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Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises a group of multisystem disorders involving severe, systemic, small-vessel vasculitis with short- and long term serious and life-threating complications. Despite the simplification of treatment, fundamental aspects concerning assessment of its efficacy and its adaptation to encountered complications or to the relapsing/remitting/subclinical disease course remain still unknown. The pathogenesis of AAV is complex and unique, and despite the progress achieved in the last years, much has not to be learnt. Foremost, there is still no accurate marker enabling us to monitoring disease and guide therapy. Therefore, the disease management relays often on clinical judgment and follows a" trial and error approach". In the recent years, an increasing number of new molecules s have been explored and used for this purpose including genomics, B- and T-cell subpopulations, complement system factors, cytokines, metabolomics, biospectroscopy and components of our microbiome. The aim of this review is to discuss both the role of known historical and clinically established biomarkers of AAV, as well as to highlight potential new ones, which could be used for timely diagnosis and monitoring of this devastating disease, with the goal to improve the effectiveness and ameliorate the complications of its demanding therapy.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Metabolômica , Humanos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , GenômicaRESUMO
BACKGROUND: Oral submucous fibrosis (OSMF) is a crippling slowly progressive disease of oral cavity that predominantly affects people habit of consuming areca nut and its commercial preparations which generates high levels of reactive oxygen species (ROS) during their metabolism. OBJECTIVE: The objective of this present study is to evaluate the role of oxidative stress in causation and progression of OSMF by measuring the levels of nonenzymatic antioxidants in OSMF patients. MATERIALS AND METHODS: For this study we selected 27 newly diagnosed OSMF patients of both sex with age group between 23 to 40 years and the same number of age and sex matched healthy individuals were selected as control group. In both the groups we measured plasma non enzymatic antioxidants like vitamin A. E, C and reduced glutathione. Total antioxidant activity was also assessed in both the groups. RESULTS AND CONCLUSIONS: We observed a very low levels of plasma non-enzymatic antioxidants (p < 0.001) and at the same time a very poor antioxidant activity (p < 0.001) in OSMF patients when compared to controls. Therefore, consumption of tobacco or areca quid creates an oxidative stress environment which might plays a major role in the causation of OSMF.
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Antioxidantes/análise , Glutationa/sangue , Neoplasias Bucais/sangue , Fibrose Oral Submucosa/sangue , Estresse Oxidativo , Lesões Pré-Cancerosas/sangue , Vitamina A/sangue , Vitamina E/sangue , beta Caroteno/sangue , Adulto , Areca , Biomarcadores/sangue , Estudos de Casos e Controles , Progressão da Doença , Regulação para Baixo , Feminino , Humanos , Índia , Masculino , Mastigação , Neoplasias Bucais/etiologia , Nozes/efeitos adversos , Fibrose Oral Submucosa/etiologia , Lesões Pré-Cancerosas/etiologia , Adulto JovemRESUMO
BACKGROUND: Retinol binding protein-4 (BP-4) a new adipocytokine, specifically binds to retinol, through experimental studies, reported its link between obesity and insulin resistance (IR). But till date no studies are available on influence of genetic predisposition of diabetes on RBP-4 expression. Hence, we aimed to study the influence of genetic predisposition of diabetes on the serum RBP-4 and its role in development of IR and diabetes in genetically high risk population. MATERIALS AND METHODS: Healthy non diabetic individuals (age 18 to 22) were grouped into Group I: Control (n = 81), whose parents are non diabetic, non hypertensive and does not have any family history of coronary heart diseases. Group II: (n = 157) with one of their parents diabetic and Group III: (n = 47) with both parents diabetic. In all the participants, we estimated fasting serum RBP-4, insulin and glucose. Homeostasis model for assessment-insulin resistance (HOMA-IR) and homeostasis model for assessment-beta cell dysfunction (HOMA-B) were calculated from fasting serum insulin and glucose levels. RESULTS: In this study, we observed significantly higher RBP-4 levels 12.71 ± 2.3 in Group-II and 13.25 ± 2 in Group-III, respectively when compared to Group-I 11.4 ± 1.8 (P < 0.01). RBP-4 showed a significantly strong positive correlation with plasma insulin, glucose and HOMA-IR in genetically high risk population (group II and III) P < 0.01. Linear regression analysis revealed a strong positive association of RBP-4 with parental diabetes even after adjusting for BMI, age and sex (OR 1.53, 95% CI 1.089-1.40). CONCLUSION: Higher serum RBP-4 and its positive correlation with Insulin, glucose, and HOMA-IR in healthy non diabetic participants of genetically high risk population, indicating its role as predictor for the onset of diabetes in coming future.
