- Effects of mu opioid receptors in paraventricular nucleus on ejaculation through mediating sympathetic nerve system activity. [Journal Article]
- NNeuropharmacology 2019 Jul 13; :107709
- To investigate the roles of mu opioid receptors (MORs) in paraventricular nucleus of the hypothalamus (PVN) on ejaculation and its underlying mechanism in the rats, we performed copulation behavioral…
To investigate the roles of mu opioid receptors (MORs) in paraventricular nucleus of the hypothalamus (PVN) on ejaculation and its underlying mechanism in the rats, we performed copulation behavioral testing and acute experiments. During the acute experiments, mean arterial pressure (MAP), heart rate (HR), bulbospongiosus muscle-electromyogram (BSM-EMG) and pressure of vas deferens (PVD) were all recorded. The expression levels and distributions of opioid receptors were also assessed in PVN of male rats. Moreover, adeno-associated virus type 1 (AAV1) was microinjected into PVN to demonstrate whether there are direct projections from PVN to lumbar spinothalamic (LSt) cells. We found that microinjection of MOR agonist, D-A1a2-NM9-Phe4-Gly(ol)5enkephalin (DAGO), into the PVN prolonged the intromission latency and inhibited ejaculation (P = 0.0241, P = 0.0473, respectively), while the opposed results appeared in CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, MOR antagonist) group (P = 0.0021, P = 0.0286, respectively). Moreover, DAGO caused a significant decrease in MAP and HR (P = 0.0065, P = 0.0030, respectively), and PVD decreased significantly after DAGO microinjection in PVN (P = 0.0383). CTAP not only blocked the effect of DAGO but also significantly increased MAP, HR and PVD (P = 0.0003, P = 0.0010, P = 0.0074, respectively). Meanwhile, a significant increase was observed in BSM-EMG activity after microinjecting of CTAP (P = 0.0022), accompanied by visible BSM contraction. Additionally, anterograde monosynaptic transneuronal tracer AAV1 labeling revealed that neurons in PVN projected directly to LSt cells in L3-4 spinal cord. These results indicate that MORs in PVN centrally mediate ejaculation by regulating the sympathetic outflow, which may be treated as a therapeutic target for ejaculation disorders in the future.
- Hypoxic augmentation: the tale of a strange contraction. [Journal Article]
- BCBasic Clin Pharmacol Toxicol 2019 Jul 16
- Almost fifty years ago, experiments on isolated veins showed that acute hypoxia augments venoconstrictor responses in vitro and that such facilitation relied on anaerobic glycolysis. Over the years, …
Almost fifty years ago, experiments on isolated veins showed that acute hypoxia augments venoconstrictor responses in vitro and that such facilitation relied on anaerobic glycolysis. Over the years, this phenomenon was extended to a number of arterial preparations of different species and revisited, from a mechanistic point of view, with the successive demonstration that it depends on calcium-handling in the vascular smooth muscle cells, is endothelium-dependent, requires the production of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS) and the activation of soluble guanylyl cyclase (sGC). However, rather than the vasodilator cyclic nucleotide 3' ,5' -cyclic guanosine monophosphate (cGMP), its canonical product, the latter enzyme produces 3' ,5' -cyclic inosine monophosphate (cIMP) instead during acute hypoxia; this non-canonical cyclic nucleotide facilitates the contractile process in the vascular smooth muscle cells. This "biased" activity of soluble guanylyl cyclase appears to involve stimulation of NAD(P)H: quinone oxidoreductase 1 (NQO-1). The exact interactions between hypoxia, anaerobic metabolism and NQO-1 leading to biased activity of soluble guanylyl cyclase remain to be established. This article is protected by copyright. All rights reserved.
