regarding knowledge, attitude, practices and risk factors towards COVID-19. Data were analyzed by SPSS and t/F test and correlation was applied among the knowledge, attitude, risk factors and practices. A total of 1060 questionnaires were received. 1004 were included while 56 were excluded. The highest representation was from Punjab province (65.6%), female (63%) and age group of 21-30 years (62.1%). Most participants were single (85%), Muslim (99.4%), Urdu speaking (45.6%) and were graduates (51.5%). Most of the participants were students (52.9%) and were from economically middle-class families (40.8%). The knowledge was positively correlated with attitude and practices whereas negatively correlated with risk factors (P < 0.05). The attitude was negatively correlated with risk factor and positively correlated with practices. The risk factors and practices were positively correlated with each other. Health education program to improve the COVID-19 knowledge, attitude, practices and risk factors should be initiated to combat current health challenge.


Assuntos
COVID-19/prevenção & controle , Surtos de Doenças , Conhecimentos, Atitudes e Prática em Saúde , Adulto , COVID-19/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Paquistão/epidemiologia , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
6.
J Pak Med Assoc ; 71(2(B)): 677-680, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33941957

RESUMO

OBJECTIVE: To identify the mediating role of self-confidence in family cohesion and depression in adolescents. METHODS: The cross-sectional study was conducted at five mainstream government boys and girls schools in Lahore, Pakistan, from March 1 to November 30, 2019, and comprised adolescents aged 12-19 years. Data was collected using Family Cohesion Scale, Self-confidence Scale and Depression Scale for Adolescents. Data was analysed using SPSS 25. RESULTS: Of the 394 subjects, 214(54%) were boys and 180(46%) were girls. The overall mean age was 14.76±1.39 years. A significant positive association between family cohesion and self-confidence (p<0.001), and a significant negative association of family cohesion (p<0.001) and self-confidence (p<0.01) with depression was found. Self-confidence partially mediated the relationship between family cohesion and depression (p < 0.05). CONCLUSIONS: Early and timely identification of risk factors can prevent serious consequences of depression in adolescents.


Assuntos
Depressão , Relações Familiares , Adolescente , Adulto , Criança , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Masculino , Paquistão/epidemiologia , Autoimagem , Adulto Jovem
7.
J Pak Med Assoc ; 71(1(B)): 306-309, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35157669

RESUMO

OBJECTIVE: To develop a valid and reliable scale for measuring psychosocial issues of hearing-impaired school children. METHODS: The cross-sectional study with four stage model of scale development was conducted at Multan, Muzafargarh, and Dera Ghazi Khan Pakistan from August 2018 to January 2019. The four stages were item generation, expert validation, conversion of scale into sign language and psychometric study. The sample comprised hearing-impaired school children aged 18-23 years who were studying Special Education schools in Multan, Pakistan. RESULTS: Of the 230 subjects, there were 110(47.8%) boys and 120(52.2%) girls. The overall mean age was 19.90±2.46 years. Exploratory factor analysis with varimax rotation revealed 26 items in 'Depressive Affect', 'Social Isolation' and 'Feeling of Anger' sub-scales with high internal consistency (r=0.85) and validity (r=-0.32). CONCLUSIONS: The internalised nature of psychosocial issues of children with hearing impairment needs timely identification and intervention so that silent suffering can be prevented to improve psychosocial functioning of such children.


Assuntos
Audição , Instituições Acadêmicas , Adolescente , Adulto , Criança , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem
8.
Pak J Med Sci ; 37(2): 456-460, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679931

RESUMO

BACKGROUND: The current study aimed at investigating the manifestation and prevalence of the commonly reported psychosocial reactions in the university students following the onset of COVID-19 pandemic. METHODS: This cross-sectional survey was carried out during April to May, 2020 in the city of Lahore. Based on the interviews and presenting problems of thirty-nine self-referred students to student counselling service center, a list of twenty-seven self-report measure was presented through an online cross-sectional survey of 510 students enrolled in a private institute. The age range of the participants was between 17-26 years (M, 21.86; SD, 2.94). RESULTS: The results showed that the most frequently reported reactions by university students during COVID-19 is restricted daily routine (92%), preoccupation with cleanliness (86%), feeling uncertain about future (85%), feeling bored (84%) and low mood (84%). The least frequently reported reaction was financial crisis (48%). The findings further showed that 18% of the participants had mild, 34% had moderate, 29% severe and 19% very severe level of problems. CONCLUSIONS: The finding revealed that university students have significantly affected by this pandemic which need attention from mental health professionals.

