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1.
Nat Prod Res ; 37(19): 3220-3227, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35403496

RESUMO

A new sesquiterpene (Prosoterpene, 1) and eleven reported compounds (2-12) of several classes, such as flavonoids, alkaloids, phenolic acids, and long-chain alcohols, were isolated from the BuOH extract of Prosopis africana (Guill. & Perr.) Taub. Compounds 2-10 were reported for the first time from this plant. Isomers 11 and 12 were separated for the first time. Extensive spectroscopic techniques and literature comparisons were used to characterise their structures. Furthermore, compounds 3, 5-8, and 10-12 were performed for anti-glycation and cytotoxicity activities. Compound 3 (quercetin-3-O-α-L-rhamnoside) exhibited moderate anti-glycation activity. All tested compounds were non-cytotoxic against MCF-7 (breast cancer), NCI-H460 (lung cancer), Hela (cervical cancer), and BJ (normal human fibroblast) cell lines.

2.
Bioorg Chem ; 129: 106187, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36215785

RESUMO

A synthetic anabolic-androgenic steroid, methylstenbolone (1), was structurally transformed into a series of nine analogues, 2,17α-dimethyl-7α,17ß-dihydroxy-5α-androst-1-en-3-one (2), 2,17α-dimethyl-15ß,17ß-dihydroxy-5α-androst-1-en-3-one (3), 2,17α-dimethyl-6α,9α,17ß-trihydroxy-5α-androst-1-en-3-one (4), 2-methyl-17ß-hydroxy-17α-(hydroxymethyl)-5α-androst-1-en-3-one (5), 2-methyl-11ß,17ß-dihydroxy-17α-(hydroxymethyl)-5α-androst-1-en-3-one (6), 2-methyl-17ß-hydroxy-17α-(hydroxymethyl)-5α-androst-1-en-3,6-dione (7), 2-methyl-17ß-hydroxy-17α-(hydroxymethyl)-5ß-androst-1-en-3,6-dione (8), 2,17α-dimethyl-7ß,17ß-dihydroxy-5α-androst-1-en-3-one (9), and 2,17α-dimethyl-12ß,17ß-hydroxy-5α-androst-1-en-3,7-dione (10) by fungal cell suspension cultures, Macrophomina phaseolina and Cunninghamella blakesleeana for the first time. Among those, compounds 2-4 and 6-10 were identified as new. Herein, spectral data of metabolite 5 was reported for the first time. Their structures were elucidated by NMR, MS, UV, and IR spectroscopic methods. Substrate 1 (IC50 10.1 ± 0.3 µg/mL) was identified as a potent anti-inflammatory agent against nitric oxide (NO) production. Its transformed products 3 (IC50 as 27.8 ± 1.1 µg/mL) and 9 (26.9 ± 0.4 µg/mL) displayed good inhibition. Compounds 2 (IC50 = 45.9 ± 0.8 µg/mL) and 6 (IC50 = 36.6 ± 1.2 µg/mL) were also active moderately against NO production, in comparison to standard LNMMA (IC50 = 24.2 ± 0.8 µg/mL). Cytotoxicity assay showed 1 was active to cancer cell line MCF7 (IC50 = 12.26 ± 0.35 µg/mL), compared to the standard Doxorubicin having IC50 as 1.25 ± 0.11 µg/mL. However, it is also toxic to human normal cell line (BJ) with IC50 as 8.69 ± 0.02 µg/mL. More importantly, all transformed products are non-cytotoxic on BJ. Therefore, biotransformation can be an efficient approach to reduce the toxicity of methylstenbolone.


