RESUMO
STUDY DESIGN: This is a retrospective longitudinal review. OBJECTIVE: The purpose of this review was to identify predictors of developing clinical scoliosis and compare between traumatic and neurological aetiologies of SCI. SETTING: This study was conducted at the Midland Centre of SCI. METHOD: Case notes of all patients injured at an age up to 18 years and admitted between 1971 and 2013 were reviewed. RESULTS: Sixty-nine individuals were identified, of which seven were excluded: three with pre-existing scoliosis and four with spina bifida. The remaining 62 (44 males, 18 females) had a median age at injury of 17 years (inter quartile range 13-17). Of these, 51 (82%) had traumatic and 11 (18%) had neurological injury. Most (42/51; 82%) of the children who had a traumatic injury were older than 13 years. The risk of developing scoliosis was lower for older patients (RR 0.68 per year, 95% CI 0.52-0.83) or following a traumatic injury (RR 0.36, 95% CI 0.20-0.66). A multivariable analysis based on age and trauma showed that only older age decreased the risk. A robust Receiver Operator Curve analysis suggested 14.6 years as the optimal threshold to predict development of scoliosis within 10 years (Area Under the Curve; AUC 0.83 (95% CI 0.73-0.93), sensitivity 70% (95% CI 50-89%), specificity 89% (95% CI 74-100%). CONCLUSION: Our results suggest that age below 14.6 years was a predictor for scoliosis. Once adjustment is made for age, the incidence of scoliosis does not differ between traumatic and neurological aetiologies of paediatric SCI injury.
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Escoliose/etiologia , Traumatismos da Medula Espinal/complicações , Adolescente , Fatores Etários , Criança , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Prognóstico , Estudos Retrospectivos , Risco , Escoliose/diagnóstico , Escoliose/epidemiologia , Sensibilidade e Especificidade , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/etiologia , Ferimentos e Lesões/complicaçõesRESUMO
STUDY DESIGN: Review study. OBJECTIVES: The identification of prognostic biomarkers of spinal cord injury (SCI) will help to assign SCI patients to the correct treatment and rehabilitation regimes. Further, the detection of biomarkers that predict permanent neurological outcome would aid in appropriate recruitment of patients into clinical trials. The objective of this review is to evaluate the current state-of-play in this developing field. SETTING: Studies from multiple countries were included. METHODS: We have completed a comprehensive review of studies that have investigated prognostic biomarkers in either the blood or cerebrospinal fluid (CSF) of animals and humans following SCI. RESULTS: Targeted and unbiased approaches have identified several prognostic biomarkers in CSF and blood. These proteins associate with cellular damage following SCI and include components from neurons, oligodendrocytes and reactive astrocytes, that is, neurofilament proteins, glial fibrillary acidic protein, Tau and S100 calcium-binding protein ß. Unbiased approaches have also identified microRNAs that are specific to SCI, as well as other cell damage-associated proteins. CONCLUSIONS: The discovery and validation of stable, specific, sensitive and reproducible biomarkers of SCI is a rapidly expanding field of research. So far, few studies have utilised unbiased approaches aimed at the discovery of biomarkers within the CSF or blood in this field; however, some targeted approaches have been successfully used. Several studies using various animal models and some with small human patient cohorts have begun to pinpoint biomarkers in the CSF and blood with putative prognostic value. An increased sample size will be required to validate these biomarkers in the heterogeneous clinical setting.
