RESUMEN
Herein, we report the synthesis of different novel sets of coumarin-6-sulfonamide derivatives bearing different functionalities (4a, b, 8a-d, 11a-d, 13a, b, and 15a-c), and in vitro evaluation of their growth inhibitory activity towards the proliferation of three cancer cell lines; HepG2 (hepatocellular carcinoma), MCF-7 (breast cancer), and Caco-2 (colon cancer). HepG2 cells were the most sensitive cells to the influence of the target coumarins. Compounds 13a and 15a emerged as the most active members against HepG2 cells (IC50 = 3.48 ± 0.28 and 5.03 ± 0.39 µM, respectively). Compounds 13a and 15a were able to induce apoptosis in HepG2 cells, as assured by the upregulation of the Bax and downregulation of the Bcl-2, besides boosting caspase-3 levels. Besides, compound 13a induced a significant increase in the percentage of cells at Pre-G1 by 6.4-folds, with concurrent significant arrest in the G2-M phase by 5.4-folds compared to control. Also, 13a displayed significant increase in the percentage of annexin V-FITC positive apoptotic cells from 1.75-13.76%. Moreover, QSAR models were established to explore the structural requirements controlling the anti-proliferative activities.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Cumarinas/química , Relación Estructura-Actividad Cuantitativa , Sulfonamidas/química , Antineoplásicos/síntesis química , Células CACO-2 , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cumarinas/farmacología , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Células MCF-7 , Estructura Molecular , Sulfonamidas/farmacologíaRESUMEN
A facile one-pot four-component reaction was utilized to construct 2-oxo-1,2-dihydropyridine-3-carbonitrile as a scaffold for the synthesis of many fused heterocyclic systems, namely, furopyridine, pyridothiadiazepinthione, and pyridotriazine, as well as non-fused heterocyclic systems such as phthalazin-2(1H)-ylnicotinonitrile, pyridin-2-yl-1H-pyrazole, and pyrazol-1-ylnicotino-nitrile,1-(3-cyanopyridin-2-yl)-1H-pyrazole. The new compounds were evaluated as antimicrobial and antiviral agents.
Asunto(s)
Antibacterianos/farmacología , Antivirales/farmacología , Compuestos Heterocíclicos/farmacología , Piridinas/farmacología , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Antivirales/síntesis química , Antivirales/química , Línea Celular , Línea Celular Tumoral , Compuestos Heterocíclicos/síntesis química , Compuestos Heterocíclicos/química , Humanos , Piridinas/síntesis química , Piridinas/química , Relación Estructura-ActividadRESUMEN
Primary pyogenic abscess in the conus medullaris in a healthy adult has never been reported. An urgent MRI scan with contrast and prompt surgical evacuation may lead to good neurological recovery.
Asunto(s)
Absceso/cirugía , Paraparesia/microbiología , Enfermedades de la Médula Espinal/cirugía , Infecciones Estreptocócicas/cirugía , Absceso/tratamiento farmacológico , Antibacterianos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Médula Espinal/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus intermedius , Streptococcus milleri (Grupo)RESUMEN
BACKGROUND: In transnasal endoscopic surgical procedures, the lens of the endoscope often becomes fogged or smeared with mucus or blood. The surgeon has to clean the lens and reintroduce the endoscope multiple times during the surgery, making it a tiring process. METHODS: This paper describes an innovative lens irrigation system comprising a modified 16 Fr Foley catheter, a 20 cc or 50 cc syringe filled with warm normal saline (0.9 per cent), and a commercially available intravenous infusion set. The rigid endoscope is introduced into the catheter through the urine draining port. When the lens gets smudged with blood or mucus, the irrigating saline in the syringe is forced through the inflating port. RESULTS: A clear vision was restored immediately on flushing the syringe. The system did not compromise the operative space or hinder manoeuvrability. CONCLUSION: This cost-effective, innovative lens irrigation system saves the time spent in cleaning the lens and enhances operational efficiency, especially in a low-income setting.
Asunto(s)
Endoscopios , Endoscopía , Análisis Costo-Beneficio , Endoscopía/métodos , HumanosRESUMEN
Rupture of cerebral aneurysm during CT angiogram is a rare occurrence. Here we present such a case where an aneurysmal re-rupture during CT angiogram was demonstrated.
