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Krause's corpuscles are typical of cutaneous mucous epithelia, like the lip vermillion or the glans clitoridis, and are associated with rapidly adapting low-threshold mechanoreceptors involved in gentle touch or vibration. PIEZO1 and PIEZO2 are transmembrane mechano-gated proteins that form a part of the cationic ion channels required for mechanosensitivity in mammalian cells. They are involved in somatosensitivity, especially in the different qualities of touch, but also in pain and proprioception. In the present study, immunohistochemistry and immunofluorescence were used to analyze the occurrence and cellular location of PIEZO1 and PIEZO2 in human clitoral Krause's corpuscles. Both PIEZO1 and PIEZO2 were detected in Krause's corpuscles in both the axon and the terminal glial cells. The presence of PIEZOs in the terminal glial cells of Kraus's corpuscles is reported here for the first time. Based on the distribution of PIEZO1 and PIEZO2, it may be assumed they could be involved in mechanical stimuli, sexual behavior, and sexual pleasure. [ABSTRACT FROM AUTHOR]

The clitoris is a leading player in female sexual arousal, if not the main protagonist. Despite this role, studies performed on this structure with specific neuroanatomical techniques are few. This study focuses on glans clitoris innervation, with special emphasis on sensory corpuscles and the presence of the mechanotransducer protein PIEZO2 in these structures. Six glans clitoris samples were obtained at autopsy covering an age spectrum between 52 and 83 years old. Several types of nerve terminations including free nerve endings, genital endbulbs as well as Meissner‐like corpuscles and Pacinian corpuscles, but not Ruffini corpuscles, were found. Although corpuscular morphology in the glans clitoris was subtly different from the cutaneous digital counterparts, their basic composition was comparable for both Pacinian and Meissner‐like corpuscles. Genital endbulbs showed heterogeneous morphology, and the axons usually exhibited a typical "wool ball" or "yarn ball" aspect. Some of them were lobulated and variably encapsulated by endoneurial elements (65%); from the capsule originate septa that divides the genital endbulbs, suggesting that they are found in clusters rather than as single corpuscles. In addition, most corpuscles in the glans clitoris showed axonal PIEZO2 immunoreactivity, thus, suggesting a mechanical role and molecular mechanisms of mechanosensibility similar to those of digital Meissner's corpuscles. Our results demonstrate that sensory corpuscles of the glans clitoris are similar to those of other glabrous skin zones, as most genital organs are characterized by clusters of corpuscles and the occurrence of the mechanoprotein PIEZO2 in the axons. These findings strongly suggest that PIEZO2 participates in erotic and sexual mechanical sensing. [ABSTRACT FROM AUTHOR]

Ruffini's corpuscles are present as long fusiform encapsulated sensory structures in different tissues including the skin. Although physiological analyses strongly suggest their existence in glabrous digital skin, such localisation remains unconfirmed. Here, we have investigated the occurrence of typical Ruffini's corpuscles in 372 sections of human digital skin obtained from 186 subjects of both sexes and different ages (19–92 years). S100 protein, neuron‐specific enolase and neurofilament proteins were detected, and the basic immunohistochemical profile of these corpuscles was analysed. Fewer than 0.3 Ruffini's corpuscles/mm2 were detected, with density distribution across the fingers being F4 > F3 > F2 > F1 > F5 and absolute values being F2 > F1 > F3 > F4 > F5. Axons displayed neuron‐specific enolase immunoreactivity, glial cells forming the core contained S100 protein, and the capsule was positive for CD34 but not Glut1, demonstrating an endoneurial origin. Present results demonstrate the existence of Ruffini's corpuscles in human glabrous digital skin at very low densities. Moreover, the identified Ruffini's corpuscles share the basic immunohistochemical characteristics of other dermal sensory corpuscles. [ABSTRACT FROM AUTHOR]

Meissner corpuscles are cutaneous mechanoreceptors that are usually located in the dermal papillae of human glabrous skin. Structurally, these sensory corpuscles consist of a mechanoreceptive sensory neuron surrounded by non‐myelinating lamellar Schwann‐like cells. Some authors have described a partially developed fibroblastic capsule of endoneurial or perineurial origin around Meissner corpuscles; however, others have noted that these structures are non‐encapsulated. As there is continuity between the periaxonic cells forming the sensory corpuscles and the cells of the nerve trunks, we used immunohistochemistry to examine the expression of endoneurial (CD34 antigen) or perineurial [Glucose transporter 1 (Glut1)] markers in human cutaneous Meissner corpuscles. We also investigated the immunohistochemical patterns of nestin and vimentin (the main intermediate filaments of the cytoskeleton of endoneurial and perineurial cells, respectively) in Meissner corpuscles. The most important finding from this study was that CD34‐positive cells formed a partial/complete capsule of endoneurial origin around most Meissner corpuscles, without signs of other perineurial Glut1‐positive elements. However, the cytoskeletal proteins of the capsular CD34‐positive cells did not include either nestin or vimentin, so the cytoskeletal composition of these cells remains to be established. Finally, the intensity of the immunoreactivity for CD34 in the capsule decreased with ageing, sometimes becoming completely absent in the oldest individuals. In conclusion, we report the first immunohistochemical evidence of the capsule of Meissner corpuscles in humans and demonstrate the endoneurial origin of the capsule. [ABSTRACT FROM AUTHOR]