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Mediadores da Inflamação/sangue , Mediadores da Inflamação/líquido cefalorraquidiano , Proteínas de Neurofilamentos/sangue , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/líquido cefalorraquidiano , Animais , Biomarcadores/sangue , Humanos , Prognóstico , Traumatismos da Medula Espinal/diagnósticoRESUMO
Hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide also in Bangladesh. Prevalence of Hepatitis C virus infection in rural adult population of Bangladesh is reported to be 0.6% but the exact pattern of existing genotype has not been well studied. Genotyping of HCV is important for the planning of treatment duration and predicting the response to treatment in HCV infection. This study was done to identify the existing HCV genotypes in the diagnosed cases of chronic hepatitis C infection in Bangladesh. This study was a prospective as well as retrospective cross-sectional observational study done in the department of Gastroenterology of Bangabandhu Sheikh Mujib Medical University, Dhaka Bangladesh. Cases were also taken from department of Hepatology of Bangabandhu Sheikh Mujib Medical University and Square General Hospital, Dhaka. The study was from January 2010 to March 2011. In total, 417 patients having chronic HCV confirmed by positive anti-HCV and HCV-RNA tests attending to above mentioned institutions were included in this study. Out of the 417 study subjects, 303 were males (72.66%) and 114 (27.34%) were females between 05 to 78 years of age. Most cases were in the age group 30-50 years (57.06%). The study showed that 209 (50.19%) were infected with Genotype 3. Next common identified genotype of HCV was a combination of type 3 & 4, which accounted for 120 (28.77%) and genotype -1 represented 59 (14.14%) of the cases. Other less common identified genotypes were 2, 4, 5 and mixed genotypes -1 & 3, 5 & 6 and 2 & 3; the figure being 12(2.87%), 8(1.91%), 1(0.23%), 5(1.19%), 2(0.47%) and 1(0.23%) respectively. Several subtypes were also found. Genotype 3 was the commonest HCV genotype among the Bangladeshi population. Different HCV genotypes will give a good idea regarding the plan of treatment and possible response rate as well as prognosis of HCV infection in Bangladesh. This study had some limitation like relatively smaller sample size and shorter period for the study. Further studies over a larger population are needed to draw any conclusive opinion.
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Hepacivirus/classificação , Hepatite C/virologia , Adolescente , Adulto , Idoso , Bangladesh , Criança , Pré-Escolar , Estudos Transversais , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos RetrospectivosRESUMO
STUDY DESIGN: Retrospective review of findings during cystourethroscopic surveillance of symptomatic and asymptomatic patients with indwelling urethral catheters (IUC) and suprapubic catheters (SPC) monitored between January 2003 and December 2008. OBJECTIVES: To audit and compare findings between symptomatic and asymptomatic patients and between SPC and IUC population. To systematically review the literature including the recent National Institute for Health and Clinical Excellence guidelines on cystoscopic surveillance. METHODS: Theater management system and the electronic patient records used to retrieve demographics, injury details and operative findings. RESULTS: Of 925 cystoscopies performed in 507 patients, 449 were performed in 277 patients with IUC/SPC. Only 419 procedures (SPC 264; IUC 155) in 262 patients fit the inclusion criteria. Thirty procedures in fifteen non traumatic patients were excluded. Statistically there was no significant difference in incidence of findings between the symptomatic and asymptomatic group. Recurrent blockage of catheter was predominant in the SPC group and symptomatic urinary tract infections (UTIs) were the most common indications in the IUC group. In the asymptomatic group, there were 44 squamous metaplastic changes in 27 patients. Two of these patients had keratinizing variants. The duration of catheterization ranged from 20 months to 27 years and mean of 13.7 years. The average duration between two cystoscopies in the symptomatic group was 16 months compared with an average 21 months in the asymptomatic group. CONCLUSION: Cystourethroscopic surveillance in high-risk patients with IUC/SPC is essential to diagnose and manage at an early-stage complications associated with IUC/SPC, minimize symptomatology, mitigate aggravation of complications, maintain good health and probably good quality of life.
