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1.
Sensors (Basel) ; 23(15)2023 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-37571565

RESUMEN

This paper develops a novel approach for reliable vehicle-to-vehicle (V2V) communication in various environments. A switched beam antenna is deployed at the transmitting and receiving points, with a beam management system that concentrates the power in each beam using a low-computation algorithm and a potential mathematical model. The algorithm is designed to be flexible for various environments faced by vehicles. Additionally, an anti-failure system is proposed in case the intelligent transportation system (ITS) system fails to retrieve real-time Packet Delivery Ratio (PDR) values related to traffic density. Performance metrics include the time to collision in seconds, the bit error rate (BER), the packet error rate (PER), the average throughput (Mbps), the beam selection probability, and computational complexity factors. The proposed system is compared with traditional systems. Extensive experiments, simulations, and comparisons show that the proposed approach is excellent and reliable for vehicular systems. The proposed study demonstrates an average throughput of 1.7 Mbps, surpassing conventional methods' typical throughput of 1.35 Mbps. Moreover, the bit error rate (BER) of the proposed study is reduced by a factor of 0.1. Additionally, the proposed framework achieves a beam power efficiency of touching to 100% at computational factor of 34. These metrics indicate that the proposed method is both efficient and sufficiently robust.

2.
J Pak Med Assoc ; 71(Suppl 5)(8): S55-S58, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34634017

RESUMEN

OBJECTIVE: To evaluate the difference in the infection rates between Ilizarov wires and half-pins in routine practice. METHODS: This was an observational, prospective; single-centre study approved by the institutional ethics committee. Hundred cases were treated from June 2014 to May 2018 at Ilizarov Surgery Unit, Department of Orthopaedic Surgery & Traumatology Liaquat University of Medical & Health Sciences Jamshoro Sindh Pakistan. All patients were subjected to an evaluation of half-pins and Ilizarov wires. Patients with monolateral fixators were excluded from the study. The demographic data included patient's age and sex, surgical indication, application and removal of Ilizarov fixator, follow-up duration and type of pin (transverse wire or half pin) used. Non probability consecutive sampling technique was used and sample size was calculated randomly. RESULTS: Of the total 100 cases, 79(79%) were male and 21(21%) were female with a mean age of 42.8±8.2 years. A total of 890 pins were applied in 100 patients with 170(19.10%) Half pins and 720(80.89%) wires. The transverse wire's infection rate according to Paley's grading system of Pin tract infection was, 46(53.48%), 25(29.06%) and 15(17.44%) in Grade I, Grade II and Grade III respectively. In case of half pin's infection, the majority of the cases were categories in grade II 22(55.0%) followed by Grade I 12(30.0%) and Grade III 06(15.0%). CONCLUSIONS: The tensioned transverse wires had a significantly low infection rate as compared to half pins.


Asunto(s)
Clavos Ortopédicos , Fijadores Externos , Adulto , Hilos Ortopédicos , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
3.
J Pak Med Assoc ; 69(12): 1910-1914, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31853128

RESUMEN

Anti-NMDA receptor antibody encephalitis (anti-NMDAR Encephalitis) is the most common subtype of autoimmune encephalitis in which IgG antibodies directed against NR1 subunit of NMDA receptors are present. It is a potentially lethal encephalitis which responds favourably to timely immunosuppressive therapy. If untreated, its progression leads from delusions, paranoia, movement disorder, memory deficit and seizures into a state of unresponsiveness with autonomic instability and even death. We present clinicopathological features, treatment and outcomes of eight autoantibodyproven cases of anti-NMDAR Encephalitis. There were 7 females and 1 male with a mean age of 15 years (age range: 1 to 28 years). Clinical features included seizures, altered consciousness, memory deficit, delusions, paranoia and hallucinations. Hyperactivity and irritability were prominent features among the children. Patients treated with immunosuppressive therapy including steroids, IVIg, plasmapheresis and Rituximab, recovered completely within a month of therapy. Whereas patients who received only steroids as immunosuppressive therapy suffered from residual brain damage.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/patología , Encefalitis Antirreceptor N-Metil-D-Aspartato/terapia , Autoanticuerpos/sangre , Línea Celular , Niño , Preescolar , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/uso terapéutico , Lactante , Masculino , Pakistán , Plasmaféresis , Adulto Joven
4.
J Pak Med Assoc ; 68(8): 1222-1227, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30108390