9.
Pak J Pharm Sci ; 34(4(Supplementary)): 1615-1620, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34799339

RESUMO

Benzodiazepine administration is known to be related to tolerance and a withdrawal syndrome on sudden cessation. Thymol possesses multiple biological properties especially in the pathogenesis of different brain disorders. However, to the best of our knowledge there is no study that relates the use of thymol to benzodiazepine induced withdrawal symptoms. Therefore the aim of the current study was to investigate the usefulness of thymol in the treatment of benzodiazepine withdrawal syndrome in rats. Animals were divided into four groups, thymol (40mg/kg/ml), diazepam (4 mg/kg), thymol + diazepam and vehicle control group. The treatment was given for 14 days and then suddenly ceased. After 24 h animals were tested in different behavioral paradigms such as physical signs for withdrawal, marble burying test, inverted screen test, elevated plus maze, passive avoidance test and open field activity. The results of the present study revealed that co-administration of thymol significantly reduced the withdrawal symptoms induced by diazepam. Our results further suggest that administration of thymol not only ameliorates rebound anxiety associated with diazepam withdrawal but also improves motor and memory impairment in rats.


Assuntos
Diazepam/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Fármacos Neuroprotetores/uso terapêutico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Timol/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Ratos , Ratos Wistar
10.
Pak J Pharm Sci ; 33(6(Supplementary)): 2785-2791, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33879438

RESUMO

Exposure to cadmium has been extensively increased due to its usage in modern daily life. Inside the human body it induces deteriorating effects in every vital organ including brain. Oxidative stress has been widely implicated in neurotoxicity induced by cadmium exposure. Consumption of dietary source of exogenous antioxidants is one of the recommended ways to extenuate heavy metal-induced oxidative stress. The potential of nuts against heavy-metal induced neurotoxicity has not been investigated earlier. This study was, therefore, conducted to find out the antioxidant ability of almond and walnut in the prevention of cadmium-induced oxidative stress. Rats were treated with nuts (400 mg/kg) daily for 28 days whereas, cadmium (50 mg/kg) was given once in a week. Brain function was monitored in terms of memory performance using Morris water maze and elevated plus maze. Moreover, oxidative stress status was also evaluated. Results showed that weekly exposure of cadmium significantly reduced %memory retention, increased lipid per oxidation and inhibited antioxidant enzymes activity. When nuts supplemented rats were monitored for these parameters, it was observed that almond and walnut have a great potential to reduce cadmium-induced neurotoxicity as evident by decreased oxidative stress and improved memory function in cadmium intoxicated rats.


Assuntos
Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Cádmio/toxicidade , Juglans , Estresse Oxidativo/efeitos dos fármacos , Prunus dulcis , Animais , Catalase/metabolismo , Suplementos Nutricionais , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
11.
Pak J Pharm Sci ; 32(1): 53-60, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30772790

RESUMO

Curcumin possesses wide spectrum of biological actions, on that account the current study was aimed to investigate the beneficial effectiveness of curcumin on memory and oxidative stress if any, over synthetic drug donepezil approved for the treatment of memory disorders. Eighteen Albino wistar (male) rats were divided into 3 groups namely vehicle control which received neutral oil orally and 0.9% saline intraperitoneally, curcumin which received curcumin orally dissolved in neutral oil at the dose of 100mg/ml/kg for seven days, donepezil which received donepezil intraperitoneally at the dose of 1mg/ml/kg for seven days. To assess memory and cognition Elevated Plus Maze and Morris Water Maze tests were performed. Rats were sacrificed after behavioral analysis and their brains were removed for biochemical assays including lipid peroxidation and antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase. Acetylcholine esterase activity and acetylcholine levels were also determined. Our results showed that both curcumin and donepezil improved memory and inhibited acetylcholinesterase, however curcumin inhibited AchE with more potency than donepezil when compared to vehicle control rats. Moreover curcumin exhibited greater antioxidant potential to decrease the load of oxidative stress in brain cells than donepezil as compared to vehicle control rats. In conclusion present study proposed that increased antioxidant potential of curcumin may be responsible for its increased acetylcholine levels and associated enhanced memory performance.


