Inflammatory cardiac fibroblast phenotype underlies chronic alcohol-induced cardiac atrophy and dysfunction.

AIMS: The purpose of this study was to investigate mechanisms of chronic alcohol-induced cardiac remodeling and dysfunction. We also sought to determine the role of cardiac fibroblasts, which play a dynamic role in cardiac remodeling, in mediating these effects. MAIN METHODS: Adult male Wistar rats were exposed to ethanol (EtOH) vapor inhalation for 16 weeks. Echocardiography was performed to assess terminal cardiac structure and function. Cardiac fibroblasts were isolated from the left ventricle (LV) for both ex vivo and in vitro analysis. Cultured H9C2 cells were also exposed to conditioned media from alcohol-exposed cardiac fibroblasts. Gene expression in whole LV tissue, isolated cardiac fibroblasts, or cultured H9C2 cells was determined by real-time PCR, and protein expression was determined by Western blot. KEY FINDINGS: EtOH led to LV wall thinning and impaired systolic function, and decreased contractile protein mRNA levels. EtOH increased LV inflammatory markers, JNK and Akt activation, and decreased mTOR expression. EtOH induced myofibroblast activation as assessed by flow cytometry, and increased LV collagen III expression. EtOH increased expression of several inflammatory mediators in cardiac fibroblasts both ex vivo and in vitro. Administration of conditioned media from EtOH-treated fibroblasts decreased contractile protein mRNA levels and impaired Akt and mTOR signaling in differentiated H9C2 cardiomyocytes. SIGNIFICANCE: Our results indicate that EtOH-induced cardiac atrophy and dysfunction is associated with activation of inflammatory pathways. Furthermore, EtOH may induce a pro-inflammatory cardiac fibroblast phenotype, leading to aberrant fibroblast-myocyte cross-talk. Thus, EtOH may promote cardiac muscle wasting in part by activation of pro-inflammatory fibroblasts.

Estrogen receptor antagonism exacerbates cardiac structural and functional remodeling in female rats.

We have previously demonstrated the cardioprotective effects of ovarian hormones against adverse ventricular remodeling imposed by chronic volume overload. Here, we assess the estrogen receptor dependence of this cardioprotection. Four groups of female rats were studied: sham-operated (Sham), volume overloaded [aortocaval fistula (ACF)], Sham treated with estrogen receptor antagonist ICI 182,780 (Sham + ICI), and ACF treated with ICI. Cardiac function was assessed temporally using echocardiogram, and tissue samples were collected at 5 days and 6 wk postsurgery. All rats with volume overload had significantly increased cardiac output (96 ± 32 ml/min for ACF and 108 ± 11 ml/min for ACF + ICI vs. 31 ± 2 for Sham, P < 0.05). At 6 wk, volume overload induced significant left ventricular (LV) hypertrophy in both untreated and treated ACF groups. Both ACF groups developed significantly increased LV end-diastolic diameter (LVEDD), indicating LV dilatation, with the ACF + ICI group having the greatest increase (340%, relative to Sham). Ejection fraction was significantly reduced in the ACF + ICI group (23% reduction) at 6 wk postsurgery compared with untreated ACF (P < 0.05). Interstitial collagen staining was significantly reduced by volume overload, with estrogen receptor antagonism causing greater collagen loss at both 5 days and 6 wk postsurgery. Furthermore, volume overload induced a significant increase in LV wall stress only in rats treated with estrogen antagonist. These data indicate that estrogen receptor signaling is essential for sex hormone-dependent cardioprotection against adverse remodeling. The maintenance of myocardial extracellular matrix collagen appears to play a key role in this cardioprotection. NEW & NOTEWORTHY: We assessed the estrogen receptor (ER) dependence of female-specific cardioprotection using a rat model of chronic volume-overload stress. ER antagonism worsened ventricular wall stress, ventricular dilation, and cardiac dysfunction induced by volume overload. Further, blocking ERs resulted in cardiac remodeling and functional changes similar to that previously found in ovariectomized rats.

[False positive urinary cytology. Diagnostic and prognostic value in the detection and surveillance of urothelial tumors. Apropos of 57 false positive cases in a series of 1000 cytologies]. / Les cytologies urinaires "faussement positives". Valeur diagnostique et pronostique dans le dépistage et la surveillance des tumeurs urothéliales. A propos de 57 cas de "faux positif" sur une série de 1,000 cytologies.

