Antiretroviral therapy (ART) has transformed HIV into a chronic condition, lengthening and improving the lives of individuals living with this virus. Despite successful suppression of HIV replication, people living with HIV (PLWH) are susceptible to a growing number of comorbidities, including neuroHIV that results from infection of the central nervous system (CNS). Alterations in the dopaminergic system have long been associated with HIV infection of the CNS. Studies indicate that changes in dopamine concentrations not only alter neurotransmission, but also significantly impact the function of immune cells, contributing to neuroinflammation and neuronal dysfunction. Monocytes/macrophages, which are a major target for HIV in the CNS, are responsive to dopamine. Therefore, defining more precisely the mechanisms by which dopamine acts on these cells, and the changes in cellular function elicited by this neurotransmitter are necessary to develop therapeutic strategies to treat neuroHIV. This is especially important for vulnerable populations of PLWH with chemically altered dopamine concentrations, such as individuals with substance use disorder (SUD), or aging individuals using dopamine-altering medications. The specific neuropathologic and neurocognitive consequences of increased CNS dopamine remain unclear. This is due to the complex nature of HIV neuropathogenesis, and logistical and technical challenges that contribute to inconsistencies among cohort studies, animal models and in vitro studies, as well as lack of demographic data and access to human CNS samples and cells. This review summarizes current understanding of the impact of dopamine on HIV neuropathogenesis, and proposes new experimental approaches to examine the role of dopamine in CNS HIV infection.
HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System. Both substance abuse disorders and the use of dopaminergic medications for age-related diseases are associated with changes in CNS dopamine concentrations and dopaminergic neurotransmission. These changes can lead to aberrant immune function, particularly in myeloid cells, which contributes to the neuroinflammation, neuropathology and dysfunctional neurotransmission observed in dopamine-rich regions in HIV+ individuals. These changes, which are seen despite the use antiretroviral therapy (ART), in turn lead to further dysregulation of the dopamine system. Thus, in individuals with elevated dopamine, the bi-directional interaction between aberrant dopaminergic neurotransmission and HIV infection creates a feedback loop contributing to HIV associated neurocognitive dysfunction and neuroHIV. However, the distinct contributions and interactions made by HIV infection, inflammatory mediators, ART, drugs of abuse, and age-related therapeutics are poorly understood. Defining more precisely the mechanisms by which these factors influence the development of neurological disease is critical to addressing the continued presence of neuroHIV in vulnerable populations, such as HIV-infected older adults or drug abusers. Due to the complexity of this system, understanding these effects will require a combination of novel experimental modalities in the context of ART. These will include more rigorous epidemiological studies, relevant animal models, and in vitro cellular and molecular mechanistic analysis.
One hundred eight serum samples from 106 patients were examined by Western blot analysis for the presence of antibodies to a recombinant fusion protein containing the sequence of the newly described serine-rich Entamoeba histolytica protein (SREHP). Among patients with invasive amebiasis from Durban, Republic of South Africa; San Diego, Calif; Mexico City, Mexico; and St Louis, Mo, 53 (82%) of 65 had antibodies to SREHP. In contrast, only one patient (2%) of 43 without acute invasive amebiasis had antibodies to SREHP. The predictive value of a positive test for anti-SREHP antibodies in the detection of acute invasive amebiasis was most marked when analyzed in the patients from Durban, where 11 (92%) of 12 patients who were seropositive for SREHP had acute invasive amebiasis vs 17 (65%) of 26 patients who had a positive serologic diagnosis as determined by agar gel diffusion. The use of a serologic test based on the recombinant SREHP fusion protein may be a useful adjunct to the diagnosis of acute invasive amebiasis in endemic regions. 相似文献
The question of whether somatic complaints are a significant feature of depression independent of anxiety was explored. Structured interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children) and Child Behavior Checklist data from depressed and nondepressed psychiatric controls were analyzed to explore the interaction of somatic complaints, anxiety, and depression. Seventy percent of the children who met criteria for depression also had significant somatic complaints in contrast to 34% of the controls. Findings revealed that frequency of somatic complaints increased with severity of depression regardless of coexisting anxiety. 相似文献