RESUMEN

OBJECTIVE: To compare the frequency and the functional state of the collagen II reactive T cells with disease activity in rheumatoid arthritis patients and healthy controls. METHODS: This case-control cross-sectional study was carried out at the Department of Immunology; Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from June to October 2014. Rheumatologist from Rehmat Noor Rheumatology Clinic, a private health facility of the city, was requested to send in patients with clinical diagnosis of rheumatoid arthritis. Samples were obtained and relevant investigations were carried out. Data were compared with a group of age and gender-matched healthy subjects. T cell proliferative response was assessed against bovine collagen II by measuring incorporation of bromodeoxyuridine into deoxyribonucleic acid of proliferating cells and by expression of CD25 on proliferating cells as percentage of CD3+/bromodeoxyuridine+ and CD3+/CD25+ T-cells, respectively. Among the patients, the frequency of T cells with disease activity was compared. Patients were classified into groups of mild, moderate and severe disease and frequency of CD3+/bromodeoxyuridine+, frequency of CD3+/CD25+ cells, mean fluorescent intensity of bromodeoxyuridine-fluorescein isothiocyanate and mean fluorescent intensity of CD25-fluorescein isothiocyanate were compared in the groups. RESULTS: Of the 60 subjects, 30(50%)were patients and 30(50%) were controls. Of the patients, 5(16.66%) were males and 25(83.33%) were females with an overall mean age of 42±12 years. The mean age of the controls was 41±9.28 years. Mean disease duration of the patients was 10.5 ± 4.2 years. Percentage of CD3+/CD25+ cells and CD3+/bromodeoxyuridine+ cells stimulated with collagen II, in patients was much higher than the controls(p<0.05).Statistically significant differences were observed when frequency of CD3+/bromodeoxyuridine+ cells and CD3+/CD25+ cells was compared among the mild, moderate and severe patient groups (p<0.05). CONCLUSIONS: Collagen II was found to be an important auto antigen in joints of rheumatoid arthritis patients.


Asunto(s)
Artritis Reumatoide/diagnóstico , Colágeno Tipo II/inmunología , Activación de Linfocitos/inmunología , Linfocitos T/inmunología , Adulto , Artritis Reumatoide/inmunología , Biomarcadores , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Masculino , Pronóstico
5.
J Pak Med Assoc ; 67(6): 939-941, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28585599

RESUMEN

Neonatal lupus erythematosus is an autoimmune disease resulting from the trans-placental passage of maternal anti-SSA/Ro, anti-SSB/La, and less frequently anti-RNP antibodies to the foetus. At the time of diagnosis 50% of mothers are asymptomatic. Neonatal manifestations of this multisystem disease may include congenital heart block, cutaneous lesions and haematological abnormalities. We present the case of congenital neonatal lupus erythematosus in non-identical twins, showing variability in clinical manifestation of this disease,despite receiving the same level of antibodies from the mother. This case adds to the growing body of evidence about the role of genetics and other feto-maternal contributing factors in addition to the presence of auto antibodies. It raises interesting questions about discordant disease expression in offspring's of the same mother.


Asunto(s)
Bradicardia/diagnóstico , Bloqueo Cardíaco/congénito , Lupus Eritematoso Sistémico/congénito , Gemelos , Adulto , Anticuerpos Antinucleares/inmunología , Antígenos Nucleares/inmunología , Autoanticuerpos/inmunología , Bradicardia/etiología , Bradicardia/fisiopatología , Femenino , Bloqueo Cardíaco/diagnóstico , Bloqueo Cardíaco/etiología , Bloqueo Cardíaco/fisiopatología , Frecuencia Cardíaca Fetal , Humanos , Recién Nacido , Yoduro Peroxidasa/inmunología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/fisiopatología , Embarazo
7.
J Pak Med Assoc ; 66(1): 97-100, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26712191

RESUMEN

Chronic granulomatous disease is a rare inherited disorder characterised by inability of phagocytes to generate reactive oxygen species needed for intracellular killing of phagocytosed microorganisms. We report the case of an 8-month-old male child with recurrent chest infections and perianal abscess that had no response to conventional antibiotic treatment. His two elder brothers died due to similar complaints at the ages of 4 and 5 months. Four elder sisters were healthy and alive. This history indicated that the patient might have X-linked chronic granulomatous disease. A definite absence of superoxide activity in the patient's granulocytes detected by dihydrorhodamine test and nitroblue tetrazolium dye reduction test confirmed this diagnosis.


