Tachykinin-like immunoreactivity in the mammalian urinary bladder: correlation with the functions of the capsaicin-sensitive sensory nerves

The tachykinin-like immunoreactivity of the urinary bladder has been measured in various species by means of an antiserum (K12) having negligible cross-reactivity with substance P. The rank order for bladder content of tachykinin-like immunoreactivity was guinea-pig greater than mice greater than rat, similar to that found for substance P-like immunoreactivity. In all three species, both substance P- and tachykinin-like immunoreactivities were depleted by systemic capsaicin desensitization. The time course for depletion of substance P- and tachykinin-like immunoreactivities of the rat bladder following extrinsic denervation was almost superimposable. At reverse phase high pressure liquid chromatography, the major constituent of tachykinin-like immunoreactivity of the rat bladder co-eluted with neurokinin A. In vitro, the contractile response of the rat bladder to capsaicin (1 microM) was directly proportional to bladder tachykinin-like immunoreactivity while the response to field stimulation was not. In vivo, the volume threshold for reflex micturition was inversely proportional to bladder tachykinin-like immunoreactivity while amplitude of micturition contraction was not. Similar correlations were found in a previous study for substance P-like immunoreactivity. The contractile response to capsaicin or neurokinin A of the rat isolated bladder were significantly reduced by incubation with phenoxybenzamine at a concentration reported to produce a selective alkylation of neurokinin-2 receptors, while the response to substance P or KCl was unaffected. These findings indicate that multiple neurokinins co-exist in those bladder sensory nerves which are capsaicin-sensitive in adult rats. Both substance P- and tachykinin-like immunoreactivities in the rat bladder appear to be good functional markers of the sensory and "efferent" functions mediated by capsaicin-sensitive nerves, consistent with the hypothesis of a transmitter role for the corresponding peptides.     

The Nutraceutical N-Palmitoylethanolamide (PEA) Reveals Widespread Molecular Effects Unmasking New Therapeutic Targets in Murine Varicocele

Varicocele is an age-related disease with no current medical treatments positively impacting infertility. Toll-like receptor 4 (TLR4) expression is present in normal testis with an involvement in the immunological reactions. The role of peroxisome proliferator-activated receptor-α (PPAR-α), a nuclear receptor, in fertility is still unclear. N-Palmitoylethanolamide (PEA), an emerging nutraceutical compound present in plants and animal foods, is an endogenous PPAR-α agonist with well-demonstrated anti-inflammatory and analgesics characteristics. In this model of mice varicocele, PPAR-α and TLR4 receptors’ roles were investigated through the administration of ultra-micronized PEA (PEA-um). Male wild-type (WT), PPAR-α knockout (KO), and TLR4 KO mice were used. A group underwent sham operation and administration of vehicle or PEA-um (10 mg/kg i.p.) for 21 days. Another group (WT, PPAR-α KO, and TLR4 KO) underwent surgical varicocele and was treated with vehicle or PEA-um (10 mg/kg i.p.) for 21 days. At the end of treatments, all animals were euthanized. Both operated and contralateral testes were processed for histological and morphometric assessment, for PPAR-α, TLR4, occludin, and claudin-11 immunohistochemistry and for PPAR-α, TLR4, transforming growth factor-beta3 (TGF-β3), phospho-extracellular signal-Regulated-Kinase (p-ERK) 1/2, and nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) Western blot analysis. Collectively, our data showed that administration of PEA-um revealed a key role of PPAR-α and TLR4 in varicocele pathophysiology, unmasking new nutraceutical therapeutic targets for future varicocele research and supporting surgical management of male infertility.     

Home care. An emerging solution to the healthcare crisis

As the nation's policy makers and healthcare professionals have wrestled with changing the fundamental way that medical care is delivered in this country, they have considered many options. Home care is one option that should be considered seriously. It is one of the fastest growing segments of the U.S. healthcare system because it's cost-effective, improves patients' quality of life, and can efficiently treat patients with a broad range of medical conditions.     

