PREPARATION AND IN VITRO EVALUATION OF NAPROXEN AS A pH SENSITIVE OCULAR IN-SITU GEL

Objective: The aim of this study was to prepare and evaluate a pH sensitive ocular in-situ gel of Naproxen, to increase the ocular residence time. Methods: pH sensitive in situ gel formulations were prepared using different concentrations of Carbomer CB [0.5%, 0.6%, 0.7%] in combination with hydroxypropyl methylcellulose HPMC K40 [0.75%, 1%, 1.5%] or HPMC K100 [0.5%, 0.75%, 1%, 1.5%]. The prepared in situ gels were evaluated for appearance, pH, gelling capacity [sol-to-gel transition/in vitro], tonicity, viscosity, in vitro release studies, release kinetic analysis, and the selected formulas were subjected to rheological studies, and the finally selected formula was subjected to drug content, FT-IR studies, and ocular irritancy tests. Results: Increasing the concentration of the carbomer polymer improved the gelling capacity and gelation time, also the higher the viscosity and concentration of the hydrophilic HPMC polymer, the higher the viscosity of the formula, which affected the release, gelation capacity and time. The overall results showed that formula F10 [CB 0.7%, HPMC K100 0.75%] exhibited excellent pH-triggered in-situ gelation time, sustained the release of naproxen for 3 h’ time with a release rate of more than 90%. Conclusion: Ocular in situ gel of naproxen offers a potential dosage form to increase the residence time in the ocular cul de sac, decreasing the drug drainage, and increasing the effectiveness of the drug

A rate-insensitive linear viscoelastic model for soft tissues

It is well known that many biological soft tissues behave as viscoelastic materials with hysteresis curves being nearly independent of strain rate when loading frequency is varied over a large range. In this work, the rate-insensitive feature of biological materials is taken into account by a generalized Maxwell model. To minimize the number of model parameters, it is assumed that the characteristic frequencies of Maxwell elements form a geometric series. As a result, the model is characterized by five material constants: micro(0), tau, m, rho and beta, where micro(0) is the relaxed elastic modulus, tau the characteristic relaxation time, m the number of Maxwell elements, rho the gap between characteristic frequencies, and beta=micro(1)/micro(0) with micro(1) being the elastic modulus of the Maxwell body that has relaxation time tau. The physical basis of the model is motivated by the microstructural architecture of typical soft tissues. The novel model shows excellent fit of relaxation data on the canine aorta and captures the salient features of vascular viscoelasticity with significantly fewer model parameters

Studying the Effect of Variables on Acyclovir Microsponge

The aim of the present investigation was to develop a microsponge delivery system of acyclovir to control its release when applied topically thereby reducing dosing frequency and enhancement patient compliance. The microsponges were produced by the oil in oil emulsion solvent diffusion method. The effect of different formulation and process variables such as internal phase volume, polymer type, drug-polymer ratio, stirring speed and stirring duration on microsponge production yield, loading efficiency, particle size and in-vitro drug release was evaluated. The result showed that the microsponge F2 prepared from Eudrajet RS polymer had optimum physical properties regarding the loading efficiency of 99.71_+ 0.7% and production yield which was 85%. Also, F2 showed 66% drug release within 8 hours. Accordingly, the oil in oil emulsion solvent diffusion method is an effective technique to formulate microsponges with maximum production yield and loading efficiency for acyclovir

Medical students’ views about having different types of problem-based learning tutors

