FACTORS GOVERNING THE PATTERN OF SPINDLE MICROTUBULE REGROWTH AFTER TUBULIN DEPOLYMERIZATION.

We analyzed the pattern of spindle microtubule (MT) regrowth after cold- or colcemid-induced MT depolymerization in Drosophila S2 cells. Cold-induced MT disassembly at low temperature (­2 °C) destroyed kinetochore-driven MT regrowth without affecting astral MT formation. Conversely, colcemid-induced MT depolymerization strongly impaired centrosome-dependent MT nucleation, allowing kinetochore-driven MT regrowth. Collectively, these results indicate that the kinetochore- and the centrosome-mediated MT assembly pathways exploit molecular mechanisms that are at least in part different.

Metformin-associated lactic acidosis requiring hospitalization. A national 10 year survey and a systematic literature review.

BACKGROUND: Metformin is known to be rarely associated with lactic acidosis, a serious condition with a poor prognosis. AIM: To review the National Pharmacovigilance Network of the Italian Medicines Agency reporting cases of metformin-associated lactic acidosis. MATERIALS AND METHODS: The National Pharmacovigilance Network of the Italian Medicines Agency, was searched for cases of lactic acidosis that occurred in a 10 years period (from November 2001 to October 2011). Data were analyzed, to identify associated clinical features. A systematic literature research was performed to identify other large case series on metformin associated lactic acidosis. RESULTS: Metformin was the antidiabetic drug most frequently associated with lactic acidosis in the assessed period. Metformin-associated lactic acidosis was the most frequent serious adverse reaction related to metformin reported to the national authority (18.2% of all 650 adverse drug reactions reported). There were 59 cases of metformin-associated lactic acidosis (mortality rate of 25.4%). In most patients (89.8%) there was at least one risk factor for the occurrence of lactic acidosis. The predictors of death were low arterial blood pH and absence of acute renal failure. The systematic research of the literature identified only six case-series with more than 30 patients. CONCLUSIONS: This is the second largest case series ever reported on metformin-associated lactic acidosis. We confirmed that this rare complication of metformin is frequently fatal. Death can be predicted when the patient arrive in the hospital with low pH and, not intuitively, if the patient has no acute kidney injury. Risk minimisation measures taken at national level to prevent this serious complication are described.

Modelling cephalopod-inspired pulsed-jet locomotion for underwater soft robots.

Cephalopods (i.e., octopuses and squids) are being looked upon as a source of inspiration for the development of unmanned underwater vehicles. One kind of cephalopod-inspired soft-bodied vehicle developed by the authors entails a hollow, elastic shell capable of performing a routine of recursive ingestion and expulsion of discrete slugs of fluids which enable the vehicle to propel itself in water. The vehicle performances were found to depend largely on the elastic response of the shell to the actuation cycle, thus motivating the development of a coupled propulsion-elastodynamics model of such vehicles. The model is developed and validated against a set of experimental results performed with the existing cephalopod-inspired prototypes. A metric of the efficiency of the propulsion routine which accounts for the elastic energy contribution during the ingestion/expulsion phases of the actuation is formulated. Demonstration on the use of this model to estimate the efficiency of the propulsion routine for various pulsation frequencies and for different morphologies of the vehicles are provided. This metric of efficiency, employed in association with the present elastodynamics model, provides a useful tool for performing a priori energetic analysis which encompass both the design specifications and the actuation pattern of this new kind of underwater vehicle.

Learning the inverse kinetics of an octopus-like manipulator in three-dimensional space.

