Vasorelaxation in isolated bone arteries. Vasoactive intestinal peptide, substance P, calcitonin gene-related peptide, and bradykinin studied in pigs

We assessed the effects of vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and bradykinin in arteries (diameter approximately 230 microns) isolated from cancellous bone from pigs. Arterial segments (2 mm long) were mounted on a myograph for measurement of isometric force development. After submaximal precontraction with norepinephrine, VIP (10(-10)-10(-7) M), CGRP (10(-11)-10(-7) M), SP (10(-6) M), and bradykinin (10(-11)-10(-6) M) were added. 44 arterial segments (23 pigs) were investigated. VIP-, CGRP-, and bradykinin induced a concentration-dependent vasorelaxation, while SP mediated a transient relaxation. After mechanical removal of the endothelium, the effects of SP and bradykinin were completely abolished, while the relaxation to CGRP was still pronounced. This indicates that the effects of SP and bradykinin are mediated by the endothelium, while CGRP mainly mediates relaxation by a direct effect on vascular smooth muscle cells. The relaxations to CGRP and bradykinin were still significant after inhibition of nitric oxide synthase with 10(-4) M N omega-nitro-L-arginine (L-NNA) and inhibition of prostaglandin synthesis with 10(-5) M indomethacin, indicating the existence of an alternative vasorelaxing pathway. Our findings support the theory of a vasoregulatory role of neuropeptides in bone.     

Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells

One of the key limiting factors in the treatment of advanced stage human epithelial malignancies is the lack of new, selective molecular targets for antineoplastic therapy. A substantial subset of human breast, ovarian, endometrial, colorectal, and prostatic cancers express elevated levels of fatty acid synthase, the major enzyme required for endogenous fatty acid biosynthesis, and carcinoma lines are growth inhibited by cerulenin, a noncompetitive inhibitor of fatty acid synthase. We have shown previously that the difference in fatty acid biosynthesis between cancer and normal cells is an exploitable target for metabolic inhibitors in the in vitro setting and in vivo in a human ovarian carcinoma xenograft in nude mice. Here, we report that cerulenin treatment of human breast cancer cells inhibits fatty acid synthesis within 6 h after exposure, that loss of clonogenic capacity occurs within the same interval, and that DNA fragmentation and morphological changes characteristic of apoptosis ensue.     

Use of endometrial measurement as an exclusion criterion for in vitro fertilization using clomiphene citrate

OBJECTIVE: Previous reports have indicated an association between endometrial development and pregnancy outcome for patients treated with clomiphene citrate (CC) in conjunction with intrauterine insemination or intercourse. We expanded the use of CC for ovulation induction in association with in vitro fertilization (IVF). This study was designed to determine if endometrial thickness should be used as an inclusion or exclusion criterion for CC-IVF. STUDY DESIGN: One hundred twenty-eight patients were enrolled in an ovulation-induction regimen using CC for expected IVF-ET between January 1992 and December 1992. A total of 81 patients met inclusion criteria for CC-IVF and had endometrial measurement performed prior to human chorionic gonadotropin administration. Patients were categorized on the basis of endometrial measurement as follows: (A) > 4 - < 7 mm, (B) > or = 7 - < or = 10 mm, and (C) > 10 mm. Standard IVF was performed, and pregnancy rates for each category were evaluated. RESULTS: A total of 23 pregnancies (28% per retrieval) were established. Pregnancy rates were not different by category (P > .10, Fisher's Exact Test): (A) 3/15 (20%), (B) 13/41 (32%), and (C) 7/25 (28%). CONCLUSION: These data suggest that for CC-IVF. endometrial measurement should not be used as an exclusion criterion since pregnancies occurred at comparable frequencies in all the groups.     

The effect of spermine on protein kinase activity and number of cytosolic estradiol receptors

Spermine decreased distinctly the activity of Ca2+ -phospholipid-dependent protein kinases, whereas not affected the protein kinase A activity. Content of cytosol estradiol receptors was drastically decreased in rat uterine in presence of the polyamine. The data obtained and literature data suggest that activation of estradiol receptors appears to occur after phosphorylation by means of Ca2+ - dependent protein kinases, which are regulated via phosphoinositide-involving mechanism, i.e. these receptors acquire the ability to bind hormones.     

Attention deficit hyperactivity disorder and anxiety: is there an association with neurodevelopmental deficits?

OBJECTIVE: The co-occurrence of attention deficit hyperactivity disorder (ADHD) and anxiety is a well-established clinical observation. However, its status as a clinical construct is debated. We review the prevalence of 'ADHD and anxiety', its definitions, and its clinical correlates and we hypothesise that neurodevelopmental deficits may be increased in 'ADHD and anxiety'. METHOD: The authors identified empirical studies in the psychiatric and psychological literature. The search categories included hyperactivity, attention deficit hyperactivity disorder, attention deficit disorder and anxiety. RESULTS: 'ADHD and anxiety' is considerably more common in clinical than epidemiological samples. There are a range of definitions which address the situational variation in both ADHD and anxiety symptoms and the use of categorical and continuous variables to define them. Yet the nature of the anxiety is still unclear. It is associated with a poor response to psychostimulant medication treatment, and alternative pharmacotherapy approaches have been suggested. There is a controversy about whether neurodevelopmental deficits are associated with hyperactivity alone, or anxiety, or both. CONCLUSIONS: 'ADHD and anxiety' is important clinically because it is common and less responsive to psychostimulant medication. Important research issues include its heterogeneity which necessitates the collection of parent, teacher, and child self-reports of symptoms' presence or absence and the hypothesis that neurodevelopmental deficits may be increased in this group of children.     

Prolonged and monosymptomatic dysphasic status epilepticus

Dysphasic seizures are an infrequent form of epilepsy, and their serial appearance as a partial status epilepticus is quite exceptional. The young patient reported here had a partial dysphasic status epilepticus of 3 weeks' duration without other temporal lobe seizures. Simultaneous serial electroencephalograms, tape recordings of the seizures, and repeated neuropsychologic ictal examinations permitted studies of increased impairment of neuropsychologic function on testing and the appearance of new irritative discharges on encephalography.