Genista sessilifolia DC. extracts induce apoptosis across a range of cancer cell lines.

OBJECTIVES: Restorative properties of medicinal plants such as Genista sessilifolia DC. have often been suggested to occur, in epidemiological studies. However, full characterization of effective principles responsible for this action has never previously been performed. Here, we have characterized G. sessilifolia's anti-cancer effects and identified the chemical components involved in this anti-tumour action. MATERIALS AND METHODS: Cell cycle, apoptosis, necrosis, differentiation analyses, high-performance liquid chromatography, western blotting, RNA extraction, real-time PCR and primers have all been observed/used in the study. RESULTS: We report that G. sessilifolia methanol extract has anti-cancer activity on solid and haematological cancer cells. G. sessilifolia extract's anti-proliferative action is closely bound to induction of apoptosis, whereas differentiation is only weakly modulated. Analysis of G. sessilifolia extract, by high-performance liquid chromatography, identifies fraction 18-22 as the pertinent component for induction of apoptosis, whereas fractions 11-13 and 27-30 both seem to contribute to differentiation. G. sessilifolia extract induces apoptosis mediated by caspase activation and p21, Rb, p53, Bcl2-associated agonist of cell death (BAD), tumour necrosis factor receptor super-family, member 10 (TRAIL) overexpression and death receptor 5 (DR5). Accordingly, fraction 18-22 inducing apoptosis was able to induce TRAIL. CONCLUSIONS: Our results indicate that G. sessilifolia extract and its fraction 18-22 containing genistin and isoprunetin, were able to induce anti-cancer effects supporting the hypothesis of a pro-apoptotic intrinsic content of this natural medicinal plant.

[An experimental model for assessing the risk factors for work-related stress in four Italian universities]. / Un modello sperimentale di valutazione del rischio stress lavoro-correlato: risultati ottenuti in ambito universitario.

This study, a collaborative effort among the Local Health Authority 2 of Perugia, Italy, the National Coordination of Worker's Safety Representatives for University and Research Institutions and the National Coordination for Protection and Prevention Services for Universities and Research Institutions, describes the results of a method used to evaluate work-related stress. Personnel from four Italian universities, which we call University I, II, III and IV geographically distributed in nord (1), center (2) and south (1) of Italy, responded to a questionnaire regarding risk evaluation of work-related stress in response to the Italian Law 81/2008. The methodology includes a preliminary analysis of the physical/technological and organizational/relational aspects of the company in order to determine a risk factor of work-related stress. This is followed by an evaluation by agencies competent in the areas of prevention and protection, (Administrative personnel of the company, Medical support persons, heads of the Prevention and Protection Service, employee representatives, and others) that apply a specific algorithm and by the employees through the completion of a questionnaire. The employees, mostly men, of the various universities, completed 510 questionnaires. Based on the results of the questionnaires and on a comparison between the expectations of the administration and the employees, the preventative measures that need to be adopted were identified. The results of this study show that there is not complete agreement between the administration and the employees regarding the work-related expectations. This difference in viewpoints could be a source of work-related stress. Some aspects of the study were shown to be of common concern in the various universities, while for other aspects, there were significantly different perceptions between male and female employees. An immediate response is needed with respect to some aspects in the work context and to plan further investigations where the results are not clear. The method used provides an adequate response to the legislative requirements and labor principles, in evaluating the risk of work related stress. In addition the method allows employees to contribute directly to the evaluation process.

Ligamentous reconstruction of scapholunate dislocation through a double dorsal and palmar approach.

Six patients were treated for scapholunate dissociation by reconstruction of both the palmar and dorsal parts of the scapholunate interosseous ligament through a combined palmar and dorsal approach. The mean active range of motion of the wrist at final follow-up was 44 degrees of flexion and 58 degrees of extension and the mean hand grip strengths was 88% of that of the contralateral hand. The average time to return to work was 105 days and the mean DASH score at a mean follow-up of 32 months was 18. At follow-up, radiographs showed maintenance of the anatomical reduction of the scapholunate articulation in all cases and the scapholunate angle was normal in five patients.

The upper limb in cerebral palsy: surgical management of shoulder and elbow deformities.

