Interactions between heme and tau-derived R1 peptides: binding and oxidative reactivity.

The interaction of hemin with the first 18-amino acid repeat in tau protein has been investigated at both the N-terminal free-amine (R1τ) and N-acetylated (AcR1τ) forms for its potential relevance in traumatic brain injury and possibly other neurodegenerative diseases. The binding properties of hemin-R1τ and hemin-AcR1τ were compared with those of the hemin complex with amyloid-ß peptide fragment 1-16 (Aß16) and synthetic hemins. AcR1τ and R1τ bind with moderate affinity to both monomeric and dimeric hemin to form 1 : 1 complexes, but for the acetylated peptide, the affinity is one order of magnitude larger (K1 = 3.3 × 10(6) M(-1)). The binding constants were similar to that of Aß16 for hemin, but unlike the latter, neither of the two R1τ peptides forms a 2 : 1 complex with hemin. This is mostly due to electrostatic repulsion between R1τ chains, and in particular the C-terminal proline-15 kink, while structural features of the hemin-R1τ complexes do not seem to play a role. In fact, the same features are observed for the interaction between ferric heme and peptide R1τ*, where the P15 residue is replaced by an alanine. Imidazole neither binds to [hemin(R1τ)] nor [hemin(AcR1τ)], whereas small ligands such as CN and CO easily bind to the ferric and ferrous forms of the complexes, respectively. A detailed comparative study of the peroxidase activity of [hemin(R1τ)] and [hemin(AcR1τ)] shows that such activity is very low. Thus, the association between heme and unfolded neuronal peptides does not, per se, involve a significant gain of toxic pseudo-enzymatic activity. However, under conditions of heavy heme release occurring on traumatic brain injury or when this activity is prolonged for long time, it can contribute to neuronal oxidative stress. In addition, the presence of hemin increases the aggregation propensity of R1τ.

Intracerebral haematoma following spinal anaesthesia for caesarean section: case report.

Several complications are known to occur with spinal anaesthesia and all of them are easily recognizable. We report the case of a 25 year old woman presenting with intracerebral hemorrhage secondary to spinal anaesthesia for caesarean section. She underwent surgical evacuation of the haematoma with complete recovery. The relevant literature is also reviewed.

[Urethral and prostatic urologic endoscopic surgery in day hospital]. / Chirurgia endoscopica urologica uretrale e prostatica in Day Hospital.

We evaluated urethral and prostatic urological endoscopical surgery in Day Hospital, following rules proposed by Veneto Region in 1996. We made surgical treatments for urethral strictures, BPH obstruction, and sclerosis of the bladder neck in 44 patients (age: 67-84). Laser therapy and classical surgical techniques were used. Our results were good: complete resolution of obstruction, lack of bleeding, early catheter removal, and acceptable costs.

High-Repetition-Rate Q-Switched Diode-Pumped Nd:YAG Laser at 1.444 mum.

A diode-pumped Q-switched Nd:YAG laser that operates at the eye-safe 1444 nm wavelength has been developed. When pumped by a 10-W fiber-coupled array at 808 nm, it generated 1 W in cw operation and 560 mW at 20-kHz repetition rate with active Q-switching. Design issues such as thermal lensing characterization and beam quality are discussed.

Design and characterization of a diode-pumped, single longitudinal and transverse mode, intracavity-doubled cw Nd:YAG laser.

We report on the experimental results of a diode-pumped, intracavity-doubled cw Nd:YAG laser, pumped by a 10-W fiber-coupled semiconductor laser at 808 nm and emitting as much as 600 mW in a stable single longitudinal mode and TEM(00) spatial mode. We discuss the main issues of the resonator design and the optimization of the intracavity second harmonic conversion by interpreting our results using simple models. Improvements for the current project are also discussed.

[Orthotopic ileal neobladder of the Emikock type: technical points and functional results]. / La neovescica ileale ortotopica tipo Emikock: attualità tecniche e risultati funzionali.