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HIV-related stigma has been recognized as a significant public health issue, yet gaps remain in development and evaluation of mass media interventions to reduce stigma. The Malawi 'Radio Diaries' (RD) program features people with HIV telling stories about their everyday lives. This study evaluates the program's effects on stigma and the additional effects of group discussion. Thirty villages with 10 participants each were randomized to listen to RD only, to the program followed by group discussion or to a control program. Post-intervention surveys assessed four stigma outcomes: fear of casual contact, shame, blame and judgment and willingness to disclose HIV status. Regression analyses indicated that fear of casual contact was reduced by the intervention. Shame was reduced by the radio program, but only for those reporting prior exposure to the radio program and for those who did not have a close friend or relative with HIV. Shame was not reduced when the radio program was followed by discussion. The intervention reduced blame for men and not women and for younger participants but not older participants. Including people with HIV/AIDS in mass media interventions has potential to reduce stigma.
Assuntos
Infecções por HIV/psicologia , Preconceito , Rádio , Adolescente , Feminino , Humanos , Malaui , Masculino , Adulto JovemRESUMO
INTRODUCTION: Body mass index (BMI) is widely accepted as one of the best indicators of nutritional status in adults. Mid-upper arm circumference (MUAC) is another anthropometric measure that has also been used to evaluate adult nutritional status. The objective of this study was to evaluate the use of MUAC as a simpler and reliable alternative to BMI. A suitable cut-off value was also proposed for identification of chronic energy deficiency (CED) in relation to self-reported illness among the adult Oraon males of Jharkhand state in India. METHODS: The study was based on a cross-sectional survey involving 205 rural adult men belonging to the Oraon tribal group of Jharkand State in India. Height and weight were measured for each participant. The BMI was calculated as kg/m2. The internationally accepted cut-off points of BMI and MUAC were utilised to determine nutritional status. An episode of illness was recorded for each subject if any working day was lost. Receiver operating characteristic curve analyses were undertaken to discover the most suitable values of MUAC both for CED and illness. RESULTS: The MUAC values of 243 and 239 mm were identified as the best cut offs to identify CED (BMI<18.5) and illness, respectively. There were marked increases in both CED and illness prevalence rates at a MUAC level lower than 240 mm. Therefore, a MUAC value of close to 240 mm seemed appropriate as a simple and efficient cut-off point for the determination of undernutrition and higher rates of illness and loss of working days in adult Oraon males. CONCLUSION: Because MUAC is a much simpler measure than BMI, the use of MUAC 240 mm as a cut-off point is predicted to have considerable public health implications, especially with respect to primary health care related to CED and morbidity.
Assuntos
Antropometria/métodos , Braço/anatomia & histologia , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Tamanho Corporal , Estudos Transversais , Ingestão de Energia , Nível de Saúde , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Curva ROC , Saúde da População Rural , População Rural , Adulto JovemRESUMO
An inimitable urea-based multichannel chemosensor, DTPH [1,5-bis-(2,6-dichloro-4-(trifluoromethyl)phenyl)carbonohydrazide], was examined to be highly proficient to recognize CN- based on the H-bonding interaction between sensor -NH moiety and CN- in aqueous medium with explicit selectivity. In the absorption spectral titration of DTPH, a new peak at higher wavelength was emerged in titrimetric analytical studies of CN- with the zero-order reaction kinetics affirming the substantial sensor-analyte interaction. The isothermal titration calorimetry (ITC) experiment further affirmed that the sensing process was highly spontaneous with the Gibbs free energy of -26 × 104 cal/mol. The binding approach between DTPH and CN- was also validated by more than a few experimental studies by means of several spectroscopic tools along with the theoretical calculations. A very low detection limit of the chemosensor toward CN- (0.15 ppm) further instigated to design an RGB-based sensory device based on the colorimetric upshots of the chemosensor in order to develop a distinct perception regarding the presence of innocuous or precarious level of the CN- in a contaminated solution. Moreover, the reversibility of the sensor in the presence of CN- and Hg2+ originated a logic gate mimic ensemble. Additionally, the real-field along with the in vitro CN- detection efficiency of the photostable DTPH was also accomplished by using various biological specimens.