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Cateteres de Demora/efeitos adversos , Cistoscopia , Traumatismos da Medula Espinal/complicações , Neoplasias da Bexiga Urinária/diagnóstico , Cateteres Urinários/efeitos adversos , Cistoscopia/estatística & dados numéricos , Humanos , Estudos Retrospectivos , Bexiga Urinaria Neurogênica/etiologiaRESUMO
Parkinson's disease (PD) patient presents with both motor and non-motor symptoms. This was descriptive type of interventional study carried out in the department of Neurology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2009 to December 2010. Among the total 59 cases, 51 completed the proposed five months follow up. The rest eight cases attended Neurology department irregularly and were ultimately dropout from follow up. The case selection technique was purposive type of non probability sampling. Each patient was treated with levodopa+carbidopa. Then the effect of levodopa+carbidopa on non-motor symptoms and signs were evaluated in subsequent five visits at four week interval. All relevant information and follow-up were recorded in a pre-designed individual case record form. Chi square test was done and probability value <0.05 were considered as level of significance with 95% confidence limit. Among the non-motor symptoms (NMS), the most frequent symptoms at base line visit were fatigue 56.8%, excessive sweating 54.9%, insomnia 54.9%, akathisia 47.1%, anxiety 45.1%, constipation 17.6%. After five months of levodopa+carbidopa therapy, frequencies of most of the NMS decreased slightly in comparison to base line symptoms but there were no significant effect of levodopa+carbidopa on NMS of study subjects.
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Antiparkinsonianos/uso terapêutico , Carbidopa/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Resultado do TratamentoRESUMO
The co-doping of vanadium pentoxide (V2O5) with rare-earth (RE) elements, namely 1.5 % holmium (Ho) and 1.5 % ytterbium (Yb) has been conducted using an eco-friendly, straightforward hydrothermal approach to assess the combined effects on structural, optical, and photocatalytic properties. The application of the density functional theory (DFT) approach effectively examined the impact of RE ions on the photocatalytic efficiency of co-doped V2O5. The stable orthorhombic crystal structure of co-doped V2O5 has been confirmed using DFT and X-ray diffraction without a secondary phase. It appears that homogeneous nucleation occurs while heterogeneous nucleation slows down in co-doped samples, as evidenced by the larger crystallite sizes in co-doped samples compared to doped ones. It means a result, the co-doped samples exhibit photodegrades more quickly and have a higher rate constant than the doped samples. This is because they have less dislocation density (4.26 × 10-3 nm-2) and internal micro-strain (4.93 × 10-3). The bandgap and degradation efficiency are determined by the UV-vis spectroscopy and found to be 2.33 eV and 95 %, respectively, at the optimal pH of 7 in the visible range. The co-doped sample has a rate constant of 24 × 10-3 min-1, which is the highest in the RE-doped V2O5 system. This is a good reason to think of co-doped V2O5 as a possible catalyst.
RESUMO
We administered recombinant SV40-derived viral vectors (rSV40s) intravenously to mice with or without prior intraperitoneal injection of mannitol to deliver transgenes to the central nervous system (CNS). We detected transgene-expressing cells (mainly neurons) most prominently in the cortex and spinal cord; prior intraperitoneal mannitol injection increased CNS gene delivery tenfold. Intravenous injection of rSV40s, particularly with mannitol pretreatment, resulted in extensive expression of multiple transgenes throughout the CNS.
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Córtex Cerebral/metabolismo , Técnicas de Transferência de Genes , Vírus 40 dos Símios/genética , Medula Espinal/metabolismo , Transgenes , Animais , Células COS , Chlorocebus aethiops , Terapia Genética , Injeções Intravenosas , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Gestational diabetes mellitus (GDM) is a heterogeneous group of metabolic disorder, which result in varying degrees of maternal hyperglycemia and pregnancy associated risk. Glucose intolerance usually returns to normal range within 6 weeks after delivery. This study was undertaken to determine the glycemic status who attended for antenatal care. This study enrolled pregnant women, with their gestational age between 24th - 28th weeks. This analytical cross sectional study was carried out in the department of Biochemistry, BIRDEM General Hospital, Dhaka, Bangladesh from July 2014 to June 2015. Total 135 subjects were selected to evaluate the glycemic status among Bangladeshi pregnant women attending BIRDEM General Hospital. Among them 41 were GDM subjects and 94 were non GDM subjects. The mean fasting plasma glucose values (mmol/L) and 2 hours after 75gm glucose values of GDM were 6.06±1.26 and 9.78±2.74 respectively compared to non GDM patients were 4.82±0.38 and 7.26±0.41 respectively and the mean of HbA1C (%) of GDM and non GDM were 5.87±0.73 and 5.43±0.31 respectively.