Assuntos
Androstenóis , Anti-Inflamatórios , Humanos , Biotransformação , Anti-Inflamatórios/farmacologia
3.
Fitoterapia ; 160: 105226, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35659522

RESUMO

A new clerodane diterpene, named 6α-hydroxy-3,13E-clerodien-15-oic acid (1), together with a known clerodane diterpene (2), four known labdane diterpenes (3-6), a triterpenoid (7), a known steroid (8), and two benzenoid compounds (9 and 10) were isolated from Detarium microcarpum Guill. & Perr. The structures of all obtained compounds were determined by chemical properties and spectroscopic evidence, accompanied by comparisons with data in the literature. Electronic circular dichroism (ECD) was performed for compounds 1-4 to confirm the absolute configuration. Compounds 1-3 and 8-10 were evaluated for the protective effect on osteoblasts. Compound 1 was observed to increase the proliferation of dexamethasone (DEX)-treated MC3T3-E1 cells significantly at 1 µM, which was comparable with the positive control geniposide at 10 µM. The results were further confirmed by flow cytometry analysis. In addition, compound 1 increased the level of alkaline phosphatase (ALP) and mineralization in osteoblasts inhibited by DEX. Moreover, Compound 9 (vanillic acid) showed a pronounced inhibition (IC50 6.5 ± 0.6 µM) on reactive oxygen species (ROS) production, and 10 (4-O-methyl gallic acid) showed a good inhibition with IC50 as 103.3 ± 2.2 µM, compared with the standard drug ibuprofen (IC50 54.2 ± 9.2 µM). Besides, compounds 1-3 and 8-10 were non-cytotoxic against MCF-7, NCI-H460, Hela, and BJ cell lines.


Assuntos
Diterpenos Clerodânicos , Diterpenos , Osteoporose , Triterpenos , Diterpenos/química , Diterpenos/farmacologia , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/farmacologia , Humanos , Estrutura Molecular , Osteoporose/tratamento farmacológico , Espécies Reativas de Oxigênio
4.
RSC Adv ; 12(15): 9494-9500, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35424863

RESUMO

An anabolic-androgenic synthetic steroidal drug, methasterone (1) was transformed by two fungi, Cunninghamella blakesleeana and Macrophimina phaseclina. A total of six transformed products, 6ß,7ß,17ß-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (2), 6ß,7α,17ß-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (3), 6α,17ß-dihydroxy-2α,17α-dimethyl-5α-androstane-3,7-dione (4), 3ß,6ß,17ß-trihydroxy-2α,17α-dimethyl-5α-androstane-7-one (5), 7α,17ß-dihydroxy-2α,17α-dimethyl-5α-androstane-3-one (6), and 6ß,9α,17ß-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (7) were synthesized. Among those, compounds 2-5, and 7 were identified as new transformed products. MS, NMR, and other spectroscopic techniques were performed for the characterization of all compounds. Substrate 1 (IC50 = 23.9 ± 0.2 µg mL-1) showed a remarkable anti-inflammatory activity against nitric oxide (NO) production, in comparison to standard LNMMA (IC50 = 24.2 ± 0.8 µg mL-1). Whereas, its metabolites 2, and 7 showed moderate inhibition with IC50 values of 38.1 ± 0.5 µg mL-1, and 40.2 ± 3.3 µg mL-1, respectively. Moreover, substrate 1 was found to be cytotoxic for the human normal cell line (BJ) with an IC50 of 8.01 ± 0.52 µg mL-1, while metabolites 2-7 were identified as non-cytotoxic. Compounds 1-7 showed no cytotoxicity against MCF-7 (breast cancer), NCI-H460 (lung cancer), and HeLa (cervical cancer) cell lines.

5.
Molecules ; 27(4)2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35209101

RESUMO

Two new ursane-type triterpenoids, named Polyanside A (1) and B (2), along with eleven known compounds (3-13), were isolated and elucidated from Maranthes polyandra (Benth.) Prance. The structures of these compounds were elucidated based on chemical evidence and multiple spectroscopic data. Isolated compounds were evaluated for anti-cancer, anti-inflammatory activities, and cytotoxicity on a normal human cell line (BJ). None of them showed activity and cytotoxicity. The hexane fraction was analyzed by GC-MS, resulting in the identification of forty-one compounds. This is the first comprehensive study on the phytochemistry of M. polyandra.


