Patient perspectives on current and potential therapies and clinical trial approaches for cocaine use disorder.

Background: Cocaine use disorder (CUD) is characterized by the continued use of cocaine despite serious impacts on life. This study focused on understanding the perspective of individuals with current CUD, individuals in CUD remission, and their supporters regarding current therapies, future therapies, and views on clinical trials for CUD. Methods: The online bulletin board (OBB) is a qualitative tool where participants engage in an interactive discussion on a virtual forum. Following completion of a screening questionnaire to determine eligibility, individuals in CUD remission and their supporters logged in to the OBB and responded to questions posed by the moderator. Individuals with current CUD participated in a one-time virtual focus group. Results: All individuals with current CUD and 94% of those in CUD remission reported a diagnosis consistent with CUD or substance use disorder during screening. Individuals with current CUD and their supporters were recruited from the United States (US). Individuals in CUD remission were recruited from five countries, including the US. Individuals with current CUD reported hesitation about seeking treatment due to stigma, a lack of privacy, and being labeled as a drug seeker; barriers to therapy included time, cost, and a lack of privacy. Participants wanted a safe therapy to stop cravings and withdrawal symptoms. Seven clinical trial outcomes, including long-term abstinence and craving control, were suggested based on collected insights. Conclusion: This study can help inform the design of clinical trials and emphasize the need for effective, safe, and accessible therapies. Recruiting participants will require significant trust building.

PPAR-γ and Akt regulate GLUT1 and GLUT3 surface localization during Mycobacterium tuberculosis infection.

The success of Mycobacterium tuberculosis (Mtb) as a pathogen stems from its ability to manipulate the host macrophage towards increased lipid biogenesis and lipolysis inhibition. Inhibition of lipolysis requires augmented uptake of glucose into the host cell causing an upregulation of the glucose transporters GLUT1 and GLUT3 on the cell surface. Mechanism behind this upregulation of the GLUT proteins during Mtb infection is hitherto unknown and demands intensive investigation in order to understand the pathways linked with governing them. Our endeavor to investigate some of the key proteins that have been found to be affected during Mtb infection led us to investigate host molecular pathways such as Akt and PPAR-γ that remain closely associated with the survival of the bacilli by modulating the localization of glucose transporters GLUT1 and GLUT3.

Ultrastructural observations on Raillietina echinobothrida exposed to crude extract and active compound of Securinega virosa.

Securinega virosa has been used traditionally by the natives of Mizoram, India, to control intestinal worm infections. In the present study, the crude ethanol extract of the plant and its active component virosecurinine were tested in vitro on Raillietina echinobothrida to evaluate its potential anthelmintic efficacy and ultrastructural changes. The test parasites were exposed to different concentrations of the plant extract, active compound virosecurinine and reference drug praziquantel. Scanning and transmission electron microscopic observations on the paralyzed worms revealed wide scale destruction of the tegument with intense vacuolization of the syncytium and swellings of the basal lamina accompanied by deformities in the cell organelles. Extensive structural alteration of tegument indicates that the plant extract and its active component alter membrane permeability of the parasite leading to paralysis and subsequent death, as confirmed by in vitro tests.

Effects of Acacia oxyphylla and Securinega virosa on functional characteristics of Raillietina echinobothrida (Phylum: Platyhelminthes; Class: Cestoidea), a poultry cestode parasite.

The histochemical distribution and quantification of alkaline phosphatase, acid phosphatase, and adenosine triphosphatase have been investigated in the adult cyclophyllidean cestode, Raillietina echinobothrida after treatment with crude ethanol extract of traditionally used medicinal plants Acacia oxyphylla and Securinega virosa. Estimation of free amino acid pool and vital trace elements like calcium and magnesium were also performed to study the effect of the plant extracts on the parasite. A decrease in the levels of phosphatases and trace elements was noticed in the treated parasites when compared to control groups. At the same time, a lot of disparity was noted in the free amino acid pool as the levels of many amino acids were seen to increase or decrease in relation to the levels observed in control parasites. Role of phyto-products in the changed physiology of cestode and their possible chemotherapeutic targets are discussed.