The authors report a simple chart that offers a comprehensive picture of spasticity of the upper limb and provides a more objective method of recording data. Distinction is made between fixed postures and the residual active range of motion at the shoulder and elbow. The presence and function of the muscles can be identified easily on dynamic EMG studies, which are essential for understanding the degree of spasticity and dyssynergy related to a single muscle. When spasticity of the upper arm is managed with a global approach and objectives are defined clearly in advance with the patient and caregivers, treatment of shoulder and elbow deformities can achieve important results for personal hygiene or functional targets.

Tetraplegia: update on assessment.

The overall assessment in the tetraplegic patient should be comprehensive and detailed. This paper discusses aspects of the medical and physical assessment that normally may go unrecognized but are extremely important in the outcome of the tetraplegic patient. A comprehensive classification also is provided as a new guideline for rehabilitation and surgery. Additionally, the power of [figure: see text] cultural, social, and personal dimensions of disability are illustrated and the importance of these dimensions as they relate to assessment is examined. Finally, the COPM is introduced as an outcome measure capable of crossing cultural [table: see text] boundaries and allowing for the comparison of interventions.

Nitric oxide donors in pregnancy: fetomaternal hemodynamic effects induced in mild pre-eclampsia and threatened preterm labor.

OBJECTIVE: The present study was performed to determine whether there are significant differences in the effects of the nitric oxide donor, glyceryl trinitrate, administration in pregnancies complicated by mild pre-eclampsia compared to the effects in pregnancies which are uncomplicated by this pathology. Glyceryl trinitrate is able to release nitric oxide (NO); deficiency of NO has been hypothesized in the pathogenesis of pre-eclamptic disorders. METHODS: In this prospective study, ten patients with threatened preterm labor and ten patients with mild preeclampsia were studied at around 30 weeks of pregnancy. The maternal blood pressure, maternal heart rate, fetal heart rate and flow velocity waveforms of the placental uterine artery, umbilical artery and fetal middle cerebral artery, evaluated by means of color Doppler and pulsed Doppler, were recorded before and 10, 20 and 30 min after the sublingual administration of 0.3 mg of glyceryl trinitrate or placebo. The pulsatility index (PI) was calculated. The percentage change from the control period (delta %) was calculated for each parameter at 10, 20 and 30 min. Ten normal pregnant women at the same gestational age were used as controls and were administered a placebo. RESULTS: The maternal blood pressure recorded as systolic and diastolic values, demonstrated a significant decrease in the pre-eclampsia group after glyceryl trinitrate administration; the delta % at any time considered was significantly higher in the pre-eclampsia group than in the threatened preterm labor group. The PI of the placental uterine artery showed a significant decrease in both groups after 20 and 30 min from drug administration; the delta % at 20 and 30 min was significantly higher in the pre-eclampsia group than in the threatened preterm labor group. The PI of the umbilical artery showed a significant decrease after 30 min from the glyceryl trinitrate administration. The fetal heart rate showed no significant variations during the study in either group. The PI of the fetal middle cerebral artery showed no significant variations during the study in either group. No parameter was changed in the control group. CONCLUSION: Glyceryl trinitrate administration was followed by a greater reduction of the resistance to blood flow in the fetoplacental circulation of the pregnancies affected by mild pre-eclampsia compared to pregnancies uncomplicated by this pathology. This effect can be attributed to the NO released by the drug which offsets the decreased production of NO, postulated to contribute to the pathogenesis of pre-eclampsia.

[Endoscopic sphincterotomy in acute biliary pancreatitis: the complications]. / La sfinterotomia endoscopica nella pancreatite acuta biliare: complicanze.