Asunto(s)
Aneurisma Roto/diagnóstico por imagen , Angiografía Cerebral/efectos adversos , Aneurisma Intracraneal/diagnóstico por imagen , Tomografía Computarizada por Rayos X/efectos adversos , Aneurisma Roto/patología , Arterias Cerebrales/diagnóstico por imagen , Extravasación de Materiales Terapéuticos y Diagnósticos/diagnóstico por imagen , Femenino , Humanos , Aneurisma Intracraneal/patología , Persona de Mediana Edad , Recurrencia , Rotura Espontánea/diagnóstico por imagen , Rotura Espontánea/patologíaRESUMEN
A series of eighteen azomethines has been synthesized by the reaction of appropriate primary aromatic amines with aryl and/or heteroaryl carboxaldehydes. The synthesized azomethines have been evaluated for their in vitro antileishmanial, antibacterial and antifungal activities. The results revealed some antifungal activity of most of the synthesized compounds, whereas the antileishmaniasis activity results highlighted that all synthesized azomethines inhibited parasite growth and most of them showed highly potent action towards Leishmania major promastigotes. No remarkable bactericidal activities were observed.
Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Antiparasitarios/farmacología , Compuestos Azo/farmacología , Tiosemicarbazonas/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Antiparasitarios/síntesis química , Antiparasitarios/química , Compuestos Azo/síntesis química , Compuestos Azo/química , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacos , Leishmania major/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Pruebas de Sensibilidad Parasitaria , Tiosemicarbazonas/síntesis química , Tiosemicarbazonas/químicaRESUMEN
Intracranial aspergillus infection is an uncommon finding. The importance of a high index of clinical suspicion, coupled with an early diagnosis, can potentially be lifesaving. We illustrate the case in a patient who developed right-sided visual disturbance and facial paresthesia, where radiological diagnosis was meningioma but histopathology revealed an amyloid tumor with synchronous aspergillus infection and lymphoma at the same site. This diagnosis should always be considered, especially in immunodeficient patients, using a combination of neurological and thoracic imaging and histopathology of a resected specimen.
RESUMEN
Studies on the molecular biology of lipoprotein lipase (LPL) deficiency have been facilitated by the availability of LPL gene probes and the recent characterization of gene mutations underlying human LPL deficiency. Typically, missense mutations have predominated and show a preferential localization to exons 4 and 5. This distribution supports earlier studies attributing functional significance to residues encoded by these exons. We now report a further missense mutation within exon 5 of the LPL gene in three unrelated patients. Amplification of individual exons by the polymerase chain reaction and direct sequencing revealed a T----C transition at codon 194 of the LPL cDNA which results in a substitution of threonine for isoleucine at this residue. The catalytic abnormality induced by this mutation was confirmed through in vitro mutagenesis studies in COS-1 cells. Transfection with a LPL cDNA containing the codon 194 transition resulted in the synthesis and secretion of a catalytically defective protein. The Thr194 substitution was associated with two different DNA haplotypes, consistent with a multicentric origin for this mutation.
Asunto(s)
Lipoproteína Lipasa/deficiencia , Lipoproteína Lipasa/genética , Alelos , Secuencia de Aminoácidos , Secuencia de Bases , Sitios de Unión , Evolución Biológica , Análisis Mutacional de ADN , Amplificación de Genes , Haplotipos , Humanos , Lipoproteína Lipasa/química , Datos de Secuencia Molecular , Mutación , Linaje , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Conformación Proteica , Relación Estructura-Actividad , TransfecciónRESUMEN
Multiple forms of GnRH have been detected in brain tissue of species from all nonmammalian vertebrate classes, but in mammals it is generally believed a single molecular form of GnRH is present. We have investigated the possibility that additional structural variants of GnRH are present in mammalian (sheep, rat, and human) hypothalamus. Hypothalami were extracted with acetic acid and subjected to gel filtration chromatography and reverse phase HPLC systems specifically designed to separate GnRH analogs. Column fractions were assayed for immunoreactive GnRH using a library of specific antisera raised against the five known vertebrate GnRHs. Biological activity of the fractions was assessed by measuring their ability to release LH and FSH from cultured rat pituitary cells and/or LH release from dispersed chicken pituitary cells. Receptor binding activity was also measured in fractions from the human extract, using rat pituitary membranes. Several immunoreactive and biologically active forms of GnRH were found in sheep, rat, and human hypothalami. The major immunoreactive peptide consistently coeluted with mammalian GnRH. The other forms were not identifiable as any of the other known vertebrate GnRHs. Control experiments suggest these are modified forms of mammalian GnRH, which are artifacts generated during HPLC purification. Chromatographic and immunological studies indicate these forms of GnRH include peptides eluting both earlier and later than mammalian GnRH and which appear to be modified in the middle region and/or at the COOH-terminus of the molecule. Novel immunoreactive forms of GnRH, distinct from modified mammalian GnRH, were not apparent in any of the species. In chicken and rat pituitary cell bioassays and in rat receptor binding studies, the mammalian form of GnRH in HPLC fractions of the sheep and human hypothalamus displayed activity appropriate for this immunoreactive peak being mammalian GnRH. Some of the additional immunoreactive peaks (thought to be modified forms of mammalian GnRH) also displayed LH-releasing activity in the chicken and rat systems. Gonadotropin-releasing activity or receptor binding activity due to a second, novel, GnRH-like substance in HPLC fractions of the sheep and human hypothalamus was not detected. These data provide evidence for a single form of GnRH in sheep, rat, and human hypothalamus, unlike species from other vertebrate classes where two or more GnRHs are present within a single tissue.