The histopathological and electron microscopic features of experimental dermatophytosis due to Trichophyton quinckeanum in Balb/c mice have been studied in animals with primary, secondary and chronic infections. Infected animals all showed pathological changes with adherence of microconidia to keratinocytes within 4 h of infection. Other features were the early infiltration of neutrophils, the formation of a mycelial mass (scutulum) in the epidermis, and epidermal oedema. Increased thickness of the epidermis was measured within 3 days of infection, although this was mainly due to oedema. The main differences seen in secondary infections were the paucity of fungal elements, even after 24 h, a sustained increase in epidermal thickness, and the dense dermal infiltrate of mononuclear cells. Chronically infected animals showed similar changes to those at the peak of a primary infection, but in addition there were large numbers of mast cells in the dermis. Cells carrying Ia markers were identified in the epidermis (Langerhans cells) and the dermis (macrophages) in all infections and their distribution did not appear to change. Although recovery from infection has been correlated previously with T lymphocyte mediated responses an increase in the number of cell layers of the epidermis and a dense infiltrate of neutrophils at the zone of infection were both seen within 2 days of infection. It is suggested that neutrophil killing of fungi and increased epidermal proliferation, not dependent on T cell activation, may also be implicated in host defence against dermatophytes. 相似文献
The aim of the study was to determine whether a prior diagnostic testicle
biopsy can predict success or failure of testicular sperm extraction (TESE)
with intracytoplasmic sperm injection (ICSI) in patients with
non-obstructive azoospermia caused by testicular failure, and what is the
minimum threshold of sperm production in the testis which must be surpassed
for spermatozoa to reach the ejaculate. Forty- five patients with
non-obstructive azoospermia caused by testicular failure underwent
diagnostic testicle biopsy prior to a planned future TESE-ICSI procedure.
The diagnostic testicle biopsy was analysed quantitatively, and correlated
with the quantitative findings of spermatogenesis in patients with normal
spermatogenesis, as well as with the results of subsequent attempts at
TESE-ICSI. Men with non- obstructive azoospermia caused by germinal failure
had a mean of 0-6 mature spermatids/seminiferous tubule seen on a
diagnostic testicle biopsy, compared to 17-35 mature spermatids/tubule in
men with normal spermatogenesis and obstructive azoospermia. These findings
were the same for all types of testicular failure whether Sertoli cell
only, maturation arrest, cryptorchidism, or post-chemotherapy azoospermia.
Twenty-two of 26 men with mature spermatids found in the prior testis
biopsy had successful retrieval of spermatozoa for ICSI, 12 of their
partners became pregnant, and are either ongoing or delivered. The study
suggests that 4-6 mature spermatids/tubule must be present in the testis
biopsy for any spermatozoa to reach the ejaculate. More than half of
azoospermic patients with germinal failure have minute foci of
spermatogenesis which are insufficient to produce spermatozoa in the
ejaculate. Prior diagnostic testicle biopsy analysed quantitatively (for
the presence of mature spermatids) can predict subsequent success or
failure with TESE-ICSI. Incomplete testicular failure may involve a sparse
multi-focal distribution of spermatogenesis throughout the entire testicle,
rather than a regional distribution. Therefore, it is possible that massive
testicular sampling from many different regions of the testes may not be
necessary for successful TESE-ICSI.
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β-Lactoglobulin was isolated from infant formulae that were ultra high temperature (UHT) -treated, sterilized or spray-dried. The effect of the isolated β-lactoglobulin on SfaII-fimbriae-mediated adhesion of Escherichia coli to human ileostomy glycoproteins was studied in vitro. β-Lactoglobulin isolated from sterilized formulae was found to perform significantly less well than preparations from spray-dried formulae (p = 0:05). Great heterogeneity was observed in the adhesion inhibitory capacity of β-lactoglobulin isolated from UHT-treated formulae. Therefore, no significant difference was observed between UHT-treated and sterilized formulae or spray-dried formulae (p < 0:10). It can be hypothesized that β-lactoglobulin from spray-dried and some UHT-treated infant formulae may affect the colonization of mucous membranes by E. coli strains causing neonatal septicaemia and meningitis. 相似文献