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This cross-sectional study was conducted in two districts of West Bengal, to report the prevalence of leanness among rural adolescent school children. Leanness was evaluated using age and sex specific cut-off points of triceps skinfold thickness of < 5th percentile of NCHS reference population as recommended by World Health Organization. A total of 2016 students, of these, 51.39% boys and 48.61% girls aged 10-15 years were studied. Overall (age and sex combined) 18.35% children were lean. Moreover, prevalence of leanness was significantly higher in girls (22.04%) as compared to boys (14.86%).
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Magreza/epidemiologia , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Masculino , Prevalência , População Rural , Fatores Sexuais , Dobras CutâneasRESUMO
Undernutrition among tribal children is a major public health problem in India. Our study attempted to evaluate the prevalence of malnutrition among Lodha children of Paschim Medinipur, West Bengal. A cross sectional study was conducted among 165 children aged 1-14 years in a village of Paschim Medinipur district during January to March 2008. Children were considered underweight, stunting and wasting following the NCHS standards. Overall the prevalence of underweight, stunting and wasting was 33.9%, 26.1% and 19.4 %, respectively. Of these, 9.1%, 9.7% and 3.6% children were found to be severely underweight, stunted and wasted. Moreover, the prevalence of underweight and stunting was significantly higher in pre-school children compared to school going children. There is an urgent need for appropriate steps to be taken to improve nutritional status of children in this ethnic group.
Assuntos
Transtornos da Nutrição Infantil/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Lactente , Masculino , Inquéritos Nutricionais , MagrezaRESUMO
BACKGROUND: Results from observational studies suggest that the oxidative stress and hyperlipidemic status, which prevails in hypertension, plays an important role in causation of secondary complications. So the aim of the present study is to evaluate the beneficial effect of tomatoes, which are a rich source of lycopene, a relatively new carotenoid known to play an important role in human health and disease. METHODS: In this study lipid peroxidation rate was measured by estimating malondialdehyde (MDA) and the activity of plasma enzymes involved in antioxidant activities like superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GR), reduced glutathione (GSH), and serum lipid profile which includes total cholesterol and triglycerides were estimated in a grade I hypertensive group (n = 40) and an age-matched control group (n = 50). RESULTS: Significantly lower plasma antioxidant enzyme activity, very high lipid peroxidation rate and very high serum total cholesterol, triglycerides in the grade I hypertensive group was observed when compared to the control group (p < 0.001). Sixty days of tomato supplementation in the hypertensive group (n = 30) showed a significant improvement in the levels of serum enzymes involved in antioxidant activities and decreased lipid peroxidation rate (F value highly significant), but there were no significant changes in lipid profile (F value insignificant). CONCLUSION: These findings suggest that tomato lycopene may have considerable natural therapeutic potential as an antioxidant but may not be used as a hypolipidemic agent in hypertension.
Assuntos
Antioxidantes/farmacologia , Carotenoides/farmacologia , Hipertensão/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Solanum lycopersicum/química , Adulto , Estudos de Casos e Controles , Feminino , Glutationa/sangue , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Humanos , Hipertensão/sangue , Licopeno , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
The Global Alliance for the Elimination of Lymphatic Filariasis (GAELF) has recommended exploring local health traditions of skin care and a low cost treatment paradigm for rural communities has been proposed by Vaqas and Ryan. Our case study incorporates these promising treatments for use in treating filariasis in rural communities. Patients having lymphedema of one or both lower limbs (skin: normal, thickened or with trophic/warty changes) received treatment components from ayurveda, yoga and biomedicine simultaneously: including soap wash, phanta soaking, Indian manual lymph drainage (IMLD), pre- and post-IMLD yoga exercises, and compression using bandages for 194 days, along with diet restrictions and oral herbal medicines indicated for "elephantiasis" in Ayurveda. Entry points when infected were treated with biomedical drugs. The study was conducted in the reverse pharmacology design. 112 patients and 149 lower limbs completed 194 days of treatment during 2003-2006. Significant improvements were observed in the limb circumference measurements and the frequency of acute dermatolymphangioadenitis, use of preventive antibiotics, and reduction in the number of entry points were also improved. The objective to obtain significant benefit for a common problem using locally available, sustainable and affordable means has been achieved. It has not been our purpose to show that the regimen employed is better than another but the results do pose the question--"Are there components of Ayurvedic medicine that deserve further study?" It is important to understand that the regimen has been delivered mostly at home and that participants we have treated, representing a population suffering from a common problem, have not had access to effective conservative therapy that is culturally acceptable, safe, and efficacious.