Asunto(s)
Hormona Liberadora de Gonadotropina/análisis , Hipotálamo/análisis , Animales , Bioensayo , Pollos , Cromatografía Líquida de Alta Presión , Hormona Folículo Estimulante/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Liberadora de Gonadotropina/farmacología , Humanos , Inmunoensayo , Hormona Luteinizante/metabolismo , Adenohipófisis/efectos de los fármacos , Adenohipófisis/metabolismo , Radioinmunoensayo , RatasRESUMEN
Craniofacial distraction osteogenesis (DO) was found to be a procedure with low preoperative and postoperative morbidity. Direct current electrical stimulation is used clinically to treat different orthopaedic problems. It provided a significant increase in new-bone formation, and a higher mechanical strength of healing. The purpose of this study was to test the effect of electric current on distraction osteogenesis and to establish the best period to apply an electric current during the different distraction phases. Twelve healthy adult goats were subjected to a vertical osteotomy in the symphyseal area. A distraction device was fixed to the bone. Animals were divided into two groups, Group I (three goats) and group II (nine goats). In group I, the device was activated 1mm per day for 10 days; while in group II, the device was activated 1mm per day for 10 days with the application of direct electric current stimulation of 10 microA either during the first 3 days of latency in a continuous mode (ESL group), or during the first 3 days of the activation period in a continuous mode (ESA group); or during the first 3 days of the consolidation period in a continuous mode (ESC group). After the activation period was completed, the distraction device left in place for additional 15 days for bone consolidation in all animals. Animals were then sacrificed, the mandible was harvested, and the distracted areas were removed and processed for mechanical and histological studies. The results of this study suggested that direct current electrical stimulation display synergism on mandibular distraction when this stimulation applied to the distraction zone during activation or consolidation periods.
Asunto(s)
Estimulación Eléctrica , Mandíbula/cirugía , Osteogénesis por Distracción , Osteogénesis/fisiología , Análisis de Varianza , Animales , Estimulación Eléctrica/instrumentación , Estimulación Eléctrica/métodos , CabrasRESUMEN
A young male patient presented with right lower abdominal pain and fever. He had tenderness in the right lumbar region, with no palpable lump. Subsequently he developed a tender fluctuant lump in the right loin. Abdominal ultrasonography showed heterogenous collection in the right lumber region near the posterior abdominal wall. Making a diagnosis of right-sided perinephric abscess, drainage was done. The patient was discharged. Eight months after his discharge, he developed fever and painful swelling in the previous operation site followed by spontaneous discharge of pus. Sinogram showed the contrast passed through the sinus tract into the large bowel and into the terminal ileum. Laparotomy, fistula tract was found communicating with the appendix. Appendicectomy and curettage of the fistula tract was followed by complete cure.
Asunto(s)
Absceso Abdominal/cirugía , Apéndice , Drenaje/efectos adversos , Fístula Intestinal/etiología , Absceso Abdominal/etiología , Apendicitis/complicaciones , Humanos , Fístula Intestinal/diagnóstico , Fístula Intestinal/cirugía , Masculino , Adulto JovenRESUMEN
The aim of this study was to evaluate the therapeutic and protective efficacy of ivermectin and permethrin against wound myiasis induced by fleshflies in Riyadh region in sheep. Three different protocols were planned to evaluate efficacy of the selected drugs in addition to recording the myiasis incidence and prevalence among infested farms. The obtained results revealed that genital organs were the most common sites of infestation with myiasis in male and females, with high prevalence in spring and autumn seasons and complete disappearance in summer and winter seasons. Application of permethrin and ivermectin resulted in significant reduction in the number of live larvae in comparison with control, untreated group. Both drugs significantly protected sheep against re-infestation, with full protection recorded for 22 days in ivermectin-treated group, whereas permethrin only produced partial protection for 13 days. Ivermectin appeared more effective than permethrin in eradication of larvae from infested wounds. In addition, ivermectin significantly protected sheep from fatal outcomes of the infestation, and the emergence rate of pupa to adult was significantly reduced in ivermectin-treated animals.
