The high incidence of serious chest infections in patients with Parkinson's disease is unexplained, but an impairment in cough reflex may have a role. Maximal voluntary cough (MVC) and reflex cough ...(RC) to inhalation of ultrasonically nebulized distilled water were analyzed in patients with Parkinson's disease and age-matched control subjects by monitoring the integrated electromyographic activity (IEMG) of abdominal muscles. The peak amplitude of IEMG activity (IEMGP) was expressed as a fraction of the highest IEMGP value observed during MVC corrected to account for possible losses in abdominal muscle force due to reduced central muscle activation. Cough intensity was indexed in terms of both the IEMGP and the ratio of IEMGP to the duration of the expiratory ramp (TEC), i.e., the rate of rise of IEMG activity. Cough threshold was slightly higher in patients than in control subjects, but the difference failed to reach statistical significance. Compared with control subjects, patients displayed a lower IEMGP during maximal expiratory pressure maneuvers (PEmax), MVC, and RC (p always < 0.01); TEC during RC was longer (p < 0.01) than in controls. Consequently, the rate of rise of IEMG activity during cough was always lower in patients (p < 0. 01), especially during RC. Finally, PEmax, and both the peak and rate of rise of IEMG activity during RC were inversely related to the level of clinical disability (Spearman rank correlation coefficient, rs = -0.88, -0.86, and -0.85, respectively, p always < 0.01). The results indicate that the central neural mechanisms subserving the recruitment of motor units and/or the increase in their frequency of discharge during voluntary and, even more markedly, RC are impaired in patients with Parkinson's disease.
Olvanil (N-9-Z-octadecenoyl-vanillamide) is an agonist of transient receptor potential vanilloid type 1 (TRPV1) channels that lack the pungency of capsaicin and was developed as an oral analgesic. ...Vanillamides are unmatched in terms of structural simplicity, straightforward synthesis, and safety compared with the more powerful TRPV1 agonists, like the structurally complex phorboid compound resiniferatoxin. We have modified the fatty acyl chain of olvanil to obtain ultra-potent analogs. The insertion of a hydroxyl group at C-12 yielded a compound named rinvanil, after ricinoleic acid, significantly less potent than olvanil (EC(50) = 6 versus 0.7 nM), but more versatile in terms of structural modifications because of the presence of an additional functional group. Acetylation and phenylacetylation of rinvanil re-established and dramatically enhanced, respectively, its potency at hTRPV1. With a two-digit picomolar EC(50) (90 pM), phenylacetylrinvanil (PhAR, IDN5890) is the most potent vanillamide ever described with potency comparable with that of resiniferatoxin (EC(50), 11 pM). Benzoyl- and phenylpropionylrinvanil were as potent and less potent than PhAR, respectively, whereas configurational inversion to ent-PhAR and cyclopropanation (but not hydrogenation or epoxidation) of the double bond were tolerated. Finally, iodination of the aromatic hydroxyl caused a dramatic switch in functional activity, generating compounds that behaved as TRPV1 antagonists rather than agonists. Since the potency of PhAR was maintained in rat dorsal root ganglion neurons and, particularly, in the rat urinary bladder, this compound was investigated in an in vivo rat model of urinary incontinence and proved as effective as resiniferatoxin at reducing bladder detrusor overactivity.
An array of poly- and mononuclear complexes of Pt(II) with polypyridyl ligands is reported. The framework complexes (PtCl(2))(2)(bpp)(2)(micro-PtCl(2))(H(2)O)(2) bpp=2,3-bis(2-pyridyl)pyrazine, ...PtCl(2)(micro-tptz)PtClNCPhCl tptz=2,4,6-tris(2-pyridyl)-1,3,5-triazine, and mononuclear PtCl(2)(NH(2)dpt) NH(2)dpt=4-amino-3,5-bis(2-pyridyl)-1,2,4-triazole have been prepared and structurally characterized. Both neutral and ionic complexes are present, with bifunctional and monofunctional Pt(II) moieties, whose size and shape enable them to behave as novel scaffolds for DNA binding. Pt(II) complexes were tested for their biological activity. Cell viability assay and flow cytometric analysis demonstrated that these complexes, particularly PtCl(2)(micro-tptz)PtClNCPhCl, were effective death inducers in human colon rectal carcinoma HT29 cells and their cytotoxic activity was higher than that exerted by cisplatin. Morphological analysis of treated HT29 cells, performed by fluorescence microscopy after Hoechst 33258 staining, showed the appearance of the typical features of apoptosis. Moreover, our results suggested that mitochondria are involved in apoptosis induced by Pt(II) complexes in HT29 cells as demonstrated by dissipation of mitochondrial transmembrane potential.
Hicks was never tired of saying that monetary theory is in history. What he meant was that monetary theory is intrinsically related to real events, and more importantly that monetary issues need to ...be analysed in a dynamic sequential context in which time plays an essential part. He went on developing a particular sequential analysis: the study of what happens within a single period (‘single-period theory’) and the study of the linkages between a succession of those periods (‘continuation theory’). It is suggested that this distinction provides a useful lesson for modern endogenous money theorists.
To identify clinical application of intermittent hormonotherapy in prostatic carcinoma.
We conducted a systematic review in MEDLINE database and COCHRANE Library using the words MeSH "prostate ...cancer, androgenic deprivation and intermittent". There were included those with the best level of evidence and published in the last 10 years.
Intermittent hormone therapy is one of the tools we use in urological armamentarium for special circumstances. This analysis highlights: possibility to regain sexual function during the period of suspension of treatment (time off) due to the recovery of testosterone levels also demonstrating an improvement in symptoms, decreased costs preserving the same oncological control compared to complete androgenic deprivation.
There is still controversy about the benefits in quality of life and the emergence of long-term side effects typical of continuous hormonal therapy. Therefore and until now, we should only propose intermittent therapy in selected patients.
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