Ileal orthotopic neobladder represents, nowadays, the best urinary diversion after cystectomy. Emikock procedure was performed, in our institution, in 26 patients with bladder cancer T2-T4. At 6-60 months of follow-up 3 pts were died with local or at distance neoplastic recurrence, 2 were alive with neoplasms and 21 were NED. Nocturnal continence was good in 22 cases (88%) and only 3 patients were obstructed because of pseudodyssynergia in 2 and stricture in 1. Emikock neobladder even if needs a longer surgical time than other procedure and a long ileal tract is almost free from severe metabolic disorders. This technique offers a good protection of high urinary tract because of antireflux nipple and avoid the uretero-intestinal stricture. It not feasible, now, to know the functional trend of this reservoir on the long term. Adequate postoperative training is recommended to avoid the pseudodyssynergia and functional obstruction of reservoir.

[Iatrogenic obstructive azoospermia]. / Azoospermie ostruttive iatrogene.

Obstructive azoospermia is a common cause of sterility in men. In the past infection played an important role in the aetiology of obstructive azoospermia. Recently, however, the aetiology of obstructive azoospermia appears to be changing. So iatrogenic obstructive azoospermia has reached an important role in the field of obstructive azoospermia. In this work we show international literature about iatrogenic obstructive azoospermia. Unfortunately it is poor, in spite of an interesting item. We divided iatrogenic obstructive azoospermia into six groups, considering the possible anatomical site of obstruction. So we show the possible damages at the different levels: testis, epididymis, vas deferens, seminal vesicles, prostate and ejaculatory ducts.

Gonadotropin levels in women with polycystic ovary syndrome: their relationship to body weight and insulin levels.

The purpose of this work was to investigate the relationship of gonadotropin levels to body weight and insulin levels in woman with polycystic ovary syndrome (PCOS). Specifically, we wished to test the hypothesis that circulating luteinizing hormone (LH) and insulin levels are different in obese and normal weight patients with PCOS. The basal plasma levels of gonadotropins, estrogens, androgens and sex hormone-binding globulin, the gonadotropin responses to gonadotropin releasing hormone (GnRH) and the insulin and C-peptide responses to a 3-hour oral glucose tolerance test (OGTT) were measured in 19 obese and 19 normal weight patients with PCOS and 7 obese and 8 normal weight ovulatory controls. Data of the patients were evaluated according to body weight (obese vs normal weight) and basal LH (high vs normal). There was no significant difference in basal LH and androgen levels and in the insulin response to oral glucose between obese and normal weight patients with PCOS. Compared to the weight matched controls, both obese and non obese patients showed significantly higher LH responses to GnRH and C-peptide responses to OGTT. When the high LH patients (no = 18) were compared those with normal LH (no = 20), the high LH subjects exhibited significantly higher androstenedione levels. Both obese (no = 10) and normal weight (no = 8) patients with high LH showed significantly greater C-peptide responses to OGTT than obese (no = 9) and non obese (no = 11) patients with normal LH. However, as compared with the weight matched controls, both the high LH and normal LH patients had significantly greater C-peptide responses to OGTT. We conclude that obese and non obese patients with PCOS do not seem to differ in the prevalence of elevated LH levels or in the LH secretory pattern. Insulin resistance, expressed by an enhanced pancreatic sensitivity to oral glucose, is present in both the high LH and the normal LH subjects, even though the PCOS patients with elevated LH tend to be more insulin resistant and hyperandrogenic than the normal LH patients.

Effects of interferon-beta on steroid receptors, prostaglandins and enzymatic activities in human endometrial cancer.

Steroid receptors, prostaglandin output and enzymatic activities were determined in explants derived from human endometrium exposed to natural interferon-beta (IFN-beta). Receptors and cell metabolism were evaluated before culturing the tissue fragments and after a 3-day treatment with varying concentrations of IFN-beta. Total steroid receptor levels were unchanged when explants were set up, but there was a redistribution of both estrogen and progesterone receptors (ER and PR). A decrease in cytoplasmic receptors corresponded to an increase in receptor molecules within the nucleus. Treatment with low concentrations of IFN-beta caused a significant enhancement (p < 0.05) of ER and PR in neoplastic endometrium. In basal conditions the ratio between prostaglandin F2 alpha (Pgf2 alpha) and prostaglandin E2 (PgE2) was higher in normal than in neoplastic endometrium. The addition of low concentrations of IFN-beta to the culture medium determined a significant increase (p < 0.02) in PgF2 alpha and a parallel increase in the above ratio in neoplastic tissue, while no variation was found in normal endometrium. Analysis of the results concerning the variations in hormone-related enzymatic activities due to IFN-B revealed a significant increase (p < 0.05) in 17 beta-hydroxy-steroid-dehydrogenase (17 beta-HSD) activity. The data presented here indicate that treatment with IFN-beta modifies those biological characteristics of neoplastic cells which are involved in hormone-responsiveness.

