Different Effect of Rho Kinase Inhibition on Calcium Signaling in Rat Isolated Large and Small Arteries

In addition to its role in the regulation of artery contraction, Rho kinase (ROCK) was reported to be involved in the cytosolic calcium response to vasoconstrictor agonists in rat aorta and superior mesenteric artery (SMA). However, it remains to be determined whether ROCK also contributes to calcium signaling in resistance arteries, which play a major role in blood pressure regulation. The investigation of the effect of ROCK inhibition on the calcium and contractile responses of rat resistance mesenteric artery (RMA), in comparison with aorta and SMA, indicated that the calcium response to noradrenaline was inhibited by the ROCK inhibitor Y-27632 in aorta and SMA but not in RMA. The effect of Y-27632 on the calcium signal was unaffected by cytochalasin-D. ROCK activation in noradrenaline-stimulated arteries was confirmed by the inhibition of myosin light chain phosphorylation by Y-27632. Moreover, noradrenaline-induced calcium signaling was similarly inhibited by nimodipine in aorta, SMA and RMA, but nimodipine sensitivity of the contraction increased from the aorta to the RMA, suggesting that the contraction was controlled by different sources of calcium. In pressurized RMA, Y-27632 and H-1152 depressed pressure-induced calcium responses and abolished myogenic contraction. These results stress the important differences in calcium signaling between conductance and resistance arteries.     

A switch from GnRH agonist to GnRH antagonist in castration-resistant prostate cancer patients leads to a low response rate on PSA

Purpose

At the time of castration resistance, it is recommended to realize hormonal manipulations before chemotherapy. We evaluated the impact of a switch from GnRH agonist to antagonist in patients with castration-resistant prostate cancer on PSA and testosterone levels at 3 months.

Methods

Retrospectively, 17 patients from 5 different centers undergoing androgen deprivation therapy and presenting rising PSA confirmed on 3 blood samples 2 weeks apart and despite a castrate testosterone level (<0.5 ng/ml) were reviewed. Antiandrogen withdrawal syndrome had been tested before the switch. Degarelix was administered as followed: 240 mg for the first injection and then 80 mg every month, subcutaneously. We evaluated the PSA and testosterone level variation 3 months after the switch. Patients who experienced a variation in PSA of less than 10% compared to the baseline or who had a more than 10% PSA decrease were defined as responders.

Results

Mean PSA level at the switch was 34.3 ± 50.3 ng/ml, with a mean testosterone level of 0.21 ± 0.13 ng/ml. Three months after the switch, mean PSA level was 59.9 ± 81.6 ng/ml (P = 0.061), with a mean testosterone level of 0.19 ± 0.08 ng/ml (P = 0.086). At 3 months, 4 patients (23%) responded to therapy. Thirteen patients (77%) experienced a rise in PSA of more than 10% compared to baseline; 41% of patients decreased their testosterone level. The limitations of this study are its retrospective nature and the limited number of patients.

Conclusion

Switch from an agonist to an antagonist of GnRH has a limited impact on PSA at 3 months in castration-resistant prostate cancer patients.     

Érythrocytes et tonus microvasculaire au cours du choc hémorragique traumatique

Haemorrhagic shock remains a leading cause of death in trauma patients. The concept of haematologic damage control is gradually taking place in the management of traumatic haemorrhagic shock. It is based primarily on the early implementation of a quality blood transfusion involving erythrocytes, plasmas and platelets transfusion. Red blood cell transfusion is mainly supported by the oxygen carrier properties of erythrocytes. However, it appears that erythrocytes ability to modulate the bioavailability of nitric oxide (NO) plays a major role in capillary opening and perfusion. Erythrocytes are also actively involved in the processes of hemostasis and coagulation. In this context, it seems difficult to define a threshold of hemoglobin concentration to determine the implementation of a blood transfusion in traumatic haemorrhagic shock.     