The ret protooncogene is expressed in normal human parafollicular thyroid-cells

The RET proto-oncogene has been demonstrated to be expressed in medullary thyroid carcinomas and pheochromocytomas, and was mutated in patients with the multiple endocrine neoplasia type 2A (MEN 2A). The results presented herein show its expression in normal human thyroid parafollicular C cells. Since RET is predicted to encode a receptor for a still unknown ligand, these data confirm its involvement in the regulation and growth of these cells.     

Transthoracic 2D echo color Doppler assessment of internal mammary artery to left anterior descending coronary artery graft

For noninvasive evaluation of anatomy and flow characteristics of internal mammary artery graft (IMA-graft), 2D echo-Color-Doppler (CDE) was performed in 60 patients (54 M, 6 F, mean age 54.1±6.9 y), who underwent coronary angiography 20.1 ±13 months after a coronary artery bypass graft (CABG).CDE was performed, using an echocardiographic unit equipped with a 5 MHz linear transducer.In all patients, measurements of IMA-graft diameter (mm), and peak systolic and diastolic flow velocity (cm/sec) were obtained at baseline and also in 16 patients after dipyridamole infusion (0.54 mg/Kg/min) and in 10 patients after sublingual nitroglycerin (NTG) (0.4 mg). Angiography showed the IMA-graft patency in 58/60 patients (96.8%).A typical biphasic flow was displayed by CDE in 49/58 patients (84.4%) with angiographic patency.Dipyridamole infusion increased both IMA-graft diameter and peak diastolic flow velocity (PDFV) from 2.28 ±0.51mm to 2.9 ±0.42mm and from 19.4 ±6.2 cm/sec to 93.9 ±29 cm/sec, respectively (p<0.0001).No significant modifications of peak systolic flow velocity (PSFV) were observed.NTG increased PDFV from 29.11 ±8 cm/sec to 41.88 ±7.20 cm/sec (p<0.005), while diameter and PSFV showed no statistically significant modifications.CDE is a useful diagnostic tool for noninvasive evaluation of IMA-graft patency both early after surgery and during long-term follow-up. CDE pharmacological stress improves the sensibility of the technique and it can provide indirect information about pathophysiology of recipient coronary vessel.     

Production of tgf-Beta and hgf receptor by a differentiated papillary thyroid-carcinoma cell-line (B-cpap) - implication in malignancy

The B-CPAP cell line was obtained from a human differentiated papillary thyroid carcinoma. Previous studies showed that the cells present thyroid characteristics such as thyroglobulin production, phenotypic alterations such as synthesis of human chorionic gonadotropin hormone (HCG), expression of neuron specific enolase (NSE) and protein S100, and also somatic mutations of p53 and K-rns oncogenes. The present data further characterize this cell line and show an overexpression of transforming growth factor (TGF beta 1) and c-met gene product i.e. the receptor for human growth factor (HGF). The relation between the phenotypic and somatic alterations in the process of malignancy are discussed.     

Socioeconomic differences in mortality in Rome, 1990-1995

Population groups with a lower socioeconomic status (SES) have a greater risk of disease and mortality. The aim of this study was to investigate the relationship between SES and mortality in the metropolitan area of Rome during the six-year period 1990-1995, and to examine variations in mortality differentials between 1990-92 and 1993-95. Rome has a population of approximately 2,800,000, with 6,100 census tracts (CTs). During the study period, 149,002 deaths occurred among residents. We compared cause-specific mortality rates among four socioeconomic categories (SES) defined by a socioeconomic index, derived from characteristics of the CT of residence. Among men, total mortality and mortality for the major causes of death showed an inverse association with SES. Among 15-44 year old men, the strong positive association between total mortality and low SES was due to AIDS and overdose mortality. Among women, a positive association with lower SES was observed for stomach cancer, uterus cancer and cardiovascular disease, whereas mortality for breast cancer was higher in the groups with higher SES. Comparing the periods 1990-92 and 1993-95, differences in total mortality between socioeconomic groups widened in both sexes. Increasing differences were observed for tuberculosis and lung cancer among men, and for uterus cancer, traffic accidents, and overdose mortality among women. The use of an area-based indicator of SES limits the interpretations of the findings. However, despite the possible limitations, these results suggest that social class differences in mortality in Rome are increasing. Time changes in life style and in the prevalence of risk behaviors may produce differences in disease incidence. Moreover inequalities in the access to medical care and in the quality of care may contribute to an increasing differentials in mortality.     