Asunto(s)
Enfermedad Granulomatosa Crónica/diagnóstico , Absceso/etiología , Absceso/inmunología , Enfermedades del Ano/etiología , Enfermedades del Ano/inmunología , Enfermedad Granulomatosa Crónica/complicaciones , Enfermedad Granulomatosa Crónica/inmunología , Humanos , Lactante , Masculino , Neumonía/etiología , Neumonía/inmunología , Recurrencia
8.
Pulm Pharmacol Ther ; 28(1): 77-86, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24355631

RESUMEN

The tetrasaccharide sequence of heparin oligosaccharides is the minimum chain length possessing anti-allergic activity, as the disaccharide fraction is inactive. Since sulfation pattern can modify the biological actions of heparin, we hypothesized that "supersulfation" of the inactive heparin disaccharide could confer anti-allergic activity to this molecule. To test this, we produced a supersulfated heparin disaccharide (Hep-SSD) and evaluated its anti-allergic activity in sheep with documented antigen-induced early and late airway responses (EAR and LAR) and airway hyperresponsiveness (AHR). Porcine intestinal heparin was depolymerized with nitrous acid, the disaccharide fraction separated by size exclusion chromatography, and then treated with pyridine-sulfur trioxide complex to yield Hep-SSD. Its chemical structure [IdoU2',3',4'S (1→4) AMan1,3,6S] was confirmed by HPLC, Mass Spectrometry and NMR analysis. Inhaled doses of 5 mg, 10 mg and 20 mg Hep-SSD produced inhibition of EAR (8%, 35% and 35%), LAR (50%, 80%, and 77%) and AHR (67%, 100% and 75%), respectively. A single oral dose of 2 mg/kg Hep-SSD given 90 min before challenge significantly inhibited EAR, LAR and AHR, but 1 mg/kg was ineffective. Multi dose oral treatment with Hep-SSD had a cumulative effect, as a once daily dose of 2 mg/kg for 3 days (last dose, 16 h before antigen) inhibited EAR, LAR and AHR by 30%, 75% and 74%, respectively. Finally, the oral activity of Hep-SSD could be enhanced 4 fold by formulating it with Carbopol(®)934P, in an enteric coated capsule. These data demonstrate that "supersulfation" can confer biological activity to the inactive heparin disaccharide. Both inhaled and oral Hep-SSD demonstrate significant anti-allergic activity and, therefore, may have therapeutic potential.


Asunto(s)
Antígenos/inmunología , Hiperreactividad Bronquial/tratamiento farmacológico , Disacáridos/farmacología , Heparina/análogos & derivados , Acrilatos/química , Administración por Inhalación , Administración Oral , Animales , Hiperreactividad Bronquial/inmunología , Cromatografía en Gel , Cromatografía Líquida de Alta Presión/métodos , Disacáridos/administración & dosificación , Disacáridos/química , Relación Dosis-Respuesta a Droga , Heparina/administración & dosificación , Heparina/química , Heparina/farmacología , Espectroscopía de Resonancia Magnética/métodos , Espectrometría de Masas/métodos , Ovinos , Sulfatos/administración & dosificación , Sulfatos/química , Sulfatos/farmacología , Porcinos , Factores de Tiempo
9.
Neurobiol Dis ; 51: 120-32, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23146994

RESUMEN

BACKGROUND AND PURPOSE: Current models dictate that, depending on occurrence of early reperfusion, the ischemic penumbra either undergoes or escapes infarction (i.e., "pan-necrosis"). However, tissue outcome following temporary middle-cerebral artery occlusion (tMCAo) in rodents can also include selective neuronal loss (SNL), which even if subtle may impede functional recovery. In order to explore the pathophysiology of ischemic stroke, determine potential therapeutic targets and monitor effects of therapy, in vivo imaging surrogates of these varied histopathological outcomes applicable in the clinical setting would be useful. Although hyperintense signal on T(2)-weighted MRI in the chronic post-stroke stage is considered a reliable surrogate of tissue infarction, SNL is not associated with T(2)W abnormal signal. In the clinical setting, the neuron-specific PET ligand (11)C-flumazenil (FMZ) has been used to identify both pan-necrosis and peri-infarct SNL, but this inference has not been histopathological confirmed so far. Here we investigated the late tissue sequelae of tMCAo in the rodent using in vivo T(2)W MRI and FMZ-PET against post mortem immunohistochemistry as gold standard. METHODS: Adult spontaneously hypertensive rats (SHRs) underwent 45 min distal-clip middle-cerebral artery occlusion and, 28 days later, FMZ-PET and T(2)W-MRI, immediately followed by immunohistochemistry for neuronal loss (NeuN), activated microglia and astrocytosis. Based on standard histopathological definitions, ischemic lesions were classified into pan-necrosis, partial infarction or SNL. NeuN changes and FMZ binding across the whole hemisphere were quantified in the same set of 44 regions-of-interest according to previously validated protocols; linear regressions between these two measures were carried out both within and across subjects. RESULTS: Both cortical pan-necrosis/partial infarction and SNL were present in all rats except one, where SNL was isolated and extensive. Infarction/partial infarction, but not SNL, was associated with T(2)W hyperintense signals and cortical atrophy. In contrast, FMZ binding was decreased in all types of lesions including SNL, in proportion with NeuN staining intensity both within (p<0.05 to <0.001) and across (p<0.001) subjects, including the subject that showed pure SNL (p=0.01). CONCLUSION: This novel study revealed three main facts: i) long-term histopathological cortical changes following 45 min tMCAo in SHRs included all three of SNL, partial infarction and frank infarction; ii) T2W MRI showed conspicuous high signal lesions for complete or partial infarction, but no changes for SNL; and iii) FMZ-PET was sensitive to all three types of tMCAo-induced histopathological changes, including isolated SNL, suggesting it is a valid surrogate for the histological sequelae of focal cerebral ischemia. In addition, the finding of almost universal completed cortical infarction at 28 days differed from our previous findings at 14-day survival using the same model and rat strain, where SNL was the almost exclusive outcome, possibly representing delayed infarct maturation. Prospective studies are needed to investigate this interesting possibility.


