RESUMO
Cancer is one of the most devastating disease and leading cause of death worldwide. The conventional anticancer drugs are monotarget, toxic, expensive and suffer from drug resistance. Development of multi-targeted drugs from natural products has emerged as a new paradigm to overcome aforementioned conventionally encountered obstacles. Hispidulin (HIS), is a biologically active natural flavone with versatile biological and pharmacological activities. The anticancer, antimutagenic, antioxidative and anti-inflammatory properties of HIS have been reported. The aim of this review is to summarize the findings of several studies over the last few decades on the anticancer activity of HIS published in various databases including PubMed, Google Scholar, and Scopus. HIS has been shown to reduce the growth of cancer cells by inducing apoptosis, arresting cell cycle, inhibiting angiogenesis, invasion and metastasis via modulating multiple signaling pathways implicated in cancer initiation and progression. Multitargeted anticancer activity of HIS remains the strongest point for developing it into potential anticancer drug. We also highlighted the natural sources, anticancer mechanism, cellular targets, and chemo-sensitizing potential of HIS. This review will provide bases for design and conduct of further pre-clinical and clinical trials to develop HIS into a lead structure for future anticancer therapy.
Assuntos
Produtos Biológicos/uso terapêutico , Flavonas/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Produtos Biológicos/farmacologia , Flavonas/farmacologia , Humanos , CamundongosRESUMO
Ingestion of a toxic dose of the analgesic drug, acetaminophen (also called paracetamol or APAP), is among the most common causes of acute liver injury in humans. We tested the hypothesis that the combined polyphenolic compounds, resveratrol (RES) and quercetin (QUR), can substantially protect against hepatocyte ultrastructural damage induced by a toxic dose of APAP in a rat model of APAP-induced acute liver injury. The model group of rats received a single dose of APAP (2 g/kg), whereas the protective group of rats was pretreated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP. All rats were then sacrificed 24 hours post APAP ingestion. Harvested liver tissues were prepared for transmission electron microscopy (TEM) staining, and liver homogenates were assayed for biomarkers of inflammation, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and oxidative stress, such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx). In addition, blood samples were assayed for the liver injury enzyme alanine aminotransferase (ALT) as an indicator of liver damage. TEM images showed that APAP overdose induced acute liver injury as demonstrated by profound hepatocyte ultrastructural alterations, which were substantially protected by RES+QUR. In addition, APAP significantly (p < 0.05) modulated TNF-α, IL-6, MDA, SOD, GPx, and ALT biomarkers, which were completely protected by RES+QUR. Thus, RES+QUR effectively protects against APAP-induced acute liver injury in rats, possibly via the inhibition of inflammation and oxidative stress.
Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/ultraestrutura , Animais , Hepatócitos/patologia , Microscopia Eletrônica de Transmissão , Quercetina/farmacologia , Ratos , Ratos Sprague-Dawley , Resveratrol/farmacologiaRESUMO
Tuberculosis (TB) is one of the major public health problem among contagious diseases in Pakistan. TB diagnosis mainly depends on sputum smear microscopy. The main objective of this study was to evaluate the effects of household bleach on sputum smear microscopy to concentrate acid fast bacilli for the diagnosis of pulmonary tuberculosis. Sputum specimens of 200 suspected TB patients were collected for the study. Smears were prepared from the purulent part of sputum sample before and after bleach treatment, heat fixed and stained with the ZN technique. The obtained data were analyzed by chi-squared test using SPSS software. Out of 200 isolates, 22 (11%) patients had positive smears for acid fast bacilli (AFB) by direct ZN staining. After treatment with household bleach (NaOCL) and centrifugation, the number of AFB positive patients were increased from 22 (11%) to 37 (18.5%). The bleach-concentration method for sputum samples significantly increased the TB detection rate as compared to direct sputum smear microscopy. Thus, a shift from direct sputum microscopy to bleach-concentration technique should be considered a better method for detection of AFB in sputum through smear microscopy.