Assuntos
Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Curcumina/farmacologia , Donepezila/farmacologia , Memória/efeitos dos fármacos , Nootrópicos/farmacologia , Acetilcolinesterase/metabolismo , Animais , Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Relação Dose-Resposta a Droga , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar
12.
Pak J Pharm Sci ; 32(4(Supplementary)): 1893-1900, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31680089

RESUMO

Unpredictable chronic mild stress (UCMS) model is the most established method to study neurobiological mechanisms of depression. This work was intended to explore the efficacy of curcumin to revert the UCMS-induced oxidative burden and associated depression as well as potential of curcumin as an acetyl cholinesterase (AchE) inhibitor. Animals were initially grouped into control and curcumin (200mg/kg, p.o) and further subdivided into unstressed and stressed groups. Depression and anxiety were evaluated by forced swim test (FST) and light/dark transition (LDT) while memory function was assessed by passive avoidance test (PAT). Effect of curcumin on oxidative stress following UCMS was determined by measuring peroxidation of lipid (LPO) and antioxidant enzyme activities. AchE activity was also determined. Findings showed that curcumin supplementation significantly attenuated the UCMS-induced depression and anxiety like symptoms, decreased the load of UCMS propagated oxidative stress by improving antioxidant enzymes activities. Curcumin also improved the memory function and exhibited inhibitory effect on AchE activity. In conclusion it can be suggested that supplementation of curcumin in daily life can help in combating the stress-induced depression and ever increasing load of oxidative stress. Study also highlights the anti-acetylcholinesterase potential of curcumin which may be responsible for improved memory function following UCMS.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Curcumina/farmacologia , Depressão/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Depressão/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Transtornos da Memória/metabolismo , Camundongos , Ratos Wistar , Estresse Psicológico/metabolismo
13.
Pak J Pharm Sci ; 31(3(Supplementary)): 1075-1079, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29731446

RESUMO

Post-traumatic stress disorder (PTSD) is a condition which is triggered shortly after experiencing traumatic events. PTSD is complicated by the fact that people with PTSD often develop additional disorders such as phobias, addiction, depression, panic disorder and obsessive-compulsive disorder. Beta-adrenergic and cholinergic system both are involved in memory formation as well as in emotional response associated with memory. It is reported that the administration of beta-adrenergic and cholinergic antagonist results in the impairment in memory formation. Here, we examined the potential of beta-adrenergic antagonist propranolol and muscarinic cholinergic antagonist atropine for impairing the recently formed fear memory associated with PTSD. Reconsolidation is the memory process during which labile memory converts into permanent memory. In this study it is hypothesized that if recently formed fear memory is disturbed during reconsolidation phase by pharmacological intervention then it could be possible to impair well-consolidated fear memory. Atropine and propranolol were injected in separate set of rats (n=6) just after the reactivation of fear memory. Short term memory and long term memory were monitored after 2 h and 24 h of reactivation respectively. Results of current study demonstrated that only atropine showed significant impairment of reconsolidation of newly formed fear memory whereas propranolol did not show fear memory disrupting effects. The results emphasize the significance of pharmacological intervention to impair reconsolidation of newly formed fear memory.


Assuntos
Atropina/farmacologia , Medo/efeitos dos fármacos , Consolidação da Memória/efeitos dos fármacos , Propranolol/farmacologia , Animais , Condicionamento Clássico/efeitos dos fármacos , Masculino , Ratos
14.
Pak J Pharm Sci ; 30(6(Supplementary)): 2375-2381, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29188772

