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BACKGROUND: Ageing is the primary risk factor for Parkinson's disease. Progressive motor and coordination decline that occurs with ageing has been linked to nigrostriatal dysfunction. Few studies have investigated the efficacy of mesenchymal stem cells in ameliorating the structural and functional alterations in the ageing nigrostriatal system. This study is the first to evaluate the effects of intravenous injection of bone marrow-derived mesenchymal stem cells (BMMSCs) in a D-galactose- induced rat model of nigrostriatal ageing. MATERIALS AND METHODS: BMMSCs were intravenously injected once every 2 weeks for 8 weeks. The transplanted cells survived, migrated to the brain, and differentiated into dopaminergic neurones and astrocytes. RESULTS: BMMSC transplantation improved locomotor activity, restored dopaminergic system function, preserved atrophic dopaminergic neurones in the substantia nigra, exerted antioxidative effects, and restored neurotrophic factors. CONCLUSIONS: Our findings demonstrate the efficacy of BMMSC injection in a nigrostriatal ageing rat model, and suggest that these cells may provide an effective therapeutic approach for the ageing nigrostriatal system.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Ratas , Animales , Dopamina , Galactosa , Médula Ósea , Encéfalo , EnvejecimientoRESUMEN
OBJECTIVE: To investigate the possible protective mechanisms of piperine against acetaminophen (APAP)-induced hepatotoxicity in mice. MATERIALS AND METHODS: Mice were given APAP (650 mg/kg i.p. once) with or without pretreatment with piperine (50 mg/kg/day orally for 3 days). RESULTS: APAP caused liver toxicity as indicated by increased serum alanine aminotransferase and liver microscopic pathology, decreased hepatic superoxide dismutase and glutathione reductase activities, without affecting nuclear factor erythroid 2-related factor 2 (Nrf2) expression. APAP administration induced inflammation and apoptosis manifested as increased NF-κB p65 and dysregulation of caspase 3/Bcl2 expression, respectively. In addition, APAP increased the expression of transforming growth factor-ß receptor-associated binding protein 1 (TGFBRAP1). On the other hand, pretreatment with piperine improved liver function and structure, reserved hepatic antioxidative defense, and attenuated inflammatory and apoptotic markers. Interestingly, piperine administration enhanced hepatic TGFBRAP1 expression compared to APAP alone. CONCLUSIONS: The hepatoprotective effects of piperine against APAP are mediated via its antioxidant, anti-inflammatory, and anti-apoptotic effects, in addition to regulation of TGFBRAP1.
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Acetaminofén , Alcaloides/uso terapéutico , Analgésicos no Narcóticos , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Benzodioxoles/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Proteínas HSP90 de Choque Térmico/metabolismo , Piperidinas/uso terapéutico , Alcamidas Poliinsaturadas/uso terapéutico , Alcaloides/farmacología , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Benzodioxoles/farmacología , Caspasa 3/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Piperidinas/farmacología , Alcamidas Poliinsaturadas/farmacología , Factor de Transcripción ReIA/metabolismoRESUMEN
BACKGROUND AND AIM: Cancer is a fatal and serious disease. Cyclophosphamide (CYC) is a commonly used anticancer drug. Cardiotoxicity and myelotoxicity are life-threatening side effects of CYC treatment. We aimed to evaluate the effect of the xanthine oxidase (XO) inhibitors, allopurinol (ALL) and febuxostat (FEB), on CYC-induced cardio- and hematopoietic toxicity in rats. METHODS: ALL (100 mg/kg/day) or FEB (10 mg/kg/day) were administered orally to rats in the presence and absence of CYC (200 mg/kg kg i.p. single dose) treatment. Serum creatine kinase-MB creatine kinase myocardial band (CK-MB) and lactate dehydrogenase (LDH) activities were estimated. Complete blood counting (CBC), cardiac and bone marrow XO activity, malondialdehyde level, and superoxide dismutase activity were determined. Cardiac and bone marrow histopathological changes were also evaluated. RESULTS: ALL and FEB significantly decreased CK-MB and LDH induced by CYC. Disturbed levels of XO, oxidative stress parameters, and CBC were also corrected by both XO inhibitors tested, with amelioration of cardiac histopathological changes caused by CYC. Treatment with FEB, but not ALL, prior to CYC challenges normalized bone marrow histopathological changes. CONCLUSION: These results suggest that both XO inhibitors tested; ALL and FEB can ameliorate CYC-induced cardiotoxicity. However, only FEB can protect against CYC-induced myelotoxicity, whereas ALL, to the contrary, might aggravate it.