[External devices: for which patients?]. / Dispositivi esterni: a quali pazienti proporli?

Vacuum therapy is a reversible, non-invasive form of treatment for partial impotence, with great success in USA. The story of vacuum therapy begins about 1960, when Osbon developed a vacuum tumescence device which he personally used for more than 20 years. The device was made commercially available many years ago and has been marketed under several names. The newer systems have incorporated a negative pressure pump to achieve vacuum. Osbon's system was patented in 1983, sale is permitted by the U.S. Food and Drug Administration, and it is available by prescription only. More than 10,000 units have been sold. There are four different types of vacuum therapy: 1) loading cone + constriction band; 2) external splint + negative pressure; 3) Negative pressure + constriction band; 4) Negative pressure + intracavernous injections, without the use of constriction band. Each basic system will be described. The authors make a comparison between the use of negative pressure devices plus tension band and the use of negative pression devices without tension band (plus C.I.D. with vaso-active agents). In the second case there's a sort of synergistic action between vaso-active agents and vacuum therapy, representing a sort of "vaso-active exercise" of the erectile tissue. There are no absolute contraindications to use of external penile devices and potential contraindications are few. The external penile devices described represent a reversible therapeutic modality that can augment an inadequate erection and they should prove useful in any man who needs erectile enhancement. These devices appear to be particularly effective in men with partial impotence in whom only erectile enhancement is needed.

[Radical prostatectomy: our experience]. / Prostatectomia radicale: la nostra esperienza.

Between July 1989 and June 1994 32 men (48-73 years old) underwent radical retropubic prostatectomy for prostate cancer. 26 patients (70%) presented with symptoms of bladder outflow obstruction. The primary tumour was understaged preoperatively in 5 patients (15.5%). At follow-up (6-66 months, average 24) significant urinary incontinence not occurred in our patients; sixty-two per cent reported a substantial problem with reduced or absent erection. A total of 23 patients was free of clinical or biochemical progression, observed in 28% of cases as distant or local progression. Radical prostatectomy is being performed with increasing frequency: trends in morbidity have been identified.

Prognostic role of laparoscopic salpingoscopy of the only remaining tube after contralateral ectopic pregnancy.

OBJECTIVE: To evaluate the prognostic value of laparoscopic salpingoscopy in detecting patients who are at increased risk for a repeat ectopic pregnancy (EP). DESIGN: Patients with secondary infertility after a previous contralateral salpingectomy for EP were evaluated by laparoscopy with tubal perfusion and salpingoscopy of the only remaining tube. Subsequent reproductive outcome was evaluated and correlated to laparoscopic and salpingoscopic findings. SETTING: Department of Obstetrics and Gynecology of the Catholic University, a tertiary care university center in Rome, Italy. PATIENTS: Eighteen patients submitted to laparoscopy and salpingoscopy after a previous salpingectomy for EP. INTERVENTION: A two- to three-puncture laparoscopy with tubal perfusion and salpingoscopy. MAIN OUTCOME MEASURE: Reproductive outcome after a mean follow-up of 42.6 months. RESULTS: Salpingoscopy revealed a normal tubal mucosa in 13 patients (72%) and intra-ampullary adhesions in 5 patients (28%). Eight of the 13 patients with a normal mucosa conceived an intrauterine pregnancy. In the 5 patients with intra-ampullary adhesions, there were 3 repeat EPs, with one patient having first a term pregnancy and then a repeat EP. The presence of peritubal adhesions at laparoscopy was not of prognostic significance. CONCLUSION: Direct visualization of the ampullary mucosa by salpingoscopy can allow the detection of intraluminal adhesions that put the patient at increased risk for a repeat EP.