Assuntos
Clareadores/química , Mycobacterium tuberculosis , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Feminino , Humanos , Masculino , Microscopia/métodosRESUMO
In this study, we define the genetic landscape of mantle cell lymphoma (MCL) through exome sequencing of 56 cases of MCL. We identified recurrent mutations in ATM, CCND1, MLL2, and TP53. We further identified a number of novel genes recurrently mutated in patients with MCL including RB1, WHSC1, POT1, and SMARCA4. We noted that MCLs have a distinct mutational profile compared with lymphomas from other B-cell stages. The ENCODE project has defined the chromatin structure of many cell types. However, a similar characterization of primary human mature B cells has been lacking. We defined, for the first time, the chromatin structure of primary human naïve, germinal center, and memory B cells through chromatin immunoprecipitation and sequencing for H3K4me1, H3K4me3, H3Ac, H3K36me3, H3K27me3, and PolII. We found that somatic mutations that occur more frequently in either MCLs or Burkitt lymphomas were associated with open chromatin in their respective B cells of origin, naïve B cells, and germinal center B cells. Our work thus elucidates the landscape of gene-coding mutations in MCL and the critical interplay between epigenetic alterations associated with B-cell differentiation and the acquisition of somatic mutations in cancer.
Assuntos
Linfócitos B/metabolismo , Cromatina/genética , Genômica , Linfoma de Célula do Manto/genética , Mutação , Proteínas Mutadas de Ataxia Telangiectasia/genética , Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Cromatina/metabolismo , Ciclina D1/genética , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Epigênese Genética , Exoma/genética , Redes Reguladoras de Genes , Centro Germinativo/metabolismo , Centro Germinativo/patologia , Histona-Lisina N-Metiltransferase/genética , Histonas/genética , Histonas/metabolismo , Humanos , Linfoma de Célula do Manto/patologia , Metilação , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Proteína do Retinoblastoma/genética , Análise de Sequência de DNA , Complexo Shelterina , Proteínas de Ligação a Telômeros/genética , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma in adults. The disease exhibits a striking heterogeneity in gene expression profiles and clinical outcomes, but its genetic causes remain to be fully defined. Through whole genome and exome sequencing, we characterized the genetic diversity of DLBCL. In all, we sequenced 73 DLBCL primary tumors (34 with matched normal DNA). Separately, we sequenced the exomes of 21 DLBCL cell lines. We identified 322 DLBCL cancer genes that were recurrently mutated in primary DLBCLs. We identified recurrent mutations implicating a number of known and not previously identified genes and pathways in DLBCL including those related to chromatin modification (ARID1A and MEF2B), NF-κB (CARD11 and TNFAIP3), PI3 kinase (PIK3CD, PIK3R1, and MTOR), B-cell lineage (IRF8, POU2F2, and GNA13), and WNT signaling (WIF1). We also experimentally validated a mutation in PIK3CD, a gene not previously implicated in lymphomas. The patterns of mutation demonstrated a classic long tail distribution with substantial variation of mutated genes from patient to patient and also between published studies. Thus, our study reveals the tremendous genetic heterogeneity that underlies lymphomas and highlights the need for personalized medicine approaches to treating these patients.
