Non-Surgical Ablative Therapy for Management of Small Renal Masses-Current Status and Future Trends.

A large number of small renal masses (SRMs) with size less than 4 cm are being identified due to advances in diagnostic imaging. As the natural history of these tumours remains unknown, there is no reliable way to predict their behaviour or future growth. Although, partial nephrectomy is the gold standard for treatment of these tumours, ablative non-surgical therapies such as cryoablation and radiofrequency ablation provide a less invasive option of treatment with comparable oncological outcomes. In this systematic review, the principle, indications, methods of treatment, oncological control, complication and renal function of ablative therapies are critically reviewed. Cryotherapy utilizes the principle of inducing tissue destruction by freezing and thawing using argon and helium gasses, respectively. Radiofrequency ablation (RFA) works on the principle of tissue heating. Ablative treatments are particularly useful in the elderly patients, those with comorbidities or in patients with SRMs in solitary kidneys or renal impairment. Ablative therapies have less procedure-related complications and have promising medium-term oncological outcome. Longer-term results are accumulating. Cryotherapy may be a better modality for oncological control than RFA. Ablative therapy has emerged as a viable treatment options for SRMs with recurrence free survival rates approaching that of extirpative surgery. However, there is no consensus in the literature on the best selection criteria and this needs further refinement. Prospective long-term data with regards to oncological control is still needed.

Plant communities in multi-metal contaminated soils: a case study in the National Park of Alta Murgia (Apulia region - Southern Italy).

A phytosociological study was conducted in the National Park of Alta Murgia in the Apulia region (Southern Italy) to determine the adverse effects of metal contamination of soils on the distribution of plant communities. The phytosociological analyses have shown a na, remarkable biodiversity of vegetation on non-contaminated soils, while biodiversity appeared strongly reduced on metal-contaminated soils. The area is naturally covered by a wide steppic grassland dominated by Stipa austroitalica Martinovsky subsp, austroitalica. Brassicaceae such as Sinapis arvensis L. are the dominating species on moderated contaminated soils, whereas spiny species of Asteraceae such as Silybum marianum (L.) Gaertn. and Carduus pycnocephalus L. subsp, pycnocephalus are the dominating vegetation on heavily metal-contaminated soils. The presence of these spontaneous species on contaminated soils suggest their potential for restoration of degraded lands by phytostabilization strategy.

Involvement of the cholinergic basal forebrain nuclei in spinocerebellar ataxia type 2 (SCA2).

AIMS: Spinocerebellar ataxia type 2 (SCA2) belongs to the CAG repeat or polyglutamine diseases. Along with a large variety of motor, behavioural and neuropsychological symptoms the clinical picture of patients suffering from this autosomal dominantly inherited ataxia may also include deficits of attention, impairments of memory, as well as frontal-executive and visuospatial dysfunctions. As the possible morphological correlates of these cognitive SCA2 deficits are unclear we examined the cholinergic basal forebrain nuclei, which are believed to be crucial for several aspects of normal cognition and may contribute to impairments of cognitive functions under pathological conditions. METHODS: We studied pigment-Nissl-stained thick tissue sections through the cholinergic basal forebrain nuclei (that is, medial septal nucleus, nuclei of the diagonal band of Broca, basal nucleus of Meynert) of four clinically diagnosed and genetically confirmed SCA2 patients and of 13 control individuals according to the pathoanatomical approach. The pathoanatomical results were confirmed by additional quantitative investigations of these nuclei in the SCA2 patients and four age- and gender-matched controls. RESULTS: Our study revealed a severe and consistent neuronal loss in all of the cholinergic basal forebrain nuclei (medial septal nucleus: 72%; vertical nucleus of the diagonal band of Broca: 74%; horizontal limb of the diagonal band of Broca: 72%; basal nucleus of Meynert: 86%) of the SCA2 patients studied. Damage to the basal forebrain nuclei was associated with everyday relevant cognitive deficits only in our SCA2 patient with an additional Braak and Braak stage V Alzheimer's disease (AD)-related tau pathology. CONCLUSIONS: The findings of the present study: (1) indicate that the mutation and pathological process underlying SCA2 play a causative role for this severe degeneration of the cholinergic basal forebrain nuclei and (2) may suggest that degeneration of the cholinergic basal forebrain nuclei per se is not sufficient to cause profound and global dementia detrimental to everyday practice and activities of daily living.