Inequality in health: socioeconomic differentials in mortality in Rome, 1990-95

STUDY OBJECTIVE: Population groups with a lower socioeconomic status (SES) have a greater risk of disease and mortality. The aim of this study was to investigate the relation between SES and mortality in the metropolitan area of Rome during the six year period 1990-1995, and to examine variations in mortality differentials between 1990-92 and 1993-95. DESIGN: Rome has a population of approximately 2,800,000, with 6100 census tracts (CTs). During the study period, 149,002 deaths occurred among residents. The cause-specific mortality rates were compared among four socioeconomic categories defined by a socioeconomic index, derived from characteristics of the CT of residence. MAIN RESULTS: Among men, total mortality and mortality for the major causes of death showed an inverse association with SES. Among 15-44 year old men, the strong positive association between total mortality and low SES was attributable to AIDS and overdose mortality. Among women, a positive association with lower SES was observed for stomach cancer, uterus cancer and cardiovascular disease, whereas mortality for lung and breast cancers was higher in the groups with higher SES. Comparing the periods 1990-92 and 1993-95, differences in total mortality between socioeconomic groups widened in both sexes. Increasing differences were observed for tuberculosis and lung cancer among men, and for uterus cancer, traffic accidents, and overdose mortality among women. CONCLUSIONS: The use of an area-based indicator of SES limits the interpretations of the findings. However, despite the possible limitations, these results suggest that social class differences in mortality in Rome are increasing. Time changes in lifestyle and in the prevalence of risk behaviours may produce differences in disease incidence. Moreover, inequalities in the access to medical care and in the quality of care may contribute to an increasing differentials in mortality.     

Endovascular treatment in diseases of the thoracic aorta

PURPOSE: To determine whether endovascular treatment of thoracic aorta conditions can be an effective alternative approach to surgical repair. MATERIAL AND METHODS: July 1997 to February 1999, eighteen patients (16 men and 2 women; 58.6 +/- 14.8 years) presenting with different kinds of descending aorta conditions were selected for the endovascular treatment. All patients exhibited severe comorbid pulmonary and/or cardiovascular medical conditions which increased surgical risk. All implants were performed in the operating room under fluoroscopic and TEE guidance. Clinical and imaging follow-up was performed 1, 3, 6 and 12 months later. RESULTS: The endovascular treatment was successful in 17 cases. No deaths or major complications occurred. No leakage was evident at post-procedure angiography. The patients were discharged after 6 +/- 4 days. MRI or CT study performed before hospital discharge showed aneurysms exclusion in 16 patients. In the four cases of dissection, thrombosis of the false lumen was evident since the first follow-up study. In the group of patients (11 cases) with 6 months follow-up, the diameters of stented aortic segments decreased. No late leakage was observed and thrombosis was complete in all cases. DISCUSSION: The natural history of aortic aneurysms and dissection is progressive toward dilation and aortic rupture. Surgery of descending thoracic aorta is burdened with a mortality of 8-12% in elective cases and over 50% in emergency cases or aortic dissection. The endovascular treatment of aortic conditions was introduced in clinical practice in 1991 and literature data show that it is effective, with lower mortality and morbidity rates than surgical treatment. CONCLUSION: Our results stress the feasibility and effectiveness of endovascular procedure in the treatment of complex thoracic aorta conditions even in high risk patients. Thus, endovascular treatment of thoracic aorta can be considered an effective alternative approach to conventional surgery.