Multifunctional gallium doped bioactive glasses: a targeted delivery for antineoplastic agents and tissue repair against osteosarcoma.

Osteosarcoma (OS) is the mostly commonly occurring primary bone cancer. Despite comprehensive treatment programs including neoadjuvant chemotherapy and tumour resection, survival rates have not improved significantly since the 1970s. Survival rates are dramatically reduced for patients who suffer a local recurrence. Furthermore, primary bone cancer patients are at increased risk of bone fractures. Consequently, there is an urgent need for alternative treatment options. In this paper we report the development of novel gallium doped bioactive glass that selectively kill bone cancer cells whilst simultaneously stimulating new bone growth. Here we show, using a combination of 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide, LIVE/DEAD assays and image analysis, that bioactive glasses containing gallium oxide are highly toxic and reduce both the proliferation and migration of bone cancer cells (Saos-2) in a dose dependant manner. Glasses containing 5 mol% gallium oxide reduced the viability of OS cells by 99% without being cytotoxic to the non-cancerous normal human osteoblasts (NHOst) control cells. Furthermore, Fourier transform infrared and energy-dispersive x-ray spectroscopy results confirmed the formation of an amorphous calcium phosphate/hydroxyapatite like layer on the surface of the bioactive glass particulates, after 7 d incubating in simulated body fluid, indicating the early stages of bone formation. These materials show significant potential for use in bone cancer applications as part of a multimodal treatment.

Formulation and optimization of coated PLGA - Zidovudine nanoparticles using factorial design and in vitro in vivo evaluations to determine brain targeting efficiency.

In the current study zidovudine loaded PLGA nanoparticles were prepared, coated and further investigated for its effectiveness in brain targeting. IR and DSC studies were performed to determine the interaction between excipients used and to find out the nature of drug in the formulation. Formulations were prepared by adopting 2(3) factorial designs to evaluate the effects of process and formulation variables. The prepared formulations were subjected for in vitro and in vivo evaluations. In vitro evaluations showed particle size below 100 nm, entrapment efficiency of formulations ranges of 28-57%, process yield of 60-76% was achieved and drug release for the formulations were in the range of 50-85%. The drug release from the formulations was found to follow Higuchi release pattern, n-value obtained after Korsemeyer plot was in the range of 0.56-0.78. In vivo evaluations were performed in mice after intraperitoneal administration of zidovudine drug solution, uncoated and coated formulation. Formulation when coated with Tween 80 achieved a higher concentration in the brain than that of the drug in solution and of the uncoated formulation. Stability studies indicated that there was no degradation of the drug in the formulation after 90 days of preparation when stored in refrigerated condition.

Days lost due to disability of diclofenac-induced adverse drug reactions.

UNLABELLED: Disability Adjusted Life Years (DALY) is a widely used measure to quantify the burden of diseases or illness. DALYs for a disease is calculated as the sum of the Years of Life Lost (YLL) due to premature mortality in the population and the equivalent healthy Years Lost due to Disability (YLD). The only difference from the YLD and Days Lost due to Disability (DLD) calculation is that instead of considering the duration of Adverse Drug Reaction (ADR) in years, it is calculated in days. OBJECTIVE: DLD was measured for diclofenac tablets to prepare the ADR profile. METHODS: The study was done on the patients (18-65 years old) attending the community pharmacy at Kasaragod district, South India, with prescription of diclofenac tablets. Patients reported ADRs on their next visit to the pharmacy or they had called to the provided phone number and reported it. Disability Weight (DW) was calculated in an analogue scale from 0-1. Zero represent complete health and 1 represent death or equivalent condition. DW was multiplied with occurrence and duration of ADRs in days. RESULTS: About 943 patients received diclofenac tablets in 1000 prescriptions were successfully followed up for possible, probable and definite ADRs. A total of 561 reactions reported in 2010 for diclofenac tablet in the study population. There were 34 different types of ADRs under 12 physiological systems/organs. Most common reactions were on gastrointestinal (GI) system (48%), followed by skin (14%), Central Nervous System (10%), renal (7%), and cardiovascular (7%). Abdominal pain, cramps or flatulence was the highest occurring GI ADR (107), followed by 43 rashes, 42 nausea/vomiting, 37 indigestion, 34 peptic ulcers, 31 edema etc. DLD for peptic ulcer was considerably high (0.078) per 1000 of the study population on diclofenac. The most damaging ADR were peptic ulcer with or without perforation, followed by rash 0.036 DLD and edema 0.027 DLD. There was considerable DLD by acute renal failure (0.012) Steven-Johnson syndrome (0.013) even though few cases were reported. CONCLUSIONS: Diclofenac has a complex adverse drug profile. Around 34 types of reactions were reported. Diclofenac was widely prescribed because of the experiential belief of comparative safety with other NSAIDs. The study shows the importance of pharmacovigilance even on the most prescribed medicine. Most disabling ADR for the study population was peptic ulcer with or without perforation. YLD or DLD are useful measures of calculating disability caused by ADRs. Future studies could focus on improving the usefulness & precision of DLD.