This work addresses the inverse kinematics problem of a bioinspired octopus-like manipulator moving in three-dimensional space. The bioinspired manipulator has a conical soft structure that confers the ability of twirling around objects as a real octopus arm does. Despite the simple design, the soft conical shape manipulator driven by cables is described by nonlinear differential equations, which are difficult to solve analytically. Since exact solutions of the equations are not available, the Jacobian matrix cannot be calculated analytically and the classical iterative methods cannot be used. To overcome the intrinsic problems of methods based on the Jacobian matrix, this paper proposes a neural network learning the inverse kinematics of a soft octopus-like manipulator driven by cables. After the learning phase, a feed-forward neural network is able to represent the relation between manipulator tip positions and forces applied to the cables. Experimental results show that a desired tip position can be achieved in a short time, since heavy computations are avoided, with a degree of accuracy of 8% relative average error with respect to the total arm length.

Feeding-induced stimulation of luteinizing hormone secretion in male rhesus monkeys is not dependent on a rise in blood glucose concentration.

Recent studies have suggested a role for glucose availability in the central control of reproductive function. Various experimental paradigms have shown that a large pharmacological reduction in circulating or cellular glucose levels can suppress LH secretion, ovulation, and reproductive behavior. In contrast, states of undernutrition, which are also associated with a suppression of reproductive function, are accompanied by very mild changes in circulating glucose levels. In monkeys, 1 day of fasting leads to a significant suppression of LH secretion before any significant change in blood glucose levels, and by 2 days of fasting, circulating glucose levels only decrease by about 20%. Refeeding a normal meal after 2 days of fasting results in a restoration of euglycemia and a rapid stimulation of LH secretion. To test the hypothesis that physiological changes in glucose levels occurring during brief periods of fasting and refeeding can modulate LH secretion, we provided monkeys that had been fasted for 2 days with meals that differed in the ability to raise blood glucose levels. Meals consisting of mixed nutrients, carbohydrate only, or protein and fat were provided to monkeys through indwelling gastric cannulas. Mixed nutrient infusions and carbohydrate infusions caused a rise in blood glucose as well as a robust stimulation of LH secretion. However, protein and fat meals also stimulated LH secretion, even though no rise in blood glucose concentrations occurred. Thus, the restoration of pulsatile LH secretion when fasted animals are refed is not dependent on an elevation in circulating glucose levels. These results do not support the hypothesis that physiological changes in circulating glucose levels play a necessary role in mediating the changes in LH secretion that occur with fasting and refeeding. Alternatively, these results support the hypothesis that the availability of metabolizable fuels, regardless of their nature, provides a critical cue that regulates the central drive to the reproductive axis under physiological conditions of fasting and feeding.

Microalbuminuria, renal dysfunction and cardiovascular complication in essential hypertension.

OBJECTIVE: To evaluate the prevalence of microalbuminuria (albumin excretion rate, AER) in a wide hypertensive population, and to evaluate any relationship with cardiovascular damage and renal dysfunction. DESIGN: A transversal study. SUBJECTS AND METHODS: In 383 hospitalized Caucasian essential hypertensives (198 men, 185 women) of mean age 44 +/- 0.5 years and mean clinic blood pressure 170.3 +/- 0.95/ 103.4 +/- 0.47 mmHg, metabolic parameters, serum creatinine level (Cs), creatinine clearance rate (Ccs), 24 AER and plasma renin activity (PRA) were measured. Furthermore, each patient underwent 24 h ambulatory blood pressure monitoring (ABPM) and echocardiography to measure left ventricular mass, which was indexed both by body surface area to obtain left ventricular mass index (LVMI) and by height to obtain the left ventricular mass indexed for height (LVMH). By Doppler echocardiography, the diastolic compliance by early:late peak filling velocity ratio was analysed. The fundus oculi was also observed. Three subsets of hypertensives were obtained by dividing the 383 essential hypertensives on the basis of their AER: < or = 11 (group A), 11 < or = 20 (group B) and > 20 micrograms/min (group C). MAIN OUTCOME MEASURES: Microalbuminuria, creatinine clearance, PRA, ABPM, LVMI, LVMH, early:late peak filling velocity ratio, hypertensive retinopathy. RESULTS: Among the 383 essential hypertensives, AER was < 11 micrograms/min in 55% of the patients (group A), 18% had AER in the range 11-20 micrograms/min (group B) and 27% had AER > 20 micrograms/min (group C). In the entire essential hypertensive population the prevalence of left ventricular hypertrophy was 44.39% and hypertensive retinopathy was observed in 54.83%. Moreover, AER significantly correlated with clinic systolic blood pressure (SBP) and diastolic blood pressure (DBP), with 24 SBP and DBP and with 24 h daytime and night-time mean blood pressure (MBP). AER was correlated also with LVMH and creatinine clearance. The analysis of the three subsets revealed no differences in age, body mass index, serum creatinine level and PRA. Group C in comparison with group A showed higher values of clinic SBP, 24 h SBP, DBP and MBP, and of daytime and night-time MBP. Furthermore, in group C, LVMI and LVMH were significantly greater than in group A, with a prevalence of left ventricular hypertrophy of 55% in the former group. Group C showed a prevalence of hypertensive retinopathy of 69% whereas in group A the prevalence was 48%. In group C, AER was significantly correlated with serum creatinine level. CONCLUSIONS: The transversal phase of our research, performed in a homogeneous population of Caucasian essential hypertensives with no metabolic disturbances, confirms the relationship between blood pressure pattern and early glomerular changes in essential hypertensives without overt proteinuria. Furthermore, these results emphasize the role of microalbuminuria as a marker of early cardiac, renal and retinal structural and functional changes in essential hypertension. The longitudinal study, which is in progress, will confirm the prognostic value of microalbuminuria in essential hypertension.