[Benign prostatic hypertrophy. Optimized diagnosis]. / Ipertrofia prostatica benigna. Diagnostica ottimizzata.

The optimal diagnostics of B.P.H. must be efficient, cheap and of spare invasiveness either physical than psychological. The optimization of diagnosis is the obtainment of high quality in the services provided, matched to a correct and shrewd utilisation of resources. To optimise a diagnosis efficiency is necessary, which means the largest degree of standardization of diagnostical procedures, with responsible management of economical factors. A course of standardization, cause his excessive simplification, cannot shared to a lot of Urologists, because in their opinion there is a risk to lose informations in every single patient, but is essential to use a universal language that make easy the comparison with patients and with results whether in order to clinics or trails. The standardisation of diagnostics consists to obtain the maximum of informations from present methodology and that is possible to realize in two way: improving the technique of execution and including the diagnostic test in the appropriate point of algorithm.

[TURP: what and when. Indications, results, complications: our experience]. / TURP: quale e quando. Indicazioni--risultati--complicanze: nostra esperienza.

Transurethral resection of the prostate (T.U.R.P.) has indeed replaced open surgery in the great majority of cases, particularly when the gland is estimated to weight 50-60 g or less. After prostatectomy the patient resumes a normal voiding pattern and obstructive symptoms quickly disappear, although irritative symptoms tend to persist for some time.

[Penile nuclear magnetic resonance (NMR)]. / La risonanza magnetica nucleare (RMN) peniena.

Nuclear Magnetic Resonance (NMR) is a new diagnostic technique with great opportunities of application in the field of the penile pathologies. A new interest for this diagnostic technique was born when the use of vasoactive agents, like papaverine or PGE1, and the use of para-magnetic contrast agents, like gadolinium, were introduced. The introduction of dynamic NMR in andrology allowed a better definition of anatomical details and a better knowledge of penile micro-circulation. N.M.R. is showing a great diffusion, because of a little invasiveness (X-rays are not used in this technique). The Authors show a wide spread of possible applications of NMR in penile pathologies, helping in the interpretation of the images. In conclusion the authors describe NMR as a diagnostic technique with great possibilities of improvement, even if the high costs don't allow a better diffusion until now.

[Sexuality and neoplastic disease]. / Sessualità e malattia neoplastica.

Authors review principles and occurrence of sex-impairment correlated with neoplasia and related treatments. Main altering effects appear due to chemotherapy and hormone manipulation, but even surgery and radiotherapy, as well as supportive care are able to induce sex dysfunctions, either physically or psychologically. A specific grading scale (with increasing intensity from 0 to 4) is proposed, following general WHO suggestions in medical oncology, with the aim of recording and prospectively evaluating clinical data in a reproducible fashion.

Interferon-beta increases the sensitivity of endometrial cancer cells to cell-mediated cytotoxicity.

Established monolayer cell lines derived from human endometrial carcinoma (Ishikawa and HEC-50) were sensitive to the cytotoxic activity of peripheral blood lymphocytes (PBLs). The percentages of hormone-responsive Ishikawa cells lysed by the cytotoxic activity of lymphocytes were 45.7 +/- 4.3 (mean +/- SE), 31.5 +/- 4.1, and 20.1 +/- 1.6, at effector/target (E/T) ratios of 50:1, 25:1, and 12:1, respectively. Values of 44.7 +/- 5.4%, 29.4 +/- 4.6%, and 20 +/- 4.9% were obtained when non-hormone-responsive HEC-50 cells were used as targets at the same E/T ratio. The percentages of epithelial and stromal cells, isolated from human endometrial cancer, lysed by the cytotoxic activity of lymphocytes were 40 +/- 5.4 and 25.2 +/- 3.8, respectively, at an E/T ratio of 25:1. The addition of interferon-beta (IFN-beta) to the culture increased tumor target cell sensitivity to the lytic activity of untreated PBL. The increase produced by 10 IU/ml of IFN-beta ranged between 0.60- and 0.89-fold (P < 0.01 Student's t test, two-tailed, unpaired) in Ishikawa cells and between 0.37- and 0.72-fold P < 0.05) in HEC-50 cells. Higher concentrations of IFN-beta (100 and 1000 IU/ml) were less effective in increasing the sensitivity of the target cells. There was no significant increase in the cytotoxic activity of lymphocytes treated with IFN-beta whereas cytotoxic activity toward untreated tumor target cells increased when lymphocytes were treated with IFN-alpha. The effects of IFN-beta were also evaluated using epithelial and stromal cells derived from human endometrial cancer. It was found that IFN-beta at low concentrations (10 IU/ml) significantly increased the sensitivity of both epithelial and stromal cells, by 48 and 73%, respectively. Our data indicate that Ishikawa, HEC-50, epithelial, and stromal cells may provide a useful experimental model for studying the effects of immunomodulant agents such as IFN-beta in hormone-related tumors. IFN-beta increases endometrial target cell sensitivity, rather than the lytic activity of lymphocytes.