- Inactivation of Sox9 in fibroblasts reduces cardiac fibrosis and inflammation. [Journal Article]
- JIJCI Insight 2019 Jul 16; 5
- Fibrotic scarring drives the progression of heart failure after myocardial infarction (MI). Therefore, the development of specific treatment regimens to counteract fibrosis is of high clinical releva…
Fibrotic scarring drives the progression of heart failure after myocardial infarction (MI). Therefore, the development of specific treatment regimens to counteract fibrosis is of high clinical relevance. The transcription factor SOX9 functions as an important regulator during embryogenesis, but recent data point towards an additional causal role in organ fibrosis. We show here that SOX9 is upregulated in the scar after MI in mice. Fibroblast specific deletion of Sox9 ameliorated MI-induced left ventricular dysfunction, dilatation and myocardial scarring in vivo. Unexpectedly, deletion of Sox9 also potently eliminated persisting leukocyte infiltration of the scar in the chronic phase after MI. RNA-sequencing from the infarct scar revealed that Sox9 deletion in fibroblasts resulted in strongly downregulated expression of genes related to extracellular matrix, proteolysis and inflammation. Importantly, Sox9 deletion in isolated cardiac fibroblasts in vitro similarly affected gene expression as in the cardiac scar and reduced fibroblast proliferation, migration and contraction capacity. Together, our data demonstrate that fibroblast SOX9 functions as a master regulator of cardiac fibrosis and inflammation and might constitute a novel therapeutic target during MI.
- Jackhammer esophagus with and without esophagogastric junction outflow obstruction demonstrates altered neural control resembling type 3 achalasia. [Journal Article]
- NMNeurogastroenterol Motil 2019 Jul 16; :e13678
- CONCLUSIONS: The balance of excessive excitation and abnormal inhibition defines clinical and manometric manifestations in esophageal hypercontractile disorders.
- Evaluation of an accelerometer-based digital health system for the treatment of female urinary incontinence: A pilot study. [Journal Article]
- NUNeurourol Urodyn 2019 Jul 16
- CONCLUSIONS: Pilot testing of this accelerometer-based system demonstrates improvements in objective PFM measures, patient-reported UI severity and condition-specific quality of life, with results evident after 1 week of use.
- A Physiological Biomimetic Culture System for Pig and Human Heart Slices. [Journal Article]
- CircRCirc Res 2019 Jul 16
- CONCLUSIONS: We have developed and optimized a reliable medium-throughput culture system for pig and human heart slices as a platform for testing the efficacy of novel heart failure therapeutics and reliable testing of cardiotoxicity in a 3D heart model.
- Irritability and Brain Volume in Adolescents: Cross-sectional and Longitudinal Associations. [Journal Article]
- SCSoc Cogn Affect Neurosci 2019 Jul 16
- Irritability is garnering increasing attention in psychiatric research as a transdiagnostic marker of both internalizing and externalizing disorders. These disorders often emerge during adolescence, …
Irritability is garnering increasing attention in psychiatric research as a transdiagnostic marker of both internalizing and externalizing disorders. These disorders often emerge during adolescence, highlighting the need to examine changes in the brain and in psychological functioning during this developmental period. Adolescents were recruited for a longitudinal study examining the effects of early life stress on the development of psychopathology. 151 adolescents (73 M/78 F, average age=11.5 years, standard deviation=1.1) were scanned with a T1-weighted MRI sequence and parents completed reports of adolescent irritability using the Affective Reactivity Index. Of these 151 adolescents, 94 (46 M/48 F) returned for a second session (average interval=1.9 years, SD=0.4). We used tensor-based morphometry to examine cross-sectional and longitudinal associations between irritability and regional brain volume. Irritability was associated with brain volume across a number of regions. More irritable individuals had larger hippocampi, insula, medial orbitofrontal cortex, and cingulum/cingulate cortex, and smaller putamen and internal capsule. Across the brain, more irritable individuals also had larger volume and less volume contraction in a number of areas that typically decrease in volume over the developmental period studied here, suggesting delayed maturation. These structural changes may increase adolescents' vulnerability for internalizing and externalizing disorders.
