Neuroprotective Effect of Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide on Spinal Cord Injury

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuroprotective peptide expressed in the central nervous system. To date, changes in the expression and effect of endogenous PACAP have not been clarified with respect to spinal cord injury (SCI). The aim of this study was to elucidate the expression pattern and function of endogenous PACAP on the contusion model of SCI using heterozygous PACAP knockout (PACAP(+/-)) and wild-type mice. Real-time polymerase chain reaction methods revealed that the level of PACAP mRNA increased gradually for 14?days after SCI and that PAC1R mRNA levels also increased for 7?days compared with intact control mice. PACAP and PAC1R immunoreactivities colabeled with a neuronal marker in the intact spinal cord. Seven days after SCI, PAC1R immunoreactivity was additionally co-expressed with an astrocyte marker. Wild-type mice gradually recovered motor function after 14?days, but PACAP(+/-) mice showed significantly impaired recovery from 3?days compared with wild-type mice. The injury volume at day?7 in PACAP(+/-) mice, and the number of single-stranded DNA-immunopositive cells as a marker of neuronal cell death at day?3 were significantly higher than values measured in wild-type mice. These data suggest that endogenous PACAP is upregulated by SCI and has a neuroprotective effect on the damaged spinal cord.     

Axillary ultrasound scanning in the follow-up of breast cancer patients undergoing sentinel node biopsy

In breast cancer patients with negative sentinel node biopsy (SNB), surveillance of the unremoved nodes is recommended. Clinical examination has poor sensitivity. The aim of this study was to evaluate the role of axillary ultrasound scan (AUS) in the follow-up of these patients. AUS was performed every 12 months in a series of 165 patients with negative SNB. During the follow-up (median 45.6 months), in 154 patients, the AUS was carried out as a routine examination and in three cases (1.9%) it showed suspicious nodes, which underwent core biopsy. No evidence of axillary recurrence was found. Conversely, in 11 patients, AUS was performed to clarify a palpable lymphadenopathy; none of them was suspicious at US. We conclude that routine AUS to follow-up patients who have had a negative SNB is unnecessary. However, AUS may be useful in the presence of palpable nodes, to select those patients who do not require biopsy.     

Estradiol-dependent decrease in the orexigenic potency of ghrelin in female rats

Ghrelin, the only known orexigenic gut hormone, is secreted mainly from the stomach, increases with fasting and before meal initiation in humans and rats, and increases food intake after central or peripheral administration. To investigate sex differences in the action of ghrelin, we assessed the effects of exogenous ghrelin in intact male and female rats, the effects of exogenous ghrelin in ovariectomized (OVX) and estradiol (E2)-treated female rats, as well as the effects of OVX on plasma ghrelin and hypothalamic orexigneic neuropeptide expression in rats and on food intake and weight gain in transgenic mice lacking the ghrelin receptor (Ghsr(-/-) mice). Male and OVX female rats were significantly more sensitive than intact female rats to the orexigenic effects of both centrally (intra-third ventricular, i3vt, 0.01, 0.1, and 1.0 nmol) and systemically (ip, 3, 6, and 9 nmol) administered ghrelin. This difference is likely to be estradiol dependent because E2 attenuated the orexigenic action of ghrelin in OVX female and male rats. Furthermore, OVX increased food intake and body weight in wild-type mice, but not in Ghsr(-/-) mice, suggesting that OVX increases food intake by releasing ghrelin from a tonic inhibitory effect of estradiol. In addition, following OVX, there was an increase in plasma ghrelin that was temporally associated with increased food intake, body weight, and hypothalamic neuropeptide Y and Agouti-related protein mRNA expression. Collectively, these data suggest that estradiol inhibits the orexigenic action of ghrelin in females, that weight gain associated with OVX is ghrelin mediated, and that this endocrine interaction may account for an important sex differences in food intake and the regulation of body weight.     