Assuntos
Chrysobalanaceae/química , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/química , Fracionamento Químico , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/análise , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
6.
J Ethnopharmacol ; 279: 113675, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33301919

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Schefflera is the largest genus in the family Araliaceae, which contains 602 known species indigenous to Asia, Africa, and the southwest Pacific region, several of which are used in traditional medicine. AIM OF THE REVIEW: The review discusses current knowledge of the traditional uses, phytochemistry, and biological activities of Schefflera species, to assess the medicinal potential of this genus. MATERIALS AND METHODS: The literature were explored using the keyword "Schefflera" in SciFinder®, Google Scholar®, and PubMed® databases. The taxonomy of all reported plants was authenticated using "The Plant List". Additional data on traditional uses was obtained from secondary references including books and online resources. RESULTS: Fourteen species were documented as traditional medicines in China, India, Vietnam, Thailand, and Indonesia, specifically to manage rheumatism, pain, and trauma. Other species are used in the treatment of liver disorders, skin conditions, respiratory infections, cancer, diarrhea, malaria, paralysis, and many other conditions. The main phytochemical constituents identified were triterpenoids and saponins, with sesquiterpenes, phenylpropanoids, and lignans. Pharmacological properties of extracts and pure isolated compounds included analgesic, anti-inflammatory, anticancer, hypoglycemic, antimicrobial, hepatoprotective, neuroprotective, antimalarial, and antiallergic effects. CONCLUSION: The reported biological activities of Schefflera species support their traditional uses, although the available data, even for medicinal species, was limited. Reports of chemical constituents or biological activities could be found for only about 20 species, but suggest that further investigation of efficacy and safety of the largely unexplored genus Schefflera is necessary.


Assuntos
Araliaceae/química , Medicina Tradicional/métodos , Extratos Vegetais/farmacologia , Animais , Etnofarmacologia , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Fitoterapia/métodos , Extratos Vegetais/química
7.
Eur J Med Chem ; 209: 112863, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33032082

RESUMO

Nucleotide-binding oligomerization domain 2 (NOD2) is cytosolic surveillance receptor of the innate immune system capable of recognizing the bacterial and viral infections. Muramyl dipeptide (MDP) is the minimal immunoreactive unit of murein. NOD2 perceives MDP as pathogen-associated molecular pattern, thereby triggering an immune response with undesirable side-effects. Beneficial properties of MDP, such as pro-inflammatory characteristics for the rational design of new vaccine adjuvants, can be harnessed by strategically re-designing the molecule. In this work, a new class of amphiphilic desmuramylpeptides (DMPs) were synthesized by replacing the carbohydrate moiety (muramic acid) of the parent molecule with hydrophilic arenes. A lipophilic chain was also introduced at the C-terminus of dipeptide moiety (alanine-isoglutamine), while conserving its L-D configuration. These novel DMPs were found to set off the release of higher levels of tumour necrosis factor alpha (TNF-α) than Murabutide, which is a well-known NOD2 agonist. Molecular docking studies indicate that all these DMPs bind well to NOD2 receptor with similar dock scores (binding energy) through a number of hydrogen bonding and hydrophobic/π interactions with several crucial residues of the receptor. More studies are needed to further assess their immunomodulatory therapeutic potential, as well as the possible involvement of NOD2 activation.


Assuntos
Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Peptídeos/química , Peptídeos/farmacologia , Adjuvantes Imunológicos/síntese química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Proteína Adaptadora de Sinalização NOD2/metabolismo , Peptídeos/síntese química , Tensoativos/síntese química , Tensoativos/química , Tensoativos/farmacologia , Células THP-1 , Fator de Necrose Tumoral alfa/metabolismo
8.
BMC Urol ; 19(1): 97, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640663

