Mechanistic pathways for the degradation of SMX drug and floatation of degraded products using F–Pt co-doped TiO2 photocatalysts

This work presents smart pathways to enhance the photocatalytic activity of TiO₂via co-doping with fluorine (F) and platinum (Pt) to form F–Pt co-doped TiO₂ photocatalysts and investigates the unique and unusual fluorination of the floated products. Our investigations indicate that the crystalline structure of the photocatalysts was a mixture of anatase and brookite phases and that the nanoparticles of the synthesized nanocomposites had nanometric sizes (4–25 nm). The F–Pt co-doped TiO₂ nano-photocatalysts demonstrated degradation of sulfamethoxazole (SMX) drug of >93% within 90 min under direct solar light and 58% degradation within 360 min under a solar simulator. Thus, co-doping TiO₂ with F and Pt atoms to form F–Pt co-doped TiO₂ nanocomposite is an efficient pathway to achieve high photocatalytic performance escorted with the formation of floating metal-fluoropolymer, unlike pristine TiO₂ which has less photocatalytic degradation and no generation of a floating polymer. Our photocatalytic protocol demonstrates that the degradation of SMX started with redox reactions of oxygen and water absorbed on the surface of the prepared nanocomposites to form superoxide anions (O₂˙⁻) and hydroxy radicals (˙OH) which have oxidation superpower. The resultant products were subsequently fluorinated by fluoride radical ions and floated as metal-fluoropolymer.

This work presents smart pathways to enhance the photocatalytic activity of TiO₂via co-doping with fluorine (F) and platinum (Pt) to form F–Pt co-doped TiO₂ photocatalysts and investigates the unique and unusual fluorination of the floated products.     

An Innovative and Simple Approach to Functional Salivary Reservoir Fabrication

Saliva is a valuable oral fluid that is often taken for granted. Impaired salivary function is a major and a debilitating sequela of radiation treatment for patients with head and neck cancer. It can persist for years and thereby increases the risk of oral infection significantly. Moreover, it has a notably negative impact on the quality of life of such patients. To help overcome this problem, a number of techniques have been proposed for incorporating a reservoir containing salivary substitute into a removable prosthesis. A new design for a functional salivary reservoir is presented here. This design is simple to construct and easily maintained by the wearer. Details of its design, construction, and other potential advantages are presented.     

Fracture Union in Closed Interlocking Nail in Humeral Shaft Fractures

Background:

Fracture shaft humerus is a major cause of morbidity in patients with upper extremity injuries. The aim of this study was to evaluate the outcome of interlocking nail in humeral shaft fractures.

Methods:

This study was conducted in the Department of Orthopedic Surgery in SMS and R Sharda University from January 2010 to November 2013. Seventy-eight patients were recruited from emergency and out-patient department having a close fracture of humerus shaft. All patients were operated under general anesthesia and closed reamed interlocking nailing was done. All patients were followed for 9 months.

Results:

Out of 78 patients, 69 patients underwent union in 90–150 days with a mean of 110.68 days. Complications found in four patients who had nonunion, and five patients had delayed union, which was treated with bone grafting. All the patients were assessed clinically and radiologically for fracture healing, joint movements and implant failure. The results were excellent in 88.46% and good in 6.41% patients. Complete subjective, functional, and clinical recovery had occurred in almost 100% of the patients.

Conclusions:

The results of the present study indicates that in the presence of proper indications, reamed antegrade intramedullary interlocked nailing appears to be a method of choice for internal fixation of osteoporotic and pathologic fractures.     

Predictors of renal replacement therapy and mortality in children with chronic kidney disease

Objectives:

To study the epidemiology of chronic kidney disease (CKD) in children, and to look for risk factors to predict renal replacement therapy (RRT) and mortality.

Methods:

This is a retrospective cohort study conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between 2006 and 2014, where the files of 1,000 children with CKD were reviewed. We determined the effect of consanguinity and hypertension, and being a Saudi indigene on mortality and RRT. We compared children with congenital versus non-congenital causes of CKD.

