Structural changes in axillary eccrine glands following long-term treatment with aluminium chloride hexahydrate solution

Endothelin receptor antagonists (ERAs) are used for the treatment of pulmonary arterial hypertension (PAH). Macitentan, a dual (ETA+ETB) ERA approved for the long-term treatment of PAH, was discovered through a tailored research program aimed at improving efficacy and safety over the existing ERAs. The goal of improved efficacy was based on the understanding that not only the ETA receptor but also the ETB receptor contributed to the hemodynamic and structural changes induced by endothelin-1 (ET-1) in pathological conditions and on the predefined requirements for optimal tissue penetration and binding kinetics of the antagonist. The goal of improved safety was based on the discovery of the role of ETB receptors in vascular permeability and vasopressin release and on the elucidation of the mechanism by which bosentan (the first approved oral dual ETA/ETB ERA) caused liver enzyme changes. Our intention was to design a molecule that would block ETA and ETB receptors optimally and would not interfere with bile salt elimination. This review takes us through the drug discovery journey that led to the discovery, development, and registration of macitentan.

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Effect of long-term treatment with EGb 761 on age-dependent structural changes in the hippocampi of three inbred mouse strains

Life Sciences ◽

10.1016/0024-3205(94)00915-5 ◽

1994 ◽

Vol 56 (4) ◽

pp. 213-222 ◽

Cited By ~ 38

Author(s):

Martine Barkats ◽

P. Venault ◽

Yves Christen ◽

Charles Cohen-Salmon

Keyword(s):

Structural Changes ◽

Inbred Mouse ◽

Term Treatment ◽

Mouse Strains ◽

Inbred Mouse Strains ◽

Egb 761 ◽

Long Term Treatment ◽

Age Dependent

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Strontium chloride hexahydrate as a candidate molecule for long-term treatment of allergic rhinitis

The Indian Journal of Medical Research ◽

10.4103/ijmr.ijmr_894_15 ◽

2017 ◽

Vol 146 (1) ◽

pp. 121 ◽

Cited By ~ 1

Author(s):

EmineElif Altuntas ◽

NergizHacer Turgut ◽

Kasım Durmuş ◽

ÖmerTamer Doǧan ◽

Melih Akyol

Keyword(s):

Allergic Rhinitis ◽

Term Treatment ◽

Strontium Chloride ◽

Long Term Treatment ◽

Chloride Hexahydrate ◽

Candidate Molecule

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A Novel Dipeptidyl Peptidase-4 Inhibitor DA-1229 Ameliorates Tubulointerstitial Fibrosis in Cyclosporine Nephrotoxicity in Mice

Life ◽

10.3390/life11030251 ◽

2021 ◽

Vol 11 (3) ◽

pp. 251

Author(s):

Hye Sook Min ◽

Ji Eun Lee ◽

Jung Yeon Ghee ◽

Young Sun Kang ◽

Jin Joo Cha ◽

...

Keyword(s):

Renal Disease ◽

Structural Changes ◽

Immunosuppressive Agent ◽

Term Treatment ◽

Dipeptidyl Peptidase 4 ◽

Dipeptidyl Peptidase 4 Inhibitor ◽

Long Term Treatment ◽

Cyclosporine Nephrotoxicity ◽

Progression Of Renal Disease

Cyclosporine A (CyA) is an immunosuppressive agent that induces nephrotoxicity with long-term treatment. The roles of DPP-4 and its inhibitors in cyclosporine nephrotoxicity are not fully understood. Therefore, we investigated the effects of a novel DPP-4 inhibitor, DA-1229, on the progression of renal disease in an experimental cyclosporine nephrotoxicity model. Chronic cyclosporine nephrotoxicity was induced in six-week-old male ICR mice by subcutaneous injections of CyA at a dose of 30 mg/kg for four weeks. Animals were treated with DA-1229 at a dose of 300 mg/kg per day in food for four weeks. Although DPP-4 activity did not increase in the kidneys of mice with induced cyclosporine nephrotoxicity, DA-1229 treatment significantly suppressed DPP-4 activity in both plasma and renal tissues. DPP-4 inhibition by DA-1229 led to significantly decreased albuminuria and urinary excretion of 8-isoprosatane. DPP-4 inhibition also substantially suppressed pro-inflammatory effects, profibrotic molecules, and macrophage infiltration, and led to the improvement in renal structural changes. Our results suggest that DPP-4 inhibition by DA-1229 provides renoprotective effects in an animal model of cyclosporine nephrotoxicity via antioxidant, anti-inflammatory, and anti-fibrotic mechanisms. DPP-4 inhibition may be a useful new therapeutic approach for the management of progressive renal disease in cyclosporine nephrotoxicity.

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Haemodynamic Effects of Withdrawal of Long-Term Treatment with β-Adrenoceptor Blocking Agents in Subjects with Essential Hypertension

Clinical Science ◽

10.1042/cs061421s ◽

1981 ◽

Vol 61 (s7) ◽

pp. 421s-423s ◽

Cited By ~ 4

Author(s):

C. Bengtsson ◽

Y. Larsson ◽

V. Panfilov ◽

R. Sivertsson ◽

H. Åström

Keyword(s):

Blood Pressure ◽

Cardiac Output ◽

Essential Hypertension ◽

Structural Changes ◽

Peripheral Resistance ◽

Blocking Agent ◽

Term Treatment ◽

First Year ◽

Long Term Treatment

1. After 10 years of β-adrenoceptor blockade in five female patients with essential hypertension, the β-adrenoceptor-blocking agent was withdrawn, and the women were then followed up for 1 year, with measurements of cardiac output and peripheral resistance. 2. Blood pressure remained low during the first year after withdrawal in spite of the fact that the heart rate increased within the first few days. 3. Cardiac output was found to increase during the first year after withdrawal, although total peripheral resistance was essentially unchanged. 4. The maintenance of low blood pressure after withdrawal of the antihypertensive drug might indicate a regression of structural changes in the resistance vessels during successful long-term antihypertensive treatment. 5. Minimal resistance in hands and calves did not increase during the year after withdrawal.

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