- Histopathological changes induced by the digenean intestinal parasite Masenia nkomatiensis Dumbo, Dos Santos, & Avenant-Oldewage, 2019 of the catfish Clarias gariepinus (Burchell) from Incomati Basin, Mozambique. [Journal Article]
- JFJ Fish Dis 2019 Jul 15
- The intestines of 154 Clarias gariepinus were examined of which 29 were naturally infected with Masenia nkomatiensis, and of these, seven (intensity ranging from 8 to 231) were examined for pathology…
The intestines of 154 Clarias gariepinus were examined of which 29 were naturally infected with Masenia nkomatiensis, and of these, seven (intensity ranging from 8 to 231) were examined for pathology. Destruction of the epithelium covering the villi, detachment of epithelial cells and parts of villi were observed. Excessive mucus secretion occurred in the vicinity of the worm and catarrh was observed, indicative of an inflammatory response. The number of mucous and mast cells was higher at the attachment site than at an area 5,000 µm away and in uninfected individuals, suggesting that the parasite triggered a localized innate immune response. The number of neutrophils, basophils and lymphocytes in infected tissue was not significantly different from uninfected tissue confirming that no acquired immune response was produced against the maseniid. The caecae in the anterior part of the parasites' intestine consisted of convoluted epithelium forming invaginations or "crypts." Contraction of the thick layer of circular muscle fibres of the caeca facilitates the movement of digested material. Observation of digested host cells and cell debris within the caecae provides further evidence that M. nkomatiensis is consuming host cells.
- Intracoronary arterial retrograde thrombolysis with percutaneous coronary intervention: a novel use of thrombolytic to treat acute ST-segment elevation myocardial infarction. [Journal Article]
- JGJ Geriatr Cardiol 2019; 16(6):458-467
- CONCLUSIONS: ICART was accurate and effective for treating intracoronary thrombi in patients with STEMI in this preliminary study. ICART was an effective, feasible, and simple approach to the management of STEMI, and no intraprocedural complications occurred in any of the patients. ICART may be a breakthrough in the treatment of acute STEMI.
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- Current understanding and treatment of cardiac and skeletal muscle pathology in laminin-α2 chain-deficient congenital muscular dystrophy. [Journal Article]
- ACAppl Clin Genet 2019; 12:113-130
- Congenital muscular dystrophy (CMD) is a class of severe early-onset muscular dystrophies affecting skeletal/cardiac muscles as well as the central nervous system (CNS). Laminin-α2 chain-deficient co…
Congenital muscular dystrophy (CMD) is a class of severe early-onset muscular dystrophies affecting skeletal/cardiac muscles as well as the central nervous system (CNS). Laminin-α2 chain-deficient congenital muscular dystrophy (LAMA2 MD), also known as merosin-deficient congenital muscular dystrophy type 1A (MDC1A), is an autosomal recessive CMD characterized by severe muscle weakness and degeneration apparent at birth or in the first 6 months of life. LAMA2 MD is the most common congenital muscular dystrophy, affecting approximately 4 in 500,000 children. The most common cause of death in early-onset LAMA2 MD is respiratory tract infection, with 30% of them dying within the first decade of life. LAMA2 MD is caused by loss-of-function mutations in the LAMA2 gene encoding for the laminin-α2 chain, one of the subunits of laminin-211. Laminin-211 is an extracellular matrix protein that functions to stabilize the basement membrane and muscle fibers during contraction. Since laminin-α2 is expressed in many tissue types including skeletal muscle, cardiac muscle, Schwann cells, and trophoblasts, patients with LAMA2 MD experience a multi-systemic clinical presentation depending on the extent of laminin-α2 chain deficiency. Cardiac manifestations are typically associated with a complete absence of laminin-α2; however, recent case reports highlight cardiac involvement in partial laminin-α2 chain deficiency. Laminin-211 is also expressed in the brain, and many patients have abnormalities on brain imaging; however, mental retardation and/or seizures are rarely seen. Currently, there is no cure for LAMA2 MD, but various therapies are being investigated in an effort to lessen the severity of LAMA2 MD. For example, antisense oligonucleotide-mediated exon skipping and CRISPR-Cas9 genome editing have efficiently restored the laminin-α2 chain in mouse models in vivo. This review consolidates information on the clinical presentation, genetic basis, pathology, and current treatment approaches for LAMA2 MD.