In our study injection of botulinum toxin into the detrusor muscle did not lead to increased fibrotic activity within the bladder wall, on the contrary patients with previous botulinum toxin injection revealed significant less fibrosis than patients without toxin injection.
The antimalarial agents, chloroquine (CQ) and hydroxychloroquine (HCQ) are used in long-term treatment of connective tissue diseases and dermatological disorders and are generally regarded as safe. We present one case of cardiotoxicity in a 59-year-old woman treated with antimalarials during 13 years for a discoid lupus erythematosus. She progressively developed conduction disturbances and congestive heart failure (CHF). When the diagnosis of antimalarials toxicity was suspected, CQ was withdrawn. However, heart transplantation had to be performed in the following 4 months for severe CHF. Indeed, rare but severe cardiotoxicity may develop following prolonged use of antimalarials with both conduction disturbances (45 patients) and CHF (25 patients). These cardiac toxic effects have been reported with CQ and less frequently with HCQ use alone. Diagnoses are often delayed since the toxicity of the drug might be misattributed to other factors in these patients. The endomyocardial biopsy, or in some cases the muscle biopsy, are essential to confirm the antimalarials toxicity. Antimalarials have been stopped in 12 cases of CHF, leading to improvement in 8 cases (within 3 months to 5 years) and to deaths or to heart transplantation in 4 cases (within 1 week to 3 months). In the latter cases, as in our patient, the lack of improvement may have been explained by the severity of the cardiomyopathy at diagnosis and the short delay since withdrawal. As a consequence, the potential for reversibility and the severity in undiagnosed cases of these toxic cardiomyopathies emphasize the importance of recognizing early signs of toxicity in order to withdraw antimalarials before the occurrence of life-threatening CHF.
Background:
End‐stage of human dilated cardiomyopathy (DCM) is characterized by myocyte loss and fibrosis, and associated with ventricular dilatation and reduced cardiac function. Matrix metalloproteinases (MMPs) and their natural tissue inhibitors (TIMPs) have been involved in the myocardial remodeling.
Aims:
To evaluate the potential role of matrix gelatinases (MMP‐2 and MMP‐9) in DCM, the balance between gelatinases and TIMPs and the gelatinase localization were investigated in left free wall ventricles from six normal donors and six patients with DCM at the transplantation time.
Methods:
TIMP‐(1, 2, 3 and 4) mRNAs were analyzed by quantitative reverse transcription‐polymerase chain reaction (RT‐PCR). TIMP‐1 and ‐2 protein content was assessed by ELISA. MMP‐2 and MMP‐9 expression were examined by zymography and immunological techniques.
Results:
All TIMPs were down‐regulated in DCM hearts, especially TIMP‐1 (reduced by 80%). Gel zymography revealed similar activity of MMP‐2 and MMP‐9 in both tissues. By in situ zymography and immunohistochemistry, active and immunoreactive gelatinases were pericardiomyocyte in control hearts and intracardiomyocyte in DCM hearts. Intracellular MMPs were associated with sarcomeric structure in DCM. To estimate a putative role of these gelatinases, several sarcomeric contractile proteins were digested in vitro by purified active MMP‐9. Only myosin‐heavy chain was cleaved in vitro giving 180‐, 120‐, 80‐ and 20‐kDa proteolytic fragments. In vivo, two major myosin‐heavy chain proteolytic fragments (80 and 20 kDa) were detected by specific monoclonal antibody against myosin‐heavy chain in DCM left ventricular homogenates, only.
Conclusions:
Taken together, these data highly suggest that MMP‐2 and MMP‐9 may be involved in the disorganization of the contractile apparatus in DCM hearts.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.