Assuntos
Heterogeneidade Genética , Linfoma Difuso de Grandes Células B/genética , Adulto , Sequência de Bases , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases , Análise Mutacional de DNA , DNA de Neoplasias/genética , Exoma , Expressão Gênica , Variação Genética , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Modelos Moleculares , Dados de Sequência Molecular , Terapia de Alvo Molecular , Mutação , Oncogenes , Fosfatidilinositol 3-Quinases/química , Fosfatidilinositol 3-Quinases/genética , Conformação Proteica , Proteínas Proto-Oncogênicas c-kit/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Homologia de Sequência do Ácido Nucleico , Transdução de Sinais/genéticaRESUMO
This study was planned to investigate the comparative effect of vitamins C (L-ascorbic acid), E (DL-α-tocopherol acetate), probiotics, lower than normal protein level (14%) and combination of these treatments on immune response of male broiler breeders after zinc-induced moulting. One hundred and eighty birds at the age of 65 weeks were induced to moult by mixing zinc oxide (ZnO) in feed at the rate 3000 IU/kg of feed. Upon completion of moulting, birds were divided into six groups (five replicates per group) in a completely randomized design and were fed vitamin C (500 IU/kg), vitamin E (100 IU/kg), lower protein level, probiotics (50 mg/l), and a combination of these components, while one group was kept as control. After completion of moulting phase (5 weeks), the treatment effects were tested as in vitro macrophages engulfment percentage, nitric oxide (NO) production, serum antibody titres against Newcastle disease (ND) and infectious bronchitis (IB). The results showed that in vitro macrophage engulfment percentage in unopsonized conditions was significantly higher in vitamin E-supplemented group. In addition, in opsonized condition, the macrophage engulfment percentage was significantly higher in both vitamin E- and C-supplemented groups. The NO (opsonized and unopsonized) production and antibody titre against ND and IB were significantly higher in vitamin E-supplemented group. It was concluded that vitamin E is a better option for enhanced immune response in broiler breeders after zinc-induced moulting.
Assuntos
Ácido Ascórbico/farmacologia , Galinhas/imunologia , Proteínas Alimentares/administração & dosagem , Muda , Probióticos , alfa-Tocoferol/farmacologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Ácido Ascórbico/administração & dosagem , Células Cultivadas , Dieta/veterinária , Macrófagos Peritoneais , Masculino , Óxido Nítrico/metabolismo , Vitaminas , alfa-Tocoferol/administração & dosagemRESUMO
Pituitary aspergillosis is a very rare disease, documented in only 12 cases. Although seen in both immunocompetent and immunocompromised patients, serious invasive sequelae, such as meningoencephalitis and death, have been noted in immunocompromised patients. Immunocompromised patients are susceptible and require complex multidisciplinary care to contain the spread of infection and maximize outcomes. This is the first case report, to our knowledge, of pituitary aspergillosis in the setting of an organ transplant. A 68-year-old woman presented with cephalgia, left temporal hemianopsia, and ptosis. Non-contrast magnetic resonance imaging of the head revealed a sellar mass, which was believed to be a benign pituitary adenoma. She underwent trans-sphenoidal resection, and subsequent histopathologic examination showed aspergillosis. She was subsequently started on voriconazole. On postoperative day 3, she developed a left anterior cerebral artery ischemic stroke, likely from Aspergillus angioinvasion and occlusion. Her mental status declined further and she died when care was withdrawn.
Assuntos
Antifúngicos/administração & dosagem , Aspergilose/diagnóstico , Infarto da Artéria Cerebral Anterior/complicações , Transplante de Rim/efeitos adversos , Doenças da Hipófise/diagnóstico , Voriconazol/administração & dosagem , Idoso , Aspergilose/complicações , Aspergilose/tratamento farmacológico , Aspergilose/cirurgia , Aspergillus/efeitos dos fármacos , Aspergillus/isolamento & purificação , Evolução Fatal , Feminino , Humanos , Hifas , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Infarto da Artéria Cerebral Anterior/diagnóstico , Infarto da Artéria Cerebral Anterior/microbiologia , Doenças da Hipófise/complicações , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/cirurgia , Hipófise/microbiologia , Esporos FúngicosRESUMO
1. A study was designed to investigate the comparative effect of supplementary vitamin E, vitamin C, probiotics and dietary crude protein concentration on semen traits and seminal plasma biochemical parameters in male broiler breeders after Zn-induced moulting. 2. A total of 180 male broiler breeders were induced to moult at 65 weeks of age by mixing ZnO in diet at the rate 3000 mg/kg of feed. After moulting, the males were divided into six groups that were given feed supplemented with: vitamin C (500 IU/kg), vitamin E (100 IU/kg), protein (140 g CP/kg), probiotics (50 mg/kg) and the combination of these components, while one group was kept as a control. Semen samples were collected weekly and semen volume, spermatozoa concentration, motility and dead spermatozoa percentage were determined. Seminal plasma was separated to determine the concentration of total antioxidant capacity (TAC), homocysteine, paraoxonase (PON1), arylesterase, ceruloplasmin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. 3. Semen volume was significantly higher in the vitamin E and C groups compared to the control. Spermatozoa motility was higher in the vitamin E group and dead spermatozoa percentage was significantly lower in the vitamin C group compared with the control group. 4. Seminal plasma TAC was higher in the vitamin E group, homocysteine was lower in the vitamin C and E groups. PON1 was higher in the combination group. Arylesterase increased significantly in the vitamin C and combination groups over time. Seminal plasma AST was significantly lower in the vitamin C and E supplemented groups whereas ALT decreased significantly only in the vitamin E group compared with the control. Higher concentrations of ceruloplasmin were observed in the combination group compared with the other treatments. 5. It was concluded that additional vitamin E and C or their combination was the most potent nutrient treatment for improving the semen traits and seminal plasma biochemical characteristics in male broiler breeders after Zn-induced moulting.
