ABSTRACT
P2X4 receptors modulate synaptic transmission and communication among neurons in the CNS. An increased level of neuronal P2X4 is associated with altered memory in the hippocampal region. Additionally, some evidence suggests that P2X receptors downregulate the GABAA receptors. In the microglia of drug users, methamphetamine (METH) modifies the expression of certain genes. Therefore, the alterations of P2X4 and GABAA gene expression on memory following treatment with/without buprenorphine (BUP) in METH rats were evaluated. Seventy-seven rats were allocated into eleven groups at random (n = 7). Control, METH (10 mg/kg), BUP (6 and 10 mg/kg) for 5 days, BUP (6 and 10 mg/kg) for 14 days, METH (10 mg/kg) + BUP (6 and 10 mg/kg) for 5 days, METH + BUP (6 and 10 mg/kg) for 14 days and withdrawal group. They received their treatments intraperitoneally. After memory assessment, the animals were decapitated, and the gene expression of P2X4 and GABAA receptors in the hippocampus was assayed using RT-PCR. The memory and P2X4 and GABAA receptor gene expression in METH rats were reduced compared to the control group. The administration of all the different BUP doses increased gene expression in (BUP 6 or 10 mg/kg. 5 days and BUP.10 mg/kg.14 days) + METH groups compared to METH rats. These results demonstrated that METH toxicity severely decreased the level of P2X4 gene expression. Meanwhile, treatment of BUP led to increasing levels of the mentioned gene. Therefore, the potential role of P2X4 and GABAA receptor genes in modulating METH addiction is addressed.
ABSTRACT
Introduction: People living in many parts of the world have limited access to diagnostic studies and therapies for rheumatologic, musculoskeletal, and connective tissue diseases. The challenge has been particularly poignant for rural areas of low- and middle-income countries. Objectives: We report on the implementation of a telemedicine program in Iran for the evaluation and treatment of patients with rheumatologic and musculoskeletal diseases. More than 4,800 patients were seen remotely over a span of 5 years by a rheumatologist in the United States. The remote rheumatologist was aided by a general physician and a nurse at a local charity hospital in northeastern Iran that has a catchment area that includes rural regions extending to the border of Afghanistan. Seventy to 90 patients were evaluated online by the remote rheumatologist 3 days a week. A subset of patients was evaluated by the rheumatologist in person every 4 months. Materials and Methods: The population of rheumatology patients was evaluated using descriptive statistics. Information collected included demographic information consisting of age, gender, and primary rheumatologic diagnosis. Results: The average age of patients who were seen was 52 years and 89% of patients were women. Approximately 50% of patients were Afghan refugees. The most common disorders included osteoarthritis (1,149, 23.6%), rheumatoid arthritis (653, 13.4%), axial spondyloarthropathies (647, 13.3%), lumbar spinal stenosis (427, 8.8%), meniscal tear of the knee (326, 6.7%), and psoriatic arthritis (217, 4.5%). Certain conditions were lower than expected such as lupus (19, 0.4%) and fibromyalgia (169, 3.5%). Diagnostic tests included serologic tests (1,328, 27.3%), plain radiographs (946, 19.5%), magnetic resonance imaging (899, 18.5%), bone densitometry (147, 3.0%), and electromyography and nerve conduction study (132, 2.7%). The most common medications prescribed were non-steroidal anti-inflammatory drugs (791, 16.3%), methotrexate (764, 15.7%), pregabalin (234, 4.8%), duloxetine (230, 4.7%), sulfasalazine (177, 3.6%), etanercept (97, 2.0%), tofacitinib (64, 1.3%), adalimumab (18, 0.4%), and infliximab (9, 0.2%). Conclusions: Telemedicine is becoming more prevalent. We report the successful use of this service in evaluation and management of rheumatic diseases in a region with limited access to rheumatologic care. We have shown that patients can be seen, evaluated, and successfully treated with a variety of medications, including biologic agents.