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Alopurinol/farmacología , Médula Ósea/efectos de los fármacos , Ciclofosfamida/toxicidad , Febuxostat/farmacología , Cardiopatías/inducido químicamente , Xantina Oxidasa/antagonistas & inhibidores , Animales , Forma MB de la Creatina-Quinasa , Inhibidores Enzimáticos/farmacología , Supresores de la Gota/farmacología , Cardiopatías/tratamiento farmacológico , Inmunosupresores/toxicidad , L-Lactato Deshidrogenasa , Masculino , Ratas , Ratas WistarRESUMEN
Steno-occlusive disease of the internal carotid arteries and/or the circle of Willis with development of collateral perforator vessels attempting to supply under-perfused parenchyma are the basis for moya-moya phenomenon with the classic "puff of smoke" appearance on cerebral angiogram. We describe two cases of moya-moya with unilateral macroangiopathy of the internal carotid artery and ipsilateral middle cerebral artery in two 11-year-old girls: a Down's syndrome patient, and a second idiopathic patient. The arteriopathy in our cases differs from typical or classically described moya-moya disease in that it was exclusively unilateral rather than symmetric and bilateral. The association of predominant deep grey matter (basal ganglia) strokes in children with coexisting ipsilateral parainsular infarcts, as in our cases, is potentially a red flag for ipsilateral macroangiopathy.
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This study was conducted on patients attending Al-Hussein University Hospital and Mansura University Hospitals. Sheets were filled out on each patient (age, residence, occupation, family similar condition, travelling, disease duration, symptoms suggesting acute dermatolymphangitis attacks, frequency and duration. They were 25 lymphoedema patients and 8 controls (17 males & 16 females) and subjected to clinical and parasitological examinations. According to residence, five patients were from Giza Govemorate (18.18%), four from Dakahlia G. (12.12%), four from Gharbia G. (12.12%), five from Menoufia G. (15.15%), four from Sharkia G. (12.12%), two cases from Kafr Elsheikh G. (6.06%) and one patient from Assiut G. (3.03%). In controls, 6 were from Al-Hussein Cairo G. (15.15%), and two cases (6.06) from Al-Abbassia. They were 48% farmers (10 male & 2 female); 4% grocers (1 male); 8% carpenters (2 male); and 40% house wife (10 female). According to lymphedema site: 3 cases (12%) were bilateral lower limbs lymphedema (2 female & 1 male), 13 cases (52%) had right lower limb lymphedema (6 female & 7 male), and 9 cases (36%) had left lower limb lymphedema (4 female & 5 male). They were 18 (72%) with below knee extension of lymphedema (10 male & 8 female) and 7 (28%) above knee extension of lymphedema (3 male & 4 female). Grade of lymphedema was one case (male) with grade II lymphedema (4%), 13 cases (52%) with grade III (7 male & 6 female) and 11 cases (44%) with grade IV (5 male & 6 female). Duration of lymphedema was one case with grade II lymphedema in a period of 3 years, 13 cases with grade III lymphedema and the durations of lymphedema for these cases were (one case with 5 years duration, 3 cases were > 6-9 years,6 cases were > 9-12 years and 3 cases were > 12 years) and 11 cases with grade IV lymphedema and duration of lymphedema for these cases were (one case with 6 years duration, 2 cases were > 6-9 years,3 cases were > 9-12 years and 5 cases were > 12 years).