Assuntos
Ácido Ascórbico/farmacologia , Galinhas/fisiologia , Proteínas Alimentares/farmacologia , Probióticos/farmacologia , Sêmen/efeitos dos fármacos , Sêmen/metabolismo , Vitamina E/farmacologia , Alanina Transaminase/metabolismo , Animais , Antioxidantes/metabolismo , Arildialquilfosfatase/metabolismo , Aspartato Aminotransferases/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Ceruloplasmina/metabolismo , Homocisteína/metabolismo , Masculino , Muda/efeitos dos fármacos , Análise do Sêmen/veterinária , Zinco/farmacologiaRESUMO
1. L-carnitine is a quaternary ammonium compound biologically synthesised from the amino acids methionine and lysine while vitamin E (α-tocopherol) is an important antioxidant. The objective of the present study was to evaluate the ameliorative effects of L-carnitine and vitamin E upon haematological and serum biochemical parameters in ochratoxin A intoxicated birds. 2. Day-old White Leghorn cockerels were acclimatised for 2 d, divided in 12 groups with 20 birds in each group. From d 3 of age, they were given different combinations of ochratoxin A (1.0 and 2.0 mg/kg), L-carnitine (1 g/kg) and vitamin E (200 mg/kg) in feed. Haematological (erythrocyte count, leucocyte count, haemoglobin concentration and haematocrit percentage) and serum biochemical parameters (serum urea, creatinine, albumin, total proteins and alanine aminotransferase) were evaluated. 3. Results confirmed that L-carnitine and vitamin E given alone or combined with 1.0 mg/kg ochratoxin A ameliorated toxin induced alterations in haematological and serum biochemical parameters. This amelioration, however, did not occur when ochratoxin of 2.0 mg/kg was given. 4. L-carnitine and vitamin E in combination have the ability to ameliorate ochratoxin altered haematological and serum biochemical parameters. However, the optimum ratio of L-carnitine + vitamin E, to be used to assure such mitigation of ochratoxin A altered changes in haematological and serum biochemical parameters in cockerels, has yet to be determined. The combination used in this study was indeed sufficient to ameliorate the alterations induced by ochratoxin A up to 1.0 mg/kg feed.
Assuntos
Antioxidantes/farmacologia , Carnitina/farmacologia , Galinhas/fisiologia , Ocratoxinas/toxicidade , alfa-Tocoferol/farmacologia , Ração Animal/análise , Animais , Antioxidantes/administração & dosagem , Análise Química do Sangue/veterinária , Carnitina/administração & dosagem , Dieta/veterinária , Testes Hematológicos/veterinária , Masculino , Ocratoxinas/administração & dosagem , alfa-Tocoferol/administração & dosagemRESUMO
A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes. We identified the expression of 333 known miRNAs, which is more than twice the number previously recognized in any tissue type. We further identified the expression of 286 candidate novel miRNAs in normal and malignant B cells. These miRNAs were validated at a high rate (92%) using quantitative polymerase chain reaction, and we demonstrated their application in the distinction of clinically relevant subgroups of lymphoma. We further demonstrated that a novel miRNA cluster, previously annotated as a hypothetical gene LOC100130622, contains 6 novel miRNAs that regulate the transforming growth factor-ß pathway. Thus, our work suggests that more than a third of the miRNAs present in most cellular types are currently unknown and that these miRNAs may regulate important cellular functions.