The authors report on a multicentric trial performed on early endoscopic sphincterotomy in severe pancreatitis. A large figure (7.764) of biliary pancreatitis was collected and 4.285 sphincterotomies were carried out. The results have been highly satisfactory: removal of hypertension and infection in biliary tree, stopped the trend toward necrosis and infection in almost all cases precociously treated. However, answering to the many doubts raised by some colleagues about the danger of this method, the authors examined all the complications that were reported. Hemorrhages and perforations of the biliary tree were the most common one. There were 120 (2.8%) hemorrhages, most frequently treated by medical means; in 20 cases a surgical hemostasis (1 death) had to be performed. Perforations, 24 (0.56%) were treated by medical therapy in 18 cases; 6 patients underwent surgical approach, with no deaths. Other complications (cholangitis, stent ruptures), less frequent, were treated successfully without surgical operations. The authors believe the main cause of this complications to be lack of experience and delay of endoscopic procedure (papillary oedema, fragility). What they suggest, is that endoscopic sphincterotomy has to be performed by an expert endoscopist, and within 48-72 hours from disease onset. Observing also that contrast introduced in the biliary tree could be harmful, they suggest to practice cholangiography at low pressure, and always leaving a nose-biliary drain. Endoscopic sphincterotomy, therefore, if correctly performed, reduces the necessity of surgery in severe pancreatitis. In this way, operations have to be carried out only in those patients with septic complications, with encouraging results and a sharp reduction of mortality.

[Endoscopic sphincterotomy in acute biliary pancreatitis. A multicenter study]. / La sfinterotomia endoscopica nella pancreatite acuta biliare. Studio multicentrico.

BACKGROUND: Severe acute pancreatitis are still dangerous, as can be seen from the high mortality rate (around 30%). It's commonly known that in the last years diagnostic ability, precise stadiation and control over the disease development were increased. Surgical therapy is directed mainly to achieve the control over septic evolution, and in biliary pancreatitis to resolve hypertension and infection inside the biliary tree (now widely accepted as the real cause of this disease). Recently, some authors demonstrated that the prognosis of a pancreatitis can be greatly improved by stopping the evolution toward a severe phase with necrosis and multiple organ failure without any surgical operation. They believe that's possible to achieve this result performing an early endoscopic sphincterotomy in all biliary pancreatitis (recognised by means of echography and CT scan), before the development of necrosis. METHODS: In our department, following this address, very good results have been obtained: that's why a multicentric trial has been carried out to appraise the results obtained by endoscopic sphincterotomy within 48 hours from the disease onset. Answers from 114 hospitals were received, with a total survey of more than 10,000 pancreatitis. Endoscopic sphincterotomy was performed in 55% of billiary pancreatitis, which were estimated at the onset, on second or third degree of Balthazar classification. RESULTS: In 86% of patients, endoscopic sphincterotomy was performed within 48 hours from symptoms onset. Complications related to this treatment are reported in less than 4% of patients. CONCLUSIONS: The procedure, avoiding the evolution toward necrosis and sepsis, allowed the reduction of surgical operations to 6.7%, and of the mortality amongst all cases gathered to 2.5%.

Doppler velocimetry of different sections of the fetal middle cerebral artery in relation to perinatal outcome.

To assess the standard curves of pulsatility index (PI) in different segments of middle cerebral artery (MCA): initial segment (MI) and subcortical segment (M2); to determine the variation of the flow velocity waveforms (FVW) of the M1 and M2 segments of MCA in presence of fetal distress and to establish the possible correlation between the two segments of MCA. 50 normal pregnancies from 25 weeks of gestation to term and 20 pregnancy with alteration of fetal growth rate were investigated with serial records of the FVW of the M1 and M2 segments of the MCA and of the umbilical artery (UA) with a colour Doppler system. Severe fetal distress was associated to cerebral-placental ratio below 1 (C/P < 1). The perinatal outcome was established on the basis: 1) abnormal intrapartum CTG, 2) emergency cesarean section, 3) Apgar score at 1st and 5th minute after birth and 4) birth eight centiles. In normal pregnancy P1 of M2 was always higher than that of M1: therefore M2/M2 resulted below 1, with a maximum peak near 32 weeks of gestation. In presence of moderate fetal distress only P1 of M2 was reduced (M1/M2 > 1). It exists a significant difference of PI in M1 and M2 segments of fetal MCA during gestation: thus MCA so it is important to identify the tract of fetal MCA when recording its FVW. Moreover we suppose that an initial "cerebral sparing" effect exists in order to protect the cortex by the initial hypoxic injury: this is shown by a M1/M2 > 1. The progression of fetal distress results in a greater haemodynamic modification, the so called "brain sparing" which is usually present when C/P < 1.