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Filariose Linfática/terapia , População Rural , Análise de Variância , Bandagens , Drenagem , Filariose Linfática/epidemiologia , Comportamento Alimentar , Feminino , Seguimentos , Temperatura Alta , Humanos , Índia/epidemiologia , Extremidade Inferior/patologia , Pessoa de Meia-Idade , Cooperação do Paciente , População Rural/estatística & dados numéricos , Índice de Gravidade de Doença , Higiene da Pele , Sabões , Meias de Compressão , Fatores de Tempo , Resultado do Tratamento , YogaRESUMO
A cross-sectional study was conducted among a total of 598 men and women to investigate age and sex variations in the prevelence of overweight, obesity and hypertension among adult (>18 years) residents of Dearah, Hooghly District, West Bengal. Height, weight and systolic (SBP) and diastolic (DBP) blood pressure mesurements were made on each subject. Prevelence of overweight was significantly higher among women. There existed significant age-group differences among men in the frequency of overweight and obese individuals. The overall (both sexes combined) prevelence of hypertension was 25.9%. There was significant age-group difference in the prevelence of hypertension. There was a consistent trend in increasing rates of hypertension as well as mean BMI, SBP, DBP and mean arterial pressure (MAP) with increasing age.
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Hipertensão/epidemiologia , Sobrepeso/epidemiologia , Adulto , Fatores Etários , Idoso , Estudos Transversais , Feminino , Humanos , Hipertensão/complicações , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/complicações , Prevalência , População Rural , Fatores SexuaisRESUMO
Childhood obesity is increasing globally, and Poland is no exception. Studies indicate that relationship between obesity and psychological well-being is a complex issue and this needs further research. The objective of the present cross sectional study was to analyze the relationship between some temperament components and fatness among children in two developmental periods, approximately before and after adolescence. Participants included 122 children aged 11 years (57 boys and 65 girls), and 153 adolescents aged 17 years (64 boys and 89 girls) from 6 primary and 4 secondary schools in Wroclaw, Poland. Height, weight, triceps-, subscapular and abdominal skinfold thicknesses were measured. Temperament was assessed by a questionnaire of Buss and Plomin (1984) in two versions: EAS-C for children completed by parents and EAS-D for youth and adults. Physical activity (PAL) was also assessed by a questionnaire. Mean, median and standard deviation (SD) were calculated and Student's t tests were performed to test for significance of differences between groups. Chi squared (χ2) statistic was used to test the significance of differences in frequencies. Analyses of covariance (ANCOVA) were performed to show the effect of the social - psychological factors on fatness. Controlling for socioeconomic status and physical activity level, activity, as a component of temperament had a significant effect on body fatness. The only component of temperament, which significantly influenced level of fatness in girls, was emotionality. These relationships differed according to sex and the two age groups concerned.
Assuntos
Tecido Adiposo/fisiopatologia , Antropometria/métodos , Índice de Massa Corporal , Obesidade/psicologia , Temperamento , Adolescente , Criança , Estudos Transversais , Exercício Físico , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Obesidade/fisiopatologia , Polônia/epidemiologiaRESUMO
BACKGROUND: Innovation in the treatment of lower extremity lymphedema has received low priority from the governments and pharmaceutical industry. Advancing lymphedema is irreversible and initiates fibrosis in the dermis, reactive changes in the epidermis and subcutis. Most medical treatments offered for lymphedema are either too demanding with a less than satisfactory response or patients have low concordance due to complex schedules. A priority setting partnership (PSP) was established to decide on the future priorities in lymphedema research. METHODS: A table of abstracts following a literature search was published in workshop website. Stake holders were requested to upload their priorities. Their questions were listed, randomized, and sent to lymphologists for ranking. High ranked ten research priorities, obtained through median score, were presented in final prioritization work shop attended by invited stake holders. A free medical camp was organized during workshop to understand patients' priorities. RESULTS: One hundred research priorities were selected from priorities uploaded to website. Ten priorities were short listed through a peer review process involving 12 lymphologists, for final discussion. They were related to simplification of integrative treatment for lymphedema, cellular changes in lymphedema and mechanisms of its reversal, eliminating bacterial entry lesions to reduce cellulitis episodes, exploring evidence for therapies in traditional medicine, improving patient concordance to compression therapy, epidemiology of lymphatic filariasis (LF), and economic benefit of integrative treatments of lymphedema. CONCLUSION: A robust research priority setting process, organized as described in James Lind Alliance guidebook, identified seven priority areas to achieve effective morbidity control of lymphedema including LF. All stake holders including Department of Health Research, Government of India, participated in the PSP.