Results:

The mean±standard deviation age at presentation was 4.9±4.3 years. The median duration of follow up was 1.5 (interquartile range [IQR]: 0.4-4.0) years. Only 9.7% of children received RRT, and 8.3% died. The underlying etiology for CKD was congenital in 537 children. The congenital CKD group presented at a younger age group (3.5±4.0 versus 6.6±3.9 years, p<0.0001), had more advanced stages of CKD (p<0.0001), higher rates of consanguinity (75.4% versus 47.1%, p<0.0001), and RRT (p<0.004) than children with non-congenital CKD. Risk factors for RRT among children with CKD include being a Saudi indigene (relative risk [RR]=1.49, 95% confidence interval (CI): 1.01-2.21), and hypertensive (RR=5.29, 95% CI: 3.54-7.91). The risk factor for mortality was hypertension (RR=2.46, 95% CI: 1.66-3.65).

Conclusion:

Congenital causes of CKD represent the main etiology of CKD in children living in the western province of Saudi Arabia. Significant risk factors for RRT include congenital CKD, Saudi nationality, and hypertension. Hypertension is also a predictor of mortality in children with CKD.Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function, present for more than 3 months with implications for health.1 Children with CKD who are on renal replacement therapy (RRT) have higher mortality rate, which is at least 30-fold higher than their age-matched peers.2 Epidemiological information on the incidence and prevalence of pediatric CKD in children is currently limited,3 particularly in developing countries. Furthermore, most of the available epidemiological data are from end-stage kidney disease (ESKD) registries, and information on the earlier stages of pediatric CKD is still lacking.4 The early stages of CKD in the pediatric population are in most cases asymptomatic, and are therefore under-diagnosed and under-reported.4 Direct comparisons of the incidence and prevalence rate of pediatric CKD are complex since each pediatric CKD registries uses different definition; some depend on the estimated glomerular filtration rate (eGFR), while others use serum creatinine levels. The incidence in Europe was consistent between 11-12 per million of the age-related population (pmarp) for CKD stages 3-5, and 8 pmarp for CKD stages 4-5.4 Data available on the exact prevalence of various kidney diseases in the Arab world is very limited. Most of the data come from small studies and are of limited generalizability.5 In Kuwait, the mean incidence was found to be as high as 38 pmarp, while the prevalence was as also high at 329 pmarp in 2003.6 An incidence of 11 pmarp and a prevalence of 51 pmarp has been reported in Jordanian children.7 The epidemiological data of CKD in children is very scarce in Saudi Arabia. One study from Asir reported that the mean annual incidence of CRF of 15.6 per million children, the mean annual incidence of ESRF is 9.2 per million children, and congenital anomalies of the urinary system constitute the most common cause of chronic renal failure (CRF).8 Another study from Jeddah reported similar results.9 All these studies enrolled a small number of children (less that 100). In the light of a limited data available regarding the epidemiology of CKD in children in Saudi Arabia, we performed a retrospective study to examine the risk factors for RRT and mortality among children with CKD.     

Structural approaches to HIV prevention

Recognition that social, economic, political, and environmental factors directly affect HIV risk and vulnerability has stimulated interest in structural approaches to HIV prevention. Progress in the use of structural approaches has been limited for several reasons: absence of a clear definition; lack of operational guidance; and limited data on the effectiveness of structural approaches to the reduction of HIV incidence. In this paper we build on evidence and experience to address these gaps. We begin by defining structural factors and approaches. We describe the available evidence on their effectiveness and discuss methodological challenges to the assessment of these often complex efforts to reduce HIV risk and vulnerability. We identify core principles for implementing this kind of work. We also provide recommendations for ensuring the integration of structural approaches as part of combined prevention strategies.     

Activation of p38 mitogen-activated protein kinase contributes to the early cardiodepressant action of tumor necrosis factor.

