Peripheral amplification of sweating – a role for calcitonin gene-related peptide

Neuropeptides are the mediators of neurogenic inflammation. Some pain disorders, e.g. complex regional pain syndromes, are characterized by increased neurogenic inflammation and by exaggerated sudomotor function. The aim of this study was to explore whether neuropeptides have a peripheral effect on human sweating. We investigated the effects of different concentrations of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and substance P (SP) on acetylcholine-induced axon reflex sweating in healthy subjects (total n = 18). All substances were applied via dermal microdialysis. The experiments were done in a parallel setting: ACh alone and ACh combined with CGRP, VIP or SP in various concentrations were applied. Acetylcholine (10⁻² m ) always elicited a sweating response, neuropeptides alone did not. However, CGRP significantly enhanced ACh-induced sweating ( P < 0.01). Post hoc tests revealed that CGRP in physiological concentrations of 10⁻⁷–10⁻⁹ m was most effective. VIP at any concentration had no significant effect on axon reflex sweating. The duration of the sweating response ( P < 0.01), but not the amount of sweat, was reduced by SP. ACh-induced skin blood flow was significantly increased by CGRP ( P < 0.01), but unaltered by VIP and SP. The results indicate that CGRP amplifies axon reflex sweating in human skin.     

The Community Placement Scale: an adaptation of the Community Competence Scale for placement of the deinstitutionalized mentally ill

The Community Placement Scale (CPS), an abbreviated form of the Community Competence Scale (Anderten, 1979) suitable for placement of deinstitutionalized mental patients in the community, was developed in a combined sample of 87 subjects placed in the community in California and Missouri. Although the Community Competence Scale has shown considerable promise as a placement instrument with the deinstitutionalized mentally ill, a briefer measure is needed in order to increase acceptance by both patients and professional staff. Other improvements sought were determining the acceptability of items to placement personnel nationwide, eliminating nondiscriminating items, and heightening internal consistency reliability of subscales. In a series of discriminant analyses, remaining subscales were used to predict community placement with minimal and maximal degrees of structure. From these analyses, a measure that consisted of 5 subscales and 41 items and required approximately 20 minutes to administer was selected. This short form has many similarities to and a few important differences from the previously published short form.     

Predicting protein complex membership using probabilistic network reliability

Evidence for specific protein-protein interactions is increasingly available from both small- and large-scale studies, and can be viewed as a network. It has previously been noted that errors are frequent among large-scale studies, and that error frequency depends on the large-scale method used. Despite knowledge of the error-prone nature of interaction evidence, edges (connections) in this network are typically viewed as either present or absent. However, use of a probabilistic network that considers quantity and quality of supporting evidence should improve inference derived from protein networks. Here we demonstrate inference of membership in a partially known protein complex by using a probabilistic network model and an algorithm previously used to evaluate reliability in communication networks.     

Morphological and cytochemical alterations of the Golgi apparatus and GERL in rat parotid acinar cells during ethionine intoxication and recovery

The present electron microscopic cytochemical investigation was undertaken to characterize the alterations in the Golgi apparatus and GERL of rat parotid acinar cells during ethionine intoxication and recovery. Although the Golgi apparatus and GERL were reduced in size, and some broadening of the Golgi saccules occurred as the result of ethionine treatment, the relative localization of thiamine pyrophosphatase (TPPase) activity in the Golgi saccules, and acid phosphatase activity (AcPase) in GERL, remained unchanged. Shortly after ethionine treatment was stopped, a dramatic redistribution of enzyme activities was noted. Within the first 24 hours of recovery, the Golgi apparatus began to enlarge, and the content of secretory granules increased. By day 3 of recovery, cisternae morphologically identifiable as GERL and forming secretory granules possessed TPPase activity, while AcPase activity was virtually undetectable. After seven days of recovery, the Golgi apparatus and GERL appeared both morphologically and cytochemically normal. The enzyme modulation observed during recovery may be correlated with increased secretory granule production. Furthermore, the presence of TPPase activity in GERL and forming secretory granules lends support to the suggestion that GERL may be derived from the trans Golgi saccule.     

Biopsy of breast microcalcifications using an 11-Gauge vacuum-assisted device: roles and challenges for the pathologist

Stereotactic 11-Gauge vacuum-assisted biopsy provides a valuable tool in the diagnosis of mammographically detected breast microcalcifications. However, this new diagnostic technology presents some limitations and requires a close collaboration between radiologists, pathologists and physicians. The aim of this work is to propose a practical approach in the management of large core biopsies and to summarize the different difficulties faced by the pathologist in the management and histological interpretation of specimens issuing from this device.     