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Filariasis Linfática/epidemiología , Filariasis Linfática/parasitología , Wuchereria bancrofti/fisiología , Adulto , Animales , Filariasis Linfática/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Caracteres Sexuales , Adulto JovenRESUMEN
The development of chloroquine as an antimalarial drug and the subsequent evolution of drug resistant Plasmodium strains had major impacts on global public health in the 20th century. In P. falciparum, the cause of the most lethal human malaria, chloroquine resistance is linked to multiple mutations in PfCRT, a protein that likely functions as a transporter in the parasite's digestive vacuole membrane. Rapid diagnostic assays for PfCRT mutations are already employed as surveillance tools for drug resistance. However, several reports have been published demonstrating cases with CO resistance. Sporadic cases have been reported as well as one large scale study demonstrated 12.4% resistance. However, all these reports were based on treatment failure (in vivo). rather than in vitro or molecular bases. Evidence suggests a crucial role for a point mutation in the P. falciparum chloroquine resistance transporter (pfcrt) gene on chromosome 7 in conferring CQ resistance. The mutation in the K76 codon in 3 cases out of 60 (5%) using ApoI restriction enzyme was detected. Although the percentage of drug resistance was not quite disturbing, but represented the possible establishment of chloroquine-resistant P. falciparum in Saudi Arabia, or the beginning of resistant strains by labors coming from abroad. Cross-border importation of resistant strains from neighboring countries must be considered. In vivo tests must be conducted parallel with the molecular markers to estimate more precisely the actual prevalence of resistance. Validation of molecular markers is urgently required and needs strong collaborative partnerships between subregional and regional networks.
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Antimaláricos/uso terapéutico , Cloroquina/uso terapéutico , Resistencia a Medicamentos/genética , Malaria Falciparum/tratamiento farmacológico , Proteínas de Transporte de Membrana/genética , Plasmodium falciparum/efectos de los fármacos , Proteínas Protozoarias/genética , Animales , Secuencia de Bases , ADN Protozoario/análisis , Marcadores Genéticos , Humanos , Malaria Falciparum/parasitología , Técnicas de Amplificación de Ácido Nucleico , Mutación Puntual/genética , Arabia Saudita , Insuficiencia del TratamientoRESUMEN
BACKGROUND AND PURPOSE: The xanthine oxidase inhibitors allopurinol and oxypurinol are used to treat hyperuricaemia, whereas loop and thiazide diuretics can cause iatrogenic hyperuricaemia. Some uricosuric drugs and salicylate have a bimodal action on urate renal excretion. The mechanisms of action of these hypo- and hyperuricaemic drugs on the handling of urate in renal tubules have not been fully elucidated. Recently, we identified the multidrug resistance protein (MRP) 4 as a luminal efflux transporter for urate in the proximal tubule. EXPERIMENTAL APPROACH: Here, we studied the effect of these drugs on [(14)C]urate transport using human embryonic kidney 293 cells overexpressing human MRP4 and in membrane vesicles isolated from these cells. KEY RESULTS: Allopurinol stimulated MRP4-mediated cellular urate efflux and allopurinol and oxypurinol both markedly stimulated urate transport by MRP4 in membrane vesicles. Bumetanide and torasemide had no effect, whereas furosemide, chlorothiazide, hydrochlorothiazide, salicylate, benzbromarone and sulfinpyrazone inhibited urate transport, at concentrations ranging from nanomolar up to millimolar. Probenecid stimulated urate transport at 0.1 microM and inhibited transport at higher concentrations. CONCLUSIONS AND IMPLICATIONS: These data suggest that inhibition of MRP4-mediated urate efflux by furosemide and thiazide diuretics could have an important function in their hyperuricaemic mechanisms. Furthermore, stimulation of MRP4-mediated renal urate efflux could be a new mechanism in the hypouricaemic action of allopurinol and oxypurinol. In conclusion, MRP4 may provide a potential target for drugs affecting urate homoeostasis, which needs to be further evaluated in vivo.
