New approaches to making the microenvironment of the female reproductive tract hostile to HIV

The studies presented in this review explore three distinct areas with potential for inhibiting HIV infection in women. Based on emerging information from the physiology, endocrinology and immunology of the female reproductive tract (FRT), we propose unique 'works in progress' for protecting women from HIV. Various aspects of FRT immunity are suppressed by estradiol during the menstrual cycle, making women more susceptible to HIV infection. By engineering commensal Lactobacillus to secrete the anti-HIV molecule Elafin as estradiol levels increase, women could be protected from HIV infection. Selective estrogen response modifiers enhance barrier integrity and enhance secretion of protective anti-HIV molecules. Finally, understanding the interactions and regulation of FRT endogenous antimicrobials, proteases, antiproteases, etc., all of which are under hormonal control, will open new avenues to therapeutic manipulation of the FRT mucosal microenvironment. By seeking new alternatives to preventing HIV infection in women, we may finally disrupt the HIV pandemic.     

Adenosine A2A Antagonists in Parkinson’s Disease: What’s Next?

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, affecting up to 10 million people worldwide. Current treatment primarily involves symptom management with dopaminergic replacement therapy. Levodopa remains the most effective oral treatment, although long-term use is associated with complications such as wearing off, dyskinesias, and on-off fluctuations. Non-dopaminergic medications that improve PD symptoms and motor fluctuations are in demand. Adenosine A2A receptors are abundantly expressed within the basal ganglia and offer a unique target to modify abnormal striatal signaling associated with PD. Preclinical animal models have shown the ability of adenosine A2A receptor antagonists to improve PD motor symptoms, reduce motor fluctuations and dyskinesia, as well as protect against toxin-induced neuronal degeneration. Both istradefylline and preladenant have demonstrated moderate efficacy in reducing off time in PD patients with motor fluctuations. The safety and efficacy of this class of compounds continues to be defined and future studies should focus on non-motor symptoms, dyskinesias, and neuroprotection.     

Multiscale measurement of cardiac energetics

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Chronic Idiopathic Urticaria and Thyroid Autoimmunity: Perplexing Association

Background:

Autologous serum skin test (ASST) is the most commonly used laboratory test to differentiate chronic autoimmune urticaria patients from chronic idiopathic urticaria patients without autoantibodies. Thyroid autoimmunity is the original paradigm for autoimmune disease in general and many previous studies show increased prevalence of thyroid autoantibodies and deranged thyroid hormone profile in chronic idiopathic urticaria patients.

Aim:

To find the association between thyroid autoimmunity and chronic autoimmune urticaria, if any.

Materials and Methods:

The chronic idiopathic urticaria patients were divided into two subgroups based on autologous serum skin test. Thyroid autoantibodies were estimated in 40 patients each of ASST positive and ASST negative groups. Further, thyroid hormone profile was done in cases with significant titers of thyroid autoantibodies. Forty patients, who had never suffered from urticaria, represented the control group.

Results:

The prevalence of thyroid autoantibodies did not differ significantly among the ASST positive (20%) and ASST negative patients (15%). The control group had low prevalence of these autoantibodies (5%).

Conclusion:

The almost equal prevalence of thyroid autoantibodies in two subgroups of chronic idiopathic urticaria patients suggests possibly the same etiopathogenesis of the two subgroups. The two subgroups probably form a continuum, or even may be the same entity.