OBJECTIVES: The purpose of this study was to determine whether p38 mitogen-activated protein kinase (p38-MAPK) contributes to tumor necrosis factor-alpha (TNFalpha)-induced contractile depression. BACKGROUND: Tumor necrosis factor has both beneficial and detrimental consequences that may result from the activation of different downstream pathways. Tumor necrosis factor activates p38-MAPK, a stress-responsive kinase implicated in contractile depression and cardiac injury. METHODS: In isolated hearts from mice lacking the p38-MAPK activator, MAPK kinase 3 (MKK3), perfused at constant coronary pressure or flow, we measured the left ventricular developed pressure (LVDP) and the relationship between end-diastolic volume and LVDP in the presence and absence of 10 ng/ml TNFalpha. RESULTS: Within 15 min at constant pressure, TNFalpha significantly reduced LVDP and coronary flow in outbred and mkk3(+/+) mice. This early negative inotropic effect was associated with a marked phosphorylation of both p38-MAPK and its indirect substrate, HSP27. In hearts lacking MKK3, TNFalpha failed to activate p38-MAPK or to cause significant contractile dysfunction. The actions of TNFalpha were similarly attenuated in MAPK-activated protein kinase 2 (MK2)-deficient hearts, which have a marked reduction in myocardial p38-MAPK protein content, and by the p38-MAPK catalytic site inhibitor SB203580 (1 micromol/l). Under conditions of constant coronary flow, the p38-MAPK activation and contractile depression induced by TNFalpha, though attenuated, remained sensitive to the absence of MKK3 or the presence of SB203580. The role of p38-MAPK in TNFalpha-induced contractile depression was confirmed in isolated murine cardiac myocytes exposed to SB203580 or lacking MKK3. CONCLUSIONS: Tumor necrosis factor activates p38-MAPK in the intact heart and in isolated cardiac myocytes through MKK3. This activation likely contributes to the early cardiodepressant action of TNFalpha.     

Identification of the Human P-450 Enzymes Responsible for the Sulfoxidation and Thiono-Oxidation of Diethyldithiocarbamate Methyl Ester: Role of P-450 Enzymes in Disulfiram Bioactivation

Diethyldithiocarbamate methyl ester (DDTC-Me) is a precursor to the formation of S-methyl-N,N-diethyliolcarbamate sulfoxide, the active metabolite proposed to be responsible for the alcohol deterrent effects of disulfiram. The present study investigated the role of human cytochrome P-450 (CYP) enzymes in sulfoxidation and thiono-oxidation of DDTC-Me, intermediary steps in the activation of disulfiram. Several approaches were used in an attempt to delineate the particular P-450 enzyme(s) involved in the sulfoxidation and thiono-oxidation of DDTC-Me. These approaches included the use of cDNA-expressed human P-450 enzymes, correlation analysis with sample-to-sample variation in human P-450 enzymes in a bank of human liver microsomes, and chemical and antibody inhibition studies. Multiple human P-450 enzymes (CYP3A4, CYPlA2, CYP2A6, and CYP2D6) catalyzed the sulfoxidation of DDTC-Me, as determined with cDNA-expressed enzymes. Several lines of evidence suggest that the sulfoxidation of DDTC-Me by human liver microsomes is primarily catalyzed by CYP3A4/5, including (1) a high correlation between DDTC-Me sulfoxidation and testosterone 6β-hydroxylation; (2) increased DDTC-Me sulfoxidation in the presence of α-naphthoflavone, an activator of CYP3A enzymes; (3) inhibition of this reaction by inhibitors of CYP3A4/5 enzymes, such as troleandomycin and ketoconazole; and (4) inhibition of DDTC-Mesulfoxidation by antibodies against CYP3A enzymes. On the other hand, several lines of evidence suggested that the thiono-oxidation of DDTC-Me by human liver microsomes is catalyzed in part by CYPlA2, CYP266, CYPPEl, and CYP3A4/5, including (1) these human P450 enzymes among others have the capacity to catalyze this reaction, as determined with cDNA-expressed enzymes; (2) a high correlation between DDTC-Me thiono-oxidation and testosterone 6β-hydroxylation, weak inhibition by ketoconazole, troleandomycin, and anti-CYP3A antibodies suggested a minor role for CYP3A4; (3) a high correlation with immunoreactive CYP2B6 suggested involvement of this enzyme; (4) weak inhibition of DDTC-Me thiono-oxidation by furafylline and anti-CYPlA antibody suggested involvement of CYPlA2, and (5) inhibition of DDTC-Me thiono-oxidation by DDTC and anti-CYP2E antibodies suggested a role for CYP2E1. Collectively, these data suggested CYP3A4/5 enzymes are the major contributors to the sulfoxidation of DDTC-Me by human liver microsomes, and CYPlA2, CYP2B6, CYP2E1, and CYP3A4/5 contribute toward DDTC-Me thiono-oxidation by human liver microsomes. This study, in conjunction with others (Madan et al., Drug Metab. Dispos. 23:1153–1162, 1995), may help explain the variability in disulfiram's effectiveness as an alcohol deterrent.