Asunto(s)
Isquemia Encefálica/patología , Infarto de la Arteria Cerebral Media/patología , Imagen por Resonancia Magnética , Neuronas/patología , Tomografía de Emisión de Positrones , Animales , Isquemia Encefálica/diagnóstico por imagen , Inmunohistoquímica , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Neuronas/diagnóstico por imagen , Ratas , Ratas Endogámicas SHR
10.
Pulm Pharmacol Ther ; 26(2): 180-8, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23085243

RESUMEN

We have shown that inhaled heparin (hep) oligosaccharides attenuate allergic airway responses in sheep and that this anti-allergic activity resides in a tetrasaccharide sequence. Here we determined: (a) the anti-allergic activity of oral and intravenous hep-tetrasaccharide on allergic airway responses in the sheep model of asthma; and (b) the role of N-sulfation in mediating this anti-allergic activity. Ascaris suum-induced early (EAR) and Late (LAR) airway responses and airway hyperresponsiveness (AHR) to carbachol were measured in allergic sheep without and after treatment with different doses of oral or intravenous hep-tetrasaccharide. At doses of 0.06 mg/kg, 0.125 mg/kg, and 0.25 mg/kg, oral hep-tetrasaccharide caused a dose-dependent inhibition of EAR and LAR. Post-antigen AHR was also inhibited dose dependently. The same doses of intravenous hep-tetrasaccharide yielded comparable inhibition of EAR, LAR and AHR, confirming that orally delivered hep-tetrasaccharide has good bioavailability. The protection by hep-tetrasaccharide on EAR and LAR was dependent on N-sulfation, as N-desulfated/N-acetylated tetrasaccharide had a markedly reduced effect. However, inhibition of the post-antigen AHR was independent of N-sulfation. These results demonstrate that orally administered hep-tetrasaccharide inhibits allergic airway responses in the sheep model of asthma. Hep-tetrasaccharide has good oral bioavailability and its anti-allergic activity is critically dependent on N-sulfation of the glucosamine ring.


Asunto(s)
Asma/tratamiento farmacológico , Heparina/uso terapéutico , Oligosacáridos/uso terapéutico , Administración Oral , Animales , Disponibilidad Biológica , Femenino , Heparina/administración & dosificación , Heparina/química , Heparina/farmacocinética , Inyecciones Intravenosas , Oligosacáridos/administración & dosificación , Oligosacáridos/química , Oligosacáridos/farmacocinética , Ovinos , Relación Estructura-Actividad
11.
Biochem Genet ; 51(3-4): 323-33, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23325483

RESUMEN

This study looks at novel variants of the TGFß1 gene and their potential association with high myopia in an ethnic population from Kashmir, India. Allele frequencies of 247 Kashmiri subjects (from India) with high myopia and 176 ethnically matched healthy controls were tested for Hardy-Weinberg disequilibrium. The genotype and allele frequencies were evaluated using chi-square or Fisher's exact tests. One of the three SNPs in codon 10 showed a significant difference between patients and control subjects (rs1982073: p genotype = 0.003, p allele = 0.001). There were no statistically significant differences between patients and control subjects for the other two SNPs, rs1800471 at codon 25 and a novel variant at codon 52. SNP rs1982073, substituting proline with leucine, appeared to be significantly associated with high myopia (p < 0.05). In silico predictions show that substitutions are likely to have an impact on the structure and functional properties of the protein, making it imperative to understand their functional consequences in relation to high myopia.


