Demographic and health profiles of people with severe mental illness in general practice in Australia: a cross-sectional study.

BACKGROUND: People with severe mental illness have a higher rate of premature death than the general population, largely due to primary care preventable diseases. There has been little research on the health profile of this population attending Australian general practices. METHODS: In this nationwide cross-sectional study, MedicineInsight data for adult patients regularly attending general practices in 2018 were analysed to estimate the prevalence of schizophrenia or bipolar disorders (SBD) and investigate the health profile of people with SBD compared with other patients. Multilevel models clustered by practice (n = 565) and patient, and practice characteristics were created. RESULTS: The prevalence of recorded SBD was 1.91% (95% CI = 1.88%-1.94%) among the 618 849 patients included. Patients with recorded SBD were more likely than other patients to have records of health risk factors, particularly smoking (aOR = 3.8, 95% CI = 3.6-3.9) and substance use (aOR = 5.9, 95% CI = 5.6-6.3), and higher probabilities of comorbidities including cardiovascular diseases (aOR = 1.3, 95% CI = 1.2-1.4), cancer (aOR = 1.1, 95% CI = 1.0-1.2), diabetes mellitus type 2 (aOR = 2.2, 95% CI = 2.0-2.3), chronic kidney diseases (aOR = 1.7, 95% CI = 1.5-2.0), chronic liver diseases (aOR = 3.3, 95% CI = 2.6-4.0) and chronic respiratory diseases (aOR = 1.7, 95% CI = 1.7-1.8). CONCLUSIONS: The higher prevalence of health risk factors and comorbidities among patients with recorded SBD underscores the need for proactive health risk monitoring and preventive care to address this health inequity.

Allopregnanolone suppresses diabetes-induced neuropathic pain and motor deficit through inhibition of GABAA receptor down-regulation in the spinal cord of diabetic rats.

OBJECTIVES: Painful diabetic neuropathy is associated with hyperexcitability and hyperactivity of spinal cord neurons. However, its underlying pathophysiological mechanisms have not been fully clarified. Induction of excitatory/inhibitory neurotransmission imbalance at the spinal cord seems to account for the abnormal neuronal activity in diabetes. Protective properties of neurosteroids have been demonstrated in numerous cellular and animal models of neurodegeneration. MATERIALS AND METHODS: Here, the protective effects of allopregnanolone, a neurosteroid were investigated in an in vivo model of diabetic neuropathy. The tail-flick test was used to assess the nociceptive threshold. Diabetes was induced by injection of 50 mg/kg (IP) streptozotocin. Seven weeks after the induction of diabetes, the dorsal half of the lumbar spinal cord was assayed for the expression of γ2 subunit of GABAA receptor using semiquantitative RT-PCR. RESULTS: The data shows that allopregnanolone (5 and 20 mg/kg) markedly ameliorated diabetes-induced thermal hyperalgesia and motor deficit. The weights of diabetic rats that received 5 and 20 mg/kg allopregnanolone did not significantly reduce during the time course of study. Furthermore, this neurosteroid could inhibit GABAA receptor down-regulation induced by diabetes in the rat spinal cord. CONCLUSION: The data revealed that allopregnanolone has preventive effects against hyperglycemic-induced neuropathic pain and motor deficit which are related to the inhibition of GABAA receptor down-regulation.

Neurosteroid allopregnanolone attenuates high glucose-induced apoptosis and prevents experimental diabetic neuropathic pain: in vitro and in vivo studies.

Hyperglycemia plays a critical role in the development of diabetic neuropathy. Hyperglycemia induces oxidative stress in neurons, resulting in neuronal cell apoptosis and dysfunction. Anti-apoptotic properties of neurosteroids have been demonstrated in numerous cellular models of neurodegenerative studies. Here, the protective effects of neurosteroid allopregnanolone were investigated in in vitro and in vivo models of diabetic neuropathy. The data show that glucose decreased the viability of PC12 cells in a concentration-dependent manner. Allopregnanolone at concentrations of 2.5, 5 and 10µM markedly prevented high glucose-induced toxicity in naïve and NGF-treated (neuron-like) PC12 cells. Furthermore, treatment of diabetic rats with allopregnanolone (5 and 20mg/kg) significantly ameliorated diabetic-induced thermal hyperalgesia. Moreover, this neurosteroid inhibited caspase 3 and decreased Bax/Bcl2 ratio in high glucose-treated cells and spinal cord of diabetic rats. In conclusion, the data revealed that allopregnanolone has protective effects against hyperglycemic-induced cellular damage and prevention of cell apoptosis is involved in its mechanisms. Our findings suggest that allopregnanolone has protective effect against pro-apoptotic challenges such as diabetes and hyperglycemia and propose therapeutic potential of neurosteroids in attenuation of diabetic side effects such as neuropathy.

Olive (Olea europaea L.) leaf extract attenuates early diabetic neuropathic pain through prevention of high glucose-induced apoptosis: in vitro and in vivo studies.

AIM OF STUDY: Since the leaves of olive have been recommended in the literature as a remedy for the treatment of diabetes and they also contain antioxidant agents, we decided to investigate the possible effects of olive leaf extract (OLE) on in vitro and in vivo models of diabetic pain neuropathy. MATERIALS AND METHODS: The high glucose-induced cell damage in naive and NGF-treated Pheochromocytoma (PC12) cells and streptozotocin-induced diabetic rats were used. Tail-flick test was used to access nociceptive threshold. Cell viability was determined by MTT assay. Biochemical markers of neural apoptosis were evaluated using immunoblotting. RESULTS: We found that elevation of glucose (4 times of normal) sequentially increases functional cell damage and caspase-3 activation in NGF-treated PC12 cells. Incubation of cells with OLE (200, 400 and 600 µg/ml) decreased cell damage. Furthermore, the diabetic rats developed neuropathic pain which was evident from decreased tail-flick latency (thermal hyperalgesia). Activated caspase 3 and Bax/Bcl2 ratio were significantly increased in spinal cord of diabetic animals. OLE treatment (300 and 500 mg/kg per day) ameliorated hyperalgesia, inhibited caspase 3 activation and decreased Bax/Bcl2 ratio. Furthermore, OLE exhibited potent DPPH free radical scavenging capacity. CONCLUSION: The results suggest that olive leaf extract inhibits high glucose-induced neural damage and suppresses diabetes-induced thermal hyperalgesia. The mechanisms of these effects may be due, at least in part, to reduce neuronal apoptosis and suggest therapeutic potential of olive leaf extract in attenuation of diabetic neuropathic pain.