Systemic delivery of β-blockers via transdermal route for hypertension

Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later.     

Does moxifloxacin alter oxidant status in the cornea? An experimental study

Objective: In this experimental study, we investigated the possible effects of intracameral moxifloxacin on oxidative stress parameters and endothelial cell morphology in corneal tissue.

Methods: In total, 30 rats were randomly assigned to three groups of 10 rats: the sham group (Group 1, n?=?10); the control group (Group 2), where balanced salt solution (BSS) was administered at a dose of 0.01?cc (n?=?10); and the treatment group (Group 3), where moxifloxacin was administered at a dose of 0.05?mg/0.01?cc (n?=?10). Total antioxidant status (TAS) and total oxidant status (TOS) in corneal tissue and blood samples were measured and the oxidative stress index (OSI) was calculated. Also, corneal tissue histopathology was evaluated with caspase-3 and caspase-8 staining. Apoptotic activity was also evaluated.

Results: In blood samples, TAS, TOS, and OSI levels were not statistically significantly different (all p?>?0.05). Compared with the sham and control groups, TOS and OSI levels in cornea tissue were significantly different in the moxifloxacin group (all p?p?>?0.05). Compared with the sham and control groups, apoptotic activity was higher in the moxifloxacin group, in both immunohistochemical staining for caspase-3 and caspase-8.

Conclusions: Intracameral moxifloxacin injection seems to be safe systemically, but it may have toxic effects on corneal tissues, as suggested by oxidative stress parameters and a histopathological evaluation.     

Pneumococcal infection in hospitalized patients: a four-year study in Malaysia

A total of 90 cases of pneumococcal infections were identified at a major referral hospital in Kuala Lumpur, Malaysia during a study period of four years. Pneumonia was the most common clinical presentation (41 cases) followed by meningitis (19 cases). Of 48 patients who were followed-up during the microbiology consultation round, 11 died, 9 were children below two years old. Capsular typing was carried out on 57 strains of Streptococcus pneumoniae isolated from blood and body fluids of 43 children and 14 adults. 38 strains isolated from pharyngeal specimens were also typed. Types 6A (11 strains), 6B (7 strains), 14 (8 strains) and 19A (8 strains) predominated in children. The strains from older patients comprised 3 isolates from cerebrospinal fluid (types 18B, 6B and 14), five from blood (4 strains, type 1 and 1 strain, type 4) and six from pus (1 strain, type 14, 3 strains type 23F and 2 strains type 34). The isolates from pharyngeal specimens belonged to capsular type similar to those implicated in infections. 90% of the types reported in this study are included in the 23 valent pneumococcal vaccines. Minimum inhibitory concentrations of penicillin, cefuroxime, chloramphenicol and rifampicin were determined for selected strains. 4.1% of isolates were resistant to penicillin (3/74), 4.5% to cefuroxime (2/44), 6.5% to chloramphenicol (3/46) and 14.6% to rifampicin (6/41).     

Spectroscopic characterization of the warfarin drug-binding site of folded and unfolded human serum albumin anchored on gold nanoparticles: effect of bioconjugation on the loading capacity

Protein-conjugated gold nanoparticles (AuNPs) have recently shown promising applications in medicine, owing to their inertness and biocompatibility. Herein, we studied the spectroscopy of 25 nm diameter AuNPs, coated with human serum albumin (HSA) as a model drug carrier. The morphology and coating of the AuNPs were examined using transmission electron microscopy and dynamic light scattering. Resonance energy transfer from the sole tryptophan of HSA (Trp214) to the AuNPs indicates a single layer of protein coverage. Using fluorescein (FL) to probe the warfarin drug-binding site in HSA revealed an increase in the HSA–FL binding by ∼4.5 times when HSA is anchored on the nanoparticle surface, indicating a rise in the loading capacity. Femtosecond transient absorption measurements of the surface plasmonic resonance band of the AuNPs show three ultrafast dynamics that are involved in the relaxation process. The three decay components were assigned to the electron–electron (∼400 fs), electron–phonon (∼2.0 ps) and phonon–phonon (200–250 ps) interactions. These dynamics were not changed upon coating the AuNPs with HSA which indicates the chemical and physical stability of the AuNPs upon bioconjugation. Chemical unfolding of the warfarin binding site with guanidine hydrochloride (GdnHCl) was studied by measuring the spectral shift in the Trp214 fluorescence and the appearance of the Tyr fluorescence. Unfolding was shown to start at [GdnHCl] ≥ 2.0 M and is complete at [GdnHCl] = 6.0 M. HSA anchored onto the nanoparticle surface shows more resistance to the unfolding effect which is attributed to the stability of the native form of HSA on the nanoparticle surface. On the other hand, upon complete unfolding, a larger red shift in the Trp214 fluorescence was observed for the HSA–AuNP complex. This observation indicates that, upon unfolding, the HSA molecule is still anchored on the AuNP surface in which subdomain IIA is facing the outer water molecules in the bulk solution as well as the hydration shell rather than the core of the nanoparticle. The current study is important for a better understanding of the physical and dynamical properties of protein-coated metal nanoparticles, which is expected to help in optimizing their properties for critical applications in nanomedicine.

