Neuronal NOS activation during oxygen and glucose deprivation triggers cerebellar granule cell death in the later reoxygenation phase

The present study investigated the temporal relationship between neuronal nitric oxide synthase (nNOS) activity and expression and the development of neuronal damage occurring during anoxia and anoxia followed by reoxygenation. For this purpose, cerebellar granule cells were exposed to 2 hr of oxygen and glucose deprivation (OGD) and 24 hr of reoxygenation. To clarify the consequences of nNOS activity inhibition on neuronal survival, cerebellar granule cells were exposed to OGD, both in the absence of extracellular Na(+) ([Na(+)](e)), a condition that by reducing intracellular Ca(2+) ([Ca(2+)](I)) prevents Ca(2+)-dependent nNOS activation, and in the presence of selective and nonselective nNOS inhibitors, such as N(omega)-L-allyl-L-arginine (L-ALA), N(omega)-propyl-L-arginine (NPLA), and L-nitro-arginine-methyl-ester (L-NAME), respectively. The results demonstrated that the removal of [Na(+)](e) hampered the [Ca(2+)](i) increase and decreased expression and activity of nNOS. Similarly, the increase of free radical production present in cerebellar neurons, exposed previously to OGD and OGD/reoxygenation, was abolished completely in the absence of [Na(+)](e). Furthermore, the absence of [Na(+)](e) in cerebellar neurons exposed to 2 hr of OGD led to the improvement of mitochondrial activity and neuronal survival, both after the OGD phase and after 24 hr of reoxygenation. Finally, the exposure of cerebellar neurons to L-ALA (200 nM), and L-NAME (500 microM) was able to effectively reduce NO(*) production and caused an increase in mitochondrial oxidative activity and an improvement of neuronal survival not only during OGD, but also during reoxygenation. Similar results during OGD were obtained also with NPLA (5 nM), another selective nNOS inhibitor. These data suggest that the activation of nNOS is highly accountable for the neuronal damage occurring during the OGD and reoxygenation phases.     

Optimization of power wheelchair control for patients with severe Duchenne muscular dystrophy

The extended survival of patients with Duchenne muscular dystrophy (DMD) achieved by the introduction of mechanical ventilation is raising new quality-of-life issues. We evaluated passive range of wrist extension, key pinch strength, and power wheelchair driving in 84 patients. The 47 drivers with restricted driving abilities were older than the 37 unrestricted drivers (27.2+/-5.0 y vs. 22.8+/-3.8 y) and had worse upper limb performance. By multiple logistic regression, only key pinch was significant ( R(2) = 0.224, P = 0.02. Eighteen restricted drivers were reassessed after having swapped a conventional joystick for another control system (mini-joystick, isometric mini-joystick, finger joystick, or pad) and having moved the position of the tested control system so that the patient could use it with different fingers, his chin or his mouth. All of them regained the ability to drive unrestricted. Adults with DMD gradually lose their ability to drive with a conventional joystick but can regain unrestricted driving with alternative control systems.     

Advantages and limits of percutaneous breast core biopsy with Mammotome and stereotactic equipment in upright seated patient

PURPOSE: To confirm the diagnostic accuracy of percutaneous core breast biopsy with Mammotome and stereotactic equipment in upright seated patients, and to compare results from this method with those obtained using the dedicated unit with prone table. MATERIALS AND METHODS: We analysed 72 microbioptic samples from 69 upright seated patients. These samples were obtained in the course of mammographies assisted by digital stereotactic equipment (Diamond Delta32 General Electric Medical System/Instrumen-tarium), and further equipped with a lateral arm to support the Mammotone probe. We studied the following lesions: 57 cases of isolated microcalcification clusters, 12 masses with microcalcification and three cases of plain masses. We describe in detail the various phases of our 30-minute long microbiopsy procedure. All 72 samples were extracted without problems. Only in one case a large haematoma emerged, but quickly disappeared. RESULTS: We were able to characterise the histology of the lesions in all our samples: in 39/72 cases they were identified as benign, 28 were classified as malignant, and the remaining 5 as atypia. In the 39 lesions identified as benign, the microbiopsy procedure could be carried out without surgical biopsy - consequently, these patients were available for routine follow-up exams, which confirmed the benign nature of their lesions. Our identification of the 28 malignant lesions was confirmed by surgical biopsy. The microbiopsy finding and the histological result did not agree in only two cases. The 5 cases with atypical ductal hyperplasia showed no neoplastic alteration following surgical biopsy. In our personal experience, core biopsy with Mammotome achieved a high diagnostic accuracy. CONCLUSIONS: After careful analysis of the results obtained using Mammotome in upright seated patients with stereotactic equipment, we can confirm the diagnostic accuracy of this procedure in mammography alterations not visible in sonography. In agreement with previous studies, we also confirm that the diagnostic accuracy of this approach, as well as possible complications deriving from it, do not depend on the position of the patient.     

