Articles: function.
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Sodium-glucose co-transporter 2 (SGLT2) inhibitors can block glucose reabsorption in the proximal tubule and thus play an important role in glycemic control in diabetes mellitus. In addition to glucosuric effects, surprisingly very extensive other positive effects were observed in chronic renal dysfunction and strong cardioprotective effects in heart failure. In the meantime, numerous mechanisms have been identified apart from the pure sugar-influencing effect of the SGLT2 inhibitors, which can have a direct positive influence heart and kidneys. ⋯ In a short period of 10 years, the use of SGLT2 inhibitors was established as an essential therapy for cardio-renal indications to inhibit the progression of renal failure as well as to protect against heart failure apart from pure diabetes therapy. In numerous guidelines (ESC heart failure, KDGIO diabetes, ESH hypertension), the early use of SGLT2 inhibitors is now recommended for protection against cardio-renal events and is an important first-line addition to the previously established therapies. Apart from diabetes therapy, it offers patients completely new options in cardio-renal protection.
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Parkinson disease (PD) affects up to 2% of the general population older than 65 years and is a major cause of functional loss. Chronic pain is a common nonmotor symptom that affects up to 80% of patients with (Pw) PD both in prodromal phases and during the subsequent stages of the disease, negatively affecting patient's quality of life and function. Pain in PwPD is rather heterogeneous and may occur because of different mechanisms. ⋯ This is also in line with the International Classification of Disease-11 , which acknowledges the possibility of chronic secondary musculoskeletal or nociceptive pain due to disease of the CNS. In this narrative review and opinion article, a group of basic and clinical scientists revise the mechanism of pain in PD and the challenges faced when classifying it as a stepping stone to discuss an integrative view of the current classification approaches and how clinical practice can be influenced by them. Knowledge gaps to be tackled by coming classification and therapeutic efforts are presented, as well as a potential framework to address them in a patient-oriented manner.
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Patients with chronic pain often experience exaggerated pain response and aversive emotion, such as anxiety and depression. Central plasticity in the anterior cingulate cortex (ACC) is assumed to be a critical interface for pain perception and emotion, which has been reported to involve activation of NMDA receptors. Numerous studies have documented the key significance of cGMP-dependent protein kinase I (PKG-I) as a crucial downstream target for the NMDA receptor-NO-cGMP signaling cascade in regulating neuronal plasticity and pain hypersensitivity in specific regions of pain pathway, ie, dorsal root ganglion or spinal dorsal horn. ⋯ Further mechanistic analysis revealed that PKG-I might act to phosphorylate TRPC3 and TRPC6, leading to enhancement of calcium influx and neuronal hyperexcitability as well as synaptic potentiation, which results in the exaggerated pain response and comorbid anxiety and depression. We believe this study sheds new light on the functional capability of ACC-PKG-I in modulating chronic pain as well as pain-associated anxiety and depression. Hence, cingulate PKG-I may represent a new therapeutic target against chronic pain and pain-related anxiety and depression.