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Diuréticos/farmacología , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/efectos de los fármacos , Ácido Úrico/metabolismo , Uricosúricos/farmacología , Alopurinol/administración & dosificación , Alopurinol/farmacología , Transporte Biológico/efectos de los fármacos , Línea Celular , Diuréticos/administración & dosificación , Relación Dosis-Respuesta a Droga , Sistemas de Liberación de Medicamentos , Homeostasis/efectos de los fármacos , Humanos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Oxipurinol/administración & dosificación , Oxipurinol/farmacología , Salicilatos/administración & dosificación , Salicilatos/farmacología , Uricosúricos/administración & dosificaciónRESUMEN
AIMS: To evaluate the influence of central corneal thickness (CCT) on intraocular pressure (IOP) measurements made with the Goldmann applanation tonometer (GAT), Tono-Pen XL, ocular blood flow tonograph (OBF), and Canon TX-10 non-contact tonometer (NCT). METHODS: CCT was recorded for either eye (randomly selected) of each of 105 untreated patients with ocular hypertension and glaucoma attending the glaucoma research unit at Moorfields Eye Hospital. For each of the selected eyes, IOP was measured with the GAT (two observers), Tono-Pen, OBF, and NCT in a randomised order. The relation of measured IOP and of inter-tonometer differences with CCT and subject age was explored by linear regression analysis. RESULTS: A significant association between measured IOP and CCT was found with each instrument. The change in measured IOP for a 10 mum increase in CCT was 0.28, 0.31, 0.38, and 0.46 for the GAT, Tono-Pen, OBF, and NCT, respectively (all p< or = 0.05). There was a significant association between the NCT/GAT differences and CCT, with a tendency of NCT to overestimate GAT in eyes with thicker corneas. There was a significant association between GAT/Tono-Pen and OBF/Tono-Pen differences and age, with a tendency of GAT and OBF to overestimate the Tono-Pen in eyes of older subjects. CONCLUSION: IOP measurement by all four methods is affected by CCT. The NCT is affected by CCT significantly more than the GAT. Subject age has a differential effect on the IOP measurements made by the GAT and OBF compared to the Tono-Pen.
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Córnea/patología , Glaucoma/fisiopatología , Presión Intraocular/fisiología , Hipertensión Ocular/fisiopatología , Tonometría Ocular/métodos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Glaucoma/patología , Humanos , Masculino , Persona de Mediana Edad , Hipertensión Ocular/patología , Fenómenos Fisiológicos Oculares , Flujo Sanguíneo Regional/fisiología , Tonometría Ocular/instrumentaciónRESUMEN
In the present retrospective study we compare the efficacy of gonadotropin-releasing hormone (GnRH) agonist in a long protocol and a GnRH agonist in a short protocol administration for controlled ovarian hyperstimulation (COH) in an ICSI program. A total of 424 consecutive patients with a history of male factor were included in the present study. Three hundred and three patients were included in the long protocol and 121 in the short protocol. Patients treated with the short protocol were stimulated in a shorter time and achieved lower estradiol levels. A significantly higher percentage of oocytes transferred were found in the long protocol. The clinical pregnancy rate per embryo transfer was 39.3% in the long protocol and 19.2% in the short protocol (p=0.001).
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Estudios Retrospectivos , Inyecciones de Esperma Intracitoplasmáticas/métodos , Adulto , Buserelina/administración & dosificación , Gonadotropina Coriónica/administración & dosificación , Transferencia de Embrión , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/administración & dosificación , Hormona Liberadora de Gonadotropina/agonistas , Humanos , Infertilidad Masculina/terapia , Masculino , Inducción de la Ovulación/métodos , Embarazo , Índice de Embarazo , Factores de TiempoRESUMEN
Structural engineering analysis tools have been used to improve the understanding of the biomechanical behaviour of the cornea. The research is a multi-disciplinary collaboration between structural engineers, mathematical and numerical analysts, ophthalmologists and clinicians. Mathematical shell analysis and nonlinear finite-element modelling have been used in conjunction with laboratory experiments to study the behaviour of the cornea under different loading states and to provide improved predictions of the mechanical response to disease and injury. The initial study involved laboratory tests and mathematical back analysis to determine the corneal material properties and topography. These data were then used to facilitate the construction of accurate finite-element models that are able to reliably trace the performance of cornea upon exposure to disease, injury or elevated intra-ocular pressure. The models are being adapted to study the response to keratoconus (a disease causing loss of corneal tissue) and to tonometry procedures, which are used to measure the intra-ocular pressure. This paper introduces these efforts as examples of the application of structural engineering analysis tools and shows their potential in the field of corneal biomechanics.