Prevalence of biliary lithiasis in a Sicilian population of hemodialysis patients.

Studies performed to date on the prevalence of biliary lithiasis (BL) in chronic renal failure patients on hemodialysis (HD) have given contradictory results. The aims of the present study were to evaluate the prevalence of BL and its main associated risk factors in a population of hemodialysis patients, and to compare the results with those we had obtained previously in an overt population of the same zone. The study included 171 patients (83 M, 88 F), mean age 62.5 years and mean duration of dialysis 66.7 months. The screening protocol also included body mass index (BMI), a number of biochemical parameters and an ultrasound scan of the gallbladder and biliary tract. The general prevalence of BL was 33.3% (30.1% in men and 36.4% in women), and this figure was significantly higher than that found in our previous study. Prevalence increased with age in both sexes (Mantel-Haenszel Chi-squared = 5.4, p < 0.03), but not with duration of dialysis. The main risk factors, evaluated with multiple logisstic regression, were the presence of diabetes mellitus and high serum phosphorus levels. Specific symptoms were also significantly associated in BL patients. No association was found with parity, BMI or serum lipid alterations. In conclusion, the prevalence of BL in a Sicilian population of HD patients was higher than that found in an overt population of the same area and the associated main risk factors were not coincident. Further studies are needed to establish the role played by the phase of end-stage renal disease before HD and to correct the metabolic disturbances to limit a high percentage of morbidity in a disease already in itself sufficiently disabling.

[Skeletal manifestations of primary and secondary hyperparathyroiditis. Differential radiological diagnostic problems]. / Manifestazioni scheletriche dell'iperparatiroidismo primario e secondario. Problemi di diagnostica radiologica differenziale.

Primary and secondary hyperparathyroidism are both marked by widespread skeletal demineralisation, subperiosteal erosion of the cortex, brown tumours, osteosclerosis, and extraosseous calcification. Differential diagnosis is guided by the different association of these findings. Brown tumours and more extensive erosion are marks of the primary form, whereas osteosclerosis and extra-osseous calcification are a prominent feature of secondary hyperparathyroidism. Radiologists, therefore, should direct their attention to features suggesting the presence of secondary forms in addition to looking for bone alterations associated with hyperparathyroidism.

[Liver rupture in HELLP syndrome. Report of a case]. / Rottura epatica in corso di HELLP sindrome. Descrizione di un caso.