Impact of the L-arginine/nitric oxide system in pregnancy.

Nitric Oxide (NO) recently becomes of clinical interest because of its relaxant effects on smooth muscle. In addition to endothelial cells, also myometrial cells contain the enzyme implicated in the NO production. This review is aimed toward those studies concerned with the production, metabolism, and effects of NO that could be relevant for the obstetricians. The potential clinical interest of such information covers the main areas of pregnancy complications, namely preterm delivery, preeclampsia, and intrauterine growth retardation. Moreover, original data are included in order to support the therapeutical implications of the manipulation of L-arginine-NO system in case of pregnancy disorders.

Differentially expressed mRNAs as a consequence of oxidative stress in intact cells.

Intracellular redox conditions influence the activity of several transcription factors leading to a modulation of the expression of the genes controlled by these factors. We examined the changes in cell transcription patterns after oxidative stress induced by diethylmaleate (DEM). Using the differential display technique we identified several differentially expressed sequence tags, four of which are identical or highly homologous to sequences contained in the human cDNAs encoding vimentin, c-fos, cytochrome oxidase IV and ribosomal protein L4; another one corresponds to a transcript of the mitochondrial genome of unknown function. The remaining five cDNAs are not recorded in any sequence data bank. One of these, named Rox3, lights up two mRNA species of approximately 3400 and 3600 bp, significantly increased after treatment with DEM or with other oxidizing agents. This increase appears precociously after exposure to DEM and it is completely prevented by pretreatment with N-acetylcysteine. The Rox3 fragment was used to screen a cDNA library; one fully sequenced clone showed 100% homology with the putative human guanine nucleotide regulatory protein nep1.

Tourniquet paralysis in microsurgery.

Tourniquet paralysis is a serious complication after surgery. The authors report 15 cases recorded in their institution from 1972 to 1992. Seven were a consequence of routine operations on the upper limb and 8 were after microsurgical procedures. In the first group, the incidence of tourniquet paralysis was 1 in 7000 and this does not differ from published reports. In the second group, the incidence of complications is higher: 1 in 4300 cases. In all 15 cases the Tinel sign was absent. Great care was taken to distinguish all the painful conditions which ranged from simple hyperalgesia to allodynia and causalgia. The distressing aspect of tourniquet paralysis is that all the main nerves of the upper limb (median, radial and ulnar), distally to the elbow, are usually affected by the paralysis. In the two groups, the three nerves were affected in 13 cases and the ulnar nerve was partially spared in 3 cases. In both groups the radial nerve was more severely affected. It took an average of 105 days for complete recovery for the first group (range, 30-210 days) and 115 days for the second group (range, 20-180 days). Only in 1 patient in the first group was functional recovery incomplete. According to the authors' experience, general safety factors should be considered before using tourniquet. The tourniquet should be prohibited in patients with congenital susceptibility to nerve compression and should be used with caution in cases of underlying coagulation disorders and neuropathies, in tiny cachetic patients and in patients with systemic lupus erythematosus. In microvascular procedures its use should be limited to the first phase of replantation.

The role of telemetry in perinatal monitoring.

In the field of transmission and exchange of clinical information particularly good results are foreseen with the development of data telemetry. In perinatal medicine the telemetric technologies are being employed in several situations. It is possible to subdivide the telemetric technologies into short and long distance systems. Short distance telemetry employs devices which utilize radiowaves or laser techniques to transmit data from the original source to centralized equipment; the main application is the transmission of the cardiotocographic signal to permit ambulation of the patient during recording. It may allow fetal heart rate testing to be performed in a setting more acceptable to patients telemetric not be physically confined to a bed or a chair. The telemetric transmission of the cardiotocogram (CTG) may solve problems of organization when the ratio of parturient to midwife exceeds 1:1. Long distance telemetry consists of the telephone transmission of data obtained from distant source to a consultation center where the data can be evaluated, stored and where hospital staff may suggest appropriate decision related to clinical course. In prenatal medicine, the system can offer the monitoring of maternal blood pressure, automatic urine and glucose analyses, surveillance of fetal heart rate and uterine contractions. CTG telemetry has been used with good results for the prevention of preterm labor while blood pressure control by telemetry may be useful for the prevention and management of gestational hypertension. Knowledge by the pregnant woman that it is possible to continuously monitor by telemetric technology her health and the health of her fetus provides reassurance during a delicate period.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-term effects of ritodrine, aminophylline and atropine on umbilical artery blood flow velocity waveform.