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Fenómenos Biomecánicos/métodos , Córnea/fisiología , Presión Intraocular/fisiología , Modelos Biológicos , Animales , Simulación por Computador , Análisis de Elementos Finitos , Humanos , Propiedades de SuperficieRESUMEN
The purpose of this study was to investigate the ovarian response and the receptivity of the endometrium in women pre-treated with micronized progesterone. Eighty-two normogonodotropic women undergoing in vitro fertilization were studied. Thirty received micronized progesterone 1500 mg/day from day 21 of the cycle for a minimum of 2 weeks, and 52 did not receive micronized progesterone (control group). A gonadotropin releasing hormone agonist (GnRH-a) was administered to all the patients in the follicular phase (flare-up). Twenty-five cycles were cancelled for fertilization failure due to male factor, 12 (40%) in the progesterone group and 13 (25%) in the control group (p = 0.271). There was no difference in the number of oocytes retrieved (7.3 +/- 5 vs. 8.2 +/- 4), fertilization rate (50.8% vs. 65%), clinical pregnancy rate (16.6% vs. 25%) or implantation rate (8% vs. 14%). In the progesterone group cases without fertilization, we performed two biopsies to evaluate the receptivity of the endometrium. Pinopode expression was noted 7 days after oocyte retrieval. It seems that the administration of micronized progesterone in the previous cycle does not affect the ovarian response to the combination of follicular phase GnRH-a and gonadotropins, nor the receptivity of the endometrium.
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Inducción de la Ovulación/métodos , Progesterona/administración & dosificación , Adolescente , Adulto , Biopsia , Buserelina/administración & dosificación , Recuento de Células , Endometrio/fisiología , Endometrio/ultraestructura , Femenino , Fertilización In Vitro , Fase Folicular , Humanos , Microscopía Electrónica de Rastreo , Oocitos , Embarazo , Recolección de Tejidos y Órganos , Insuficiencia del TratamientoRESUMEN
Oral administration of the novel anti-inflammatory peptide RDP58 markedly reduced the severity of dextran sulphate sodium (DSS) colitis as determined by clinical and quantitative histological criteria. The architecture of the colonic epithelium in DSS treated mice receiving RDP58 remained relatively normal compared with that of control DSS treated animals. 5-Bromo-2'-deoxyuridine (BrdU) labelling studies showed a pronounced inhibition of colonic epithelial cell proliferation during DSS treatment, which was partially reversed by RDP58 therapy. Remarkably, RDP58 almost completely prevented colonic epithelial cell death induced by DSS treatment. RDP58 therapy also inhibited the accumulation of neutrophils in the colon of DSS treated mice and effectively down regulated tumour necrosis factor (TNF) expression. Preservation of the intestinal mucosa by RDP58 may thus derive from its influence on TNF expression as well as additional anti-inflammatory properties. These findings indicate that RDP58 represents a new, orally available agent potentially useful in the treatment of inflammatory bowel disease.
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Antiinflamatorios/uso terapéutico , Colitis/prevención & control , Péptidos/uso terapéutico , Enfermedad Aguda , Administración Oral , Animales , Apoptosis/efectos de los fármacos , División Celular/efectos de los fármacos , Colitis/inducido químicamente , Colitis/patología , Sulfato de Dextran , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Femenino , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Ratones , Ratones Endogámicos C57BL , Infiltración Neutrófila/efectos de los fármacos , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Postoperative ascites is a rare complication of laparoscopic surgery. Life-threatening and serious etiologies such as unrecognized bowel or urinary tract injury should be excluded promptly to avoid prolonged morbidity and even mortality. Occasionally, no definitive cause can be identified after an extensive diagnostic work-up. In such cases, idiopathic allergic or inflammatory peritoneal reaction may be the final diagnosis.