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Diabetes Gestacional , Gestantes , Bangladesh/epidemiologia , Estudos Transversais , Diabetes Gestacional/epidemiologia , Feminino , Idade Gestacional , Teste de Tolerância a Glucose , Humanos , Lactente , GravidezRESUMO
Tuberculosis (TB) is an important cause of mortality and morbidity all over the world and is particularly relevant in developing countries like India where the disease is endemic. Female reproductive system is very vulnerable to this infection and clinical presentation of this disease in female reproductive tract is protean in nature and in a large majority of patients could be completely silent. This disease is an important cause of infertility, menstrual irregularity, pregnancy loss, and in association with pregnancy, morbidity to both the mother and child increases. Some of the effects of TB infection on female genital tract could be remote in nature due to infection elsewhere. Medicines used to treat TB infection can also have adverse effects on contraception and other areas of female reproductive health. HIV coinfection and multidrug-resistant tuberculosis (MDR-TB) and increased population migration from developed to developing countries have now added a whole new dimension to this infection. Though new, finer diagnostic tools of detection of TB are increasingly available in the form of bacterial cultures and polymerase chain reaction (PCR) based diagnostics, suspicion by clinicians remains the main tool for diagnosis of the condition. Hence, doctors need to be properly trained to become "Tuberculosis Minded".
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Países em Desenvolvimento , Transmissão Vertical de Doenças Infecciosas , Tuberculose/complicações , Tuberculose/transmissão , Antituberculosos/efeitos adversos , Feminino , Infecções por HIV/complicações , Humanos , Infertilidade Feminina/etiologia , Distúrbios Menstruais/etiologia , Gravidez , Complicações Infecciosas na Gravidez/etiologia , Tuberculose/epidemiologiaRESUMO
The present cross-sectional analytical study was carried out to observe blood pressure and serum total cholesterol in patients with type-2 diabetes mellitus. This observational study was carried out in the department of Physiology, Mymensingh Medical College, Mymensingh, Bangladesh from January 2016 to December 2016. For this purpose, 200 subjects of both sexes and age ranged from 30-60 years were selected; among them 100 were type-2 diabetic person and 100 were apparently healthy. Blood pressure and serum total cholesterol was significantly higher (p<0.0001) in both male and female of the study group in comparison to healthy control group. From this study, it may conclude that type-2 persons are considered to have significant positive relation for formation of hypertension, hypercholesterolemia and metabolic abnormalities that have high morbidity and mortality. So, prevention of type-2 diabetes mellitus by taking necessary steps like regular physical exercise, intake of healthy diet and behavior therapy may help in prevention of type-2 diabetes mellitus related complication.
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Diabetes Mellitus Tipo 2 , Hipercolesterolemia , Hipertensão , Adulto , Bangladesh/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/epidemiologia , Hipertensão/complicações , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To estimate the disease and economic burden of pertussis amongst hospitalised infants in India. DESIGN: Multicentric hospital-based surveillance study. PARTICIPANTS: Hospitalised infants with clinical suspicion of pertussis based on predefined criteria. OUTCOME MEASURES: Proportion of infants with laboratory-confirmed pertussis, economic burden of pertussis amongst hospitalised infants. RESULTS: 693 clinically suspected infants were recruited of which 32 (4.62%) infants had laboratory-confirmed pertussis. Progressive cough with post-tussive emesis (50%) and pneumonia (34%) were the common clinical presentations; apnea in young infants was significantly associated with pertussis. Infants with pertussis were more likely to be younger (median age 102.5 days vs.157 days) and born preterm (42.9% vs 24.5%). Almost 30% infants with pertussis had not received vaccine for pertussis with 50% of these infants aged less than 2 months. Pertussis was associated with higher costs of hospitalisation, pharmacy and loss of working days by caregivers as compared to non-pertussis cases. CONCLUSIONS: Younger infants, those born preterm and those inadequately immunised against pertussis are at higher risk of pertussis infection. Timely childhood immunisation and introduction of maternal immunisation for pertussis can help in reducing the disease burden.