Insulin, C-peptide, androgens, and beta-endorphin response to oral glucose in patients with polycystic ovary syndrome.

We examined the effects of an oral glucose load on plasma insulin, androgens, and beta-endorphin (beta EP) concentrations in patients carefully selected as having polycystic ovary syndrome (PCOS) and normal glucose tolerance. Our aim was to verify whether insulin resistance is a common feature of PCOS and to differentiate the metabolic abnormalities related to PCOS from those associated with obesity. Plasma immunoreactive insulin (IRI), C-peptide (C-PR), testosterone, androstenedione, dehydroepiandrosterone sulfate, ACTH, and beta EP responses to a 3-h oral glucose tolerance test (OGTT) were evaluated in 10 obese (OB-PCOS) and 10 nonobese (NO-PCOS) patients with PCOS and in 7 obese and 7 nonobese ovulatory controls. OB-PCOS and NO-PCOS did not differ significantly from weight-matched controls in the IRI response, but had a significantly higher C-PR response in terms of mean postglucose load levels and mean incremental areas. During OGTT, mean plasma levels of testosterone, androstenedione, and dehydroepiandrosterone sulfate declined in both PCOS groups as well as in controls, and no significant correlation between the plasma androgen and IRI or C-PR responses was found. The ACTH response in OB-PCOS and NO-PCOS was similar to that in controls, with a progressive decrease until 180 min. A similar decline in plasma beta EP was found in controls, whereas no change in plasma beta EP was observed in OB-PCOS and NO-PCOS. These findings indicate that independently of the presence of obesity, PCOS patients have enhanced insulin secretion in response to OGTT and show a peculiar pattern of changes in plasma beta EP.

GnRH analogs versus expectant management in minimal and mild endometriosis-associated infertility.

The aim of the present study is to compare the outcome of GnRH analog treatment versus expectant management in infertile patients with minimal and mild endometriosis. From January 1987 to December 1990, 14 patients with stage I and II endometriosis underwent a six-month course of the GnRH analog buserelin, whereas 38 patients underwent expectant management. The two groups were comparable as to mean age of the patients, mean length of infertility prior to diagnosis and mean scores of endometriosis. No major tubal or male factor of infertility was present in any patient. Cumulative pregnancy rates at 12 months were comparable in the two groups (48% for GnRH analog treatment and 42% for expectant management). Expectant management should therefore be considered the most cost-effective option in the management of mild endometriosis-associated infertility.

Preventive treatment of cortical bone loss with salmon nasal calcitonin in early postmenopausal women.

Thirty early postmenopausal women having risk factors for osteoporosis entered and 23 completed a six months double-blind placebo controlled study of the effect of nasal salmon calcitonin (SCT) (100 IU daily) plus oral calcium on bone turnover, cortical bone mass and sex-steroids. After the double-blind study SCT treatment was continued for six months in 20 women in both groups. A six months nasal SCT treatment was found to be effective in significantly increasing cortical bone mass and the gain was maintained following a 12 months treatment. The nasal SCT treatment was effective in significantly reducing parameters of bone turnover, as indicated by osteocalcin pBGP and urinary hydroxyproline levels, while during placebo administration an increasing trend of pBGP suggested a state of increasing bone remodeling. During the study, a small decrease in plasma testosterone not related to cortical bone mass and bone turnover was observed.