The water jet as a new tool for endoprosthesis revision surgery--an in vitro study on human bone and bone cement

In revision surgeries of endoprostheses, the interface between implant and bone cement or bone must be loosened. Conventional tools have many disadvantages because of their size and limited range. Taking advantage of the selective and athermic cutting process, a plain water jet is already used in order to cut soft tissues. This study investigates the possibilities of both a plain and an abrasive water jet as cutting tools for revision surgery. Samples of the mid-diaphysis of human femora and bone cement (CMW3) were cut with a plain water jet (PWJ) and an abrasive water jet (AWJ) at two different jet-to-surface angles (30 degrees,90 degrees ) and at five different pressure levels (30, 40, 50, 60, 70 MPa). For a PWJ a selective pressure range was identified, where only bone cement was cut. Injecting a bio-compatible abrasive (lactose) to the jet stream resulted in significantly higher cut depths in both materials. Material removal in bone was significantly less at the smaller jet-to-surface angle for both techniques. No clear selectivity between bone and bone cement was observed for application of the AWJ. However, the material removal rate was significantly higher for bone cement than for bone at all pressure levels. The results indicate that an AWJ might be an alternative tool for cement removal. The possibility for localised cutting at interfaces could be an advantage for revision of a non-cemented prosthesis.     

The effects of thermochemotherapy using cyclophosphamide plus hyperthermia on the malignant pleural mesothelioma in vivo

The human malignant pleural mesothelioma is related to the use of asbestos in the majority of cases. Though the use of asbestos has been prohibited since the 1990s, the incidence of pleural mesothelioma is still increasing because of a latency period of at least 20 years. This study investigated the benefit of single therapy with cyclophosphamide or hyperthermia or the combination of both on cells of a human pleural mesothelioma cell line, xenotransplanted subcutaneously in the paw of mice. A CONTROL group received the same volume of physiological saline. The oxygenation of tumours was measured, tumour growth was followed over 3 weeks, immunohistochemical studies and a light and electron microscopic evaluation were performed. Chemotherapy or hyperthermia alone was only temporarily effective. The greatest benefit was achieved using combined thermochemotherapy consisting of cyclophosphamide plus hyperthermia: 50% of this group had partial remissions, and 67% responded to this therapy. After 3 weeks tumours grew again. Superior effects could be achieved by performing additional cycles of chemotherapy or adding another drug or radiation for instance. This study shows promising results in the treatment of malignant pleural mesothelioma.     

Amphiphysin I phosphorylation on residue threonine 260 in a pentylenetetrazole-induced seizure model

A method to evaluate kinase inhibitor action was reported [L. Morgan, S.J. Neame, H. Child, R. Chung, B. Shah, L. Barden, J.M. Staddon, T.R. Patel, Development of a pentylenetetrazole-induced seizure model to evaluate kinase inhibitor efficacy in the central nervous system, Neurosci. Lett. 395 (2006) 143–148]. In this, acute administration of the GABA antagonist pentylenetetrazole triggers seizures through glutamate-dependent pathways. Under such conditions, activation of the c-Jun N-terminal kinase (JNK) pathway was detected in hippocampal extracts. Phosphorylation of the upstream JNK kinase MKK4 was also revealed through use of a phospho-MKK4-specific antibody. Here, this antibody is shown to also react with a protein of ∼125 kDa which underwent increased phosphorylation in response to pentylenetetrazole treatment. The present study aimed to identify the ∼125 kDa protein as it may provide novel insight into signalling, neuronal activity and seizures. Using chromatographic methods and mass spectrometry, the protein was identified as amphiphysin I. This was confirmed by 2D gel analysis and immunoblot with amphiphysin I-specific antibodies. Although the phospho-MKK4 antibody was raised against an MKK4-specific peptide, partial sequence homology between this sequence and a region of amphiphysin was discerned. New antibodies raised against the phospho-threonine 260-amphiphysin-specific sequence detected increased phosphorylation in response to pentylenetetrazole treatment. This particular phosphorylation site does not seem to have been described before, possibly reflecting a novel regulatory aspect of amphiphysin biology. As amphiphysin is involved in the regulation of endocytosis, phosphorylation at this site may play a role in the regulated re-uptake of synaptic vesicles after neurotransmitter release.     

Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid

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