Assuntos
Coqueluche , Idoso de 80 Anos ou mais , Criança , Hospitalização , Hospitais , Humanos , Lactente , Recém-Nascido , Vacina contra Coqueluche , Atenção Terciária à Saúde , Vacinação , Coqueluche/diagnóstico , Coqueluche/epidemiologia , Coqueluche/prevenção & controleRESUMO
Familial hypercholesterolemia (FH) is an inherited disorder in humans that is caused by a deficiency of low density lipoprotein receptors (LDLRs). An animal model for FH, the Watanabe Heritable Hyperlipidemic rabbit, was used to develop an approach for liver-directed gene therapy based on transplantation of autologous hepatocytes that were genetically corrected ex vivo with recombinant retroviruses. Animals transplanted with LDLR-transduced autologous hepatocytes demonstrated a 30 to 50 percent decrease in total serum cholesterol that persisted for the duration of the experiment (122 days). Recombinant-derived LDLR RNA was harvested from tissues with no diminution for up to 6.5 months after transplantation.
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Terapia Genética , Hipercolesterolemia/genética , Hipercolesterolemia/terapia , Receptores de LDL/genética , Transfecção , Animais , Expressão Gênica , Fígado/fisiologia , Transplante de Fígado/fisiologia , RNA/genética , RNA/isolamento & purificação , Coelhos , Receptores de LDL/análise , Proteínas Recombinantes/análise , Albumina Sérica/análise , Albumina Sérica/genética , beta-Galactosidase/análise , beta-Galactosidase/genéticaRESUMO
Isolated hepatocytes, harvested from normal rat livers by portal vein collagenase perfusion, can be attached to collagen-coated dextran microcarriers and transplanted by intraperitoneal injection into rats. Survival and function of the transplanted hepatocytes have been demonstrated in mutant rats lacking bilirubin-uridine diphosphate glucuronosyltransferase activity (Gunn strain) and rats with inherited lack of plasma albumin (Nagase analbuminemia rat strain). This simple technique promises to be useful in the treatment of acute liver failure in humans.
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Transplante de Fígado , Microesferas , Animais , Bilirrubina/sangue , Colágeno , Dextranos , Injeções Intraperitoneais , Fígado/citologia , Ratos , Ratos Gunn , Ratos Mutantes , Transplante HomólogoRESUMO
The present cross-sectional analytical study was carried out in the department of Physiology, Mymensingh Medical College, Mymensingh, from January 2016 to December 2016 to observe serum total cholesterol in type 2 diabetes mellitus patients. For this purpose, a total number of 200 subjects of both sexes with age ranged from 30-60 years were selected of whom 100 were type 2 diabetic person and 100 were apparently healthy. Serum total cholesterol was significantly higher (p<0.0001) in both male and female of the study group in comparison to healthy control group. From this study, it may conclude that type 2 persons are considered to have significant positive relation for formation of hypercholesterolemia, and metabolic abnormalities that have high morbidity and mortality. So, prevention of type 2 diabetes mellitus by taking necessary steps like regular physical exercise, intake of healthy diet and behavior therapy may help in prevention of type 2 diabetes mellitus related complication.