Asunto(s)
Miopía/genética , Polimorfismo Genético , Análisis de Secuencia de ADN , Factor de Crecimiento Transformador beta1/genética , Alelos , Estudios de Casos y Controles , Estudios de Cohortes , Genotipo , Humanos , India/etnología , Mutación Missense , Miopía/diagnóstico , Miopía/etnología , Análisis de Secuencia de ADN/métodos
12.
J Pak Med Assoc ; 63(10): 1271-4, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24392558

RESUMEN

OBJECTIVES: To investigate whether certain DR alleles might also contribute to the genetic susceptibility among Coeliac disease patients in Pakistan. METHODS: The case-control study was conducted at the Military Hospital, Rawalpindi, from October 2011 to January 2012, and analysed 25 children diagnosed to have coeliac disease as per the criteria set by the European Society of Paediatric Gastroenterology and Nutrition, which included histopathological alterations in duodenal biopsies, clinical response to gluten withdrawal, and presence of anti-endomyseal antibodies. Patients were compared with a group of 150 healthy subjects. Dioxyribonucleic acid was extracted from peripheral blood collected in ethylenediaminetetraacetic acid.K3. Human leukocyte antigen DRB1 typing was carried out on allele level (DRB1*01--DRB1*16) using sequence specific primers. Human leukocyte antigen type was determined by agarose gel electrophoresis and results were recorded. Phenotype frequency of various alleles among the patient group and the control group was calculated by direct counting, and significance of their association was determined by Fisher Exact Test. RESULTS: A total of 11 (44%) female paediatric coeliac patients in age range 1-9 (mean 7.2 +/- 4.8 years) and 14 (56%) male paediatric patients in the age range 6-14 (mean 8.6 +/- 5.1 years) were genotyped for HLA-DRB1 loci. A statistically significant positive association of the disease with HLA-DRB1*03 (n = 23; 92% versus n=31; 21% in controls, p < 0.01) was observed. CONCLUSION: HLA-DRB1*03 is associated with increased risk of developing coeliac disease.


Asunto(s)
Enfermedad Celíaca/genética , Predisposición Genética a la Enfermedad , Antígenos HLA-DR/genética , Estudios de Casos y Controles , Niño , Preescolar , Electroforesis en Gel de Agar , Femenino , Frecuencia de los Genes , Humanos , Lactante , Masculino , Pakistán , Polimorfismo Genético
13.
Sci Rep ; 13(1): 1114, 2023 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-36670231

RESUMEN

Early neonatal mortality occurs when a newborn dies within the first seven days of life. Despite interventions, neonatal mortality remains public health problem over time in Ethiopia (33 per 1000 live births). Determinants varies on level of neonatal mortality. The study's goal was to determine magnitude of early newborn death, as well as its determinants and causes in Newborn Intensive Care Unit of Referral hospital in Ethiopia's Somali region. Health facility based retrospective study review was conducted between May 2019 to May 2021 in Shiek Hassan Yabare Referral Hospital of Jigjiga University of Ethiopia. All neonates admitted at neonatal intensive care unit (NICU) with complete data and get registered using the new NICU registration book from May 2019 to May 2021 were included. Kobo toolkit was used for data collection and analyzed in SPSS 20. The magnitude of early neonatal mortality rate was defined as death between 0 and 7 days. Logistic regression model was used to estimate maternal and neonatal characteristics as a determinant variables on neonatal mortality. The statistical significance was considered at P-value < 0.05. The magnitude of early neonatal mortality rate of Ethiopia's Somali region is estimated to be 130 per 1000 live births-that is say 130 newborn couldn't celebrate their seventh day in every 1000 live births. Hypothermia, prematurity, maternal death at birth and shorter length of stay in NICU were increasing the chance of neonatal mortality at early stage while neonatal resuscitation had shown protective effect against neonatal mortality. Similarly birth asphyxia, preterm, sepsis, and congenital abnormalities were major causes of admission and death in the NICU. The magnitude of early neonatal mortality is considerable and most of the determinants are preventable. Enhancing quality of intra-partum and NICU care including infection prevention, managing hypothermia and neonatal resuscitation as per the national standard within the first golden hour is key.