With the recent introduction of Doppler technology, a non-invasive methodology which enables to evaluate qualitative changes in circulatory vessels, it is possible to investigate the possible effects of various drugs on several parameters of utero-placental-fetal circulation. In the present study we evaluate the flow velocity waveform (FVW) of umbilical artery (UA) during and after administration of aminophylline, atropine and ritodrine to healthy pregnant women. In our study we did not observe any significant short-term variation of PI after the administration of these drugs. Slight variations were detected, and they may be interpreted on the basis of the mode of action of these drugs. Doppler technology may be a useful tool for monitoring some effects on the fetus of the maternal administration of therapeutic agents.

The role of Doppler technology in the evaluation of fetal hypoxia.

Failing intrauterine support to the fetus can lead to intrauterine growth retardation (IUGR) and hypoxia and it is associated with a high risk of perinatal morbidity and mortality. The main effects of moderate to severe hypoxia on the fetus are different degrees of blood flow redistribution and reduction of oxygen consumption to maintain oxygen delivery to the central organs at the expenses of peripheral organs. The redistribution results in a 'brain sparing' effect. Recently, a Doppler ultrasonic technology (continuous wave, pulsed wave and colour flow imaging) has been developed for the non invasive measurement of flow. Doppler velocimetry detects the flow velocity waveform (FVW) which reflects the cardiac output, the vascular compliance and the resistance to the flow in a defined point of the vessel. Velocity waveform indices or even simpler criteria, such as the presence or absence of diastolic flow or flow reverse during diastole, have been applied to a number of fetal vessels. A significant relationship exists between blood oxygen, systemic lactic acidosis (determined by cordocentesis) and increase PI values in umbilical artery (UA), thoracic aorta (TA) and renal artery (RA). Moreover, in experimental animals during steady state hypoxia, several cardiovascular parameters are affected (heart rate/cardiac output decreases and blood pressure increases) while placental flow don't show a significant variation thus suggesting a raise in placental vascular resistance. Redistribution of the flow may be reliably evaluated by the cerebroplacental ratio (i.e. ratio between PI of MCA and PI of UA, c/p).(ABSTRACT TRUNCATED AT 250 WORDS)

[Ascites and carcinoma of the endometrium]. / Ascite e carcinoma dell'endometrio.

The authors exopound three cases of women affected by endometrial carcinoma in which the ascithis has represented the first clinic manifestation in absence of metrorrhage (first two cases); in the third case, instead, the ascithis has appeared four years after the surgical operation of total laparohysterectomy with bilateral annexiectomy and telecobaltotherapy. The association of the malign ascithis with endometrial adenocarcinoma is of rare observation. The Authors think very likely that the intraperitoneal semination in the cases they examined, is due to the infiltration of the myometry, of the regional and iuxtaregional lymphonoids with formation of ascithis.

Piezoelectric theory of enzymic catalysis as inferred from the electromechanochemical principles of bioenergetics.

Starting from the electromechanochemical principles of bioenergetics formulated by Green and Ji, a theory is proposed which describes enzymic catalysis in terms of piezoelectricity in semiconductors. The choice of this particular physical effect for describing catalytic processes is founded on the following experimental observations: most of the amino-acid residues of enzymes, as well as a large number of other biologically important molecules, exhibit piezoelectric resonances; besides, enzymes can behave like semiconductors. In the proposed theory the catalysis is assumed to be accomplished by means of three fundamental processes: (a) the lowering of the substrate-product energy barrier; (b) the electron-induced selective amplification of the low-frequency vibrational waves present in thermal background in the enzyme structure; and (c) the channeling into the substrate of the energy associated with the amplified waves and utilization of this energy for generating electrical or mechanical fields inside a susceptible region of the substrate. A mathematical description of the theory is outlined, and a rough estimate of some quantities involved in the process of wave amplification is also reported.