Spinocerebellar ataxia type 1 (SCA1): new pathoanatomical and clinico-pathological insights.

AIMS: Spinocerebellar ataxia type 1 (SCA1) represents the first molecular genetically characterized autosomal dominantly inherited cerebellar ataxia and is assigned to the CAG-repeat or polyglutamine diseases. Owing to limited knowledge about SCA1 neuropathology, appropriate pathoanatomical correlates of a large variety of SCA1 disease symptoms are missing and the neuropathological basis for further morphological and experimental SCA1 studies is still fragmentary. METHODS: In the present study, we investigated for the first time serial tissue sections through the complete brains of clinically diagnosed and genetically confirmed SCA1 patients. RESULTS: Brain damage in the three SCA1 patients studied went beyond the well-known brain predilection sites of the underlying pathological process. Along with neuronal loss in the primary motor cortex, it included widespread degeneration of gray components of the basal forebrain, thalamus, brainstem and cerebellum, as well as of white matter components in the cerebellum and brainstem. It involved the motor cerebellothalamocortical and basal ganglia-thalamocortical circuits, the visual, auditory, somatosensory, oculomotor, vestibular, ingestion-related, precerebellar, basal forebrain cholinergic and midbrain dopaminergic systems. CONCLUSIONS: These findings show for the first time that the extent and severity of brain damage in SCA1 is very similar to that of clinically closely related spinocerebellar ataxias (that is, SCA2, SCA3 and SCA7). They offer suitable explanations for poorly understood SCA1 disease symptoms and will facilitate the interpretation of further morphological and experimental SCA1 studies.

Effects of selected soil properties on phytoremediation applicability for heavy-metal-contaminated soils in the Apulia region, Southern Italy.

Phytoremediation is a well-known promising alternative to conventional approaches used for the remediation of diffused and moderated contaminated soils. The evaluation of the accumulation, availability, and interactions of heavy metals in soil is a priority objective for the possible use of phytoremediation techniques such as phytoextraction and phytostabilization. The soils used in this work were collected from a number of sites inside a protected area in the Apulia region (Southern Italy), which were contaminated by various heavy metals originated from the disposal of wastes of different sources of origin. Soils examined contained Cd, Cr, Cu, Ni, Pb, and Zn in amounts exceeding the critical limits imposed by EU and Italian laws. However, the alkaline conditions, high organic matter content, and silty to silty loamy texture of soils examined would suggest a reduced availability of heavy metals to plants. Due to the high total content but the low available fraction of heavy metals analyzed, especially Cr, phytoextraction appears not to be a promising remediation approach in the sites examined, whereas phytostabilization appears to be the best technique for metal decontamination in the studied areas.

A comparison of the effects of veratridine on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in isolated rat dorsal root ganglion neurons.

The effects of veratridine have been compared on tetrodotoxin-sensitive (TTXS) and tetrodotoxin-resistant (TTXR) voltage-gated sodium channels (VGSC) in rat dorsal root ganglion neurons. Veratridine caused a dose-dependent decrease in the peak amplitude of both TTXR and TTXS VGSC currents. When exposed to 25 microM veratridine, TTXS currents but not TTXR currents developed a clear persistent component. The deactivation of both TTXS and TTXR currents was slowed, as evidenced by the appearance of slowly decaying tail currents in voltage clamp records, but the slowing of deactivation was nearly 100 times greater for TTXS than for TTXR currents. Properties of the veratridine-modified VGSCs, derived from an analysis of the slow tail currents, were similar for both TTXS and TTXR in that the V50 for activation and the reversal potential were shifted to more negative potentials than control currents and by a similar amount for each. The relatively fast decay of veratridine-modified TTXR tail currents reflects a faster dissociation of veratridine from TTXR than from TTXS VGSCs. This difference probably underlies the lack of effect of veratridine on TTXR VGSCs in cells that are not voltage-clamped and undermines its value as a chemical activator of putative NaV1.8 TTXR channels.