Asunto(s)
Antiparasitarios , Insecticidas , Ivermectina , Miasis/veterinaria , Permetrina , Enfermedades de las Ovejas/tratamiento farmacológico , Animales , Antiparasitarios/administración & dosificación , Antiparasitarios/uso terapéutico , Femenino , Incidencia , Insecticidas/administración & dosificación , Insecticidas/uso terapéutico , Ivermectina/administración & dosificación , Ivermectina/uso terapéutico , Masculino , Miasis/tratamiento farmacológico , Miasis/epidemiología , Miasis/parasitología , Permetrina/administración & dosificación , Permetrina/uso terapéutico , Prevalencia , Estaciones del Año , Ovinos , Enfermedades de las Ovejas/epidemiología , Enfermedades de las Ovejas/parasitología , Enfermedades de las Ovejas/prevención & control , Resultado del TratamientoRESUMEN
Crosses and backcrosses were carried out with two commercial varieties of turkeys (Black Bronze and White Ross). The birds of the White Ross strain had higher body weights at 12 and 16 weeks of age than the Black Bronze turkeys. The F 1 crosses were intermediate between the body weights of the parent varieties. For the 12-week body weight, heritability estimates were 0.62, 0.74, and 0.68 on the basis of the sire, dam, and sire plus dam components, respectively. The h2 values for the 16-week body weight were 0.55, 1.06, and 0.80, respectively. The estimates of maternal effects were 0.03 and 0.13 for the 12- and 16-week body weights.
Asunto(s)
Peso Corporal , Vigor Híbrido , Hibridación Genética , Pavos/genética , Envejecimiento , Animales , Cruzamientos Genéticos , Femenino , Masculino , Pavos/fisiologíaRESUMEN
Edible oils have different effects on lipid profiles and on the propensity for producing lipid peroxidation products. These two properties of edible oils can affect arterial structure, ultimately leading to atherosclerosis. Hypertension is said to be a predisposing factor for atherosclerosis and can accelerate its process. This paper investigates the effects of three edible oils, namely soya bean oil, palm oil and ghee, on the ultrastructure of the aortas of spontaneously hypertensive rats at the end of a 4 month feeding period. It was found that ghee produced significant structural changes to the aortic wall when compared with palm oil or soya bean oil, and that no noticeable structural differences were seen to occur on the aortas of the palm oil-fed and soya bean oil-fed groups of rats. This study suggests that the consumption of ghee, rather than palm or soya bean oil, is more likely to lead to the development of atherosclerosis.
RESUMEN
Screening for lead poisoning can be performed by measuring either blood lead (PbB) or a haematological indicator such as erythrocyte protoporphyrin (EP). We have screened 902 infants and children aged from 3 months to 5 years amongst those attending three primary health care centres in AI Jahra governorate of Kuwait. Blood specimens were collected by finger prick on Guthrie filter paper and the dried blood samples were mailed to the Central Laboratory of the Children's Hospital, Buffalo, USA. One hundred and eighty-four (20 per cent) had an elevated EP (greater than 50 micrograms/dl). Of those 11 had values above 159 micrograms/dl; 140 children were further tested for blood lead levels (PbB) haemoglobin, mean cell volumes, and percentage of transferrin saturation; 41 had blood lead levels greater than 25 micrograms/dl which is the current definition of elevated blood lead levels. Two children (2 per cent) were in Class IV, 17 (15 per cent) and 16 (14 per cent) were in Class II and Class III, respectively. There was a significant correlation between EP and PbB (r = 0.686; P = less than 0.001). Of 72 children with elevated EP and normal PbB, 32 were anaemic (Hb less than 11 g/dl) and 20 had iron deficiency. The role of tribal practices using lead contaminated preparations and their contribution to elevated blood lead levels is discussed.
Asunto(s)
Eritrocitos/metabolismo , Intoxicación por Plomo/etnología , Porfirinas/sangre , Protoporfirinas/sangre , Biomarcadores/sangre , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Kuwait , Plomo/sangre , Intoxicación por Plomo/epidemiología , MasculinoRESUMEN
The measurement of erythrocyte protoporphyrin (EPP) has been used in screening infants for undue exposure to lead. The infants were from a high risk area, Al Jahra in Kuwait, and were selected from those attending the emergency department of Al Jahra District Hospital. Dried spots of blood on Guthrie filter paper were mailed to the Central Laboratory of the Children's Hospital in Buffalo, New York. Elevated EPP values (greater than 50 micrograms/dl) were present in 63 (66%) out of 96 tests. Forty-four of the infants with elevated values were investigated further: 16 had blood lead levels above 30 micrograms/dl (1.45 mmol/l) and 12 had evidence of iron deficiency anaemia. Five infants with blood lead levels above 80 micrograms/dl (3.9 mmol/l) needed urgent chelation and in addition an 8-month-old infant with the highest EPP value (478 micrograms/dl) died of acute lead encephalopathy. We conclude that lead poisoning is a serious problem in Al Jahra, Kuwait, and that a comprehensive programme for screening and health education are urgently needed to avoid the irreversible effects of lead toxicity.