Background At Norwich Medical School, Year 3 or 4 medical students taking a year out of the 5-year undergraduate MBBS degree to do a master’s degree in clinical education worked as near-peer problem-based learning (PBL) tutors for students in Year 2. Peer-assisted learning has been shown to benefit both peer tutors and tutees; in this study, experiences of students with near-peer PBL tutors were compared to students with other types of PBL tutor. Methods Using existing student evaluation data, we compared student views about PBL tutor performance, PBL group functioning, and overall satisfaction with PBL learning experience according to whether their PBL tutor/s were (1) a single near-peer tutor (later-year MB BS student), (2) a single staff tutor, (3) multiple staff tutors, or (4) multiple newly qualified doctor tutors. Results Results indicated that students’ evaluation of tutor performance was more positive for near-peer PBL tutors compared to both groups of staff tutors for most areas evaluated. Additionally, students’ evaluation of overall satisfaction with PBL was more positive for near-peer PBL tutors compared to multiple staff tutors. Tutor performance for multiple staff tutors was evaluated less positively compared to both single staff and multiple newly qualified doctor groups. But there were no statistically significant differences between the four groups regarding PBL group functioning. Conclusion Near-peer PBL tutors perform comparably or better to staff PBL tutors in salient measures of tutor performance and group functioning. We conclude that medical students find near-peer PBL tutors to be an acceptable addition to the PBL tutor workforce

Relation between Fibrinogen Gene Polymorphisms and Microvascular Complications in Patients with Type 1 Diabetes: A Cross-Sectional Study

Objective: The present work aimed at genotyping fibrinogen beta (FGB) gene rs1800790 polymorphism and studying its relation to plasma fibrinogen (FG) level and microvascular complications in patients with type 1 diabetes (T1D). Materials and methods: The study included 100 patients with T1D attending outpatient clinic. Full history taking and physical examination were done. Routine biochemical parameters and plasma FG level were measured. Genotyping of rs1800790 FGB gene polymorphism was done. Results: The study included 52 females and 48 males with T1D with mean diabetes duration of 7.75 ± 2.95 years. Their mean age was 14.71 ± 3.24 years. Plasma FG level was significantly higher in patients with diabetic peripheral neuropathy (DPN) (p = 0.024) and in patients with diabetic kidney disease (DKD) (p = 0.036). No significant relation was found between plasma FG level and rs1800790 FGB gene polymorphism. The GA genotype of gene polymorphism was associated with 6 times increased risk of DPN. The dominant mode GA + AA was associated with a 4 and 7 folds increased risk of DPN in univariate and multivariate analysis respectively. A cut-off values of plasma FG > 348 mg/dL and > 358 mg/dL were able to differentiate patients with DPN and DKD respectively. Conclusions: In patients with T1D, the GA and the GA + AA genotypes of rs1800790 FGB gene polymorphism were significantly associated with DPN while plasma FG level was associated with DPN and DKD but not with rs1800790 FGB gene polymorphism

Pulsatile blood flow, shear force, energy dissipation and Murray's Law

BACKGROUND: Murray's Law states that, when a parent blood vessel branches into daughter vessels, the cube of the radius of the parent vessel is equal to the sum of the cubes of the radii of daughter blood vessels. Murray derived this law by defining a cost function that is the sum of the energy cost of the blood in a vessel and the energy cost of pumping blood through the vessel. The cost is minimized when vessel radii are consistent with Murray's Law. This law has also been derived from the hypothesis that the shear force of moving blood on the inner walls of vessels is constant throughout the vascular system. However, this derivation, like Murray's earlier derivation, is based on the assumption of constant blood flow. METHODS: To determine the implications of the constant shear force hypothesis and to extend Murray's energy cost minimization to the pulsatile arterial system, a model of pulsatile flow in an elastic tube is analyzed. A new and exact solution for flow velocity, blood flow rate and shear force is derived. RESULTS: For medium and small arteries with pulsatile flow, Murray's energy minimization leads to Murray's Law. Furthermore, the hypothesis that the maximum shear force during the cycle of pulsatile flow is constant throughout the arterial system implies that Murray's Law is approximately true. The approximation is good for all but the largest vessels (aorta and its major branches) of the arterial system. CONCLUSION: A cellular mechanism that senses shear force at the inner wall of a blood vessel and triggers remodeling that increases the circumference of the wall when a shear force threshold is exceeded would result in the observed scaling of vessel radii described by Murray's Law