Asunto(s)
Hipotermia , Muerte Perinatal , Femenino , Recién Nacido , Humanos , Lactante , Estudios Retrospectivos , Etiopía/epidemiología , Somalia/epidemiología , Resucitación , Mortalidad Infantil , Hospitales , Unidades de Cuidado Intensivo Neonatal
14.
Respir Res ; 13: 6, 2012 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-22269021

RESUMEN

BACKGROUND: Previous studies showed that heparin's anti-allergic activity is molecular weight dependent and resides in oligosaccharide fractions of <2500 daltons. OBJECTIVE: To investigate the structural sequence of heparin's anti-allergic domain, we used nitrous acid depolymerization of porcine heparin to prepare an oligosaccharide, and then fractionated it into disaccharide, tetrasaccharide, hexasaccharide, and octasaccharide fractions. The anti-allergic activity of each oligosaccharide fraction was tested in allergic sheep. METHODS: Allergic sheep without (acute responder) and with late airway responses (LAR; dual responder) were challenged with Ascaris suum antigen with and without inhaled oligosaccharide pretreatment and the effects on specific lung resistance and airway hyperresponsiveness (AHR) to carbachol determined. Additional inflammatory cell recruitment studies were performed in immunized ovalbumin-challenged BALB/C mice with and without treatment. RESULTS: The inhaled tetrasaccharide fraction was the minimal effective chain length to show anti-allergic activity. This fraction showed activity in both groups of sheep; it was also effective in inhibiting LAR and AHR, when administered after the antigen challenge. Tetrasaccharide failed to modify the bronchoconstrictor responses to airway smooth muscle agonists (histamine, carbachol and LTD4), and had no effect on antigen-induced histamine release in bronchoalveolar lavage fluid in sheep. In mice, inhaled tetrasaccharide also attenuated the ovalbumin-induced peribronchial inflammatory response and eosinophil influx in the bronchoalveolar lavage fluid. Chemical analysis identified the active structure to be a pentasulfated tetrasaccharide ([IdoU2S (1→4)GlcNS6S (1→4) IdoU2S (1→4) AMan-6S]) which lacked anti-coagulant activity. CONCLUSIONS: These results demonstrate that heparin tetrasaccharide possesses potent anti-allergic and anti-inflammatory properties, and that the domains responsible for anti-allergic and anti-coagulant activity are distinctly different.


Asunto(s)
Antiasmáticos/uso terapéutico , Anticoagulantes/química , Asma/tratamiento farmacológico , Heparina/química , Oligosacáridos/uso terapéutico , Animales , Antiasmáticos/síntesis química , Antiasmáticos/química , Antígenos Helmínticos , Ascaris suum , Líquido del Lavado Bronquioalveolar/química , Carbacol , Secuencia de Carbohidratos , Femenino , Histamina , Liberación de Histamina , Leucotrieno D4 , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Oligosacáridos/síntesis química , Oligosacáridos/química , Ovinos
15.
J Pak Med Assoc ; 62(3): 297-9, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22764473

RESUMEN

Severe Combined Immunodeficiency is the term applied to a group of rare genetic disorders characterised by defective or absent T and B cell functions. Patients usually present in first 6 months of life with respiratory/gastrointestinal tract infections and failure to thrive. Among the various types of severe combined immunodeficiency, enzyme deficiencies are relatively less common. We report the case of a 6 years old girl having severe combined immunodeficiency due to adenosine deaminase deficiency.


Asunto(s)
Agammaglobulinemia/diagnóstico , Inmunodeficiencia Combinada Grave/diagnóstico , Adenosina Desaminasa/deficiencia , Agammaglobulinemia/tratamiento farmacológico , Niño , Diagnóstico Diferencial , Femenino , Humanos , Inmunodeficiencia Combinada Grave/tratamiento farmacológico
16.
J Pediatr (Rio J) ; 98(5): 513-518, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35139345

RESUMEN

OBJECTIVE: Sickle cell disease is characterized by clinical complications resulting in vaso-occlusive crisis with prominent attributes of oxidative stress, inflammation, and pain. Inflammation is an integral part of this disease which further exacerbates the pain during a crisis. Omega-3 fatty acids are known to possess anti-inflammatory and anti-aggregatory properties and assist in diminishing the slow physiological inactivation. METHODS: A pilot nutritional interventional study was conducted wherein forty-three children with sickle cell disease aged 5-16 years were supplemented with omega-3 fatty acids for a period of six months. Analysis of oxidative stress, as well as inflammatory parameters, was done pre and post-supplementation. RESULTS: Increased free oxygen radical transference values depicting free radical generation is enhanced in these patients along with a reduced antioxidant defense, as seen by decreased free oxygen radical defense values. Supplementation with omega-3 fatty acids for a period of six months significantly reduced the inflammatory marker homocysteine in all patients, whereas high sensitive C reactive protein was significantly reduced only in females of the age group 11-16years. Simultaneously a significant reduction in oxidative stress parameters with a concomitant increase of antioxidant defense was observed in all patients. CONCLUSION: The authors' findings suggest the regulatory effects of omega-3 fatty acids as cellular activators in alleviating the complications due to sickle cell disease. Omega-3 fatty acids hold promise as future therapeutic candidates in patients with sickle cell disease.