Assuntos
Linfócitos B , Perfilação da Expressão Gênica/métodos , Linfoma Difuso de Grandes Células B/genética , MicroRNAs/genética , Sequência de Bases , Imunoprecipitação da Cromatina , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , MicroRNAs/análise , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de RNARESUMO
BACKGROUND: There is no specific data on the pathological lesions underlying idiopathic nephrotic syndrome (INS) in adolescents in Pakistan. Moreover, it is not known whether the pathological lesions in adolescents differ significantly from young children with INS in our setup. Materials and methods. A retrospective analysis was carried out on all patients with INS with onset ≤ 18 years of age. They were split into two groups: patients with onset of INS ≤ 12 years (young children group) and patients with onset ≥ 13 through 18 years of age (adolescent group). Renal biopsies were evaluated by light microscopy, immunoflourescence and electron microscopy. The histopathological lesions on renal biopsies were analyzed and compared between the two groups. RESULTS: The adolescents comprised 173 (32.1%) patients, and there were 365 young children (67.8%). The mean age of adolescents at the time of onset of INS was 15.12 ± 1.5 years and there were 113 boys (65.3%) and 60 girls (34.6%). The mean age of young children was 7.26 ± 3.24 years and there were 231 boys (63.2%) and 134 girls (36.7%). Focal segmental glomerulosclerosis was the most common histopathological lesion in adolescents (36.4%) followed by minimal change disease (MCD) (28.9%). Adolescent-onset INS had a significantly higher frequency of membranous glomerulonephritis and membranoproliferative glomerulonephritis (MPGN) (P < 0.05) and significantly lower frequency of MCD (P < 0.05) than early childhood-onset INS. CONCLUSIONS: Our data indicate that the pathological lesions in adolescent INS are different from younger children and resemble more closely those seen in adults. Our findings are concordant with the few previously published studies on this subject.
Assuntos
Glomerulonefrite Membranosa/patologia , Nefrose Lipoide/patologia , Síndrome Nefrótica/epidemiologia , Síndrome Nefrótica/patologia , Adolescente , Adulto , Fatores Etários , Idade de Início , Biópsia por Agulha , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Estudos de Coortes , Progressão da Doença , Feminino , Imunofluorescência/métodos , Glomerulonefrite Membranosa/epidemiologia , Glomerulonefrite Membranosa/fisiopatologia , Humanos , Imuno-Histoquímica , Masculino , Microscopia/métodos , Nefrose Lipoide/epidemiologia , Nefrose Lipoide/fisiopatologia , Síndrome Nefrótica/fisiopatologia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de DoençaRESUMO
Steroid-resistant nephrotic syndrome (SRNS) is a common problem in pediatric nephrology practice. There is currently little information in the literature on the spectrum of histopathologic lesions in children presenting with SRNS in Pakistan. This study was designed to determine the histopathologic lesions in children presenting with SRNS at our center. The study was conducted at the Histopathology Department, Sindh Institute of Urology and Transplantation (SIUT) from January 2009 to August 2011. All children (≤ 16 years) presenting with SRNS, in whom renal biopsies were performed, were included. Their demographic, clinical, laboratory, and histopathological data were retrieved from files and original renal biopsy forms. The results were analyzed by SPSS version 10.0. A total of 147 children were included. Of these, 91 (61.9%) were males and 56 (38.1%) females, with male-to-female ratio of 1.6 : 1. The mean age was 7.03 ± 4.0 years (range: 6 months-16 years). The histopathological lesions seen on renal biopsies comprised of focal segmental glomerulosclerosis (FSGS) (38.5%), followed by minimal change disease (MCD) (23.2%), IgM nephropathy (IgMN) (13.6%), idiopathic mesangial proliferative GN (10.2%), membranous GN (8.2%), and mesangiocapillary GN (4.8%). Our results indicate that FSGS is the predominant lesion in children with SRNS, followed by MCD and IgMN.
