Molecules, whose p
K
a values can be easily fine-tuned by their microenvironment, are expected to be profoundly affected by the heterogeneous environments of membranes. Membrane parameters can have a ...strong effect in choosing a particular structural form of a molecule for incorporation/interaction. A case study has been presented for piroxicam, a non-steroidal anti-inflammatory drug of oxicam group, whose targets are cyclooxygenases, which are membrane active proteins. The structural dynamism of piroxicam is reflected in the ease with which it can switchover or convert from one prototropic form to the other guided by its environment. In this work we have studied the effect of varying hydrophobic chain length and surface charges in fine-tuning the interaction of piroxicam with micelles. Interaction of piroxicam with three types of micelles with identical negatively charged head groups and varying tail lengths viz., sodium dodecyl sulfate (S12S), sodium decyl sulfate (S10S) and sodium octyl sulfate (S8S) shows that there is a shift in the apparent p
K
a in the direction that favors the switchover or conversion from the anionic form to the global neutral form. The binding constants of piroxicam with three micelles show a linear dependence on chain length. Interaction was also studied with micelles having oppositely charged head groups and different chain lengths viz., dodecyl
N,
N,
N-trimethyl ammonium bromide (DTAB) and cetyl
N,
N,
N-trimethyl ammonium bromide (CTAB). For micelles having identical chain lengths but oppositely charged head groups viz., S12S and DTAB, p
K
a shifts in two opposite directions compared to that in the absence of any surfactant. This is expected when electrostatic force is the only driving force. This case study demonstrates the effect of hydrophobic chain length and surface charges in fine-tuning the equilibrium between different structural forms of piroxicam. Our results also imply that for structurally dynamic drugs like piroxicam the nature of the biomembranes, characterized by different membrane parameters, should play a crucial role in choosing a particular structural form of the drug that will be finally presented to their targets.
A circular plate kept zero initial temperature is heated for a certain interval of time over a concentric circular region of the upper face. Deflection is obtained by using Laplace transform ...technique. Taking the plate material to be aluminium, central deflection is obtained for several values of time and the results shown graphically.
This is a basic text of Management Accountacy that approaches the subject from the vantage point of various disciplines - management, financial and cost accountancy, and mathematics, among others. ...Each topic is presented in detail with the help of illustrations and sample problems and solutions.
Non-steroidal anti-inflammatory drugs (NSAIDs) of oxicam group are not only effective as anti-inflammatory agents but also show diverse functions. Their principal targets are cyclooxygenases, which ...are membrane-associated enzymes. To bind with the targets these drugs have to pass through the membrane and hence their interactions with biomembranes should play a major role in guiding their interactions with cyclooxygenases. Here we have studied the interactions of three NSAIDs of oxicam group viz. piroxicam, meloxicam and tenoxicam with micelles having different headgroup charges, as simple membrane mimetic systems. Spectroscopic methods have been used to understand the interaction of these drugs with Cetyl
N,
N,
N-trimethyl ammonium bromide (cationic), Sodium dodecyl sulphonate (anionic) and Triton X-100 (neutral) micelles. Our results demonstrate that the environment of the drugs i.e. the nature of the micelles plays a decisive role in choosing a specific prototropic form of the drugs for incorporation. Additionally it induces a switch over or change between different prototropic forms of piroxicam, which is correlated with the change in their reactivities in presence of different surface charges, given by the change in p
K
a values. These results together, indicate that in vivo, the diverse nature of biomembranes might play a significant role in choosing the particular form of oxicam NSAIDs that would be presented to their targets.
Small unilamellar vesicles (SUVs) formed by the dimyristoylphosphatidylcholine (DMPC), a phospholipid; serve as a membrane mimetic system that can be used to study the effect of absence of net ...surface charges on drug–membrane interaction. The targets of non-steroidal anti-inflammatory drugs (NSAIDs) are cyclooxygenases, which are membrane active enzymes. Hence, to approach their targets NSAIDs have to pass different bio-membranes. Different membrane parameters are expected to guide the first level of interaction of these drugs before they are presented to their targets. Our earlier studies have demonstrated the crucial role of surface charges of membrane mimetic systems like micelles and mixed micelles on the interaction of oxicam NSAIDs. In order to see whether net surface charges of membranes are essential for the interaction of oxicam NSAIDs, we have studied the incorporation of two oxicam NSAIDs, viz., piroxicam and meloxicam in DMPC vesicles using the intrinsic fluorescence properties of the drugs. To see whether different prototropic forms of the drugs can interact with DMPC vesicles, studies were carried out under different pH conditions. Transmission electron microscopy (TEM) was used to characterize the SUVs those were formed at different pH values. Steady state fluorescence anisotropy measurements show that both forms of the two drugs, viz., global neutral and anion can be incorporated into the DMPC vesicles. Partition coefficient (
K
P) between DMPC and the aqueous buffer used has been calculated in all cases from fluorescent intensity measurements. The
K
P values for the neutral and anionic forms of piroxicam are 219.0 and 25.8, respectively, and that for meloxicam are 896.7 and 110.2, respectively. From the
K
P values it is evident that irrespective of the nature of the prototropic forms, meloxicam has a higher
K
P value than piroxicam. This correlates with the previously calculated log
K
P values between
n-octanol and aqueous phase, which demonstrates that in absence of net surface charges of DMPC vesicles the hydrophobic interaction is the principal driving force for incorporation. Our results imply that for bio-membranes having no net surface charges hydrophobic effect plays a principal role to guide these NSAIDs to their targets.
Transmission of HIV-1 is predominantly by heterosexual contact in sub-Saharan Africa, where sexually transmitted diseases (STDs) are also common. Epidemiological studies suggest that STDs facilitate ...transmission of HIV-1, but the biological mechanism remains unclear. We investigated the hypothesis that STDs increase the likelihood of transmission of HIV-1 through increased concentration of the virus in semen.
HIV-1 RNA concentrations were measured in seminal and blood plasma from 135 HIV-1-seropositive men in Malawi; 86 had urethritis and 49 controls did not have urethritis. Men with urethritis received antibiotic treatment according to the guidelines of the Malawian STD Advisory Committee. Samples were analysed at baseline and at week 1 and week 2 after antibiotic therapy in urethritis patients, and at baseline and week 2 in the control group.
HIV-1-seropositive men with urethritis had HIV-1 RNA concentrations in seminal plasma eight times higher than those in seropositive men without urethritis (12·4
vs 1·51×10
4 copies/mL, p=0·035), despite similar CD4 counts and concentrations of blood plasma viral RNA. Gonorrhoea was associated with the greatest concentration of HIV-1 in semen (15·8×10
4 copies/mL). After the urethritis patients received antimicrobial therapy directed against STDs, the concentration of HIV-1 RNA in semen decreased significantly (from 12·4×10
4 copies/mL to 8·91×10
4 copies/mL at 1 week p=0·03 and 4·12×10
4 copies/mL at 2 weeks p=0·0001). Blood plasma viral RNA concentrations did not change. There was no significant change in seminal plasma HIV-1 RNA concentrations during the 2-week period in the control group (p=0·421).
These results suggest that urethritis increases the infectiousness of men with HIV-1 infection. HIV-1-control programmes, which include detection and treatment of STDs in patients already infected with HIV-1, may help to curb the epidemic. Targeting of gonococcal urethritis may be a particularly effective strategy.
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