Assuntos
Glicemia , Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Jejum , Hipercolesterolemia/sangue , Adulto , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Glucose , Humanos , Hipercolesterolemia/epidemiologia , Masculino , Pessoa de Meia-IdadeRESUMO
This cross-sectional analytical study was carried out to observe serum magnesium in type 2 diabetes mellitus patients and was performed in the department of Physiology, Mymensingh Medical College, Mymensingh, Bangladesh from January 2016 to December 2016. For this purpose, a total number of 200 subjects of both sexes with age ranged from 30-60 years were selected of whom 100 were type 2 diabetic person and 100 were apparently healthy. Serum magnesium was significantly lower (p<0.0001) in both male and female of the study group in comparison to healthy control group. From this study, it may conclude that type 2 persons are considered to have significant positive relation for formation of hypomagnesaemia. So, prevention of type 2 diabetes mellitus by taking necessary steps like regular physical exercise, intake of healthy diet and behavior therapy may supplementation of magnesium help in prevention of type 2 diabetes mellitus related complication.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Jejum , Magnésio/sangue , Adulto , Bangladesh , Glicemia , Estudos Transversais , Feminino , Glucose , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Dyspepsia is a symptom complex that includes epigastric pain, post-prandial fullness, bloating, early satiety, belching, nausea, vomiting, heartburn, acid regurgitations and anorexia. The most widely applied definition of dyspepsia is the Rome working team formulation namely chronic or recurrent pain or discomfort centered in the upper abdomen. Till date the prevalence of dyspepsia in Bangladesh has not been studied much. The last study was done in 1987 in a rural community and the prevalence of dyspepsia was found to be 41.4%. However, associated risk factors were not assessed and definition of dyspepsia was much narrower as well as the dysmotility type dyspepsia was not included in that study. Hence it is now high time to carry out another study to see the prevalence of dyspepsia in Bangladesh and the risk factors associated with it. To determine the prevalence of dyspepsia and the demographic risk factors associated with dyspepsia in the adult population in the rural community of Bangladesh. This cross sectional population based study carried out in Ghior Union of Manikgonj district of Bangladesh from January 2007 to April 2008. All persons 18 years or above living in Ghior Union were considered as the study populations with using a pre-designed questionnaire. This study showed that the prevalence of dyspepsia to be 61.9%. Reflux- like dyspepsia was the commonest sub-type of dyspepsia without reflux symptoms comprising 43.9% of the total population and 70.9% of the dyspeptics. Dysmotility like dyspepsia comprised more than half of the dyspeptics. Nausea (40.7%) was the most predominant dysmotility like dyspeptic symptoms followed by early satiety (38.4%); 13.9% of the population had history of recurrent upper abdominal pain and 11.9% of the population had gastro-esophageal reflux disease (GERD). There was considerable overlapping (16.7%) of IBS with dyspepsia. Female sex, younger age (<40 years), low family income (<5000 Taka per month), lower educational level (up to primary level), smoking and use of NSAIDs were significantly associated with dyspepsia. The prevalence of dyspepsia in adult population of Bangladesh is 61.9% which is very high compared to other countries and also much higher than the prevalence found in our country thirty years back. A great change in the socio-economic status and lifestyle of the people along with environmental pollution and food adulteration may be responsible for this increase in prevalence. This study was conducted in only one union of this country, so it was not representative of the whole population of the country. Therefore further study with large population size including rural and urban peoples from different parts of Bangladesh is needed to estimate the accurate prevalence of dyspepsia in our country.
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Dispepsia/epidemiologia , Refluxo Gastroesofágico/epidemiologia , População Rural , Adulto , Bangladesh/epidemiologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Náusea/etiologia , Prevalência , Vômito/etiologia , Adulto JovemRESUMO
This research aims to investigate the protective effects Leea macrophylla Roxb polyphenols on streptozotocin-induced diabetic rats. Polyphenolic assays were undertaken through established methods. To conduct animal intervention study, forty Wistar albino male rats (average body weight 188.42 ± 7.13 g) of different groups were diabetized by streptozotocin (60 mg/kg) only in the animals of diabetic control (DC) and L. macrophylla extract (LM) groups. At the end of 4 weeks of intervention, serum was analyzed for insulin, liver and cardiac enzymes, lipid profiles, uric acid, and creatinine using ELISA method. In vitro α-amylase inhibition of LM was evaluated and compared with reference drug acarbose. Pancreatic tissues were undertaken for histopathological screening. Food and fluid intake, weekly blood glucose level, liver glycogen, aspartate transaminase (AST), creatinine kinase (CK-MB), cholesterol, and lactate dehydrogenase (LDH) were significantly decreased, whereas oral glucose tolerance (OGTT) ability, serum insulin concentration, and pancreatic islets morphology were significantly improved in the LM300 treatment group compared to the DC group. Alpha-amylase inhibition was not found to be very promising for guiding the α-amylase inhibition pathway. Results suggest that L. macrophylla can exert a potential effort to restore pancreatic ß-cell damaged by streptozotocin induction.