Decreased expression of reelin receptor VLDLR in peripheral lymphocytes of drug-naive schizophrenic patients

Reelin, a secretory protease that plays major roles in neurodevelopment and synaptic plasticity, may also play a role in the pathogenesis of schizophrenia. The present study was undertaken to examine whether the expression of two receptors for reelin, very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor type 2 (ApoER2), were abnormal in peripheral blood lymphocytes of schizophrenic patients. In this study, we measured the mRNA levels of VLDLR and ApoER2 in blood lymphocytes from patients with schizophrenia (drug-naive patients (n=20) and medicated patients (n=20)) and age-and gender-matched healthy controls (n=40) using quantitative real-time RT-PCR. Furthermore, we examined the correlation between mRNA levels and clinical variables in patients. Levels of VLDLR mRNA in drug-naive, unmedicated patients with schizophrenia were significantly lower than those of controls. In contrast, levels of ApoER2 mRNA in drug-naive patients did not differ from those of controls, although the levels of ApoER2 mRNA in medicated patients were significantly lower than those of controls. Interestingly, levels of VLDLR mRNA in drug-naive patients showed significant increases with respect to baseline after six months of antipsychotic treatment, whereas levels of ApoER2 mRNA were significantly lower than baseline after six months of treatment. In all patients, there was a negative correlation between VLDLR mRNA levels and the severity of clinical symptoms. Our findings suggest that peripheral VLDLR mRNA levels may serve as a reliable peripheral biological marker of schizophrenia, and that the reelin-VLDLR/ApoER2 signaling pathway plays a role in the pathophysiology of schizophrenia.     

Metformin effect on internal carotid artery blood flow assessed by area under the curve of carotid artery Doppler in women with polycystic ovarian syndrome

BACKGROUND Insulin resistance(IR) was reported in most polycystic ovarian syndrome(PCOS) cases. Metformin, a biguanide drug, successfully reduced IR. Homeostatic Model Assessment for IR(HOMA-IR) and Doppler parameters assessed metformin’s effectiveness.AIM To verify whether the area under the curve of the internal carotid artery(AUCICA) Doppler wave can be a useful marker for assessing IR among PCOS cases who presented with menstrual irregularity and were treated with metformin over 6 mo.METHODS...     

Non‐covalent chemical modification of crown ether side‐chain polymethacrylates with a secondary ammonium salt: a family of new polypseudorotaxanes

Here we report syntheses of copolymeric polymethacrylates ( 5 ) bearing dibenzo‐24‐crown‐8 (DB24C8) moieties and their non‐covalent chemical modification with dibenzylammonium hexafluorophosphate ( 7 ) to form side‐chain polypseudorotaxanes. The complexation process, primarily driven by hydrogen bonding and π‐stacking interactions, was investigated in solution with ¹H NMR spectroscopy. By the use of Scatchard and Hill plots it was shown that this system is anticooperative, with a Hill coefficient, n_H ≈︂ 0.45; that is, in addition to the usual entropic effects associated with multiple binding sites, the addition of subsequent ligands to an already complexed macromolecule is retarded. Thus, the more crown moieties per macromolecule or the higher the fraction of complexed sites, the lower the effective macroscopic binding or association constant. Films of the side‐chain polypseudorotaxanes showed significant increases in T_g compared to the parent polymers. The effects of pseudorotaxane formation on surface morphology of films are also reported.     

Fertility outcomes following bariatric surgery

Obesity impacts human health in more than one way. The influence of obesity on human reproduction and fertility has been extensively examined. Bariatric surgery (BS) has been used as an effective tool to achieve long-term weight loss in both sexes. BS improves hormonal profiling, increasing the odds of spontaneous pregnancy and success rates following assisted reproductive techniques in infertile females. For obese males, BS does improve sexual function and hormonal profile; however, conflicting reports discuss reduced sperm parameters following BS. Although the benefits of BS in the fertility field are acknowledged, many areas call for further research, like choosing the safest surgical techniques, determining the optimal timing to get pregnant, and resolving the uncertainty of sperm parameters.     

Vaginal microbes confounders and implications on women's health

The vagina has diverse vaginal microbes (Vm). A disturbance in the delicate balance maintained in Vm is linked to women's obstetrical and reproductive tract problems. Vaginal microbes play an essential role in protecting the health of the female reproductive tract by alleviating gynecological infection. However, Vm profiling has many confounders that need to be addressed during sampling, including age, race, pregnancy, medical illness, and smoking. Vm profiling improves reproduction odds, may serve as a marker for genital malignancies and have a therapeutic application in menopausal women and women with cervical cancers.