The effect of dibutyryl cAMP on tetrodotoxin-sensitive and -resistant voltage-gated sodium currents in rat dorsal root ganglion neurons and the consequences for their sensitivity to lidocaine.

Tetrodotoxin-sensitive (TTXS) sodium currents in dorsal root ganglia (DRG) neurons were enhanced by DcAMP applied acutely or by pre-treatment. Pre-treatment increased peak TTXS by 28%. This compared to the increase of tetrodotoxin-resistant sodium currents (TTXR) of 123%. In both cases the increase was associated with a hyperpolarizing shift in activation potentials. Slow inactivation was slower for both TTXR and TTXS in DcAMP treated neurons but rates of recovery from inactivation were not altered. Lidocaine blocked TTX-R with an IC(50) of 0.51+/-0.15mM (n=9) which was reduced to 0.14+/-0.05mM (n=8, P<0.05) in DcAMP treated cells. The sensitivity of TTX-S currents to lidocaine was not altered by DcAMP (control EC(50)=0.89+/-0.16mM, n=9; DcAMP EC(50)=0.73+/-0.19mM, n=6). It is concluded that TTXS currents in DRG are, like TTX-R currents, enhanced by cAMP but whilst the pharmacology of TTXR channels with respect to lidocaine is altered, that to TTXS channels is not.

The use of the rat isolated vagus nerve for functional measurements of the effect of drugs in vitro.

In this article we describe how to dissect, set up and use the rat isolated vagus nerve in a 'grease gap' apparatus which provides a simple and practical method for measuring the effects of drugs on the membrane potential of axons in the nerve in vitro. Some discussion of the origins and development of the technique as well as the strengths and disadvantages of the preparation as a neuropharmacological tool are included. The vagus nerve conducts action potentials in at least three distinct types of axons that can be measured extracellularly as compound action potentials and distinguished on the basis of their conduction velocity and excitability. Activity in myelinated A fibres and unmyelinated C fibres can be measured separately easily. The axons express receptors for a wide range of putative neurotransmitter agents including 5-HT, GABA and ATP as well as other agents such as capsaicin, anandamide, bradykinin and prostanoids. Responses to all of these chemicals can be measured as a depolarization of the nerve fibres. The vagus nerve is an important target for a wide range of drugs and the isolated preparation provides a fairly simple preparation for studying their effects. The isolated vagus nerve is also a convenient system in which the effects of drugs that have been discovered using heterologous expression systems can be assayed on receptors and ion channels that are expressed in a native neural system.

Differential sensitivity to tetrodotoxin and lack of effect of prostaglandin E2 on the pharmacology and physiology of propagated action potentials.

1. We have studied the effects of prostaglandin E(2) (PGE(2)) on action potential propagation in the isolated, desheathed vagus and saphenous nerves of rats using an extracellular grease gap recording method. 2. PGE(2) evoked a small depolarization of vagus nerves but had no effect on the stimulation threshold, size or latency of either the A wave (corresponding to conduction in A fibres) or the C wave (corresponding to conduction in C fibres) of the compound action potential (CAP) recorded from either vagus or saphenous nerves. 3. Lidocaine (0.01 - 10 mM) reduced all components of the CAP of both vagus and saphenous nerves. PGE(2) had no significant effect on the sensitivity of any component of the CAP to lidocaine. 4. Tetrodotoxin (TTX, 10 microM) blocked completely both the A wave and the C wave of the CAP in either vagus or saphenous nerves. 5. In saphenous nerve preparations the A wave was blocked by lower concentrations of TTX than the C wave or any component of the CAP in vagus nerve preparations which suggests that somatosensory A fibres express a different sub-type of TTX-sensitive voltage-gated sodium channel (VGSC) than somatosensory C-fibres or visceral sensory fibres. 6. Chemical activation of VGSCs with veratridine (10 or 50 microM) induced a depolarization in either nerve. The depolarization induced by 50 microM veratridine was blocked by 10 microM TTX. 7. Although TTX-insensitive VGSCs are expressed by some vagal and some somatosensory neurones they do not appear to be expressed functionally in the axons.