Synthesis of photoactivable Pt(IV) prodrug loaded on NaYF4 based upconversion nanoparticles functionalized with 2-deoxy-D-glucose and its evaluation for targeted cancer therapy

21-30Nano-formulation based on Tm, Yb doped NaYF4 upconversion nanoparticles (UCNPs) functionalized with 2-deoxy-D-glucose have been synthesized to load the photoactivable Pt(IV) prodrug, cis-[PtI2(NH3)2(OCOCH2CH2COOH)2]. The Pt(IV) prodrug has been synthesized by oxidation of cis-[PtI2(NH3)2] to [PtI2(OH)2(NH3)2] and its further treatment with succinic anhydride. It is loaded through ester bond formation between the carboxyl groups of Pt(IV) prodrug with hydroxyl groups of 2-deoxy-D-glucose (2-DG) coated on UCNPs. The cytotoxicity of formulation after exposing to 385 nm UV light and in absence of light is evaluated against MCF-7 cell lines by MTT assay. The results have revealed enhanced cytotoxicity of UV exposed nano-formulation. Additionally, the clonogenic assay has exhibited the decrease in plating efficiency as inferred from decreased surviving fraction around 20% only for UV activated formulation as compared to formulation in dark, as well as merely Pt(IV) prodrug. These results are indicative that more internalization of the formulation inside the cancer cells was achieved due to the presence of 2-DG rendering more efficiency to kill cancer cells

Synthesis of photoactivable Pt(IV) prodrug loaded on NaYF4 based upconversion nanoparticles functionalized with 2-deoxy-D-glucose and its evaluation for targeted cancer therapy

Nano-formulation based on Tm, Yb doped NaYF4 upconversion nanoparticles (UCNPs) functionalized with 2-deoxy-D-glucose have been synthesized to load the photoactivable Pt(IV) prodrug, cis-[PtI2(NH3)2(OCOCH2CH2COOH)2]. The Pt(IV) prodrug has been synthesized by oxidation of cis-[PtI2(NH3)2] to [PtI2(OH)2(NH3)2] and its further treatment with succinic anhydride. It is loaded through ester bond formation between the carboxyl groups of Pt(IV) prodrug with hydroxyl groups of 2-deoxy-D-glucose (2-DG) coated on UCNPs. The cytotoxicity of formulation after exposing to 385 nm UV light and in absence of light is evaluated against MCF-7 cell lines by MTT assay. The results have revealed enhanced cytotoxicity of UV exposed nano-formulation. Additionally, the clonogenic assay has exhibited the decrease in plating efficiency as inferred from decreased surviving fraction around 20% only for UV activated formulation as compared to formulation in dark, as well as merely Pt(IV) prodrug. These results are indicative that more internalization of the formulation inside the cancer cells was achieved due to the presence of 2-DG rendering more efficiency to kill cancer cells

Factors determining the outcome of children hospitalized with severe pneumonia

<p>Abstract</p> <p>Background</p> <p>Pneumonia is one of the leading causes of morbidity and mortality in under fives. We carried out a comprehensive study to identify factors influencing both mortality and morbidity for children less than 5 years of age hospitalized with severe pneumonia.</p> <p>Methods</p> <p>200 hospitalized children aged 2–60 months with World Health Organization (WHO) defined severe pneumonia were enrolled in the study. The children were managed using a standard protocol. They were closely followed up for need for change in antibiotics, prolonged hospital stay, need for mechanical ventilation and mortality. Data on the factors influencing the outcome were collected.</p> <p>Results</p> <p>Of 200 children enrolled in the study, 113 (56.5%) needed a change in antibiotics, 102 (51%) stayed for more than 5 days in the hospital, 41 (20.5%) needed mechanical ventilation and 21 (10.5%) died. On multivariate analysis, lack of exclusive breastfeeding [RR (95%CI) 2.63 (2.16–2.86)], overcrowding [RR (95%CI) 1.94 (1.35–2.38)] and an abnormal chest x-ray [RR (95%CI) 2.29 (1.22–3.44)] were associated with the need for change of antibiotics. Lack of exclusive breastfeeding [RR (95%CI) 2.56 (2.0–2.93)], overcrowding [RR (95%CI) 2.59 (1.78–3.23)] and an abnormal chest x-ray [RR (95%CI) 2.99 (1.65–4.38)] were identified as determinants for prolonged hospital stay. Head nodding [RR (95%CI) 8.34 (2.71–12.77)], altered sensorium [RR (95%CI) 5.44 (1.34–17.56)], abnormal leukocyte counts [RR (95%CI) 5.85(1.36–17.14)] and pallor [RR (95%C) 10.88 (2.95–20.40)] were associated with mortality. Head nodding (RR (95% CI) 4.73 (1.50–6.36)] and cyanosis (RR (95%CI) 5.06 (1.80–11.34)] were the determining factors for mechanical ventilation.</p> <p>In radiographically confirmed pneumonia, the determining factors for change of antibiotics were: lack of exclusive breast feeding [RR (95% CI) 2.05 (1.69–2.2)] and low birth weight [RR (95% CI) 1.59 (1.1–1.89)]. For prolonged hospital stay, the factors identified were mothers' education less than graduation [RR (95% CI) 1.5 (1.19–1.7)], lack of exclusive breast feeding [RR (95% CI) 1.77 (1.19–2.09)] and oxygen saturation of < 90% at time of presentation [RR (95% CI) 2.06 (1.42–2.42)]. Determinants for mechanical ventilation were mothers' education less than graduation [RR (95% CI) 3.6 (1.15–6.3)] and cyanosis at presentation [RR (95% CI) 10.9 (1.56–18.9)]. For mortality, the only determinant was pallor [RR (95% CI) 10.54 (1.8–21.79)].</p> <p>Conclusion</p> <p>Children hospitalized with severe community acquired pneumonia [as defined by World Health Organization (WHO)] who had not received exclusive breast feeding, had stayed in an overcrowded homes and had an abnormal chest radiograph were more likely to fail to respond with primary antibiotic regimen and require change of antibiotics and prolonged hospital stay.</p> <p>In children with radiographically confirmed pneumonia, lack of breast feeding and low birth weight was associated with need for change in antibiotics.</p