DNA damage and ubiquitinated neuronal inclusions in the substantia nigra and striatum of mice following MDMA (ecstasy)

Rationale 3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative, which is neurotoxic to both serotonin (5HT) and dopamine (DA) nerve terminals. Previous reports, carried out in rodents and non-human primates, demonstrated neurotoxicity to monoamine axon terminals, although no study has analyzed nigral and striatal cell bodies at the sub-cellular level.Objective In this study, we examined intrinsic nigral and striatal cells, and PC12 cell cultures to evaluate whether, in mice, MDMA might affect nigral and striatal cell bodies.Methods After administering MDMA, we analyzed effects induced in vivo and in vitro using high-performance liquid chromatography (HPLC) analysis, light- and electron microscopy with immunocytochemistry, and DNA comet assay.Results We found that MDMA (5 mg/kg ×4, 2 h apart), besides a decrease of nigrostriatal DA innervation and 5HT loss, produces neuronal inclusions within nigral and intrinsic striatal neurons consisting of multi-layer ubiquitin-positive whorls extending to the nucleus of the cell. These fine morphological changes are associated with clustering of heat shock protein (HSP)-70 in the nucleus, very close to chromatin filaments. In the same experimental conditions, we could detect oxidation of DNA bases followed by DNA damage. The nature of inclusions was further investigated using PC12 cell cultures.Conclusions The present findings lead to re-consideration of the neurotoxic consequences of MDMA administration. In fact, occurrence of ubiquitin-positive neuronal inclusions and DNA damage both in nigral and striatal cells sheds new light into the fine alterations induced by MDMA, also suggesting the involvement of nuclear and cytoplasmic components of the ubiquitin-proteasome pathway in MDMA toxicity.     

New devices for imaging in nuclear medicine

Pinhole gamma camera imaging offers the ability to obtain high resolution images from single gamma ray emitting radiotracers playing a reasonable tradeoff between very small field of view (FoV) and sensitivity. On the other hand the total spatial resolution of a pinhole imaging device is predominantly affected by the detector intrinsic spatial resolution for reduced magnification factors. To design very compact pinhole SPET scanners with very high intrinsic spatial resolution, authors investigated a miniature gamma camera based on the newly developed Hamamatsu H8500 flat panel photomultiplier. The PSPMT was coupled to the following scintillation arrays: CsI(Tl) array with 0.2-mm, 1-mm, 1.4-mm pixel size and NaI (Tl) with 1-mm pixel size. The imaging performances were evaluated by 57Co spot and flood irradiations. NaI(Tl) array shows a better pixel identification for 1 mm pixel size, proving to be a good candidate to make a large area photodetector based on multi PSPMTs closely packed. Although CsI(Tl) array had the smallest pixel size, the low light output limited the best intrinsic spatial resolution to about 0.5 mm.     

Significant factors associated with fatal outcome in emergency open surgery for perforated peptic ulcer

AIM: To evaluate the main factors associated with mortality in patients undergoing surgery for perforated peptic ulcer referred to an academic department of general surgery in a large southern Italian city. METHODS: One hundred and forty-nine consecutive patients (M:F ratio=110:39, mean age 52 yrs, range 16-95) with peptic ulcer disease were investigated for clinical history (including age, sex, previous history of peptic ulcer, associated diseases, delayed abdominal surgery, ulcer site, operation type, shock on admission, postoperative general complications, and intra-abdominal and/or wound infections), serum analyses and radiological findings. RESULTS: The overall mortality rate was 4.0%. Among all factors, an age above 65 years, one or more associated diseases, delayed abdominal surgery, shock on admission, postoperative abdominal complications and/or wound infections, were significantly associated (chi2) with increased mortality in patients undergoing surgery (0.0001相似文献   

Lung transplantation in a Jehovah's witness. Case report in a twinning procedure

Jehovah's Witnesses, patients who refuse blood transfusions, are generally not considered as candidates for lung transplantation owing to the frequent requirement for transfusions. A successful procedure in a Jehovah's Witness is presented and to our knowledge this is the 2(nd) reported case. The patient, a 38-year-old female, type I diabetes, affected by idiopatic pulmonary fibrosis underwent left lung transplantation. From the same pulmonary bloc a twinning procedure was obtained by means of right lung transplantation in a 58-year-old man affected by the same pathology. Surgical strategies employed in achieving a successful outcome, ethical and moral aspects are discussed.     

Amphetamines induce ubiquitin-positive inclusions within striatal cells

Abstract. The present study explores whether effects induced by amphetamine derivatives on striatal GABA cells might be connected with effects on dopamine (DA) metabolism. Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) were administered to C57Black mice following a dosage regimen in which various doses of both drugs were injected i.p. at 2-h intervals. Neuronal inclusions produced under these experimental conditions were examined under electron microscopy. Drugs reducing DA availability prevented inclusion formation; conversely we observed that increasing DA synthesis or impairing physiological DA degradation enhanced the number of inclusions. The present study indicates that the presence of extracellular striatal DA is essential for the production of subcellular alterations induced by amphetamine derivatives. This is in line with a recent hypothesis connecting striatal DA release with degeneration of striatal GABA neurons.