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A novel feedback regulatory mechanism operating on transcription of the albumin gene is described in the rat. In 1946, it was proposed that circulating colloids, including serum albumin, may affect the synthesis and/or secretion of albumin in the liver. The molecular basis for this proposed regulation has now been investigated by adding oncotically active macromolecules to the circulation of normal or genetically albumin-deficient Nagase analbuminemic rats (NAR) and analyzing the hepatic expression of genes, including albumin after 24 h. The transcription rate of the albumin gene was higher in NAR than in normal rats and was dramatically reduced by raising serum albumin to 1.6 g/dl. Intravenous infusion of albumin into normal rats also decreased transcriptional activity of the albumin gene by 50-60%, and this decrease correlated with changes in serum colloid osmotic pressure after albumin infusion. Inhibition of albumin gene transcription was also observed upon intravenous infusion of other protein or nonprotein macromolecules, such as gamma-globulin and dextran. This down-regulation appears to control the steady-state level of albumin mRNA in the liver. Aside from a concomitant decrease in apo E gene transcription after albumin or macromolecule infusion, there was no change in the transcription rate of other genes, including those exhibiting liver-preferred or -specific expression (e.g., tyrosine amino-transferase, cytochrome P-450, alpha 1-antitrypsin, apolipoproteins A-I and B, and transferrin) or general cellular expression (e.g., alpha-tubulin, pro alpha 2 collagen, and beta-actin). Feedback regulation of albumin gene expression by serum colloids may serve as a specific homeostatic mechanism to maintain the steady-state level of total protein in the circulation.
Assuntos
Regulação para Baixo , Albumina Sérica/genética , Animais , Coloides/farmacologia , Fígado/metabolismo , Substâncias Macromoleculares , Masculino , Pressão Osmótica , Ratos , Ratos Endogâmicos , Albumina Sérica/deficiência , Albumina Sérica/fisiologiaRESUMO
Recombinant adenoviruses are highly efficient at transferring foreign genes in vivo. However, duration of gene expression is limited by the host antiviral immune response which precludes expression upon viral readministration. We tested the feasibility of prolonging gene expression by induction of central tolerance to adenoviral antigens in bilirubin-UDP-glucuronosyltransferase-1 (BUGT1)-deficient Gunn rats. Tolerance was induced by intraperitoneal injection of antilymphocyte serum, followed by intrathymic inoculation of one of the following: a recombinant adenovirus (Ad), adenovirus human UDP-glucuronosyltransferase (Ad-hBUGT1) carrying the hBUGT1 gene; a protein extract of the same virus; or viral infected hepatocytes. Controls received intrathymic injections of normal saline. After 12 d all groups were injected intravenously with 5 x 10(9) pfu of either Ad-hBUGT1 or adenovirus beta-galactosidase (Ad-LacZ) (expressing the Escherichia coli beta-galactosidase [LacZ] gene). In all three groups of tolerized rats, hBUGT1 was expressed in the liver after administration of Ad-hBUGT1, with glucuronidation of biliary bilirubin of above 95%. Serum bilirubin levels decreased from 7.2 to 1.8 mg/dl within 1 wk and remained low for 7 wk. Similar findings were observed following repeat injections given on days 45 and 112. In control rats serum bilirubin levels were reduced for only 4 wk, and viral readministration was ineffective. In all tolerized groups, but not in controls, there was a marked inhibition of appearance of neutralizing antibodies and cytotoxic lymphocytes against the recombinant adenovirus. Injection of wild type adenovirus-5 (Ad5) into the tolerized rats elicited a wild type-specific cytotoxic lymphocyte response. This is the first demonstration of Ad-directed long-term correction of an inherited metabolic disease following central tolerization with thymic antigen.