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1.
Paediatr Int Child Health ; 44(1): 18-23, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38334259

RESUMO

BACKGROUND: The aim of the study was to assess the health-related quality of life (HRQOL) and cognitive function in patients with Crigler-Najjar syndrome (CNS) type I and its impact on their lives. METHODS: Twenty-one patients diagnosed with CNS type I aged 1 month to 18 years in the Paediatric Hepatology Unit of Cairo University Children's Hospital were enrolled in this cross-sectional observational study. The patients' health-related quality of life (HRQOL) was assessed using the World Health Organization Quality Of Life BREF questionnaire (WHOQOL-BREF) and the Short Form 36 Health Survey Questionnaire (SF-36). Cognitive function was assessed using the Stanford-Binet Intelligence Scale: Fifth Edition (SB5). RESULTS: All patients had a history of admission to a neonatal intensive care unit, 17 were managed by phototherapy only and 5 also underwent exchange transfusion. According to the WHOQOL questionnaire, 11 cases (52.4%) had a low QOL score, and 7 of 13 patients had an average score for their total IQ test. Cases with poor compliance to phototherapy had statistically significantly lower QOL scores (p=0.001), while, according to the SF36 survey, cases who received exchange transfusion had statistically significantly higher cognitive function (p=0.03). There was a positive correlation between the neurological effect as a complication of the disease and poor physical QOL. CONCLUSION: Paediatric patients with CNS have significantly lower HRQOL, especially physically, psychologically and environmentally. It is recommended that assessment of HRQOL should be a routine part of follow-up in CNS patients. Patients whose HRQOL is affected receive regular psychiatric counselling, social support and rehabilitation.Abbreviations: CNS: Crigler-Najjar syndrome; HRQOL: health-related quality of life; IQ: intelligence quotient; NICU: neonatal intensive care unit; QOL: quality of life; SB5: Stanford-Binet intelligence scale: 5th edition; SF-36: Short Form 36 Health Survey Questionnaire; UDGT: uridine diphosphate glucuronosyl transferase; UGT1A1: uridine 5'-diphosphate glucuronosyltransferase; WHOQOL-BREF: World Health Organization Quality of Life Brief Version.


Assuntos
Síndrome de Crigler-Najjar , Qualidade de Vida , Criança , Humanos , Cognição , Estudos Transversais , Qualidade de Vida/psicologia , Inquéritos e Questionários , Organização Mundial da Saúde , Lactente , Pré-Escolar , Adolescente
2.
Indian J Ophthalmol ; 72(Suppl 1): S111-S118, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38131552

RESUMO

PURPOSE: Although there is increasing evidence that phosphodiesterase-5 (PDE-5) inhibitors modify the effect of diabetes on different tissues, its effect on diabetic retinopathy is not well studied. METHODS: Forty male Sprague-Dawley (SD) rats were divided into four groups: group I = control group that received no treatment; group II (diabetic group), in which diabetes was induced by a single streptozotocin injection; group III (sildenafil small dose, SSD), in which diabetes was similarly introduced (however, rats received daily oral 1 mg/kg sildenafil citrate (SC) for 3 months); and group IV (sildenafil large dose, SLD), which was as in group 3, but SC was 2.5 mg/kg. After 3 months, globes were removed and retinae were dissected; one globe from each rat was examined by light microscopy (LM), and the other by electron microscopy (EM). RESULTS: In contrast to the control group, diabetic rats in group II demonstrated well-established diabetic changes in the form of capillary congestion, decreased cell population, hyaline changes of capillary walls, and degenerated nerve fiber layer by LM. Similarly, EM demonstrated photoreceptor degeneration, mitochondrial cristolysis, and vacuolated depleted cells among other features in group II. These diabetic features were less prominent in group III and nearly absent in group IV. CONCLUSION: SC use in the early stages of DR may prevent/delay diabetic retinopathy development or progression in diabetic rat models, an effect that seems to be dose-related.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Ratos , Masculino , Animais , Citrato de Sildenafila/farmacologia , Ratos Sprague-Dawley , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Microscopia Eletrônica
3.
Int J Retina Vitreous ; 9(1): 42, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37460929

RESUMO

BACKGROUND: Sildenafil citrate (SC) attenuates endothelial dysfunction. However, its effects on diabetic retinopathy (DR), which is mainly a microvascular disease, remain unclear. Vascular endothelial growth factor (VEGF) is known to be a critical mediator of DR. Therefore, we investigated the effects of SC on diabetic retina by measuring VEGF levels. METHODS: In this study, twenty-eight rats were divided into the following groups: group I, the control group; group II, rats with streptozotocin-induced diabetes; group III, rats with streptozotocin-induced diabetes receiving daily oral sildenafil at 1 mg/kg; and group IV, rats with streptozotocin-induced diabetes receiving high-dose daily sildenafil at 2.5 mg/kg. After 3 months, VEGF was measured in the retina specimen in one eye and the vitreous body in the other eye by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. RESULTS: We found that VEGF expression in the retina was low in all rats from groups I and IV and in 30% of rats from group III; 80% of rats in group II demonstrated high VEGF expression in the retinae (P < 0.001). VEGF concentrations in the vitreous body samples were 32 ± 2, 61 ± 4, 44 ± 5, and 36 ± 3 pg/l in groups I-IV, respectively (P < 0.001). CONCLUSION: VEGF decreased significantly in the eyes of diabetic rats after chronic oral sildenafil citrate treatment. SC may have a modifying/attenuating effect on DR. However, further studies are needed to evaluate its use as an adjunctive treatment.