Asunto(s)
Anemia de Células Falciformes , Ácidos Grasos Omega-3 , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Antiinflamatorios , Antioxidantes/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Proteína C-Reactiva , Niño , Suplementos Dietéticos , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Femenino , Homocisteína/metabolismo , Homocisteína/farmacología , Humanos , Inflamación/tratamiento farmacológico , Estrés Oxidativo , Dolor/tratamiento farmacológico , Especies Reactivas de Oxígeno
17.
Sci Rep ; 12(1): 5198, 2022 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-35338207

RESUMEN

Malnutrition remains prevalent and existing health problem globally. Particularly Undernutrition is a major public health issue in developing countries. Globally the causes of severe acute undernutrition varies across context. The aim of this study was to identify the determinants of severe acute malnutrition to uncover contextual factors based on UNICEF conceptual framework, as there was no study done in a similar context in Ethiopia. Health facility based (health post) un-matched case control study with Key informant interview was conducted to identify determinant factors of severe acute malnutrition (SAM) among children between 6 and 36 months. 246 children (82 cases and 164) with their mothers or care takers participated the study which was conducted between December 20, 2019 to January 20, 2020 in Kalafo district in Shebele River. Odds ratio with 95% confidence interval was calculated to identify the determinants of SAM among children aged 6-36 months using multivariate logistic regression. The odds of severe acute malnutrition was 2.28 (1.22, 4.26); 4.68 (2.29, 9.58); 2.85 (1.26, 6.45); 2.39 (1.16, 4.96) and 3.262 (1.46, 7.31) and 3.237 (1.45, 7.23); respectively for mothers with three or more under five children, Children with inadequate dietary diversity, experienced diarrhea in past 2 weeks, their mothers had not nutrition counselling during pregnancy and younger (6-11 and 12-17 months) children as compared to controls. The finding of this study reveals the main determinants of severe acute malnutrition in riverine context are multi-level. In addition to this, poor childcare and polygamy identified in qualitative finding. Decisive and multi-sectoral approach is required to addressing SAM in the riverine area.


Asunto(s)
Desnutrición , Desnutrición Aguda Severa , Estudios de Casos y Controles , Niño , Etiopía/epidemiología , Femenino , Humanos , Lactante , Desnutrición/complicaciones , Desnutrición/epidemiología , Oportunidad Relativa , Desnutrición Aguda Severa/epidemiología
18.
J Coll Physicians Surg Pak ; 21(1): 26-9, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21276381

RESUMEN

OBJECTIVE: To determine the frequency of Human Leukocyte Antigen (HLA) class II susceptibility conferring alleles among type 2 Diabetes mellitus patients, in comparison with healthy controls. STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY: Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi, from January 2009 to April 2010. METHODOLOGY: Patients with non-insulin dependent Diabetes mellitus meeting World Health Organization criteria were studied. These were compared with age and gender matched healthy control subjects. For each subject (patients as well as controls), DNA was extracted from ethylene diamine tetra-acetate sample and HLA class II DRB1 typing was carried out at allele group level (DRB1*01-DRB1*16) by sequence specific primers. Human leukocyte antigen DRB1 type was determined by agarose gel electrophoresis and results were recorded. Frequencies were determined as number of an allele divided by total number of alleles per group; p-value was computed using Pearson's chi-square test. RESULTS: Among the 100 patients, there were 63 males and 37 females with 68 controls. A total of 13 different HLA DRB1 alleles were detected, with DRB1*15 being the commonest in both the groups. The allele DRB1*13 had statistically significant higher frequency in patient group as compared to controls (p = 0.005). CONCLUSION: HLA DRB1*13 was found with a significantly increased frequency in non-insulin dependent Diabetes mellitus.