This work investigates the steady-state and ultrafast spectroscopy of bioconjugated gold nanoparticles and the implications on the protein binding activity and drug-loading capacity.     

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment.We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1­75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.     

A comparative drug utilisation study of the treatment of diabetes in Malaysia and Australia

Background

Once a disease of developed countries, type 2 diabetes mellitus (T2DM) has become widespread worldwide. For people with T2DM, achievement of therapeutic outcomes demands the rational and quality use of medicine.

Aims

The primary aim of this study was to examine the prevalence of diabetes and prescribing patterns of anti-diabetic medications in Australia and Malaysia.

Methods

The most recent, publicly available, statistical reports (2004–2008) on the use of medicines published in Australia and in Malaysia were evaluated. Defined daily doses (DDDs/1,000 population/day) were derived from the reports and used to rank and compare individual drug use.

Results

There was an increasing trend in the prevalence of diabetes in Australia, although there is a greater predicted increase in prevalence for Malaysia. While drugs used for the treatment of diabetes were not the most highly used drugs in Australia, their use increased during the study period, from 42.64 to 48.61 DDD/1,000/day. Anti-diabetic drugs were the most frequently dispensed class of drugs in Malaysia. Although the total consumption of anti-diabetic drugs in Malaysia decreased between 2006 and 2007 (from 40.30 to 39.72), this was followed by a marked increase to 46.69 in 2008. There was a marked reduction in the dispensing of insulin in Malaysia from 2004 to 2007 (7.77 to 3.23).

Conclusion

The use of drugs to treat diabetes does not reflect the usage patterns found in Australia. Effective drug use reviews are required to ensure impartial access in middle- and low-income countries.     

Self-Rated Health Among Saudi Adults: Findings from a National Survey, 2013

Self-rated health reflects a person’s integrated perception of health, including its biological, psychological, and social dimensions. It is a predictor of morbidity and mortality. To assess the current status of self-rated health and associated factors in the Kingdom of Saudi Arabia, we analyzed data from the Saudi Health Interview Survey. We conducted a large national survey of adults aged 15 years or older. A total of 10,735 participants completed a standardized health questionnaire. Respondents rated their health with a five-point scale. Data on socio-demographic characteristics, chronic diseases, health-related habits and behaviors, and anthropometric measurements were collected. Associated factors of self-rated health were analyzed using a backward elimination multivariate logistic regression model. More than 77 % of respondents rated their health as excellent/very good. Female sex [odds ratio (OR) 1.52, 95 % confidence interval (CI) 1.24–1.88], decades of age (OR 1.35, 95 % CI 1.25–1.46), diagnosed diabetes mellitus (OR 1.54, 95 % CI 1.22–1.93), diagnosed hypercholesterolemia (OR 1.37, 95 % CI 1.06–1.79), diagnosed hypertension (OR 1.55, 95 % CI 1.22–1.96), number of other diagnosed chronic diseases (OR 1.69, 95 % CI 1.41–2.03), limited vigorous activity (OR 3.59, 95 % CI 2.84–4.53), need for special equipment (OR 2.62, 95 % CI 1.96–3.51), and more than 3 h of daily television/computer screen time (OR 1.59, 95 % CI1.11–2.29) were positively associated with poor/fair health. Smoking, obesity, and physical inactivity were not associated with self-reported health. We found that preventable risk factors are not associated with Saudis’ self-rated health. This optimistic perception of health poses a challenge for preventive interventions in the Kingdom and calls for campaigns to educate the public about the harm of unhealthy behaviors.