Vaccine strain Listeria monocytogenes bacteremia occurring 31 months after immunization.

BACKGROUND: Listeria monocytogenes is a food-borne, facultative intracellular bacterium that causes severe diseases such as sepsis and meningoencephalitis in immunocompromised hosts. Because it stimulates robust T-lymphocyte-mediated responses, attenuated L. monocytogenes are candidate vaccine vectors for tumor immunotherapy. CASE: We report a case of bacteremia caused by vaccine strain L. monocytogenes (Axalimogene filolisbac) occurring 31 months after immunization against human papilloma virus (HPV) associated cervical cancer. CONCLUSION: Receipt of a L. monocytogenes-based vaccine is a novel risk factor for delayed L. monocytogenes bacteremia.

Ovariectomy enhances SR Ca²âº release and increases Ca²âº spark amplitudes in isolated ventricular myocytes.

This study compared Ca(2+) homeostasis in ventricular myocytes from 8-month-old female C57BL/6J mice that had either a bilateral ovariectomy (OVX) or a sham surgery at 3 weeks of age. Cells were loaded with fura-2 and field-stimulated or voltage-clamped with steps to membrane potentials between -40 and +80 mV (37°C). Peak Ca(2+) transients increased by two-fold in OVX myocytes when compared to sham, and Ca(2+) transient rates of rise and decay were faster in OVX cells. In contrast, Ca(2+) current densities were similar in sham and OVX cells. Sarcoplasmic reticulum (SR) Ca(2+) content, assessed by caffeine, also was higher in OVX compared to sham cells (111.7 ± 11.9 vs. 61.2 ± 10.4 nM; p<0.05). Furthermore, the gain of Ca(2+) release (Ca(2+) release/Ca(2+) current) was significantly greater in OVX than in sham cells (16.3 ± 2.5 vs. 7.7 ± 2.0 nM/pApF(-1) at 0 mV; p<0.05). As changes in unitary Ca(2+) release might account for the increased gain in OVX cells, spontaneous Ca(2+) sparks were compared in fluo-4-loaded myocytes (37°C). Spark frequency was higher in OVX cells than in sham cells. In addition, spark amplitudes were greater in OVX than in sham myocytes (ΔF/F(0)=0.379 ± 0.006 vs. 0.342 ± 0.006; p<0.05). However, spark widths and time courses were similar in the two groups. These data suggest that the size of individual SR Ca(2+) release units is larger and the SR Ca(2+) content is greater in myocytes of OVX mice, producing augmented gain and SR Ca(2+) release. These observations show that OVX disrupts intracellular Ca(2+) homeostasis and suggest that sex steroid hormones modulate unitary Ca(2+) release in individual cardiac myocytes.

Effect of age on cardiac excitation-contraction coupling.

1. Cardiovascular diseases most commonly occur in the elderly and are a frequent cause of disability or death. However, the effect of age itself on cardiac function is not well understood. 2. Studies in both human and animal hearts indicate that contractile function is unaffected by age while at rest. However, the ability to increase cardiac contractile force during strenuous activities, such as exercise, declines with age. 3. Similar findings have been observed in individual ventricular myocytes isolated from aged hearts. When myocytes are stimulated with beta-adrenoceptor agonists or rapid pacing frequencies, aged cells show a much smaller increase in peak contractions and Ca(2+) transients than young adult cells. In addition, contractions and Ca(2+) transients are prolonged in aged cells compared with younger cells under these conditions. 4. These observations suggest that the age-related decline in cardiac contractile function originates at the cellular level and may reflect modifications in processes involved in excitation-contraction (EC) coupling. 5. Biochemical studies have shown that there are age-related modifications in the expression, regulation and function of a number of proteins essential to EC coupling in the heart. 6. Functional studies indicate that these changes in EC coupling proteins disrupt Ca(2+) homeostasis and contribute to decrease in peak contraction and prolongation of contraction duration observed in myocytes from aged hearts. 7. The present review describes modifications in cardiac contractile function that occur in the ageing heart and evaluates underlying alterations in the EC coupling pathway that may be responsible for this decline in contractile function in ageing.

The impact of ovariectomy on calcium homeostasis and myofilament calcium sensitivity in the aging mouse heart.

This study determined whether deficiency of ovarian estrogen starting very early in life promoted age-associated Ca(2+) dysregulation and contractile dysfunction in isolated ventricular myocytes. Myocytes were isolated from anesthetized C57BL/6 female mice. Animals received an ovariectomy or sham-operation at one month and were aged to ~24 months. Excitation-contraction coupling parameters were compared in fura-2 loaded myocytes (37°C). While Ca(2+) transients were larger and faster in field-stimulated myocytes from ovariectomized mice, ovariectomy had no effect on peak fractional shortening. Similarly, ovariectomy had no effect on fractional shortening measured in vivo by echocardiography (values were 60.5 ± 2.9 vs. 60.3 ± 2.5% in sham and ovariectomized, respectively; n=5 mice/group). Ovariectomy did decrease myofilament Ca(2+) sensitivity, as evidenced by a 26% increase in the Ca(2+) required to activate actomyosin MgATPase in ovariectomized hearts. Larger Ca(2+) transients were attributable to a 48% increase in peak Ca(2+) current, along with an increase in the amplitude, width and frequency of Ca(2+) sparks measured in fluo-4 loaded myocytes. These changes in Ca(2+) handling were not due to increased expression of Ca(2+) channels (Cav1.2), sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) or Na(+)-Ca(2+) exchanger in ovariectomized hearts. However, ovariectomy increased sarcoplasmic reticulum Ca(2+) stores by ~90% and promoted spontaneous Ca(2+) release from the sarcoplasmic reticulum when compared to sham controls. These observations demonstrate that long-term ovariectomy promotes intracellular Ca(2+) dysregulation, reduces myofilament Ca(2+) sensitivity and increases spontaneous Ca(2+) release in the aging female heart.

A procedure for creating a frailty index based on deficit accumulation in aging mice.

This study developed an approach to quantify frailty with a frailty index (FI) and investigated whether age-related changes in contractions, calcium transients, and ventricular myocyte length were more prominent in mice with a high FI. The FI combined 31 variables that reflect different aspects of health in middle-aged (∼12 months) and aged (∼30 months) mice of both sexes. Aged animals had a higher FI than younger animals (FI = 0.43 ± 0.03 vs 0.08 ± 0.02, p < .001, n = 12). Myocyte hypertrophy increased by 30%-50% as the FI increased in aged animals. Peak contractions decreased more than threefold from lowest to highest FI values in aged mice (p < .037), but calcium transients were unaffected. Similar results were seen with an FI based on eight noninvasive variables identified as underlying factors. These results show that an FI can be developed for murine models and suggest that age-associated changes in myocytes are more prominent in animals with a high FI.