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The objective of the present study is to evaluate the beneficial effect of tomatoes, which are a rich source of lycopene, a relatively new carotenoid known to play an important role in human health. In this study, the lipid peroxidation rate was investigated by estimating malondialdehyde (TBARS) levels of antioxidant enzymes like SOD, GSH-Px, GR, GSH, lipid profile, which includes total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, very low density lipoprotein, and glycated haemoglobin HbA1c in (n = 40) the Type 2 diabetic group (n = 40) and an age-matched control group (n = 50). Significantly lower levels of antioxidant enzymes and very high lipid peroxidation rate in the Type 2 diabetic group were observed when compared to controls (p < 0.001). Likewise, significantly higher levels of lipid profile and glycated haemoglobin (HbA1c) in the diabetic group were observed when compared with control (p < 0.001). Long term tomato supplementation in diabetes mellitus showed a significant improvement in the levels of antioxidant enzymes and decreased lipid peroxidation rate (p < 0.001), but there were no significant changes in lipid profile and glycated haemoglobin HbA1c levels (p > 0.10). These findings suggest that tomato lycopene may have considerable therapeutic potential as an antioxidant but there was no significant lipid lowering effect in Type 2 diabetes mellitus.
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Antioxidantes , Carotenoides/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Suplementos Nutricionais , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos , Solanum lycopersicum/química , Adulto , Carotenoides/uso terapêutico , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , Licopeno , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Fatores de TempoRESUMO
A cross-sectional study was undertaken to determine sex differences in mean body mass index (BMI) and nutritional status (based on BMI), as well as the effect of age on BMI and nutritional status of adult Savars, a tribal population of Orissa, India. A total of 600 adult (aged > 18 years) Savars of four villages, namely, Bonianiposi, Morabali, Panchapolli and Sailong of Keonjhar District, Orissa, India, were studied. Height and weight were measured and BMI computed. Mean ages of both sexes were similar (men: mean = 38.9 years, sd = 15.3; women: mean = 38.0, sd = 13.9). Men had significantly greater mean height (p < 0.001), weight (p < 0.001) and BMI (p < 0.05). The prevalence (sex combined) of undernutrition (BMI < 18.5) was found to be very high (43.5%). Moreover, there was a significant (chi2 = 7.39, p = 0.025) difference in the prevalence of undernutrition between men (38%) and women (49%). Age was significantly (p < 0.001) negatively correlated with BMI in both sexes (men: r = -0.20; women: r = -0.16). In general, the frequency of undernutrition increased with increasing age. In conclusion, this study demonstrated that the prevalence of adult undernutrition was very high among Savar women and high among Savar men. These rates increased with increasing age. Therefore, from the public health point of view, immediate nutritional intervention programmes are needed for implementation among Savars, especially among older individuals. Moreover, further research is needed not only among this ethnic group but also other tribal populations of India to fully understand the causes and consequences of adult undernutrition.
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Índice de Massa Corporal , Estado Nutricional/etnologia , Adulto , Fatores Etários , Estatura , Peso Corporal , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Masculino , Fatores SexuaisRESUMO
MCa-11 tumor cells in exponential monolayer cultures were pulse/chase-labeled with [3H]thymidine and then regrown in fresh, plateau-fed, or starved medium. We measured the DNA content and autoradiographic labeling of these cells by absorption cytophotometry at intervals of 0, 2, 4, 8, 12, and 24 h to follow the progress through the cell cycle of those cells which had incorporated isotope. We found that for the cells grown in plateau-fed and starved medium the G0/G1, S, and G2 phases of the cell cycle were prolonged when compared to those for cells grown in fresh medium. These results show that, under adverse microenvironmental conditions, the growth of tumor cells can be regulated in all phases of the cell cycle, and that this regulation can include lengthening and even cessation of replicative DNA synthesis.