Liver rupture and hemorrhage, are the most unusual and serious complications of HELLP syndrome (hemolysis--elevated liver enzymes--low platelet count). The management should be aggressive by treating coagulopathy and favouring a prompt delivery. Liver rupture remains a surgical emergency with control of bleeding based on trauma surgery. The aggressive approach to the management of these patients led to a remarkable decrease of mortality rates.

Intrahepatic cholestasis by paucity of interlobular bile ducts in infancy.

On the basis of an extensive review of the literature and their personal experience, the authors consider that neonatal PILBD should not be regarded as merely a malformative anomaly of the bile excretory system, but as a delayed growth of the pars cystica of the hepatic bud in comparison with the normal growth pattern of the cranial part of the same hepatic bud. This leads to the development of hepatocytes and ductal plate, and these, in turn, are the origin of the perilobular or terminal bile ducts (Hering's ampullae) which eventually fuse with interlobular bile ducts for establishing the continuity of the bile duct system. The authors base this hypothesis on their L.M. and E.M. investigations and the casual observation of two cases in which the well documented bile duct anomaly eventually turned into a normal liver histology.

[Warthin's tumor of the parotid gland]. / Il tumore di Warthin della parotide.

The Authors report 6 cases of Warthin's tumor of the parotid gland recently observed. In all cases the tumor was intraglandular, single, and no noteworthy disorders or symptoms except for a 2 to 5 cms tumefaction were present. At surgery all lesions appeared well-capsulated and the exeresis followed a cleavage plane easily identifiable which enabled the preservation of the residual glandular tissue as well as the surrounding nervous and vascular structures. All the patients, up to now, are free from relapse.

[Ulcerated carcinoma of the breast in an elderly woman. An unusual clinical case report]. / II carcinoma ulcerato della mammella nella donna anziana. Osservazioni su un caso clinico peculaire.

The authors analyze the most current methods for the treatment of ulcerated breast cancer in the elderly. They describe a peculiar case recently observed, characterized by an ulcerative lesion spreading from the hemiclavicle to the foreaxilla including the axillary cavity, causing a large phlebo-lymphaedema, anaesthesia and paresis of the homoteral upper limb. After an initial treatment with tamoxifen a scapulo-humeral disarticulation and a suture of the cutaneous wide defect were performed using a myo-skin graft which included the deltoid muscle. A radiotherapeutic treatment followed by tamoxifen therapy was carried out. No distant metastases and no local relapses were registered in the one year follow up. The Authors on the basis of their experience and according to the review of the Literature suggest that age itself is not a limiting factor to the therapeutic approach of ulcerated breast cancer.

A 3D steady-state model of a tendon-driven continuum soft manipulator inspired by the octopus arm.

Control and modelling of continuum robots are challenging tasks for robotic researchers. Most works on modelling are limited to piecewise constant curvature. In many cases they neglect to model the actuators or avoid a continuum approach. In particular, in the latter case this leads to a complex model hardly implemented. In this work, a geometrically exact steady-state model of a tendon-driven manipulator inspired by the octopus arm is presented. It takes a continuum approach, fast enough to be implemented in the control law, and includes a model of the actuation system. The model was experimentally validated and the results are reported. In conclusion, the model presented can be used as a tool for mechanical design of continuum tendon-driven manipulators, for planning control strategies or as internal model in an embedded system.

[Combined radiochemotherapeutic approach to bronchogenic carcinoma: criteria of applicability and limits]. / L'approccio combinato radio-chemioterapico al carcinoma broncogeno: criteri applicativi e limiti.

The knowledge of the natural history of pulmonary cancer had led to both an improvement of the techniques and methods of radiation treatment and the use of chemotherapy in association with radiation therapy. Such an association leads to graver and more frequent pulmonary reactions. The development of a particular discipline (the toxicology of radiation) could contribute to predict the incidence and the extent of reaction. A more precise combined approach to the treatment of pulmonary cancer would therefore be possible.