Extension of Murray's law using a non-Newtonian model of blood flow

<p>Abstract</p> <p>Background</p> <p>So far, none of the existing methods on Murray's law deal with the non-Newtonian behavior of blood flow although the non-Newtonian approach for blood flow modelling looks more accurate.</p> <p>Modeling</p> <p>In the present paper, Murray's law which is applicable to an arterial bifurcation, is generalized to a non-Newtonian blood flow model (power-law model). When the vessel size reaches the capillary limitation, blood can be modeled using a non-Newtonian constitutive equation. It is assumed two different constraints in addition to the pumping power: the volume constraint or the surface constraint (related to the internal surface of the vessel). For a seek of generality, the relationships are given for an arbitrary number of daughter vessels. It is shown that for a cost function including the volume constraint, classical Murray's law remains valid (i.e. Σ<it>R</it>^{<it>c </it>}= <it>cste </it>with <it>c </it>= 3 is verified and is independent of <it>n</it>, the dimensionless index in the viscosity equation; <it>R </it>being the radius of the vessel). On the contrary, for a cost function including the surface constraint, different values of <it>c </it>may be calculated depending on the value of <it>n</it>.</p> <p>Results</p> <p>We find that <it>c </it>varies for blood from 2.42 to 3 depending on the constraint and the fluid properties. For the Newtonian model, the surface constraint leads to <it>c </it>= 2.5. The cost function (based on the surface constraint) can be related to entropy generation, by dividing it by the temperature.</p> <p>Conclusion</p> <p>It is demonstrated that the entropy generated in all the daughter vessels is greater than the entropy generated in the parent vessel. Furthermore, it is shown that the difference of entropy generation between the parent and daughter vessels is smaller for a non-Newtonian fluid than for a Newtonian fluid.</p

Subcoronary versus supracoronary aortic stenosis. an experimental evaluation

<p>Abstract</p> <p>Background</p> <p>Valvular aortic stenosis is the most common cause of left ventricular hypertrophy due to gradually increasing pressure work. As the stenosis develop the left ventricular hypertrophy may lead to congestive heart failure, increased risk of perioperative complications and also increased risk of sudden death. A functional porcine model imitating the pathophysiological nature of valvular aortic stenosis is very much sought after in order to study the geometrical and pathophysiological changes of the left ventricle, timing of surgery and also pharmacological therapy in this patient group.</p> <p>Earlier we developed a porcine model for aortic stenosis based on supracoronary aortic banding, this model may not completely imitate the pathophysiological changes that occurs when valvular aortic stenosis is present including the coronary blood flow. It would therefore be desirable to optimize this model according to the localization of the stenosis.</p> <p>Methods</p> <p>In 20 kg pigs subcoronary (n = 8), supracoronary aortic banding (n = 8) or sham operation (n = 4) was preformed via a left lateral thoracotomy. The primary endpoint was left ventricular wall thickness; secondary endpoints were heart/body weight ratio and the systolic/diastolic blood flow ratio in the left anterior descending coronary. Statistical evaluation by oneway anova and unpaired t-test.</p> <p>Results</p> <p>Sub- and supracoronary banding induce an equal degree of left ventricular hypertrophy compared with the control group. The coronary blood flow ratio was slightly but not significantly higher in the supracoronary group (ratio = 0.45) compared with the two other groups (subcoronary ratio = 0.36, control ratio = 0.34).</p> <p>Conclusions</p> <p>A human pathophysiologically compatible porcine model for valvular aortic stenosis was developed by performing subcoronary aortic banding. Sub- and supracoronary aortic banding induce an equal degree of left ventricular hypertrophy. This model may be valid for experimental investigations of aortic valve stenosis but studies of left ventricular hypertrophy can be studied equally well by graduated constriction of the ascending aorta.</p