Role of Yoga as an Adjunct in the Management of Migraine Headache-Current Status and Future Indications.

Migraine headache is a painful, disabling condition afflicting 7% of the population. The long-term effort of coping with a chronic headache disorder predisposes the individual to other psychiatric illnesses, ischemic cerebrovascular disease as well as medicine overuse headache. The use of nonpharmacological methods to reduce the stress and pain associated with headache can improve the overall quality of life and reduce the burden of the disease. To examine the utility of yoga as an adjunct to pharmacological treatment of migraine headache. The review article is based on the secondary literature collected through the Google Scholar database between the years 2010 and 2020. Several themes were identified regarding the burden of migraine/headache and the need for the integration of yoga into the existing healthcare system. Despite the limitations and the need for greater scientific rigor, there have been consistent reports of the beneficial effects of yoga in the reduction of stress, anxiety, depression, and an enhanced quality of life, as well as better pain management in chronic diseases. Studies on the role of yoga in the treatment of migraine have been few in number. They have consistently shown that yoga can be a valuable adjunct to the existing pharmacological interventions in the management of migraine headache. In recent years, the Indian government has made enormous strides in establishing yoga outreach programs throughout the country. The need of the hour is to integrate evidence-based yoga with the wellness centers and noncommunicable diseases treatment plan. It can help to reduce the burden on the existing health care resources.

Thermodynamics of metal ion binding. 2. Metal ion binding by carbonic anhydrase variants.

The ability to construct molecular motifs with predictable properties in aqueous solution requires an extensive knowledge of the relationships between structure and energetics. The design of metal binding motifs is currently an area of intense interest in the bioorganic community. To date synthetic motifs designed to bind metal ions lack the remarkable affinities observed in biological systems. To better understand the structural basis of metal ion affinity, we report here the thermodynamics of binding of divalent zinc ions to wild-type and mutant carbonic anhydrases and the interpretation of these parameters in terms of structure. Mutations were made both to the direct His ligand at position 94 and to indirect, or second-shell, ligands Gln-92, Glu-117, and Thr-199. The thermodynamics of ligand binding by several mutant proteins is complicated by the development of a second zinc binding site on mutation; such effects must be considered carefully in the interpretation of thermodynamic data. In all instances modification of the protein produces a complex series of changes in both the enthalpy and entropy of ligand binding. In most cases these effects are most readily rationalized in terms of ligand and protein desolvation, rather than in terms of changes in the direct interactions of ligand and protein. Alteration of second-shell ligands, thought to function primarily by orienting the direct ligands, produces profoundly different effects on the enthalpy of binding, depending on the nature of the residue. These results suggest a range of activities for these ligands, contributing both enthalpic and entropic effects to the overall thermodynamics of binding. Together, our results demonstrate the importance of understanding relationships between structure and hydration in the construction of novel ligands and biological polymers.

The effects of polyethyleneglycol (PEG)-derived lipid on the activity of target-sensitive immunoliposome.

In this study, serum stability and target-sensitivity of phosphatidylethanolamine (PE) immunoliposomes prepared with dioleoylphosphatidylethanolamine (DOPE), HYB-241 monoclonal antibody that targets p-glycoproteins, and various levels of polyethyleneglycol 2000 dioleoylphosphatidylethanolamine (PEG(2000)-DOPE) were determined. Incubation of calcein-laden pegylated immunoliposomes prepared with different levels of PEG(2000)-DOPE (0.3, 0.5 and 1.0 mol%) with p-glycoprotein rich bovine brain microvessel endothelial cells in 10% serum cell culture medium, all resulted in time-dependent release of calcein from the liposomes. The release of calcein was greatest for immunoliposomes prepared with 0.3 mol% PEG(2000)-DOPE (66% in 1 h). Contrarily, the release of calcein from the other two immunoliposomes reached only approximately 10-3% after same period of incubation. When serum-induced leakage of calcein was investigated for the above liposome preparations, liposomes prepared with 0.3 and 0.5 mol% PEG(2000)-DOPE had the highest leakage level (10% in 1 h). Contrarily, the release of calcein from liposomes prepared with 1.0 mol% PEG(2000)-DOPE reached only 3% after same period of incubation. Together, it would appear that release of calcein from the immunoliposomes prepared with 0.3 mol% PEG(2000)-DOPE is a result of both serum-induced and target-induced destabilization of liposomes. The net release of calcein due to target-induced destabilization of liposomes is calculated to be at approximately 56%. In contrast, there is no target-induced leakage of calcein from immunoliposomes prepared with either 0.5 or 1.0 mol% PEG(2000)-DOPE.

Active transport of fentanyl by the blood-brain barrier.

Previous studies have shown that uptake of the lipophilic opioid, fentanyl, by pulmonary endothelial cells occurs by both passive diffusion and carrier-mediated processes. To evaluate if the latter mechanism also exists in brain endothelium, transport of [3H]fentanyl was examined in primary cultured bovine brain microvessel endothelial cell (BBMEC) monolayers. Uptake of fentanyl appears to occur via a carrier-mediated process as uptake of [3H]fentanyl by BBMECs was significantly inhibited in a dose-dependent manner by unlabeled fentanyl. Fentanyl uptake was also significantly inhibited by either 4 degrees C or sodium azide/2-deoxyglucose, suggesting that carrier-mediated uptake of fentanyl was an active process. Fentanyl was also tested to determine whether it might be a substrate of the endogenous blood-brain barrier efflux transport system, P-glycoprotein (P-gp). Release of [3H]fentanyl or rhodamine 123, a known substrate of P-gp, previously loaded in the BBMECs was studied in the presence or absence of either fentanyl or verapamil, a known competitive inhibitor of P-gp. Both fentanyl (10 microM) and verapamil (100 microM) decreased release of rhodamine 123 from BBMECs, indicating that fentanyl is a substrate of P-gp in the BBMECs. This was further supported by the observation that uptake of [3H]fentanyl was significantly increased in Mg2+-free medium, a condition known to reduce P-gp activity. However, release of [3H]fentanyl was significantly increased when incubated with either unlabeled fentanyl or verapamil. These results suggest that the active P-gp-mediated extrusion of fentanyl in these cells is overshadowed by an active inward transport process, mediated by an as yet unidentified transporter. In addition, verapamil was shown to be a substrate of both P-gp and the fentanyl uptake transporter.