Molecular cytogenetic and genetic aspects of globozoospermia: a review

Infertility is estimated to affect up to 15% of couples of reproductive age. Among the male factors, globozoospermia (also called round‐headed sperm syndrome) is a rare type of teratozoospermia accounting for <0.1% of male infertility. Lack of acrosome, whose production is a postmeiotic event in spermatogenesis, and round sperm head are its main characteristics. The acrosomeless spermatozoon is unable to go through the zona pellucida and fuse with the oolemma of the oocyte, and fertilisation failures have been attributed to a deficiency in oocyte activation capacity, even when intracytoplasmic sperm injection (ICSI) is attempted. The pathogenesis of this anomaly is still unclear but genetic factors are likely to be involved. DNA fragmentation rate has been reported for 16 globozoospermic males, usually using the terminal uridine nick‐end labelling (TUNEL) assay. Most of the patients had a DNA fragmentation index (DFI) higher than that in fertile men. The rate of aneuploidy for some specific chromosomes was increased in 12 among the 26 globozoospermic males reported in the literature. The same results (high DFI and aneuploidy rates) were observed in infertile males compared to fertile men, notably in those with oligoasthenozoospermia or teratozoospermia, independently of the origins. Mutations or deletions in three genes, SPATA16, PICK1 and DPY19L2, have been shown to be responsible for globozoospermia. Proteins coded by the first two genes localise to the Golgi apparatus and the proacrosomal granules that are transported in the acrosome. It is likely that other proteins involved in the acrosome formation remain to be identified.     

Minimally invasive surgery versus percutaneous radio frequency ablation for the treatment of single small (≤3 cm) hepatocellular carcinoma: a case–control study

Background

Patients with single small hepatocellular carcinoma (HCC) can be managed by surgical resection or radio frequency ablation (RFA), with similar recurrence and survival rates. Recently, minimally invasive surgery (MIS) has been introduced in liver surgery, and the advantage/drawback balance between surgery and RFA needs reassessment.

Methods

Patients with Child-Pugh class A or B cirrhosis, and with single 1–3 cm HCC, undergoing MIS (laparoscopic or robot-assisted) or RFA from July 1998 to December 2012 were compared.

Results

Overall, 45 patients underwent MIS, and 60 underwent RFA. Groups were not statistically different regarding type of underlying liver disease, HCC size, and AFP. However, RFA patients showed worse liver synthetic function with lower albumin and higher bilirubin serum levels, and higher ASA scores. Patients with HCC in segments 2–6 were more often treated by MIS. The incidence of complications was similar between groups (RFA: 6/60, 10 % vs. MIS: 5/45, 11 %, p = 0.854), and there was no measurable difference in the rate of procedure-related blood transfusions (RFA: 1/60, 1.7 % vs. MIS: 3/45, 6.7 %, p = 0.185). Local recurrence was only detected after RFA (11.7 %, p = 0.056, log-rank). Overall survival was higher in the MIS group (p = 0.042), with median survivals of 100 ± 13.5 versus 68 ± 15.9 months.

Conclusion

The present data need further validation. Selected patients with single ≤3-cm HCCs can be safely treated by MIS, without increased risk of perioperative complication, and with a lower risk of local recurrence. MIS should be especially favoured in patients with peripheral HCCs in segments 2–6, and/or when a histological assessment is desirable.

     

Thalamocortical and the dual pattern of corticothalamic projections of the posterior parietal cortex in macaque monkeys

The corticothalamic projection includes a main, modulatory projection from cortical layer VI terminating with small endings whereas a less numerous, driving projection from layer V forms giant endings. Such dual pattern of corticothalamic projections is well established in rodents and cats for many cortical areas. In non-human primates (monkeys), it has been reported for the primary sensory cortices (A1, V1, S1), the motor and premotor cortical areas and, in the parietal lobe, also for area 7. The present study aimed first at refining the cytoarchitecture parcellation of area 5 into the sub-areas PE and PEa and, second, establishing whether area 5 also exhibits this dual pattern of corticothalamic projection and what is its precise topography. To this aim, the tracer biotinylated dextran amine (BDA) was injected in area PE in one monkey and in area PEa in a second monkey. Area PE sends a major projection terminating with small endings to the thalamic lateral posterior nucleus (LP), ventral posterior lateral nucleus (VPL), medial pulvinar (PuM) and, but fewer, to ventral lateral posterior nucleus, dorsal division (VLpd), central lateral nucleus (CL) and center median nucleus (CM), whereas giant endings formed restricted terminal fields in LP, VPL and PuM. For area PEa, the corticothalamic projection formed by small endings was found mainly in LP, VPL, anterior pulvinar (PuA), lateral pulvinar (PuL), PuM and, to a lesser extent, in ventral posterior inferior nucleus (VPI), CL, mediodorsal nucleus (MD) and CM. Giant endings originating from area PEa formed restricted terminal fields in LP, VPL, PuA, PuM, MD and PuL. Furthermore, the origin of the thalamocortical projections to areas PE and PEa was established, exhibiting clusters of neurons in the same thalamic nuclei as above, in other words predominantly in the caudal thalamus. Via the giant endings CT projection, areas PE and PEa may send feedforward, transthalamic projections to remote cortical areas in the parietal, temporal and frontal lobes contributing to polysensory and sensorimotor integration, relevant for visual guidance of reaching movements for instance.