RESUMO

BACKGROUND: We investigated the surgical feasibility, safety and effectiveness of 50 W (low power) Holmium Laser enucleation of the prostate (HoLEP) in patients who have undergone previous template biopsy of the prostate (TPB). METHODS: Data encompassing pre-operative baseline characteristics, intra-operative measures and post-operative outcomes was collected for 109 patients undergoing HoLEP across two UK centres. Patients were stratified into two groups; group 1 (n = 24) had undergone previous TPB were compared with 'controls' (no previous TPB) in group 2 (n = 85). The primary outcome was successful HoLEP. RESULTS: There were no statistically significant differences in either key baseline characteristics or mass of prostate enucleated between groups 1 and 2. There was no statistically significant difference in enucleation or morcellation times parameters between the two groups other than enucleation efficiency in favour of group 1 (p = 0.024). Functional outcomes improved, without any statistically significant difference, in both groups. CONCLUSIONS: In patients with a previous TPB, HoLEP is surgically feasible, safe and effective. TPB should not be considered a contraindication to HoLEP. Our work provides a strong foundation for further research in this area.


Assuntos
Lasers de Estado Sólido/uso terapêutico , Próstata/patologia , Próstata/cirurgia , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Idoso , Biópsia/métodos , Estudos de Casos e Controles , Estudos de Viabilidade , Humanos , Lasers de Estado Sólido/efeitos adversos , Masculino , Pessoa de Meia-Idade , Períneo , Resultado do Tratamento
9.
Eur J Med Chem ; 141: 26-36, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29028529

RESUMO

Muramyl dipeptide (MDP) - an essential bacterial cell wall component - is recognized by our immune system as pathogen-associated molecular pattern (PAMP) which results in immune responses with adverse toxic effects. In order to harness the beneficial properties from the pro-inflammatory characteristics of the bacterial cell wall motif, MDP was strategically re-designed while conserving the L-D configurations of the dipeptide moiety. The muramic acid was replaced with a hydrophilic arene and lipophilic chain was introduced at peptide end to give the amphiphilic desmuramyl peptides (DMPs). The novel DMPs were found to modulate the immune response by amplifying the LPS-induced surface glycoprotein (ICAM-1) expression in THP-1 cells without showing significant toxicity. Furthermore, these compounds were able to trigger the secretion of higher levels of pro-inflammatory cytokine (TNF-α) than the well-studied NOD2 agonist, Murabutide.


Assuntos
Acetilmuramil-Alanil-Isoglutamina/imunologia , Citocinas/imunologia , Desenho de Fármacos , Glicoproteínas de Membrana/imunologia , Tensoativos/química , Acetilmuramil-Alanil-Isoglutamina/síntese química , Acetilmuramil-Alanil-Isoglutamina/química , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/biossíntese , Relação Dose-Resposta a Droga , Humanos , Lipopolissacarídeos/farmacologia , Glicoproteínas de Membrana/biossíntese , Estrutura Molecular , Relação Estrutura-Atividade , Tensoativos/síntese química
10.
J Hepatocell Carcinoma ; 4: 123-130, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29082223

RESUMO

BACKGROUND: A meta-analysis comparing drug-eluting beads transarterial chemoembolization (DEB-TACE) with conventional transarterial chemoembolization (cTACE) has recently been published. On balance, no significant differences were found in terms of objective response and overall survival. The impact on healthcare costs had been studied in small series based on a hypothetical model and was in favor of DEB-TACE. We aimed to evaluate and compare health-care costs and effectiveness of both modalities in a cohort of patients from Nottingham, UK. METHODS: Using a dedicated radiology database, we identified all patients who had undergone cTACE or DEB-TACE between 2006 and 2012 at a single tertiary referral center based in Nottingham. We collected clinical data, including treatment response, postprocedure complications and 30-day mortality. Costing models were constructed to present both our local hospital perspective as well as the national health service position. RESULTS: During our study period, 101 procedures were performed on 43 patients (76 cTACE procedures on 26 patients and 25 DEB-TACE procedures on 17 patients). Overall, 11/26 in cTACE and 5/17 in DEB-TACE group had progressive disease (p=0.52). Adverse events were seen in 6/76 cTACE compared with 7/25 DEB-TACE group (p=0.16). Based on the predetermined standard pathway there was an unadjusted average cost difference of £3770.30 (TACE =£9070.44, DEB-TACE =£5300.14) in favor of the DEB-TACE. Results from our costing models indicated a £2715.33 (95% CI £580.88-4849.77) cost difference in favor of the same procedure. CONCLUSIONS: Even when the extra costs of DEB-TACE were considered, the overall treatment costs per patient were lower in relation to cTACE.