Electron microscopic observations on the alterations of tegumental surface of Raillietina echinobothrida treated with root-peel extract of Potentilla fulgens.

Potentilla fulgens, a member of the family Rosaceae, has been known since ancient times in Northeast India for its antiparasitic, antitumour and antidiabetic properties. The crude ethanolic extract of the plant was assayed against Raillietina echinobothrida, the intestinal cestode parasite of domestic fowl to authenticate the putative anthelmintic efficacy and cestocidal potential in particular of the plant. Treatment of the worm in-vitro with 25, 50 and 100 mg of crude extract per ml of phosphate buffered saline caused paralysis leading to death taking 4.02-4.20, 3.05-3.75 and 2.05-2.83 h respectively. Scanning electron microscopic observations on treated worms revealed deformation of surface architecture, particularly in scolex and surface microtriches. Severe distortion and disorganization of the tegumental and subtegumental layer along with cytoplasmic organelle was also observed under transmission electron microscope. The possible use of the plant as a potential anthelmintic against cestode parasite is discussed.

Antiparasitic activity of methanolic extract of Acacia oxyphylla (Leguminosae) against Raillietina echinobothrida.

Acacia oxyphylla has been used traditionally by the natives of Mizoram against intestinal worm infections. In the present study, the crude methanolic extract of the plant was tested in vitro on the cestode parasite Raillietina echinobothrida to evaluate its potential anthelmintic efficacy. The test parasites were exposed to varying concentrations of the plant extract in phosphate buffered saline and they all slipped into a flaccid paralytic state at varying periods of time post incubation. Ultrastructural observations on the paralysed worms revealed wide scale destruction of the parasite tegument with intense vacuolization of the syncytium and swellings of the basal lamina accompanied by deformities in the cell organelles. To determine the exact mode of action of the botanicals on the parasite body surface, the tegumental enzymes viz. acid phosphatase (AcPase), alkaline phosphatase (AlkPase) and adenosine triphosphatase (ATPase) were investigated. A prominent decrease in the phosphatase activity, in comparison to the untreated control parasites was noticeable. In view of the alterations in the structural and functional integrity of the tegument, occurring in the treated parasites, it may be assumed that the changes transpire because of a compromise in the permeability of the tegument under the influence of the test plant-derived active chemical principles.

Ultrastructural observations on Fasciolopsis buski and its alterations caused by shoot extract of Alpinia nigra.

The ultrastructural alterations in the tegument of Fasciolopsis buski in response to incubation in the alcoholic extract of Alpinia nigra were evaluated using transmission electron microscopy. The body tegument of the trematode is composed of an external syncytial layer, musculature, and an inner layer containing tegumental cells. The syncytium comprises various organelles like mitochondria, lysosomes, and tegumentary bodies of the type 2 kind with rare sighting of the type 1. Severe distortion and disorganization of the tegument was revealed in the parasite exposed to the A. nigra extract in the current study. The extent of vacuolization was such that vacuoles proceeded down to the basal lamina causing the syncytium to separate from the tegument at different places. There was depletion of parenchyma material and loss of connecting tubules running down from the syncytium to the tegumental cells causing the cells to be deprived of any proper boundaries.

Ultrastructural observations on tegumental surface of Raillietina echinobothrida and its alterations caused by root-peel extract of Millettia pachycarpa.

Millettia pachycarpa Benth (Leguminosae) has a usage in traditional medicine system practiced among the Lushai tribes of Mizoram, a state in North East India, who customarily consume the aqueous extract of the root peel of the plant to get rid of intestinal worm infections. The crude ethanol, methanol, and acetone fractions of the plant were assayed against Raillietina echinobothrida, the intestinal cestode parasite of domestic fowl, to authenticate the putative anthelmintic efficacy and cestocidal potential in particular of the plants. In vitro exposure of the worm to the extract at a concentration of 25 mg/mL phosphate buffered saline (at 37 degrees C +/- 1 degrees C) revealed distortion and disruption of mitochondria, nucleus, nucleolus, nuclear membrane, basal lamina, and tegumental vacuolization in the distal cytoplasm leading to scar formation in the surface. The possible use of the plant as a potential anthelmintic against cestode parasite is discussed.