Effect of androgen suppression on bone mineral density in patients with prostate cancer.

UNLABELLED: The androgen-suppressive therapy (AST) in patients with prostate cancer (PC) may dramatically affect the bone mineral density (BMD), which puts patients at risk of severe adverse effects, such as weight-bearing bone fractures. AIM: To study the effect of AST on BMD in patients with non-metastatic hormone-sensitive PC treated with intermittent hormonal therapy, and effect of different total testosterone level on BMD. MATERIALS AND METHODS: From 2011 to 2013 we treated 56 patients with non-metastatic hormone-naïve PC. Intermittent hormonal treatment with flutamide at a dose of 250 mg 3 times per day with nine monthly injections of luteinizing gonadotropic releasing hormone (LGnRH) ["treatment" period] followed by period of observance ("no treatment") was administered. We evaluated the BMD of lumbar spine and both proximal thighs by means of dual-energy x-ray densitometry at the end of "treatment" period and at the end of "no treatment" period. RESULTS: During the first treatment period, 44 of 56 patients (78.6%) experienced the reduction in BMD in both lumbar spine and thighs. Total testosterone level in all patients dropped to castration level. During the first period of "no treatment" there was an increase in BMD (p < 0.05) in 30 (68.2%) of 44 patients. The median time to recovery of total testosterone level to the level > 50 ng/dl was 91 days (from 30 to 308 days), and > 100 ng/dl was 110 days (from 49 to 343 days). The changes in BMD positively correlated with the changes in total testosterone level (correlation 0.18 [95% CI, 0.04-0.27], p = 0.009). The decline in total testosterone level in serum was followed by the decline in BMD value in the studied areas, and vice versa. CONCLUSIONS: The changes in BMD positively correlated with changes in total testosterone level. The BMD decreases during the androgen suppression and increases during the pause in the treatment. This demonstrates the benefit of intermittent AST in preventing osteoporosis, pathological bone fractures and possibly, bone metastases.

Selective inhibition of sodium-calcium exchanger by SEA-0400 decreases early and delayed after depolarization in canine heart.

The sodium-calcium exchanger (NCX) was considered to play an important role in arrhythmogenesis under certain conditions such as heart failure or calcium overload. In the present study, the effect of SEA-0400, a selective inhibitor of the NCX, was investigated on early and delayed afterdepolarizations in canine ventricular papillary muscles and Purkinje fibres by applying conventional microelectrode techniques at 37 degrees C. The amplitude of both early and delayed afterdepolarizations was markedly decreased by 1 microM SEA-0400 from 26.6+/-2.5 to 14.8+/-1.8 mV (n=9, P<0.05) and from 12.5+/-1.7 to 5.9+/-1.4 mV (n=3, P<0.05), respectively. In enzymatically isolated canine ventricular myocytes, SEA-0400 did not change significantly the L-type calcium current and the intracellular calcium transient, studied using the whole-cell configuration of the patch-clamp technique and Fura-2 ratiometric fluorometry. It is concluded that, through the reduction of calcium overload, specific inhibition of the NCX current by SEA-0400 may abolish triggered arrhythmias.

Chemoanatomical separation of vibrissal trigeminal primary afferents in the rat: a special central representation of supraorbital vibrissae.

A choleratoxin B subunit transganglionic labelling technique and NPY immunohistochemistry were applied in the rat to achieve the chemoanatomical separation of myelinated vibrissal primary afferents, previously considered to be morphologically indistinguishable. Further, a special central representation pattern of supraorbital vibrissae was observed in the trigeminal brainstem nuclear complex: (1) Choleratoxin-labelled supraorbital vibrissal primary afferents terminated densely in their appropriate barrelettes in the trigeminal principal sensory nucleus, in the spinal oral subnucleus, in the caudal part of the spinal interpolar subnucleus, and in lamina IV of the caudal part of the spinal caudal subnucleus. (2) A second population of choleratoxin-labelled vibrissal afferents was also observed, terminating only in lamina III of the caudal subnucleus. (3) After peripheral nerve transection, NPY-immunoreactive supraorbital vibrissal primary afferent fibres appeared in their appropriate barrelettes in the principal sensory nucleus and the caudal part of the interpolar subnucleus, while in the caudal part of the caudal subnucleus NPY-immunoreactive vibrissal primary afferent terminals were found exclusively in the inner part of lamina II, extending over the outer part of lamina III. NPY-immunoreactive supraorbital vibrissal primary afferents were never found in the oral subnucleus. In contrast with the rules of the central representation of the mystacial (infraorbital) vibrissae, the multiple representation of the supraorbital vibrissae in the caudal subnucleus and the dense, barrelette-like terminal arborization of the choleratoxin-labelled supraorbital vibrissal primary afferents in the oral subnucleus apparently indicate an enhanced role of supraorbital vibrissae in reflexes that protect the eyes and the head from damage.