11.
Dig Dis ; 35(3): 191-196, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28249286

RESUMO

BACKGROUND: Bariatric surgery is a popular and effective therapeutic intervention for obesity, which is an abnormal health condition that is prevalent worldwide. Metabolic improvements that precede weight loss after bariatric surgery may be mediated, in part, through the fibroblast growth factor (FGF) 15/19 and FGF21 signaling pathways. Both FGF15/19 and FGF21 are hormone-like members of the FGF family and exert their metabolic effects in an endocrine manner. Enhanced bile acid recycling after bariatric surgery leads to increased circulating levels of FGF15/19 in the distal small intestine. Synthesis of FGF21 is upregulated predominately in the fasting state through peroxisome proliferator-activated receptor pathways and to a lesser extent by FGF15/19. Key Messages: The biological functions of FGF15/19 and FGF21 are diverse and complicated. The tissue targeted effects of FGF15/19 and FGF21 of importance after bariatric surgery include the regulation of hepatic bile acid biosynthesis and ketogenesis as well as thermogenesis in adipose tissue, respectively. Furthermore, FGF15/19 and FGF21 function to regulate carbohydrate and lipid metabolism. CONCLUSION: The long-term effects of bariatric surgery on weight loss are undisputable. However, the mechanism for improvements in glucose and lipid homeostasis observed shortly after bariatric surgery is less understood. This review article attempts to describe the known metabolic effects of FGF15/19 and FGF21 that may potentiate these improvements after bariatric surgery.


Assuntos
Bariatria , Fatores de Crescimento de Fibroblastos/metabolismo , Obesidade/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Encéfalo/metabolismo , Humanos , Fígado/metabolismo , Transdução de Sinais
13.
J Coll Physicians Surg Pak ; 26(2): 87-90, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26876391

RESUMO

OBJECTIVE: To determine the serum 25-hydroxycalciferol levels [25(OH)D] in adults with pre-diabetes and normoglycaemia to examine a possible association of vitamin D deficiency with pre-diabetes. STUDY DESIGN: Case control study. PLACE AND DURATION OF STUDY: Armed Forces Institute of Pathology, Rawalpindi, from November 2012 to July 2013. METHODOLOGY: Atotal of 272 adults including 136 pre-diabetics and 136 normoglycaemics of either gender aged 20 years and above were consecutively inducted. Patients with diabetes mellitus, pregnancy, rickets and osteomalacia, ischemic heart disease, chronic kidney disease and chronic liver disease were excluded. Fasting Plasma Glucose (FPG) was estimated with hexokinase method on Modular p800 Roche chemistry analyzer while serum 25(OH)D was measured on Diasorin Liaison immunoassay analyzer using the chemiluminescent technique. Mean 25(OH)D levels in pre-diabetic and normoglycaemic groups were compared using Mann-Whitney U test. Spearman's correlation coefficient 'rs' was determined between serum 25(OH)D and FPG. Odds ratio for vitamin D deficiency was also calculated. RESULTS: Mean serum 25(OH)D level was low in pre-diabetics (23.2 nmol/L) as compared to normoglycaemics (29 nmol/L; p=0.001). Serum 25(OH)D level had inverse correlation with FPG (rs= -0.448, p=0.000). There was also significant association of vitamin D deficiency with pre-diabetes compared with normoglycaemia (OR: 2.21, p= 0.016; 95% CI: 1.15-4.27). CONCLUSION: Vitamin D deficiency with pre-diabetes suggested that vitamin D may have an important role in pathogenesis of pre-diabetes.