Heparan sulfate proteoglycans are pericellular/cell surface molecules involved in somatosensory axon guidance in the peripheral nervous system. However, the distribution of heparan sulfate proteoglycans in the extracellular matrix of human cutaneous sensory corpuscles is unknown. Immunohistochemistry and immunofluorescence assays were performed to define the localization of heparan sulfate proteoglycans in human cutaneous Meissner's and Pacinian corpuscles using two anti-heparan sulfate antibodies together with anti-S100 protein, anti-PGP9.5, anti-CD34 (to immunolabel basement membranes, Schwann cells, axon and the intermediate endoneurial layer of Pacinian corpuscles, respectively), anti-Type IV collagen, and anti-chondroitin sulfate antibodies. Heparan sulfate proteoglycans were colocalized with Type IV collagen in Meissner's corpuscles and were located in the outer core lamellae and capsule, but not in the inner core or the intermediate layer, in Pacinian corpuscles. Chondroitin sulfate was observed in the intermediate layer of Pacinian corpuscles but was never colocalized with heparan sulfate proteoglycans. The present results strongly suggest that heparan sulfate proteoglycans are associated with the basement membranes of the lamellar cells in Meissner's corpuscles and with the complex outer core capsule in Pacinian corpuscles. The functional significance of these results, if any, remains to be elucidated., (© 2019 American Association for Anatomy.)

The cells of the intervertebral disc (IVD) have an unusual acidic and hyperosmotic microenvironment. They express acid-sensing ion channels (ASICs), gated by extracellular protons and mechanical forces, as well as neurotrophins and their signalling receptors. In the nervous tissues some neurotrophins regulate the expression of ASICs. The expression of ASIC2 and TrkB in human normal and degenerated IVD was assessed using quantitative-PCR, Western blot, and immunohistochemistry. Moreover, we investigated immunohistochemically the expression of ASIC2 in the IVD of TrkB-deficient mice. ASIC2 and TrkB mRNAs were found in normal human IVD and both increased significantly in degenerated IVD. ASIC2 and TrkB proteins were also found co-localized in a variable percentage of cells, being significantly higher in degenerated IVD than in controls. The murine IVD displayed ASIC2 immunoreactivity which was absent in the IVD of TrkB-deficient mice. Present results demonstrate the occurrence of ASIC2 and TrkB in the human IVD, and the increased expression of both in pathological IVD suggest their involvement in IVD degeneration. These data also suggest that TrkB-ligands might be involved in the regulation of ASIC2 expression, and therefore in mechanisms by which the IVD cells accommodate to low pH and hypertonicity.

Objective: To study the prevalence of delayed diagnosis of HIV infection and associated factors., Methods: A cross sectional study of patients included in the Spanish VACH cohort who had been diagnosed with HIV infection between 1997 and 2002 was performed. Delayed diagnosis was defined as patients diagnosed with HIV infection and AIDS simultaneously or within the first month after the first positive serologic test, or those with a first CD4+ cell count below 200/ml. The epidemiological characteristics of these patients were compared with those of the remaining patients, Results: Of 2,820 new cases of HIV infection, delayed diagnosis was found in 506 (18%). These patients differed from the remaining patients in their lower mean age and higher HIV viral load, as well as in their distribution by sex (higher proportion of males), occupational status, history of incarceration in prison, and HIV-risk transmission group. The median survival during follow-up was significantly lower among AIDS patients with a delayed diagnosis., Conclusions: Delayed diagnosis remains a cause for concern in our environment, due to its magnitude and its association with mortality. Some epidemiological characteristics provide clues to guide future programs directed at increasing information and improving prevention.

Background and Objective: To know the durability of consecutive regimens of antiretroviral treatment is important to design a long-term therapy, but there is not much information about this subject., Patients and Method: Retrospective epidemiological study of a sample of 401 patients who began antiretroviral treatment between January 1997 and April 2000 at ten Spanish hospitals. The duration of each consecutive antiretroviral regimen was calculated and the reasons for modification and discontinuation were described., Results: In the 3 years and 3 months covered by the study, 48.6% of the patients received more than one regimen of therapy. Seventy five of the initial prescribed combinations included protease inhibitors. Median duration of consecutive lines of therapy was decreasing: 560, 360, 330 and 202 days for the first, second, third and fourth regimens, respectively. The main reason to modification was intolerance or toxicity (46.2, 49.1 and 47.1% for the first, second and third modification). A fifth of changes was originated by difficulties to follow the therapy. Virological failure was the reason for modification in 21.8, 24.5 and 26.5% of first, second and third changes., Conclusions: Duration of consecutive antiretroviral regimens progressively decreases. Intolerance or drug toxicity were the main reasons conditioning the change of treatment.