RESUMO

This study was designed to investigate the role of enriched environment in preventing and/or reducing the neurobehavioral deficits produced after nicotine administration in albino Wistar rats. Equal numbers of rat in two groups were either placed in social environment (control group) or social along with physically enriched environment for four weeks before the administration of nicotine. Exposure to different environmental conditions was followed by the intraperitoneal injection of nicotine at the dose of 0.6 mg/kg for seven consecutive days during which addictive behavior was monitored using conditioned placed preference paradigm. Behavioral responses to locomotor activity, anxiety and retention of short term memory were investigated in control and nicotine injected groups exposed to different environments. Results of this study showed that the rats pre-exposed to physical along with social enrichment exhibited a decrease in drug seeking behavior, hyper locomotion, anxiogenic effects along with improvement of working memory as compared to control and nicotine injected groups that were kept in social environment alone. This behavioral study suggests that the exposure to physical enrichment along with socialization in young age can later reduce the chances of compulsive dependence on nicotine and related neurobehavioral deficits.


Assuntos
Comportamento Aditivo/prevenção & controle , Comportamento Animal , Comportamento Exploratório , Comportamento Social , Meio Social , Tabagismo/prevenção & controle , Animais , Ansiedade/prevenção & controle , Ansiedade/psicologia , Comportamento Aditivo/psicologia , Modelos Animais de Doenças , Memória de Curto Prazo , Atividade Motora , Ratos Wistar , Fatores de Tempo , Tabagismo/psicologia
16.
J Natl Compr Canc Netw ; 13(7): 873-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26150581

RESUMO

BACKGROUND: Adiponectin dysregulation is postulated to affect cancer risk via modulation of insulin resistance and inflammation. Epidemiologic studies evaluating this relationship have conflicting results and data from non-white cohorts are lacking. We examined the association between adiponectin and risk of cancer incidence in the multiethnic Dallas Heart Study (DHS). METHODS: Participants enrolled in the DHS and known adiponectin values were included. Incident cancer cases were identified through a systematic linkage of the DHS and the Texas Cancer Registry. Univariate/multivariate analysis were performed to test the association between adiponectin and incident cancer after adjusting for age, diabetes status, gender, ethnicity, C-reactive protein level, smoking status, and body mass index. Adiponectin level was evaluated both as a continuous variable and in race/ethnicity specific quartiles. RESULTS: Of 3444 individuals, there were 152 incident cancers. The study population was comprised of 44.4% men, and 51.05% were black. Baseline median adiponectin levels were 6.43 mcg/mL (interquartile range [IQR], 4.37-9.45 mcg/mL) in the incident cancer group versus 6.33 mcg/mL (IQR, 4.57-9.97 mcg/mL) in those without cancer. In multivariable analysis, adiponectin level was not associated with cancer incidence after adjusting for covariates. In analyses stratified by race/ethnic group, no association was observed in white, Hispanic, or African American subgroups. CONCLUSIONS: In this study of a predominant ethnic minority population, no association between adiponectin and cancer incidence was demonstrated. Despite preclinical rationale and confirmatory findings in other studies, this association may not replicate across all ethnic populations. Additional studies with strong minority representation are warranted to further examine this association.


Assuntos
Adiponectina/sangue , Neoplasias/epidemiologia , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
17.
Pak J Pharm Sci ; 27(4): 837-45, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25015449

RESUMO

Aging is a natural complex process that is regulated at genetic, cellular, molecular and systemic levels and leads to the development of a variety of changes including structural, chemical and genetic in the senescent brain. The major goal of the present study was to investigate the age associated cognitive dysfunction and other behavioral changes and their association with age related alterations in levels of neurotransmitters, such as dopamine (DA) and serotonin (5-HT) in the hippocampal region. Twelve male Albino Wistar rats were taken for the study including six young rats (04-05 months old) and six aged (20-22 months old) rats in each group. The learning and memory performance of rats was assessed by passive avoidance test (PA) and novel objective recognition task (NOR). Ambulatory activity was monitored by Open field test. Light/Dark transition test was used to monitor anxiety, whereas depression like symptoms was examined by Forced Swim Test (FST). Results showed that aged rats exhibited learning and memory impairment in PA and NOR. There was a negative relation between aging process and locomotion, consistent with previous findings. Moreover, an augmented increase in level of anxiety and depression was also observed in senescent rats. A marked decrease in DA and 5-HT was observed in the hippocampus of aged rats. Similarly, levels of 5-HIAA and DOPAC were also found to be decreased in aged rats. It is therefore concluded that age has a negative influence on cognitive function, depression, anxiety and locomotion in rats. Cells in all brain regions, especially hippocampus are affected by aging. In general aging exhibits a decline in sensory, motor and cognitive functions. These behavioral changes or functional deficits may be attributed to the age related decline in the levels of different neurotransmitters in brain/hippocampus. The present findings of behavioral deficits and altered neurotransmission in hippocampus of aged rats suggest a relationship between senescence, altered brain neurotransmitters and behavioral deficits.