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Ascitis/etiología , Infertilidad Femenina/cirugía , Laparoscopía/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Adulto , Ascitis/diagnóstico por imagen , Ascitis/terapia , Femenino , Estudios de Seguimiento , Humanos , Infertilidad Femenina/diagnóstico , Laparoscopía/métodos , Monitoreo Fisiológico , Periodo Posoperatorio , Medición de Riesgo , UltrasonografíaRESUMEN
BACKGROUND AND PURPOSE: Extracorporeal shockwave lithotripsy (SWL) is the treatment of choice for the majority of renal and ureteral stones. The Dornier HM3 lithotripter has good results but with some limitations and complications. A number of second- and third-generation machines have been developed employing different energy sources, focusing devices, and coupling media. These devices overcome some of the limitations and lessen the complications but at the expense of the success rate. Use of the consecutive double-pulse technique (as in the MFL 5000) and of combined under-table and over-table modules consecutively (as in the Siemens Lithostar Plus) improves the efficacy of fragmentation. The aim of this study was to study the effects of the use of synchronous twin pulses generated by under-table and over-table identical shockwave reflectors for stone fragmentation. MATERIALS AND METHODS: We designed a lithotripter with two identical shockwave generators and identical reflectors (twin heads). One reflector was under the table and fixed, while the second reflector was over the table and hangs on a C-arm so that the angle between the axes of the two reflectors could be changed. The second focal points (F2) of the two reflectors lay in the same position. A lucent lightweight acrylic water tank with one side sealed by a silicon rubber membrane was fixed to the SWL table so that the membrane coupled with the water cushions of both reflectors. The tank was filled with degassed water and the targeted material was fixed on a holder and immersed in the water so as to be at F2. Comparison of the use of one shockwave source and two shockwave sources simultaneously was done relative to: (1) cavitation effect on aluminum foil; (2) quality of disintegration, shape of the focal zone, and ideal position of F2 using ceramic blocks; and (3) disintegrative efficacy using dental bone cement. RESULTS: The cavitation effect became more localized with the use of two reflectors. Also, the volume and rate of stone disintegration increased with the use of the two reflectors, with production of fine (<2-mm) fragments. The focal zone became smaller and conical with no propagation of shockwaves beyond F2. These results were more evident if the angle between the axes of the reflectors was 90 degrees. CONCLUSION: This new technique of SWL may improve the efficacy of treatment of urinary tract stones. It also may be less harmful to the renal tissues, but animal experiments must be carried out to prove this.
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Litotricia/instrumentación , Cálculos Urinarios/terapia , Diseño de Equipo , Estudios de Factibilidad , Humanos , Litotricia/métodos , Modelos Teóricos , Fantasmas de ImagenRESUMEN
The pathogenetic role of interferon-gamma (IFN-gamma) in acute graft-versus-host disease (GVHD) was examined in a murine model. IFN-gamma gene expression was evaluated by northern blotting and mRNA in situ hybridization. The temporal and tissue specific patterns of IFN-gamma gene expression were related to the patterns of major histocompatibility complex (MHC) antigen induction and of tissue injury. Markedly increased levels of IFN-gamma transcripts were seen in the spleen during the early lymphoproliferative phase and coincided with widespread MHC induction in non-lymphoid tissues. Increased IFN-gamma transcripts were also found in the non-lymphoid target tissues during the phase of subsequent tissue injury. These findings support a role for IFN-gamma in leading to widespread MHC induction during acute GVHD and suggest that IFN-gamma may also contribute to target tissue injury during acute GVHD.