Asunto(s)
Diabetes Mellitus Tipo 2/genética , Genes MHC Clase II/genética , Predisposición Genética a la Enfermedad , Antígenos HLA-DR/genética , Adulto , Alelos , Estudios Transversales , Electroforesis en Gel de Agar , Femenino , Cadenas HLA-DRB1 , Humanos , Masculino , Persona de Mediana Edad
19.
Microbiol Res ; 252: 126828, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34543948

RESUMEN

Almost one-third of all proteins require metal ions as an essential component in key biological processes and approximately half of all enzymes are associated with one or more metal ions. The naturally occurring selenium is very toxic at higher levels, but few bacteria can reduce it into the less toxic insoluble elemental selenium. Selenium is required for the synthesis of selenocysteine, an essential residue involved in the active sites of various enzymes. The purple non-sulphur bacteria, Rhodobacter sphaeroidesis demonstrated for its selenite reduction capacity. The exact mechanism of selenite toxicity is unknown but it reacts with glutathione to form selenodiglutathione, producing the highly toxic compounds namely, H2O2and O2-. A R. sphaeroidesstrain with mutated takP gene, a member of the TRAP (tripartite ATP-independent periplasmic) family of transporter, was reported to be showing more resistance towards selenite in the growth medium but the reason for the resistance is unknown. TRAP transporters are the best-studied family of substrate-binding protein and in our previous study it was confirmed that the gene takP in R. sphaeroides is down-regulated by a small non-coding RNA SorY, providing more resistance to the bacterium against the oxidative stress. By comparative growth analysis and sensitivity assays in the presence of 2 mM selenite, it was observed that the SorY knockout strain is more sensitive to selenite while overexpression of the sRNA conferred more resistance to the bacterium like the takP mutant strain. TakP is involved in the import of malate into the cell, which under oxidative stress needs to be down-regulated to limit malate flux into the cell. Limited malate flux leads to metabolic rearrangements in the cell to avoid excessive generation of prooxidant NADH and facilitate constant generation of antioxidant NADPH. In the presence and absence of selenite, a drastic increase in the NADPH and decrease in the NADH levels are reported respectively. Accumulation of metallic selenium in the cytoplasm was detected via atomic absorption spectrophotometer and our analysis clearly demonstrated the presence of more selenium in the electron micrographs of the SorY knockout strain compared to the takP mutant grown under dark semi-aerobic growth conditions in the presence of selenite. Hence based on our analysis, it is confirmed that lack of TakP transporter led to reduced selenite influx into the cytoplasm, relieving cells with limited generation of ROS, eventually exhibiting more resistance against selenite-induced oxidative stress.


Asunto(s)
Proteínas Bacterianas , Estrés Oxidativo , Rhodobacter sphaeroides , Ácido Selenioso , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , NAD , NADP , Estrés Oxidativo/genética , Rhodobacter sphaeroides/efectos de los fármacos , Rhodobacter sphaeroides/genética , Rhodobacter sphaeroides/metabolismo , Ácido Selenioso/metabolismo , Ácido Selenioso/toxicidad , Selenio/toxicidad
20.
J Neurotrauma ; 38(5): 646-654, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32669032

RESUMEN

Traumatic brain injury (TBI) patients frequently develop cardiopulmonary system complications such as acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). However, the mechanism by which TBI causes ALI/ARDS is not fully understood. Here, we used a severe TBI model to examine the effects of a low-molecular-weight heparin, enoxaparin, on inflammasome activation and lung injury damage. We investigated whether enoxaparin inhibits ALI and inflammasome signaling protein expression in the brain and lungs after TBI in mice. C57/BL6 mice were subjected to severe TBI and were treated with vehicle or 1 mg/kg of enoxaparin 30 min after injury. Lung and brain tissue were collected 24 h post-TBI and were analyzed by immunoblotting for expression of the inflammasome proteins, caspase-1 and interleukin (IL)-1ß. In addition, lung tissue was collected for histological analysis to determine ALI scoring and neutrophil and macrophage infiltration post-injury. Our data show that severe TBI induces increased expression of inflammasome proteins caspase-1 and IL-1ß in the brain and lungs of mice after injury. Treatment with enoxaparin attenuated inflammasome expression in the brain and lungs 24 h after injury. Enoxaparin significantly decreased ALI score as well as neutrophil and macrophage infiltration in lungs at 24 h after injury. This study demonstrates that enoxaparin attenuates ALI and inhibits inflammasome expression in the brain and lungs after TBI. These findings support the hypothesis that inhibition of the neural-respiratory inflammasome axis that is activated after TBI may have therapeutic potential.


Asunto(s)
Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/prevención & control , Anticoagulantes/uso terapéutico , Lesiones Traumáticas del Encéfalo/complicaciones , Enoxaparina/uso terapéutico , Inflamasomas/metabolismo , Lesión Pulmonar Aguda/etiología , Animales , Lesiones Traumáticas del Encéfalo/metabolismo , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Infiltración Neutrófila
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