Assuntos
Envelhecimento/metabolismo , Aminas Biogênicas/análise , Transtornos Cognitivos/etiologia , Hipocampo/química , Neurotransmissores/análise , Envelhecimento/psicologia , Animais , Aprendizagem da Esquiva , Transtornos Cognitivos/metabolismo , Dopamina/fisiologia , Neurotransmissores/fisiologia , Ratos , Ratos Wistar , Serotonina/fisiologia
19.
Metab Brain Dis ; 28(1): 85-92, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23315312

RESUMO

Lead toxicity is known to induce a broad range of physiological, biochemical and behavioral dysfunctions that may result in adverse effects on several organs, including the central nervous system. Long-term exposure to low levels of lead (Pb(2+)) has been shown to produce behavioral deficits in rodents and humans by affecting hypothalamic-pituitary-adrenal (HPA) axis. These deficits are thought to be associated with altered brain monoamine neurotransmission and due to changes in glucocorticoids levels. This study was designed to investigate the effects of Pb(2+)exposure on growth rate, locomotor activity, anxiety, depression, plasma corticosterone and brain serotonin (5-HT) levels in rats. Rats were exposed to lead in drinking water (500 ppm; lead acetate) for 5 weeks. The assessment of depression was done using the forced swimming test (FST). Estimation of brain 5-HT was determined by high-performance liquid chromatography with electrochemical detection. Plasma corticosterone was determined by spectrofluorimetric method. The present study showed that long term exposure to Pb(2+) significantly decreased the food intake followed by the decrease in growth rate in Pb(2+)exposed rats as compared to control group. No significant changes in open field activity were observed following Pb(2+)exposure while significant increase in anxiogenic effect was observed. Increased plasma corticosterone and decreased 5-HT levels were exhibited by Pb(2+)exposed rats as compared to controls. A significant increase in depressive like symptoms was exhibited by Pb(2+)exposed rats as compared to control rats. The results are discussed in the context of Pb(2+) inducing a stress-like response in rats leading to changes in plasma corticosterone and brain 5-HT levels via altering tryptophan pyrrolase activity.


Assuntos
Corticosterona/sangue , Depressão/sangue , Chumbo/toxicidade , Administração Oral , Animais , Química Encefálica/efeitos dos fármacos , Depressão/induzido quimicamente , Ingestão de Alimentos/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Wistar , Serotonina/análise , Natação
20.
Vet Sci ; 10(1)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36669040

RESUMO

Cystic echinococcosis (CE) is a neglected zoonotic disease of worldwide geographical distribution. CE is most common in underdeveloped and herding communities where people survive on animal husbandry and agricultural activities. The prevalence of CE in livestock and its risk factors are widely underreported, because of inefficient surveillance systems. The aim of this study was to evaluate the epidemiological characteristics and prevalence of CE in cattle in Punjab, Pakistan. Data were collected from slaughterhouses from September 2021 to February 2022. Ante- and postmortem examination and cyst characterization were performed. Epidemiological, demographic, and one health data were collected. A total of 8877 animals (8096 buffalo, 781 cattle) were examined, and the prevalence of CE was 6.22% (n = 552) in all animals, with a higher prevalence in cattle (15.20% vs. buffalo 5.83%). Prevalence was not significantly different in males and females. Of the 23 districts studied, the highest prevalence was in the Haripur district of KP (20.85%). The majority of animals studied were older than 3 years. Most cysts were found in animals older than 5 years. Lungs and liver were the predominant sites for the presence of cysts (65.58% and 31.34%, respectively. Of the collected cysts, 29.71% were fertile. The findings may be useful in estimating the eco-epidemiology of CE and improving surveillance and prevention programs in Pakistan.

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