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Enfermedad Injerto contra Huésped/inmunología , Antígenos de Histocompatibilidad Clase I/análisis , Interferón gamma/genética , Animales , Northern Blotting , Encéfalo/inmunología , Expresión Génica , Hibridación in Situ , Hígado/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Miocardio/inmunología , Bazo/inmunología , Lengua/inmunologíaRESUMEN
To study the relative roles of CD4(+)and CD8(+)T cells and their cytokine products in autoimmune diabetes development, we selectively depleted CD4(+)and CD8(+)T cells in autoimmune diabetes-prone (DP) biobreeding (BB) rats, by administrations of anti-CD2 and anti-CD8 monoclonal antibody (mAb) respectively. We then analysed cytokine mRNA expression, by PCR assay, in mononuclear leukocytes isolated from islets and spleens of control and mAb-treated DP-BB rats. Depletion of CD4(+)T cells (by anti-CD2 mAb) in blood, spleen and islets prevented diabetes development in DP-BB rats, and depletion of CD8(+)T cells (by anti-CD8 mAb) delayed and significantly decreased diabetes incidence. Depletion of either CD4(+)or CD8(+)T cells completely prevented IFN-gamma mRNA upregulation in islets of DP-BB rats above the low level expressed in islets of diabetes-resistant (DR) BB rats. Also, IL-10 mRNA levels in islets of DP-BB rats were significantly decreased by depletion of either CD4(+)or CD8(+)T cells, whereas the effects of the anti-T cell mAb on mRNA levels of other cytokines in islets (IL-2, IL-4, IL-12p40, and TNF-alpha) were discordant. In contrast, both mAb treatments significantly upregulated IL-4 and TNF-alpha mRNA levels in spleens of DP-BB rats. These results demonstrate that islet infiltration by both CD4(+)and CD8(+)T cells is required for IFN-gamma and IL-10 production in islets and beta-cell destruction. Depletion of either CD4(+)or CD8(+)T cells may prevent beta-cell destruction by decreasing IFN-gamma and IL-10 production in islets and increasing IL-4 and TNF-alpha production systemically.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Interferón gamma/genética , Islotes Pancreáticos/inmunología , Animales , Anticuerpos Monoclonales/administración & dosificación , Suero Antilinfocítico/administración & dosificación , Secuencia de Bases , Citocinas/genética , Cartilla de ADN/genética , Diabetes Mellitus Tipo 1/prevención & control , Expresión Génica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas BB , Bazo/inmunologíaRESUMEN
Forces to which individual implant units are subjected when an implant-stabilised mandibular over-denture is loaded have been measured using a carbon-fibre reinforced epoxy resin replica of an edentulous mandible mounted in a loading rig which simulated physiological conditions. Three different retentive designs were used; ball attachments, a fixed-fixed bar cranked anteriorly, and a similar design with posterior cantilevers. Forces exerted on the implants were measured using resistance strain gauges mounted on their trans-mucosal abutments and the dentures were loaded at individual tooth positions with a strain gauge beam. Ball attachments were associated with the lowest detected forces on the abutments. It is concluded that variations in superstructure design affect the forces transmitted by implants stabilising a complete mandibular over-denture, when the mandible is suspended and loaded in a physiological manner.
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Diseño de Prótesis Dental , Prótesis Dental de Soporte Implantado , Análisis del Estrés Dental , Retención de Dentadura/instrumentación , Fuerza de la Mordida , Carbono , Fibra de Carbono , Pilares Dentales , Prótesis de Recubrimiento , Resinas Epoxi/química , Humanos , MandíbulaRESUMEN
Cytokines produced by islet-infiltrating mononuclear leukocytes may be involved in islet beta-cell destruction and IDDM. To determine which cytokine(s) might be involved in islet beta-cell destruction, we used a reverse transcriptase-polymerase chain reaction assay to compare levels of cytokine mRNA expression in mononuclear leukocytes freshly isolated from islets of four groups of BB rats aged 60-75 days: diabetes-prone (DP) rats, DP rats protected from diabetes by injection of complete Freund's adjuvant (CFA) at age 25 days, acutely diabetic rats, and diabetes-resistant (DR) rats. We found that islet mononuclear leukocyte levels of gamma-interferon (IFN-gamma) mRNA were significantly higher in DP and diabetic rats than in DR rats, whereas CFA-treated DP rats had similar IFN-gamma mRNA levels to DR rats. Also, interleukin (IL)-2 mRNA levels tended to be higher in islet leukocytes from DP and diabetic rats than from DR rats. Tumor necrosis factor-alpha, IL-4, and IL-10 mRNA levels were not significantly different in islet leukocytes from the four groups of rats. These findings suggest that production of T-helper 1 (Th1)-type cytokines, IFN-gamma and IL-2, by islet-infiltrating cells in BB rats is associated with beta-cell destruction and IDDM development.