Out of 1,000 optical cytological urine tests carried out over a period of two years, 84 isolated cases were "positive" and alerted 57 patients. These cases are analyzed by the authors with a follow-up period of 48 to 72 months: among those patients already under supervision for urothelial tumours, 40.4% showed urothelial recurrence of which 70%, that did not appear to carry a worse prognosis, were detected in the first twelve months. Since these patients usually underwent annual endoscopic examination, this meant that for 20% (i.e. 4.15% of the group under supervision) the diagnosis of recurrence could be made at least 6 months earlier. This alone is a justification for cytological examination which does not involve any complications but merely entails increased cystoscopic and biopsy tests. On the other hand, there appear to be no grounds to advocate mass "screening" except in populations with warning symptomatology (especially haematuria) for which the ratio of positive findings in this series was 2.3/1,000. The future development of automatic apparatus for cytological tests should obviate the significant personal factor involved in cytological examinations, as shown by a review of the literature.

[Hydatid cyst of the kidney rupturing in the kidney pelvis and associated with lithiasis. Apropos of a case]. / Kyste hydatique du rein fissuré dans le bassinet et associé à une lithiase. A propos d'un cas.

The authors report one case of renal hydatid disease, with lithiasis and rupture into the renal pelvis. Pre-operative diagnostic investigation included ultrasound and CT scan imaging. Serologic test was negative. Treatment was surgical: removal of the hydatid and resection of the protruding part of the cyst. The fistula is closed with a drainage into the pelvis.

[Ureteral stenosis following colpocystopexy of urinary stress incontinence. Apropos of 5 cases]. / Les sténoses urétérales après colpocystopexie pour incontinence urinaire d'effort. A propos de 5 cas.

The authors report 5 cases of a rare urethrovesical suspension's complication = the ureteral obstruction. Its cause is always a surgical fault, its diagnosis is based on urography. Its treatment is surgical. The kidney can be preserved by an early repair; the continence's preservation is possible when the suspension can be preserved.

[Preventive value of intravesical thiotepa on the recurrence of Ta-T1 vesical tumors treated by conservative surgery. Apropos of 247 cases a mean follow-up of 88 months]. / Valeur prophylactique du thiotepa intra-vésical sur les récidives des tumeurs vésicales Ta-T1 traitées par chirurgie conservatrice. A propos de 247 cas suivis avec un recul moyen de 88 mois.

The retrospective homogeneous study of 247 patients with follow-up from 12 months to 384 months (mean 88 months) and managed with or without intra-vesical instillations of thiotepa as prophylactic chemotherapy after surgical conservative treatment is compared with some literature's data principally multicentric randomized series. Statistics contradictions remain with no significative results for possible progression towards infiltration, better "free interval" between recurrences, and better recurrence rate for 100 patients/months. In this series the number of tumors recurrences in each bladder was evaluated: this mean rate of tumors recurrences/year is 1,7 without prophylactic thiotepa and only but always 1,08 with thiotepa. Prophylactic instillations chemoprophylaxy seems to be justified but must be emphasized: mitomycin C, BCG therapy would be better in the future?

[Cancer of kidney with venous invasiveness: prognosis. Apropos of 238 renal excisions with 64 cases of venous invasiveness]. / Cancer du rein avec extension veineuse: pronostic. A propos de 238 exérèses rénales avec 64 envahissements veineux.

About a series of 238 surgically managed renal cell carcinoma with 64 venous invasion's cases (without no lost of follow-up) the prognosis is bad: post-operative mortality: 12,5%. Overall uncorrected five-years actuarial survival: 25%. But 42% of these patients with venous invasion had associated lymph node invasion and-or visceral metastasis. About 37 cases with only venous extension five-years actuarial survival reaches 45,9%. The inferior vena cava (I.V.C.) extension is the worst. Five american data reports some cases (5 to 18 cases) with near half and half surviving patients. In this series about 14 isolated I.V.C. invasion, only 4 patients are surviving with no evidence of disease but 2 have more than six years and fourteen years follow-up.