4.
J Parasitol Res ; 2020: 8859857, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802484

RESUMO

Dementia is an ominous neurological disease. Scientists proposed a link between its occurrence and the presence of Toxoplasma gondii (T. gondii). The long-term sequels of anti-Toxoplasma premunition, chiefly dominated by TNF-α, on the neurons and their receptors as the insulin-like growth factor-1 receptor (IGF-1R), which is tangled in cognition and synaptic plasticity, are still not clear. IGF-1R mediates its action via IGF-1, and its depletion is incorporated in the pathogenesis of dementia. The activated TNF-α signaling pathway induces NF-κß that may induce or inhibit neurogenesis. This study speculates the potential impact of anti-Toxoplasma immune response on the expression of IGF-1R in chronic cerebral toxoplasmosis. The distributive pattern of T. gondii cysts was studied in association with TNF-α serum levels, the in situ expression of NF-κß, and IGF-1R in mice using the low virulent ME-49 T. gondii strain. There was an elevation of the TNF-α serum level (p value ≤ 0.004) and significant upsurge in NF-κß whereas IGF-1R was of low abundance (p value < 0.05) compared to the controls. TNF-α had a strong positive correlation with the intracerebral expression of NF-κß (r value ≈ 0.943, p value ≈ 0.005) and a strong negative correlation to IGF-1R (r value -0.584 and -0.725 for area% and O.D., respectively). This activated TNF-α/NF-κß keeps T. gondii under control at the expense of IGF-1R expression, depriving neurons of the effect of IGF-1, the receptor's ligand. We therefore deduce that T. gondii immunopathological reaction may be a road paver for developing dementia.

5.
Parasite Immunol ; 42(10): e12724, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32338371

RESUMO

AIM: Investigating the anti-angiogenic effect of bevacizumab on chronic schistosomiasis mansoni in a trial to hinder the Schistosome-induced angiogenesis and porto-systemic shunting complications. METHODS: The immunohistochemical expression of CD34, VEGF-R1, PCNA and α-SMA (angiogenesis markers) was analysed in the lung, liver and gastrointestinal junctions of chronic S mansoni infected mice after intraperitoneal injection of bevacizumab. The effect of prolonged administration of bevacizumab with praziquantel was also assessed through parasitic load, protective index, granuloma and fibrous tissue evaluation. RESULTS: A regression in the vascular activity and microvascular density was observed in the infected mice after receiving bevacizumab. They had a significantly less VEGF-R1, PCNA, CD-34 and α-SMA expression in comparison to the infected untreated mice. The least tissue egg count was reported in mice received bevacizumab for 6 weeks (Mean = 27 120). However, they had persistent liver granulomas, and massively amalgamated fibrosis. Interestingly, the least faecal egg and tissue worms counts (Mean = 112, 13.4), and the highest protection index (39.26) were reported in mice received bevacizumab for 3 weeks, with marked granuloma, and fibrous tissue resolution. CONCLUSIONS: Bevacizumab has a promising protective effect against the Schistosoma-induced angiogenesis. As an adjuvant to praziquantel, it is important to adjust the appropriate duration of administration that achieves the best schistosomicidal effect without impeding granuloma and fibrous tissue resolution.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Hepatopatias/parasitologia , Esquistossomose mansoni/tratamento farmacológico , Animais , Doença Crônica , Granuloma/tratamento farmacológico , Granuloma/parasitologia , Hepatopatias/tratamento farmacológico , Masculino , Camundongos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/parasitologia , Carga Parasitária , Praziquantel/uso terapêutico , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/fisiopatologia
6.
Pharmacol Rep ; 71(2): 330-337, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30826574

RESUMO

BACKGROUND: Food allergy (FA) is a worldwide health problem, affecting nearly 10% of all populations, with no prophylactic options or regulatory treatment available until now. Fisetin, a biologically active flavonoid, and telmisartan, the highly selective competitive AT1 receptor antagonist, recently exhibited potent anti-inflammatory and immunomodulatory activities. In the present study, we have evaluated the possible anti-inflammatory and immunomodulatory activities of fisetin and telmisartan each alone or in low-dose combination in a mouse model of FA. METHODS: For induction of FA, eight-week-old BALB/c mice, sensitized by two ip injection of 50 µg ovalbumin (OVA) and 1 mg alum at day 0 and 7. Then, each mouse challenged with 10 mg OVA at days 14, 16, 18, and 21. On the 28th day, the fifth challenge carried out by oral administration of 50 mg OVA. Either fisetin (1 or 3 mg/kg/d), telmisartan (1 or 3 mg/kg/d) or a combination of fisetin 1 mg/kg/d and telmisartan 1 mg/kg/d received orally from the 13th day till 28th day. In challenge days, the treatments received one-hour before the challenge. RESULTS: Our data showed that fisetin and telmisartan each alone or in low-dose combination attenuated the anaphylactic manifestation, decreased blood eosinophilic count, serum OVA-specific IgE, and IL-4 levels, the intestinal total and degranulated mast cells count, and CD4+ immunohistochemical expression. Furthermore, they enhanced the serum IFN-γ level and abrogated the intestinal histopathological changes induced by OVA in mice. CONCLUSION: Either fisetin, telmisartan or their low-dose combination could be promising in the management of FA.


Assuntos
Flavonoides/farmacologia , Hipersensibilidade Alimentar/tratamento farmacológico , Fatores Imunológicos/farmacologia , Telmisartan/farmacologia , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Flavonoides/administração & dosagem , Flavonóis , Hipersensibilidade Alimentar/imunologia , Fatores Imunológicos/administração & dosagem , Interferon gama/sangue , Intestinos/imunologia , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Telmisartan/administração & dosagem , Fatores de Tempo
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