Usefulness of mycophenolate mofetil in Indian patients with C3 glomerulopathy

Background C3 glomerulopathy (C3G) is a heterogeneous disease caused by alternative complement pathway abnormalities without any standardized treatment. An immunosuppressive agent, mycophenolate mofetil (MMF), has been recently shown to be useful in treating C3G, mainly in studies from the west. We report the clinical outcome of 17 Indian C3G patients treated with MMF with or without steroids. Methods The clinical and histology details of the C3G patients treated with MMF for at least 6 months with a follow-up of at least 12 months were retrieved from the medical records of our center. Results The median serum creatinine and proteinuria at presentation were 0.8 mg/dL and 3.7 g/day, respectively, with the majority (88.2%) presenting as nephrotic syndrome. The mean dose of MMF was 1.65 (±0.56) g/day, and the median duration of MMF therapy was 18 months. Two-thirds (64%) of the patients responded to the treatment, with complete remission in 4 (23%) and partial remission in 7 (41%) (median time: 9 months). Three patients progressed to end-stage renal disease (ESRD) on follow-up. Of the three patients, one (33%) had an initial response in proteinuria to MMF but did not respond after a relapse and subsequently progressed to ESRD and two (67%) other patients were nonresponsive to MMF from the start of the therapy. Conclusion Despite a small sample size and lack of a control arm, this study describes the effectiveness of MMF in treating C3G patients from Asia and forms a basis for future randomized trials

Fatores associados às complicações em crianças pré-escolares com pneumonia adquirida na comunidade Factors associated with complications of community-acquired pneumonia in preschool children

OBJETIVO: Identificar os fatores socioeconômicos e clínicos associados à evolução para complicações em crianças internadas com pneumonia adquirida na comunidade (PAC). MÉTODOS: Estudo longitudinal prospectivo em crianças diagnosticadas com PAC (12-59 meses de idade) internadas em enfermarias gerais de pediatria de dois hospitais na região de Campinas (SP). Os critérios de exclusão foram ter fibrose cística, cardiopatia, malformação pulmonar, neuropatias e doenças genéticas. PAC foi diagnosticada por características clínicas e radiológicas. Os dados foram coletados dos prontuários médicos e por um questionário semiestruturado. Os sujeitos foram divididos em dois grupos (PAC complicada e não complicada). Foram comparadas variáveis socioeconômicas e clínicas, e foi realizada análise de regressão logística multivariada. RESULTADOS: Das 63 crianças incluídas, 29 e 34, respectivamente, apresentaram PAC não complicada e PAC complicada. Não houve diferenças estatisticamente significantes entre os grupos quanto a idade na admissão, idade gestacional, peso ao nascer, gênero ou variáveis socioeconômicas. Houve diferenças significantes entre os grupos em relação a pneumonia anterior (p = 0,03), antibioticoterapia prévia (p = 0,004), tempo de início da doença (p = 0,01), duração da febre antes da internação (p < 0,001), duração da antibioticoterapia (p < 0,001) e tempo de internação (p < 0,001). Na análise multivariada, somente permaneceu no modelo a duração da febre antes da internação (OR = 1,97; IC95%: 1,36-2,84; p < 0,001). CONCLUSÕES: Variáveis biológicas, com destaque para o tempo de febre anterior à internação, parecem estar associadas com a evolução para complicação em crianças com PAC.<br>OBJECTIVE: To identify socioeconomic factors and clinical factors associated with the development of complications in preschool children hospitalized with community-acquired pneumonia (CAP). METHODS: This was a prospective longitudinal study involving children (12-59 months of age) diagnosed with CAP and admitted to the pediatric wards of two hospitals in the metropolitan area of Campinas, Brazil. Children with cystic fibrosis, heart disease, pulmonary malformations, neurological disorders, or genetic diseases were excluded. The diagnosis of CAP was based on clinical and radiological findings. Data were collected from the medical records and with a semi-structured questionnaire. The subjects were divided into two groups (complicated and uncomplicated CAP). Socioeconomic and clinical variables were compared, and multivariate logistic regression analysis was performed. RESULTS: Of the 63 children included, 29 and 34, respectively, presented with uncomplicated and complicated CAP. No statistically significant differences were found between the groups regarding age at admission, gestational age, birth weight, gender, or socioeconomic variables. Significant differences were found between the groups regarding history of pneumonia (p = 0.03), previous antibiotic therapy (p = 0.004), time elapsed since the onset of CAP (p = 0.01), duration of fever prior to admission (p < 0.001), duration of antibiotic therapy (p < 0.001), and length of hospital stay (p < 0.001). In the multivariate analysis, only duration of fever prior to admission remained in the model (OR = 1.97; 95% CI: 1.36-2.84; p < 0.001). CONCLUSIONS: Biological variables, especially duration of fever prior to admission, appear to be associated with the development of complications in children with CAP