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Ciclo Celular , Células Tumorais Cultivadas/patologia , Meios de Cultura , Replicação do DNA , DNA de Neoplasias/análise , Citometria de Fluxo , Interfase , Timidina/metabolismoRESUMO
To determine whether all tumor S-phase cells incorporate [3H]thymidine, we labeled the cells in three mouse tumors (MCa-11, colon-26, and colon-51) in vivo for 1/2 h with [3H]thymidine (10 microCi/g of body weight). Cells from the tumors, as well as control cells from the bone marrows of the tumor-bearing mice, were then placed onto slides and Feulgen stained. The positions of these Feulgen-stained cells were mapped with a computerized scanning stage, and their nuclear DNA content and nuclear areas were determined by absorption cytophotometry. Next, the slides were processed for autoradiography and exposed for 32 or 64 days to obtain plateau labeling. The cells were then relocated, and the areas of the autoradiographic grains over each nucleus were measured. We found that 99% of the S-phase bone marrow cells were labeled. The 5-mm tumors, however, showed a wide range of S-phase labeling, with 94, 89, and 85% of the MCa-11, colon-51, and colon-26 S-phase cells, respectively, being labeled. The same mice bearing both 5- and 20-mm MCa-11 tumors, however, showed 95 and 57% labeling of the S-phase cells in the small and large tumors, respectively. These results show that the [3H]thymidine labeling of S-phase cells varies greatly for experimental mouse tumors of different size and type, and they suggest that "labeling index" and flow cytometric DNA measurements may not give valid estimates of the actual proportions of cycling S-phase cells in such tumors.
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DNA de Neoplasias/biossíntese , Interfase , Neoplasias Experimentais/patologia , Animais , Medula Óssea/patologia , Divisão Celular , Núcleo Celular/ultraestrutura , Replicação do DNA , CamundongosRESUMO
The present study was performed to determine if adenylate cyclase in granulosa cells was affected by the pituitary hormone FSH and the ovarian hormone estradiol. Results demonstrate that granulosa cells of intact immature rats exhibit considerably more FSH- than hCG-stimulated adenylate cyclase activity. The FSH-responsive enzyme system was not altered by hypophysectomy or by treating hypophysectomized rats with FSH alone, but was increased slightly by treatment with estradiol alone. Sequential treatment of rats with estradiol and FSH markedly increased both FSH- and LH/hCG-stimulated adenylate cyclase activities. Thus, FSH-responsive adenylate cyclase appears to be a constitutive component of granulosa cells in prenatal follicles which exhibits a pronounced increase during the development of preovulatory follicles, a change dependent on the synergistic actions of estradiol and FSH. Desensitization of FSH-responsive adenylate cyclase in granulosa cells of preantral and antral follicles was assessed by administering 5 micrograms human FSH to estradiol or estradiol/FSH-treated rats, respectively. FSH failed to induce desensitization of adenylate cyclase in granulosa cells of preantral follicles at 2 h, but did desensitize the enzyme system in granulosa cells of antral follicles. Furthermore, the desensitization of adenylate cyclase in granulosa cells of antral follicles was heterologous; both FSH and hCG exerted this effect. The causes of the differences in the response of adenylate cyclase to high concentrations of FSH at different stages of follicular development remain unclear. The absence of desensitization in preantral follicles may be required to permit a continuous nondisruptive pattern of follicular growth when small follicles are repeatedly exposed to gonadotropin surges, whereas desensitization is required for the cessation of follicular growth and luteinization.
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Adenilil Ciclases/metabolismo , Estradiol/farmacologia , Hormônio Foliculoestimulante/farmacologia , Células da Granulosa/citologia , Folículo Ovariano/enzimologia , Animais , Diferenciação Celular/efeitos dos fármacos , Gonadotropina Coriônica/farmacologia , Feminino , Hipofisectomia , Folículo Ovariano/efeitos dos fármacos , RatosRESUMO
We analysed the effects of nitrogen mustard (HN2) on the growth, cell cycle distributions, and ratios of tumour cells to host cells for MCa-11 tumours grown in vivo. Treatment of tumour-bearing BALB/c mice with 3 mg/kg of HN2 produced a significant slowing of MCa-11 tumour growth. Seventy-two hours after treatment in vivo with either 3 or 4 mg/kg of HN2, the host cells in the treated tumours showed a significantly decreased G0/G1 peak and an increased G2/M peak (P < 0.01), whereas the cancer cells in the treated tumours showed significant increases in the G0/G1 peak coupled with relatively decreased proportions of S and G2/M tumour cells (P < 0.001). The ratio of the total number of cancer cells to the total number of host cells in the tumours was significantly increased 72 h after HN2 administration (P < 0.01). Thirty-two days after treatment with HN2, the cell cycle distributions of the host and tumour cells in the treatment and control tumours had returned to being identical, but the ratio of the total number of cancer cells to the total number of host cells remained increased in the treated tumours (P < 0.01). These results show that the administration in vivo of HN2 can lead to entirely different cell cycle effects for the host and cancer cells in the same tumour, and that the partial growth arrest of MCa-11 tumours from HN2 treatment may be due in part to the preferential destruction of host cells rather than solely to a direct cytotoxic effect on the cancer cells.