Assuntos
25-Hidroxivitamina D 2/sangue , Estado Pré-Diabético/sangue , Deficiência de Vitamina D/complicações , Vitamina D/sangue , Adulto , Glicemia/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Deficiência de Vitamina D/sangue
14.
J Pak Med Assoc ; 65(8): 851-6, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26228330

RESUMO

OBJECTIVE: To study the immunohistochemical expression of vascular endothelial growth factors in urothelial tumours of bladder and its possible association with tumour characteristics and microvessel density. METHODS: The cross-sectional descriptive study was conducted at the Histopathology Department of the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from July 2011 to December 2012, and comprised cases of non-invasive and invasive urothelial tumours of the bladder. The microvessel density and expression of vascular endothelial growth factors A, C, D were evaluated by immunohistochemistry. Specimens of transurethral bladder biopsies and surgical resection were examined. The cases were classified into non-invasive (stage pTa ) and invasive groups as well as low-grade and high-grade groups. The presence of in-situ component was evaluated in each category. To assess the microvessel density, highly vascularised foci ('hot spots') after immuno-staining with CD34 were quantified for number of vessels per square millimetre and for vascular surface area density. No distinction was made between lymphatic and blood vessels. Vascular endothelial growth factor staining was scored semi-quantitatively. RESULTS: The study examined 100 histopathology specimens, including 90(90%) transurethral bladder biopsies and 10(10%) surgical resection specimens of bladder. There were 45(45%) non-invasive (stage pTa) cases and 55(55%) invasive (stage pT1-4) cases. Besides, there were 43(43%) low-grade (grades 1 and 2) cases, and 57(57%) high-grade (grade 3) cases. Vascular endothelial growth factors A, C and D staining scores showed positive association with stage (p=0.02;p<0.01; p<0.01)and grade (p=0.007;p=0.004; p=0.002) of the tumour. Tumours with in-situ component showed association with number of vessels per square millimetre (p<0.01) and vascular surface area density (p=0.02). CONCLUSIONS: Parameters like vascular endothelial growth factor and microvessel density need to be studied further for selection of cases with potential for targeted therapy.


Assuntos
Carcinoma in Situ/metabolismo , Carcinoma de Células de Transição/metabolismo , Linfangiogênese , Neovascularização Patológica/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Fator D de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Carcinoma in Situ/patologia , Carcinoma de Células de Transição/patologia , Estudos Transversais , Feminino , Humanos , Imuno-Histoquímica , Modelos Logísticos , Masculino , Microvasos/metabolismo , Microvasos/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neovascularização Patológica/patologia , Prognóstico , Neoplasias da Bexiga Urinária/patologia
15.
J Coll Physicians Surg Pak ; 25(6): 417-21, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26100993

RESUMO

OBJECTIVE: To evaluate the diagnostic efficacy of two rapid methods i.e. Mycobacterium tuberculosis (MTB) Polymerase Chain Reaction (PCR) on Fine Needle Aspiration (FNA) samples by comparing with cytology of respective site sample. STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY: Department of Microbiology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan, from July 2010 through November 2013. METHODOLOGY: A total of 105 extra pulmonary lymph nodes aspirates obtained through fine needle aspiration were processed. Cytology and PCR were done on each specimen. Cytology was taken as gold standard. RESULTS: Out of the total 105 samples, 71 (67.6%) were positive for the MTB PCR while 34 (32.4%) showed negative status. According to FNA cytology (FNAC) results, 72 (68.6%) cases were positive for the disease while 33 (31.4%) were negative. Sensitivity of PCR was 90.3%, specificity 81.8%, positive predictive value (PPV) 91.5%, negative predictive value (NPV) 79.4%, with diagnostic accuracy of 87.6%. Area under the curve was 0.860 (p < 0.001). CONCLUSION: PCR is a sensitive tool for detection of MTB on FNA samples from EPTB cases. The results are available within few hours which is helpful for the clinicians to initiate therapy.