Assuntos
Síndrome Nefrótica/epidemiologia , Síndrome Nefrótica/patologia , Esteroides/uso terapêutico , Adolescente , Criança , Pré-Escolar , Resistência a Medicamentos , Feminino , Humanos , Lactente , Masculino , Paquistão/epidemiologia , PrevalênciaRESUMO
Dietary zinc was used to induce molt in 200 White Leghorn birds in caged housing at the age of 70 wk. The birds were equally and randomly allocated to 4 groups each of 50 birds as G1 (control; CP 16%, no supplement), G2 (CP 18%, no other supplement), G3 (CP 16%, symbiotic Perfectin: 85 mgâ¢L(-1) in drinking water daily), and G4 (CP 16%, probiotic Protexin: 85 mgâ¢L(-1) in drinking water daily) after the completion of molt. The sampling was conducted 3 times at 5% production, peak production, and end of production with 15 birds being killed at each sampling from each group to collect the blood for harvesting of serum. Serum health markers including total oxidant status, total antioxidant capacity, homocysteine concentration, and paraoxonase, arylesterase, and ceruloplasmin activity were determined by the prescribed assays. The overall total antioxidant capacity was increased, whereas total oxidant status and homocysteine concentrations were reduced significantly (P ≤ 0.01) in all the supplemented groups compared with the control. The paraoxonase and ceruloplasmin activity were enhanced (P ≤ 0.01) in the supplemented groups compared with the control, and arylesterase activity was increased (P ≤ 0.01) in only G2 compared with the other groups. Although protein supplementation significantly reduced the oxidative stress, supplementation with symbiotic and probiotic also improved the health status by decreasing the oxidative stress in the birds.
Assuntos
Galinhas , Proteínas Alimentares/farmacologia , Muda/fisiologia , Probióticos/farmacologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Biomarcadores/sangue , Dieta/veterinária , Proteínas Alimentares/administração & dosagem , Suplementos Nutricionais , Feminino , Oviposição , Probióticos/administração & dosagemRESUMO
Lead may be passed on from a mother to their unborn fetus. If she has been exposed to lead for an extended period, the lead deposited in their bones can be stimulated to be released into the bloodstream during gestation. This study was planned to examine blood lead level at the prenatal stage and its response to markers of iron deficiency during gestation. We collected 396 samples during the second trimester of gestation from women age 19 to 45 years. Hematological markers including hemoglobin, hepcidin, total iron-binding capacity (TIBC), ferritin, and blood iron were analyzed. For the detection of blood lead, we used Atomic absorption spectroscopy. The mean blood lead level of the control group was 3.25 ± .407 µg/dL, and in the iron deficiency group, it was 7.96 ± .502 µg/dL. At the same time, the women with iron deficiency anemia showed 22.12 ± 1.02 µg/dL of mean blood lead. Pearson's approach showed a non-significant negative correlation between blood lead and hepcidin, while hemoglobin, total iron-binding capacity, ferritin, and serum iron showed a significant (.01) negative correlation with blood lead. Blood lead has no direct effect on iron deficiency markers. In contrast, iron deficiency contributes to an increase in lead accumulation during pregnancy. Iron and lead both have an impact on the heme-biosynthetic pathways. The study revealed that pre-existing iron deficiency is connected with increased lead intake and can negatively impact health in gestational females.
RESUMO
AIM: In the absence of a national renal biopsy registry, there is a paucity of information on the pattern of renal disease observed in native renal biopsies in adults in Pakistan. METHODS: A retrospective review of native renal biopsies performed in adult patients was undertaken at the Sindh Institute of Urology and Transplantation (SIUT) during the period from July 1995 to December 2008. Renal biopsies were studied by light, immunofluorescence and electron microscopy. The renal biopsy diagnoses were categorized into the following groups: glomerulopathies (GN), tubulointerstitial diseases (TID), renal vascular diseases (VD), and hereditary diseases (HD). RESULTS: A total of 1793 adult patients were included in the study. GN was the commonest diagnosis representing 83.9% of all biopsies. Primary GN (PGN) accounted for 86.9% and secondary GN (SGN) for 13%. When PGN was further analyzed, focal segmental glomerulosclerosis (FSGS) was the leading histopathological diagnosis, found in 29% of PGN, followed by membranous GN (MGN), seen in 23.5% of cases. Among SGN, lupus nephritis (44.1%) was the commonest, followed by amyloidosis (42.1%) and diabetic nephropathy (8.1%). TID comprised 11.6% of all renal biopsy diagnoses. VD and HD were less frequent, found in 3.9% and 0.4%, respectively. CONCLUSION: The pattern of biopsied renal pathology is similar to that reported recently from other parts of the world with similar biopsy indications.
Assuntos
Nefropatias/epidemiologia , Nefropatias/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Amiloidose/epidemiologia , Amiloidose/patologia , Biópsia , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/patologia , Feminino , Glomerulosclerose Segmentar e Focal/epidemiologia , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Rim/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Nefrite/epidemiologia , Nefrite/patologia , Paquistão/epidemiologia , Prevalência , Estudos Retrospectivos , Doenças Vasculares/epidemiologia , Doenças Vasculares/patologia , Adulto JovemRESUMO
OBJECTIVE: To compare post-paediatric intensive care unit (PICU) rotation performance of paediatric residents (PGY-2) and emergency residents (PGY-2) on an online test developed by the subcommittee of the paediatric section of the Society of Critical Care Medicine. Also, to compare residents' performance with that of physician extenders. DESIGN AND SETTINGS: A single centre, longitudinal, retrospective, quality improvement data review in a tertiary care, 20-bed PICU. The test was securely submitted to all residents at the end of their PICU rotation from July 2005 to June 2008. The test was also submitted to physician extenders once only during the 3-year study period. RESULTS: The mean, paediatric residents' (N=30) score was 77.3%±10.8 (SD) and that of emergency residents (N=40) was 82.3%±8.2 (SD) at PGY-2 level (p=0.03). The combined paediatric residents' and emergency residents' mean score was 80.1%±9.7 (SD). The mean physician extenders' (N=7) score was 80.1%±6.5 (SD). CONCLUSION: Emergency residents performed slightly better than paediatric residents on the paediatric-focused knowledge-based online test. The physician extenders' performance was comparable to the individual resident groups' performance and their combined performance.
Assuntos
Cuidados Críticos , Avaliação Educacional/métodos , Medicina de Emergência/educação , Unidades de Terapia Intensiva Pediátrica , Internato e Residência/normas , Pediatria/educação , Competência Clínica , Humanos , Estudos Longitudinais , Assistentes Médicos/educação , Estudos RetrospectivosRESUMO
The distinction between classical Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) is not problematic in most instances. In rare situations, HL may present with a sinusoidal infiltrative pattern that may mimic ALCL. It is important to use a battery of immunohistochemical stains to differentiate between these two entities as therapy and clinical behavior are different. We present a case of a young woman who presents with the very unusual intrasinusoidal infiltrative pattern.
RESUMO
BACKGROUND: Idiopathic collapsing focal segmental glomerulosclerosis (FSGS), a rare variant of FSGS, is of interest because of its increasing incidence, frequent association with black race, HIV-1 infection, and intravenous (IV) drug abuse. This lesion has not been reported from Pakistan until now. METHODS: We reviewed our 14-year native renal biopsies record and identified 10 cases of this entity (July 1995-July 2009). Patients' demographic and clinicopathologic data were collected from case files. Renal biopsies were studied by light microscopy, immunofluorescence microscopy, and electron microscopy. A control group of 124 patients with noncollapsing FSGS was selected for comparison of clinical, laboratory, and outcome parameters. RESULTS: All the patients were young adults (mean age: 22.4 +/- 4.6 years). The majority were males (9 vs. 1 female). All presented with nephrotic syndrome (24-h urinary protein: 6.7 +/- 9.22 g). In addition, 8 had mild to moderate renal failure (serum creatinine: 4.12 +/- 4.6 mg/dl). No history of heroin or IV drug abuse was elicited and all tested negative for HIV. Only two patients (20%) responded to steroid treatment, while eight (80%) did not. Five of the patients (50%) developed endstage renal disease after a mean interval of 18 months. CONCLUSION: Idiopathic collapsing FSGS is increasingly being reported in patients who have no HIV infection or history of IV drug abuse. There is a need for increased awareness among pathologists all over the world to diagnose this condition to guide nephrologists and patients regarding the poor prognosis of this form of FSGS.
Assuntos
Glomerulosclerose Segmentar e Focal/patologia , Adolescente , Adulto , Feminino , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/epidemiologia , Humanos , Falência Renal Crônica/etiologia , Masculino , Síndrome Nefrótica/etiologia , Paquistão/epidemiologia , Estudos RetrospectivosRESUMO
Thirty-six Thalli male growing lambs were used in a completely randomized design with 2 x 2 factorial arrangement of treatments to evaluate the effect of varying levels of energy and protein on nutrient intake, digestibility, weight gain, and gain to feed ratio. Four experimental diets, i.e., low energy-low protein (LE-LP), low energy-high protein (LE-HP), high energy-low protein (HE-LP), and high energy-high protein (HE-HP) were formulated. The low- and high-energy diets contained 2.3 and 2.7 MJ/kg dry matter (DM) with 12% and 14% of crude protein. The lambs were fed ad libitum. Dietary energy and protein levels and their interactions influenced the nutrient intake. Maximum dry matter intake was noted in animals fed LE-HP diet followed by LE-LP, HE-HP, and HE-LP diets. Digestibility of DM and N increased (P < 0.01) and that of neutral detergent fiber decreased (P < 0.01) linearly with increasing levels of dietary energy and protein. Digestibility of N was only affected by protein level and interaction between energy and protein levels. Average daily gain was higher (P < 0.01) in lambs fed HE-HP diet followed by LE-HP, LE-LP, and HE-LP diets. Dietary energy and protein levels and their interaction had significant effect (P < 0.01) on gain to feed ratio.
Assuntos
Ração Animal/análise , Dieta/veterinária , Proteínas Alimentares/farmacologia , Ingestão de Energia/fisiologia , Ovinos/crescimento & desenvolvimento , Fenômenos Fisiológicos da Nutrição Animal , Animais , Digestão/efeitos dos fármacos , Metabolismo Energético , Masculino , Ovinos/fisiologia , Aumento de Peso/efeitos dos fármacosRESUMO
In the present article, we investigate the biomechanical response of a fiber reinforced solid matrix (soft tissue) saturated with an electrically conducting fluid. A constant magnetic field was exposed to the binary mixture of fluid and deformable porous solid. The governing mechanism of multiphasic deformation was based on the loading imposed at the rigid bony interface. The fluid flow through the cartilage network depends upon the rate of applied compression and strain-dependent permeability of the solid matrix. The components of the mixture were intrinsically incompressible; however, in the derivation of governing dynamics, the visco-elastic behavior of the solid and an interstitial fluid was developed. The continuum mixture theory was employed in modeling solid deformation and local fluid pressure. We incorporated strain-dependent permeability in the governing equations of binary mixture that was found in an early experimental study. The governing non-linear coupled system of partial differential equations was developed for the solid deformation and fluid pressure in the presence of Lorentz forces. In the case of strain-dependent permeability, a numerical solution is computed using the method of lines (MOL), whereas, the exact solution is provided when permeability is kept constant. Graphical results highlight the influence of various physical parameters on both solid displacement and fluid pressure.