Subpopulations of rat dorsal root ganglion neurons express active vesicular acetylcholine transporter

The vesicular acetylcholine transporter (VAChT) is a transmembrane protein required, in cholinergic neurons, for selective storage of acetylcholine into synaptic vesicles. Although dorsal root ganglion (DRG) neurons utilize neuropeptides and amino acids for neurotransmission, we have previously demonstrated the presence of a cholinergic system. To investigate whether, in sensory neurons, the vesicular accumulation of acetylcholine relies on the same mechanisms active in classical cholinergic neurons, we investigated VAChT presence, subcellular distribution, and activity. RT-PCR and Western blot analysis demonstrated the presence of VAChT mRNA and protein product in DRG neurons and in the striatum and cortex, used as positive controls. Moreover, in situ hybridization and immunocytochemistry showed VAChT staining located mainly in the medium/large-sized subpopulation of the sensory neurons. A few small neurons were also faintly labeled by immunocytochemistry. In the electron microscope, immunolabeling was associated with vesicle-like elements distributed in the neuronal cytoplasm and in both myelinated and unmyelinated intraganglionic nerve fibers. Finally, [(3)H]acetylcholine active transport, evaluated either in the presence or in the absence of ATP, also demonstrated that, as previously reported, the uptake of acetylcholine by VAChT is ATP dependent. This study suggests that DRG neurons not only are able to synthesize and degrade ACh and to convey cholinergic stimuli but also are capable of accumulating and, possibly, releasing acetylcholine by the same mechanism used by the better known cholinergic neurons.     

Obesity-associated lymphoedematous mucinosis

Background: Mucin deposition on the shins is considered as an indicator of pretibial myxoedema, which is typically seen in patients with Graves' disease.
Objective: The purpose of this study was to report the clinical and histopathological features of a group of patients with pretibial mucinosis in the absence of thyroid disease.
Methods: Five patients are included in this series and studied both clinically and histologically and compared with similar cases in the literature.
Results: All patients were middle aged or elderly. Four patients were women. They were characterized clinically by morbid obesity and bilateral lower extremity pitting oedema sparing the feet. Semitranslucent papules and/or nodules and sometimes vesicles were found on the shins. Characteristic histological features include (i) hyperorthokeratosis with epidermal atrophy and effacement of the rete ridge pattern, (ii) oedema in the papillary and upper part of the reticular dermis with mucin deposition stained positively with alcian blue and colloidal iron, (iii) angioplasia in the upper part of dermis with upward-running, increased and thickened capillary vessels and (iv) variable fibrosis in the reticular dermis with separation of collagen bundles and increased stellate or linear fibroblasts. A hypocaloric diet was given in two cases, and an important weight loss was observed, which was accompanied by a marked improvement of the pretibial mucinosis.
Conclusions: Pretibial mucinosis is a histological feature associated with morbid obesity and lymphoedematous features of the legs that should be distinguished from true pretibial myxoedema. The term of 'obesity-associated lymphoedematous mucinosis' seems to be appropriate for this condition.     

Prevalence of cutaneous bacterial infections and nasal carriage of Staphylococcus aureus in recipients of renal transplants

Background.  Renal transplant recipients (RTRs) often develop bacterial infections as a result of their long-term immunosuppressive treatment. However, there is no published case–control study of cutaneous bacterial infections in this population, and the prevalence of nasal Staphyloccus aureus carriage and its role in cutaneous bacterial infections in RTRs are not known.
Aims.  To determine whether the prevalence of cutaneous bacterial infections and nasal S. aureus carriage are increased in RTRs and to investigate the association between nasal S. aureus carriage and cutaneous staphylococcal infections.
Methods.  In total, 66 outpatient RTRs and 67 controls were investigated for the presence of cutaneous bacterial infections. Bacterial cultures were taken from clinically suspicious cutaneous lesions, and three nasal swabs were collected to detect nasal S. aureus colonization.
Results.  Cutaneous bacterial infection was suspected in 42.4% of RTRs, and in 14.2% of controls. However, of the lesions that could be cultured, microbiologically proven cutaneous bacterial [methicillin-sensitive S. aureus (MSSA)] infections were confirmed in only two RTRs and one control subject. Nasal S. aureus carriage was found in 10.6% of RTRs and 29.9% of controls ( P  < 0.05). Both RTRs with MSSA infection were nasal carriers, whereas nasal S. aureus carriage was not detected in the only control subject with MSSA infection. All S. aureus isolates were oxacillin-sensitive.
Conclusion.  Screening for nasal S. aureus carriage does not seem to assist in preventing staphylococcal bacterial infections in outpatient RTRs.     

The Subarachnoid Hemorrhage International Trialists (SAHIT) Repository: Advancing Clinical Research in Subarachnoid Hemorrhage

Researchers and other stakeholders continue to express concern about the failure of randomized clinical trials (RCT) in subarachnoid hemorrhage (SAH) to show efficacy of new treatments. Pooled data may be particularly useful to generate hypotheses about causes of poor outcomes and reasons for failure of RCT in SAH, and strategies to improve them. Investigators conducting SAH research collaborated to share data with the intent to develop a large repository of pooled individual patient data for exploratory analysis and testing of new hypotheses relevant to improved trial design and analysis in SAH. This repository currently contains information on 11,443 SAH patients from 14 clinical databases, of which 9 are datasets of recent RCTs and 5 are datasets of prospective observational studies and hospital registries. Most patients were managed in the last 15 years. Data validation and quality checks have been conducted and are satisfactory. Data is available on demographic, clinical, neuroimaging, and laboratory results and various outcome measures. We have compiled the largest known dataset of patients with SAH. The SAHIT repository may be an important resource for advancing clinical research in SAH and will benefit from contributions of additional datasets.     

Postherpetic neuralgia: From preclinical models to the clinic

Postherpetic neuralgia (PHN), a common complication of herpes zoster, which results from reactivation of varicella zoster virus, is a challenging neuropathic pain syndrome. The incidence and severity of herpes zoster and PHN increases with immune impairment or age and may become a greater burden both in terms of health economics and individual suffering. A clearer understanding of the underlying mechanisms of this disease and translation of preclinical outcomes to the clinic may lead to more efficacious treatment options. Here we give an overview of recent findings from preclinical models and clinical research on PHN.     

Blood oxygen level-dependent signal responses in corticolimbic 'emotions' circuitry of lactating rats facing intruder threat to pups

Lactating rats must continuously maintain a critical balance between caring for pups and aggressively responding to nest threats. We tested the neural response of lactating females to the presentation of their own pups and novel intruder males using blood oxygen level-dependent functional magnetic resonance imaging at 7 T. Dams were presented with a single sequence of a control stimulus, pups or a male intruder in one imaging session ( n  = 7–9). To further determine the selectivity of neural processing, dams were imaged for their response to a male intruder in both the absence and presence of their pups ( n  = 6). Several maternal cortical and limbic brain regions were significantly activated by intruder presentation but not by pups or a control stimulus. These included the nucleus accumbens, periaqueductal gray, anterior cingulate, anterior thalamus, basal nucleus of the amygdala, temporal cortex, prelimbic/orbital area and insula. The nucleus accumbens, periaqueductal gray, temporal cortex and mediodorsal thalamus still showed greater neural activity when compared with intruder presentation in the absence of pups. The present results suggest that the high emotional state generated by a threat to pups involves robust activation of classical limbic regions controlling emotional responses. This pattern of blood oxygen level-dependent activity may precede behavioral states upon which lactating rats initiate attacks against a potential threat to offspring.