Assuntos
Biópsia por Agulha Fina/métodos , DNA Bacteriano/análise , DNA Bacteriano/genética , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Adulto , Estudos Transversais , Técnicas Citológicas , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Paquistão , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Tuberculose dos Linfonodos/diagnóstico
16.
J Coll Physicians Surg Pak ; 23(2): 103-6, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23374511

RESUMO

OBJECTIVE: To determine the accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in early detection of acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery by comparing with serum creatinine. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, AFIP in collaboration with AFIC/ NIHD, Rawalpindi, from April to December 2011. METHODOLOGY: Eighty eight patients undergoing CPB surgery in AFIC/NIHD were included by consecutive sampling. Blood samples of subjects for serum creatinine analysis were drawn pre-operatively, 4 h, 24 h and 48 h after CPB surgery. Spot urine samples for NGAL were collected at 4 h after CPB surgery. Urine samples were analyzed on Abbott ARCHITECT i2000SR analyzer whereas serum creatinine samples were measured on Beckman UniCel® DxC 600 Synchron® Clinical System. RESULTS: Out of 88 patients, 11 (13%) cases developed AKI 4 h postoperatively. Urinary NGAL increased markedly at 4 h postoperatively as compared to serum creatinine which showed rise at 24 - 48 h after cardiac surgery. Analysis of urine NGAL at a cutoff value of 87 ng/ml showed area under the curve of 0.91 [95% confidence interval (CI) 0.83 - 0.96] with sensitivity of 90.9% (95% CI 58.7 - 98.5) and specificity of 98.7% (95% CI 92.9-99.8). There was a positive correlation of 4 h urine NGAL and serum delta creatinine at 48 h, which was statistically significant (rs = 0.33, p = 0.001). CONCLUSION: The study demonstrated that levels of urine NGAL in patients suffering from AKI increased significantly at 4 h as compared to serum creatinine levels. Urine NGAL is an early predictive biomarker of AKI after CPB.


Assuntos
Injúria Renal Aguda/urina , Proteínas de Fase Aguda/urina , Procedimentos Cirúrgicos Cardíacos , Ponte Cardiopulmonar/efeitos adversos , Creatinina/sangue , Lipocalinas/urina , Proteínas Proto-Oncogênicas/urina , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Humanos , Lipocalina-2 , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/urina , Período Pós-Operatório , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença
17.
J Thromb Thrombolysis ; 33(3): 267-73, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22362558

RESUMO

Persistent high on-treatment platelet reactivity in acute coronary syndrome (ACS) patients managed with appropriate antiplatelet therapy has been correlated with increased risk of cardiovascular events; however, the evolution of this phenomenon overtime is not well known. We investigated platelet activity at a three month follow-up after initial presentation with an ACS. We enrolled a total of 124 patients in the study, 65 were diagnosed with ACS and 59 controls who presented with non-cardiac chest pain for baseline comparisons. Of the enrolled patients, we had 25 ACS patients return, in stable condition, three months after their initial presentation for repeat platelet functional testing. Epinephrine (EPI), adenosine diphosphate (ADP), and arachidonic acid induced platelet aggregation were monitored at baseline with repeat measurement of EPI- and ADP-stimulated aggregation at follow-up. In addition, P-selectin and PAC-1 expression were monitored at presentation and at a three month follow-up period. ACS patients were maintained on aspirin therapy during the intervening period. At the three month follow-up visit, ACS patients initiated on aspirin had no significant percentage change in aggregation to submaximal concentrations of EPI and ADP. They also had no significant percentage change in PAC-1 or P-selectin expression. This study demonstrates persistent high on-treatment platelet reactivity in ACS patients at a three month follow-up, which may place these patients at increased risk of recurrent cardiovascular events.


Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/tratamento farmacológico , Ativação Plaquetária/fisiologia , Agregação Plaquetária/fisiologia , Idoso , Ácido Araquidônico/farmacologia , Ácido Araquidônico/uso terapêutico , Aspirina/farmacologia , Aspirina/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Resultado do Tratamento
18.
J Ayub Med Coll Abbottabad ; 24(3-4): 97-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-24669623

