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Int J Physiol Pathophysiol Pharmacol [JOURNAL]

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Alcohol and multiple sclerosis: an immune system-based review.

Fahim M, Rafiee Zadeh A, Shoureshi P … +4 more , Ghadimi K, Cheshmavar M, Sheikhinia N, Afzali M

Int J Physiol Pathophysiol Pharmacol · 2020 · PMID 32419901

Multiple sclerosis is a chronic inflammatory disease of the central nervous system (CNS). Although the exact etiology of multiple sclerosis is unknown, researchers suggest that genetic, environmental, and microbial facto... Multiple sclerosis is a chronic inflammatory disease of the central nervous system (CNS). Although the exact etiology of multiple sclerosis is unknown, researchers suggest that genetic, environmental, and microbial factors play a central role in causing multiple sclerosis. Pathology of multiple sclerosis is based on inflammation as T cells enter the brain via disruptions in the blood-brain barrier, recognizing myelin as foreign antigen; and as a result, the T cells attack myelin and start the inflammatory processes, enhancing inflammatory cytokines and antibodies. Since previous studies show ethanol can suppress the immune system such as innate, humoral, and cellular immunity and increases the production of anti-inflammatory cytokines, we hypothesized maybe ethanol also have ameliorating effects on multiple sclerosis symptoms. Although alcohol induces apoptosis in oligodendrocytes and neurons, causing demyelination and affects CNS directly, in this study we will investigate ethanol's effects on some aspects of the immune system in multiple sclerosis.

Risk factors for excessive tidal volumes delivered during intraoperative mechanical ventilation, a retrospective study.

Kowa CY, Jin Z, Longbottom R … +2 more , Cullinger B, Walker P

Int J Physiol Pathophysiol Pharmacol · 2020 · PMID 32419900

BACKGROUND: Lung Protective Ventilation (LPV) refers to a combination of measures aimed at reducing ventilator-associated lung injury. This includes: delivering tidal volumes of 6-8 ml/kg of ideal body weight, use of pos... BACKGROUND: Lung Protective Ventilation (LPV) refers to a combination of measures aimed at reducing ventilator-associated lung injury. This includes: delivering tidal volumes of 6-8 ml/kg of ideal body weight, use of positive end expiratory pressure and recruitment maneuvers. With Postoperative Pulmonary Complications (PPCs) contributing towards significant morbidity and mortality following surgery, evidence indicates that effective use of LPV measures intraoperatively has been associated with reduced rates of PPCs. METHODS: We conducted a post-hoc analysis using data from a recent clinical audit on departmental ventilation practices. Potential risk factors for excessive tidal volume ventilation were assessed using univariable and multivariable regression models. RESULTS: Obesity and gender are independently associated with risk of excessive ventilation. In contrast, the urgency and length of surgery, the choice of airway devices and the mode of ventilation were not associated with excessive ventilation. CONCLUSION: There is an association between female gender, obesity and excessive tidal volume ventilation. This may be addressed through formal, protocolized intraoperative ventilation setting.

Pectoral Nerve (PECs) block for postoperative analgesia-a systematic review and meta-analysis with trial sequential analysis.

Jin Z, Li R, Gan TJ … +2 more , He Y, Lin J

Int J Physiol Pathophysiol Pharmacol · 2020 · PMID 32211121

BACKGROUND AND OBJECTIVE: Pectoral Nerve (PECs) block is a fascial plane block first described by Blanco et al. for postoperative analgesia in breast surgery. The procedure is now widely used, and several small clinical... BACKGROUND AND OBJECTIVE: Pectoral Nerve (PECs) block is a fascial plane block first described by Blanco et al. for postoperative analgesia in breast surgery. The procedure is now widely used, and several small clinical trials have been published and reported favorably on the analgesic efficacy of PECs block. In this systematic review and meta-analysis, we will summarize the current evidence on the efficacy of PECs block. METHODS: We identified and analyzed 19 randomized control trials from PubMed, Central, EMBASE, CINAHL, