Isolated Paralysis of the Adductor Pollicis: A Case Report

We report a case of isolated paralysis of the right adductor pollicis in a 30-year-old woman. Electromyographic study showed involvement of the deep motor branch of the ulnar nerve. A ganglion and an anomalous muscle were both ruled out clinically and by MRI as a possible cause of the paralysis. At surgical exploration, we found a fibrous band joining the pisiform and the hook of the hamate bone that compressed the deep motor branch of the ulnar nerve. The fibrous band was excised, and a neurolysis of the motor branch of the ulnar nerve was performed. At followup, eight months later, the patient had fully recovered strength of the adductor muscle

Single-row vs. double-row arthroscopic rotator cuff repair: clinical and 3 Tesla MR arthrography results.

Background Arthroscopic rotator cuff repair has become popular in the last few years because it avoids large skin incisions and deltoid detachment and dysfunction. Earlier arthroscopic single-row (SR) repair methods achieved only partial restoration of the original footprint of the tendons of the rotator cuff, while double-row (DR) repair methods presented many biomechanical advantages and higher rates of tendon-to-bone healing. However, DR repair failed to demonstrate better clinical results than SR repair in clinical trials. MR imaging at 3 Tesla, especially with intra-articular contrast medium (MRA), showed a better diagnostic performance than 1.5 Tesla in the musculoskeletal setting. The objective of this study was to retrospectively evaluate the clinical and 3 Tesla MRA results in two groups of patients operated on for a medium-sized full-thickness rotator cuff tear with two different techniques. Methods The first group consisted of 20 patients operated on with the SR technique; the second group consisted of 20 patients operated on with the DR technique. All patients were evaluated at a minimum of 3 years after surgery. The primary end point was the re-tear rate at 3 Tesla MRA. The secondary end points were the Constant-Murley Scale (CMS), the Simple Shoulder Test (SST) scores, surgical time and implant expense. Results The mean follow-up was 40 months in the SR group and 38.9 months in the DR group. The mean postoperative CMS was 70 in the SR group and 68 in the DR group. The mean SST score was 9.4 in the SR group and 10.1 in the DR group. The re-tear rate was 60% in the SR group and 25% in the DR group. Leakage of the contrast medium was observed in all patients. Conclusions To the best of our knowledge, this is the first report on 3 Tesla MRA in the evaluation of two different techniques of rotator cuff repair. DR repair resulted in a statistically significant lower re-tear rate, with longer surgical time and higher implant expense, despite no difference in clinical outcomes. We think that leakage of the contrast medium is due to an incomplete tendon-to-bone sealing, which is not a re-tear. This phenomenon could have important medicolegal implications. Level of evidence III. Treatment study: Case–control study

Altered Functionality, Morphology, and Vesicular Glutamate Transporter Expression of Cortical Motor Neurons from a Presymptomatic Mouse Model of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a lethal disorder characterized by the gradual degeneration of motor neurons in the cerebrospinal axis. Whether upper motor neuron hyperexcitability, which is a feature of ALS, provokes dysfunction of glutamate metabolism and degeneration of lower motor neurons via an anterograde process is undetermined. To examine whether early changes in upper motor neuron activity occur in association with glutamatergic alterations, we performed whole-cell patch-clamp recordings to analyze excitatory properties of Layer V cortical motor neurons and excitatory postsynaptic currents (EPSCs) in presymptomatic G93A mice modeling familial ALS (fALS). We found that G93A Layer V pyramidal neurons exhibited altered EPSC frequency and rheobase values indicative of their hyperexcitability status. Biocytin loading of these hyperexcitable neurons revealed an expansion of their basal dendrite arborization. Moreover, we detected increased expression levels of the vesicular glutamate transporter 2 in cortical Layer V of G93A mice. Altogether our data show that functional and structural neuronal alterations associate with abnormal glutamatergic activity in motor cortex of presymptomatic G93A mice. These abnormalities, expected to enhance glutamate release and to favor its accumulation in the motor cortex, provide strong support for the view that upper motor neurons are involved early on in the pathogenesis of ALS

Repetitive transcranial magnetic stimulation reduces remote apoptotic cell death and inflammation after focal brain injury.

After focal brain injuries occur, in addition to the effects that are attributable to the primary site of damage, the resulting functional impairments depend highly on changes that occur in regions that are remote but functionally connected to the site of injury. Such effects are associated with apoptotic and inflammatory cascades and are considered to be important predictors of outcome. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique that is used to treat various central nervous system (CNS) pathologies and enhance functional recovery after brain damage. OBJECTIVE: This study examined the efficacy of rTMS in mitigating remote degeneration and inflammation and in improving functional recovery in a model of focal brain damage. METHODS: Rats that were undergoing hemicerebellectomy (HCb) were treated with an rTMS protocol for 7 days, and neuronal death indices, glial activation, and functional recovery were assessed. RESULTS: rTMS significantly reduced neuronal death and glial activation in remote regions and improved functional recovery. CONCLUSIONS: Our finding opens up a completely new scenario for exploiting the potential of rTMS as an anti-apoptotic and anti-inflammatory treatment

Altered Functionality, Morphology, and Vesicular Glutamate Transporter Expression of Cortical Motor Neurons from a Presymptomatic Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a lethal disorder characterized by the gradual degeneration of motor neurons in the cerebrospinal axis. Whether upper motor neuron hyperexcitability, which is a feature of ALS, provokes dysfunction of glutamate metabolism and degeneration of lower motor neurons via an anterograde process is undetermined. To examine whether early changes in upper motor neuron activity occur in association with glutamatergic alterations, we performed whole-cell patch-clamp recordings to analyze excitatory properties of Layer V cortical motor neurons and excitatory postsynaptic currents (EPSCs) in presymptomatic G93A mice modeling familial ALS (fALS). We found that G93A Layer V pyramidal neurons exhibited altered EPSC frequency and rheobase values indicative of their hyperexcitability status. Biocytin loading of these hyperexcitable neurons revealed an expansion of their basal dendrite arborization. Moreover, we detected increased expression levels of the vesicular glutamate transporter 2 in cortical Layer V of G93A mice. Altogether our data show that functional and structural neuronal alterations associate with abnormal glutamatergic activity in motor cortex of presymptomatic G93A mice. These abnormalities, expected to enhance glutamate release and to favor its accumulation in the motor cortex, provide strong support for the view that upper motor neurons are involved early on in the pathogenesis of ALS

Cannabinoid CB2 receptor (CB2R) stimulation delays rubrospinal mitochondrial-dependent degeneration and improves functional recovery after spinal cord hemisection by ERK1/2 inactivation.

Spinal cord injury (SCI) is a devastating condition of CNS that often results in severe functional impairments for which there are no restorative therapies. As in other CNS injuries, in addition to the effects that are related to the primary site of damage, these impairments are caused by degeneration of distal regions that are connected functionally to the primary lesion site. Modulation of the endocannabinoid system (ECS) counteracts this neurodegeneration, and pharmacological modulation of type-2 cannabinoid receptor (CB2R) is a promising therapeutic target for several CNS pathologies, including SCI. This study examined the effects of CB2R modulation on the fate of axotomized rubrospinal neurons (RSNs) and functional recovery in a model of spinal cord dorsal hemisection (SCH) at the cervical level in rats. SCH induced CB2R expression, severe atrophy, and cell death in contralateral RSNs. Furthermore, SCH affected molecular changes in the apoptotic cascade in RSNs - increased cytochrome c release, apoptosome formation, and caspase-3 activity. CB2R stimulation by its selective agonist JWH-015 significantly increased the bcl-2/bax ratio, reduced cytochrome c release, delayed atrophy and degeneration, and improved spontaneous functional recovery through ERK1/2 inactivation. These findings implicate the ECS, particularly CB2R, as part of the endogenous neuroprotective response that is triggered after SCI. Thus, CB2R modulation might represent a promising therapeutic target that lacks psychotropic effects and can be used to exploit ECS-based approaches to counteract neuronal degeneration

Distinct regulation of nNOS and iNOS by CB2 receptor in remote delayed neurodegeneration

Hemicerebellectomy results in remote delayed degeneration of precerebellar neurons. We have reported that such a lesion induces type 2 cannabinoid receptor (CB(2)) expression in precerebellar neurons and that stimulation of CB(2), but not CB(1), has neuroprotective effects. In this study, we found that in the same model, the CB(2) agonist JWH-015 enhances neuronal nitric oxide synthase (nNOS) expression in axotomized neurons and that CB(2)-mediated neuroprotection is abrogated by pharmacological inhibition of nNOS. JWH-015 prevented the axotomy-induced upregulation of inducible NOS (iNOS) in astrocytes but had no effect on endothelial NOS (eNOS). In addition, we observed that JWH-015 significantly reduces hemicerebellectomy-induced neuroinflammatory responses and oxidative/nitrative stress. With regard to the signaling pathways of CB(2)/nNOS-mediated neuroprotection, we noted nNOS-dependent modulation of the expression of anti-oxidative (Hsp70) and anti-apoptotic (Bcl-2) proteins. These findings shed light on the interactions between the endocannabinoid and nitrergic systems after focal brain injury, implicating distinct functions of nNOS activation and iNOS inhibition in CB(2) signaling, which protect neurons from axotomy-induced cell death

Definition of the σW regulon of Bacillus subtilis in the absence of stress

Bacteria employ extracytoplasmic function (ECF) sigma factors for their responses to environmental stresses. Despite intensive research, the molecular dissection of ECF sigma factor regulons has remained a major challenge due to overlaps in the ECF sigma factor-regulated genes and the stimuli that activate the different ECF sigma factors. Here we have employed tiling arrays to single out the ECF σW regulon of the Gram-positive bacterium Bacillus subtilis from the overlapping ECF σX, σY, and σM regulons. For this purpose, we profiled the transcriptome of a B. subtilis sigW mutant under non-stress conditions to select candidate genes that are strictly σW-regulated. Under these conditions, σW exhibits a basal level of activity. Subsequently, we verified the σW-dependency of candidate genes by comparing their transcript profiles to transcriptome data obtained with the parental B. subtilis strain 168 grown under 104 different conditions, including relevant stress conditions, such as salt shock. In addition, we investigated the transcriptomes of rasP or prsW mutant strains that lack the proteases involved in the degradation of the σW anti-sigma factor RsiW and subsequent activation of the σW-regulon. Taken together, our studies identify 89 genes as being strictly σW-regulated, including several genes for non-coding RNAs. The effects of rasP or prsW mutations on the expression of σW-dependent genes were relatively mild, which implies that σW-dependent transcription under non-stress conditions is not strictly related to RasP and PrsW. Lastly, we show that the pleiotropic phenotype of rasP mutant cells, which have defects in competence development, protein secretion and membrane protein production, is not mirrored in the transcript profile of these cells. This implies that RasP is not only important for transcriptional regulation via σW, but that this membrane protease also exerts other important post-transcriptional regulatory functions

Giant Intra-Articular Extrasynovial Osteochondroma of the Knee: A Report of Two Cases

We report two cases of a giant extrasynovial osteochondroma of the knee located in the infrapatellar fat pad region, in two females who were 58 and 71 years old respectively. Both patients had noticed the mass many years before our first clinical observation. In both patients, at physical examination a solid, firm and hard mass was palpable in the anterior part of the knee in Hoffa’s fat pad region, and the range of motion of the knee was severely restricted and painful. CT scan examination with 3D-reconstruction showed two large, calcified neoformations behind the patellar tendon, between the apex of the patella and the proximal third of the tibia. In both cases, the mass was completely resected surgically through an anterior longitudinal approach. At histological examination, the excised masses consisted of an outer layer of hyaline cartilage without significant chondrocyte atypia and an inner region of bone trabeculae formed by endochondral ossification. At follow-up, 8 and 4 years after the operation, both patients were pain-free, with complete recovery of the range of motion of the knee and without any clinical or radiographic evidence of recurrence. The authors believe that intra-articular extrasynovial osteochondroma of the knee is a primary metaplasia of Hoffa’s fat pad. Usually, the tumor develops slowly and asymptomatically over many years. The treatment of choice is a marginal resection of the mass, although a biopsy should be considered in some cases. Recurrences are extremely rare

Activation of type-2 cannabinoid receptor inhibits neuroprotective and antiinflammatory actions of glucocorticoid receptor α: when one is better than two.

Endocannabinoids (eCBs) and glucocorticoids (GCs) are two distinct classes of signaling lipids that exert both neuroprotective and immunosuppressive effects; however, the possibility of an actual interaction of their receptors [i.e., type-2 cannabinoid (CB2) and glucocorticoid receptor α (GRα), respectively] remains unexplored. Here, we demonstrate that the concomitant activation of CB2 and GRα abolishes the neuroprotective effects induced by each receptor on central neurons and on glial cells in animal models of remote cell death. We also show that the ability of eCBs and GCs, used individually, to inhibit tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) production from activated human T lymphocytes is lost when CB2 and GRα are activated simultaneously. In addition, signal transduction pathways triggered by concomitant activation of both receptors led to increased levels of GRβ, heat-shock proteins-70 and -90, and p-JNK, as well as to reduced levels of p-STAT6. These effects were reversed only by selectively antagonizing CB2, but not GRα. Overall, our study demonstrates for the first time the existence of a CB2-driven negative cross-talk between eCB and GC signaling in both rats and humans, thus paving the way to the possible therapeutic exploitation of CB2 as a new target for chronic inflammatory and neurodegenerative diseases