RESUMO

BACKGROUND: The classification of ascites as 'exudative' and 'transudative' based on ascitic fluid total protein (AFTP) has been challenged in many clinical conditions like cardiac ascites, patients on prolonged diuretic therapy and malignant ascites because it had poor diagnostic efficacy. These drawbacks have led to the development of another approach to classify ascites, which is based on Serum-Ascites Albumin Gradient (SAAG) to differentiate ascitic fluid into two categories: SAAG > or = 11 g/L in ascites due to portal hypertension and SAAG < 11 g/L in ascites unrelated to portal hypertension. Objective of this study was to compare the diagnostic efficacy of serum/ascites fluid albumin gradient and ascitic fluid total protein in patients having ascites. METHODS: This Cross-sectional comparative study was conducted in the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi from 1st Jun 2007 to 30th May 2008. Ninety-three patients were included in the study by non probability convenience sampling. The patient grouped as: (Group I) 73 cases of liver cirrhosis, (Group II) 14 cases of hepatoma and 6 cases of tuberculous ascites. Ascitic fluid specimen and 3 ml blood were obtained for ascitic fluid estimation of ascitic fluid albumin, total proteins and serum albumin. Diagnostic efficacy of SAAG and AFTP was calculated by comparing the results with clinical, ultrasonographic, histopathological findings, ascitic fluid cell count/acid fast bacilli culture and other relevant investigations. RESULTS: Seventy-three cases had liver cirrhosis (group I), 14 cases had hepatoma and 6 cases had tubercular ascites (group II). Age ranged 25-80 years with mean age 56 years. Diagnostic accuracy, Sensitivity, Specificity, Positive predictive value (PPV) and Negative predictive value (NPV) of SAAG were 96%, 97%, 95%, 98.6%, and 90% respectively, whereas those of AFTP were 56%, 53%,70%, 86%, and 29% respectively. CONCLUSION: Differential diagnosis of ascites should be based on SAAG because diagnostic efficacy of SAAG was significantly higher than AFTP in work-up of ascites.


Assuntos
Ascite/diagnóstico , Albumina Sérica , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/etiologia , Carcinoma Hepatocelular/complicações , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Hipertensão Portal/complicações , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Tuberculose Gastrointestinal/complicações
19.
Proteomics ; 11(24): 4742-6, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22038885

RESUMO

2-DE reference maps of Heterodera glycines were constructed. After in-gel digestion with trypsin, 803 spots representing 426 proteins were subsequently identified by LC-MS/MS. Proteins with annotated function were further categorized by Gene Ontology. The results showed that proteins involved in metabolic, developmental and biological regulation processes were the most abundant.


Assuntos
Proteínas de Protozoários/análise , Tylenchoidea/metabolismo , Animais , Proteoma/análise , Proteômica/métodos
20.
Cardiovasc Revasc Med ; 12(6): 367-74, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21454140

RESUMO

BACKGROUND: We aimed to elucidate the association between gamma glutamyl transferase (GGT) activity with prevalence of premature coronary artery disease (CAD) in young Pakistani patients undergoing diagnostic coronary angiography. METHODS: A total of 218 young adults (age ≤ 45 years) underwent diagnostic angiography. Serum samples were taken from all the patients and analyzed for serum GGT activity, cholesterol and triglycerides. RESULTS: Coronary artery disease patients had significantly increased GGT activity (P = .001) and exhibited a significant positive correlation with blood pressure, cholesterol, blood glucose, and smoking and negative correlation with total antioxidant status (P < .01). CONCLUSION: The study revealed good diagnostic accuracy at cutoff of 35 U/L with a sensitivity of 92%, specificity of 81%, and diagnostic odds ratio of 48 in estimation of premature CAD in young Pakistanis.


Assuntos
Ensaios Enzimáticos Clínicos , Doença da Artéria Coronariana/diagnóstico , Programas de Rastreamento/métodos , gama-Glutamiltransferase/sangue , Adulto , Idade de Início , Biomarcadores/sangue , Glicemia/análise , Pressão Sanguínea , Estudos de Casos e Controles , Colesterol/sangue , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/fisiopatologia , Feminino , Humanos , Modelos Logísticos , Masculino , Razão de Chances , Estresse Oxidativo , Paquistão/epidemiologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Fumar/epidemiologia , Triglicerídeos/sangue , Regulação para Cima
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