Ligninolytic and antioxidative enzymes of a marine cyanobacterium Oscillatoria willei BDU 130511 during Poly R-478 decolourization.

Removal of combined nitrogen and addition of Poly R-478 to the growth medium enhanced oxidative stress, and altered the activities of ligninolytic enzymes of Oscillatoria willei BDU 130511. The activities of ligninolytic and antioxidative enzymes (LiP-like, LAC, PPO, SOD, POD, CAT, and APX) were increased upon nitrogen limitation and dye supplementation. The metabolic enzymes tested (GR, GPX, EST, and MDH) showed differential expressions under varied growth conditions. Up on nitrogen limitation, O. willei BDU 130511 showed enhanced ligninolytic activity as shown by alpha-keto-gamma-methylthiolbutyric acid (KTBA) oxidation and increased H(2)O(2) production. The organism decolourized 52% of Poly R-478 due to partial degradation and adsorption of dye particles from dye-added medium after 7 days of growth. This manuscript discusses the responses of ligninolytic and antioxidative enzymes of O. willei BDU 130511 during Poly R-478 decolourization/degradation, and the organism's potential in bioremediation.

Intranasal delivery of tenoxicam in rat.

Intranasal delivery of tenoxicam was studied in male rats on single dose administration of 0.36 mg/rat and compared with intravenous administration. Tenoxicam plasma levels were determined by RP-HPLC method with UV detection that employed piroxicam as an electroactive internal standard in the analysis. Following intravenous administration the area under the plasma concentration curve was 2452.17+/-86.49 ng h/ml as compared to 1357.69+/-102.36 ng h/ml following intranasal dosing. This corresponds to a relative bioavailability of 55.36%.

Estimation of total body water in very-low-birth-weight infants by using anthropometry with and without bioelectrical impedance and H2[(18)O].

The usefulness of bioelectrical impedance (BI) with anthropometry to measure total body water (TBW) was evaluated in very-low-birth-weight (VLBW) infants. A specific regression equation to measure TBW in a VLBW population was developed by simultaneously using the H2[(18)O] dilution method and BI in 12 infants with a gestational age of 24-30 wk and weighing <1200 g at birth. After an oral dose of H2[(18)O], the tracer dilution was measured in expired carbon dioxide. BI measurements were made with a model BIA-101 apparatus (RJL Systems, Detroit). Electrodes were placed in the standard position as well as proximally on the leg and the forearm. The best correlation was observed between body weight and TBW (r = 0.989). For BI, the best correlation was obtained when gestational age was used as a covariable along with body weight and crown-heel length (r = 0.985). The correlation was comparable with proximal electrode placement (r = 0.985). The new correlation was evaluated in 6 infants weighing < 1008 g. A significant correlation between BI and H2[(18)O]-measured TBW was observed (r = 0.988). Published regression equations for infants consistently gave higher estimates of TBW in another group of 14 infants weighing <1200 g than did the new correlations. TBW represented 84-95% of body weight in these VLBW infants. TBW could be computed simply from body weight alone. Use of BI and length as covariables did not add significantly to the estimate of TBW in VLBW infants.

Detection of left anterior descending coronary artery stenosis in patients with left bundle branch block: exercise, adenosine or dobutamine imaging?

OBJECTIVES: This study sought to assess the diagnostic value of myocardial perfusion imaging during exercise and pharmacologic stress in patients with left bundle branch block. BACKGROUND: Patients with left bundle branch block often have septal perfusion defects during exercise perfusion tomography that mimic defects caused by coronary artery disease. These defects appear to be less frequent during pharmacologic stress using adenosine or dipyridamole. Data are scantly on the value of dobutamine tomography in these patients. METHODS: We studied 383 consecutive patients with left bundle branch block referred for perfusion scintigraphy over a 5-year span. Perfusion tomography was performed in conjunction with exercise in 206 patients, adenosine in 127 and dobutamine in 50. Coronary angiography was performed within 1 month of the nuclear study in 77, 50 and 27 patients, respectively. RESULTS: Exercise, adenosine and dobutamine tomography had similar sensitivity and specificity for the detection of > 50% stenosis in the left circumflex (74% and 96%; 50% and 100%; 63% and 91%, respectively) and right coronary arteries (96% and 86%; 82% and 91%; 79% and 100%, respectively) and similar sensitivity for left anterior descending coronary artery stenosis (88%, 79% and 100%, respectively). However, the false-positive rate for septal defects was higher by exercise tomography (26 [46%] of 57) than by pharmacologic methods (5 [10%] of 48, p < 0.001), and there was no significant difference between adenosine (4 [11%] of 35) and dobutamine (1 [8%] of 13, p = 0.7). The specificity and predictive value of a positive test response for left anterior descending coronary artery stenosis were 36% and 51% for exercise compared with 81% and 85% for adenosine (p < or = 0.001) and 80% and 90% for dobutamine (p < 0.05), respectively. CONCLUSIONS: In patients with left bundle branch block, pharmacologic stress is more specific than exercise tomography in the diagnosis of left anterior descending coronary artery stenosis. Dobutamine and adenosine tomography appear to be equally specific in these patients.

