Provided herein are methods and compositions, including synergistic combinations, for the treatment of tuberculosis.

Provided herein are methods and compositions, including synergistic combinations, for the treatment of tuberculosis.

Provided are formulations and methods for treating one or more genitourinary conditions. The formulations may include a therapeutic agent that includes a calcium channel blocker, a rho kinase inhibitor, or a combination thereof. The methods may include locally administering a therapeutic agent into a ureter. Systems for delivering a therapeutic agent also are provided.

Provided are formulations and methods for treating one or more genitourinary conditions. The formulations may include a therapeutic agent that includes a calcium channel blocker, a rho kinase inhibitor, or a combination thereof. The methods may include locally administering a therapeutic agent into a ureter. Systems for delivering a therapeutic agent also are provided.

Provided are formulations and methods for treating one or more genitourinary conditions. The formulations may include a therapeutic agent that includes a calcium channel blocker, a rho kinase inhibitor, or a combination thereof. The methods may include locally administering a therapeutic agent into a ureter. Systems for delivering a therapeutic agent also are provided.

The invention provides α-amino esters of a hydroxypropylthiazolidine carboxamide derivative, (2S)-3-([1,1′-biphenyl]-4-ylsulfonyl)-N-[(1S)-3-hydroxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide, as well as salts and crystal polymorphs thereof, that can be used to inhibit prostaglandin F receptor. The invention further encompasses methods of treating disorders such as preterm labor at the early gestational stage by the administration of these substances to a patient in need of treatment.

The invention provides α-amino esters of a hydroxypropylthiazolidine carboxamide derivative, (2S)-3-([1,1′-biphenyl]-4-ylsulfonyl)-N-[(1S)-3-hydroxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide, as well as salts and crystal polymorphs thereof, that can be used to inhibit prostaglandin F receptor. The invention further encompasses methods of treating disorders such as preterm labor at the early gestational stage by the administration of these substances to a patient in need of treatment.

The invention provides α-amino esters of a hydroxypropylthiazolidine carboxamide derivative, (2S)-3-([1,1′-biphenyl]-4-ylsulfonyl)-N-[(1S)-3-hydroxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide, as well as salts and crystal polymorphs thereof, that can be used to inhibit prostaglandin F receptor. The invention further encompasses methods of treating disorders such as preterm labor at the early gestational stage by the administration of these substances to a patient in need of treatment.

Heart failure with preserved ejection fraction (HFpEF) which results from diastolic dysfunction is a growing epidemiologic problem. However, the pathophysiology of this disease is poorly understood. Our goal is to investigate whether microvessel disease may promote HFpEF. To do so we have used Leptin receptor deficient (Lepr.sup.db/db) female mice as a model of HFpEF and performed a transcriptomic analysis via RNA sequencing of the cardiac vascular fraction of both these mice and their control Lepr.sup.db/+littermates. In Lepr.sup.db/db female mice, end diastolic pressure (EDP) signing diastolic dysfunction is significantly increased from 3 month of age. It is correlated with a cardiac and cardiomayocyte hypertrophy, vascular leakage, endothelial cell activation and leucocyte infiltration. As expected, the RNA sequencing analysis confirmed endothelial dysfunction. Besides, it also revealed a strong increase in several mast cell markers. We confirmed, via histology, an accumulation of mast cells in the heart of Lepr.sup.db/db mice. Importantly, it was associated with increased levels of circulating IgE. Lepr.sup.db/db mice were then treated or not with Cromolyn sodium, an inhibitor of mast cell degranulation. After a month treatment, EDP was significantly reduced in Lepr.sup.db/db mice demonstrating the critical role of mast cell in the development of diastolic dysfunction in diabetic obese mice.

Heart failure with preserved ejection fraction (HFpEF) which results from diastolic dysfunction is a growing epidemiologic problem. However, the pathophysiology of this disease is poorly understood. Our goal is to investigate whether microvessel disease may promote HFpEF. To do so we have used Leptin receptor deficient (Lepr.sup.db/db) female mice as a model of HFpEF and performed a transcriptomic analysis via RNA sequencing of the cardiac vascular fraction of both these mice and their control Lepr.sup.db/+littermates. In Lepr.sup.db/db female mice, end diastolic pressure (EDP) signing diastolic dysfunction is significantly increased from 3 month of age. It is correlated with a cardiac and cardiomayocyte hypertrophy, vascular leakage, endothelial cell activation and leucocyte infiltration. As expected, the RNA sequencing analysis confirmed endothelial dysfunction. Besides, it also revealed a strong increase in several mast cell markers. We confirmed, via histology, an accumulation of mast cells in the heart of Lepr.sup.db/db mice. Importantly, it was associated with increased levels of circulating IgE. Lepr.sup.db/db mice were then treated or not with Cromolyn sodium, an inhibitor of mast cell degranulation. After a month treatment, EDP was significantly reduced in Lepr.sup.db/db mice demonstrating the critical role of mast cell in the development of diastolic dysfunction in diabetic obese mice.