Gastropleural fistula: an unusual cause of intractable postoperative nausea and vomiting.

Gastropleural fistula is an uncommon finding (1). Gastropleural fistulae have been reported after pulmonary resection (1), perforated paraesophageal hernia (2), perforated malignant gastric ulcer at the fundus, and gastric bypass operation for morbid obesity. We present a case of gastropleural fistula that resulted acutely from intractable postoperative nausea and vomiting after ambulatory knee arthroscopic surgery under general anesthesia.

Malposition of transvenous pacing lead in the left ventricle.

Transvenous pacemaker lead malposition in the left ventricle occurs rarely and requires a high index of suspicion for proper diagnosis. The case of a woman with unintentional lead placement in the left ventricle is presented. She had two episodes of transient neurologic deficits, possible secondary to embolic events, and was started on oral anticoagulants. Chest x-ray and electrocardiogram (ECG) suggested pacemaker lead malposition and transesophageal echocardiography revealed sinus venosus atrial septal defect. The lead was shown to cross the atrial septum and the mitral valve to the left ventricle. The malpositioned lead was successfully removed from the left ventricle at the time of surgical repair of the atrial septal defect. The potential value of 12-lead ECG, chest x-ray, posteroanterior and lateral views, and echocardiography in the diagnosis of pacemaker lead malposition are discussed and recommendations to avoid this complication at the time of pacemaker implant are outlined.

Long-term follow-up of heart transplant recipients requiring permanent pacemakers.

BACKGROUND: Permanent pacemaker implantation after heart transplantation is contentious. Indications for these devices in this population are uncertain. The goals of this project were to (1) analyze the time course of donor sinus node dysfunction and atrioventricular block after heart transplantation; (2) evaluate which selected parameters (donor age, ischemic time, heart rate before pacer insertion, and number of rejection episodes) might relate to persistent permanent pacing need, and (3) assess pacemaker complications during follow-up. METHODS: A retrospective analysis of pacemaker implantations (22 cases) was performed in 286 consecutive heart transplantations performed between February 1984 and April 1994 at The Methodist Hospital and Baylor College of Medicine, Houston, Texas. RESULTS: Permanent pacemakers were inserted early after transplantation in 19 patients (mean 24 days); 14 pacemakers were for sinus node dysfunction (bradycardia in five, sinus arrest with junctional escape in eight, and optimization of hemodynamics in one). Symptomatic complete heart block prompted insertion late in two patients (3 and 47 months), and symptomatic sinus pause was the indication for late insertion in one. Recipient mean age was 52.4 years, with mean donor age 29.7 years in patients with pacemakers. By 3 months, 13 of 19 patients receiving pacemakers early (mean preinsertion heart rate 58.3 beats/min) became pacer independent with subsequent mean intrinsic heart rate of 97 beats/min. Recipient or donor age, ischemic time, and rejection episodes did not appear related to long-term pacing need early or late after transplantation. CONCLUSIONS: Inferences from these observations include the fact that many patients with early sinus node dysfunction and bradycardia are not pacer dependent at 3 months. However, those with atrioventricular block early appear to require long-term pacing support. However, the possibility that more aggressive and long-term oral chronotropic medication use after transplantation would obviate early permanent pacemaker need is not addressed. Finally, prospective clinical trials are necessary to precisely characterize benefit of permanent pacemakers and define optimal pacing modes after heart transplantation.

Influence of anticardiolipin antibodies on immediate patient outcome after myocardial infarction.

AIMS: To determine whether the presence of anticardiolipin antibodies in patients with suspected myocardial infarction is predictive of complications during hospital stay or after discharge. METHODS: Anticardiolipin antibodies were serially measured in a cohort of 111 patients, from the time of admission to the coronary care until till eight weeks after discharge. Associations with fatal and non-fatal cardiac complications were documented. RESULTS: The incidence of raised titres of IgG and IgM anticardiolipin antibodies (ACA) in patients with myocardial infarction was comparable with that in patients with ischaemic heart disease. ACA titres in patients with a previous myocardial infarct were not significantly different from those found in patients without a previous history of infarction. Over the period of the study, ACA titres in the myocardial infarct group did not change significantly from those recorded on admission, nor did those patients with raised ACA titres have a higher prevalence of complications in hospital or in the early period after discharge. CONCLUSIONS: There is no evidence that patients with an acute or previous myocardial infarct have higher ACA titres than those found in patients with ischaemic heart disease. Raised ACA titres soon after myocardial infarction do not influence immediate patient outcome.

Nephrotic-range proteinuria associated with right atrial myxoma.

A case of right atrial myxoma presenting with right heart failure and proteinuria is described. Proteinuria was variable and this corresponded with the degree of systemic venous congestion. On one occasion the proteinuria was within the nephrotic range. There was no evidence of intrinsic renal pathology. The right heart failure and proteinuria resolved after tumour removal, suggesting that the etiology of urinary protein loss was a reversible increase in glomerular permeability.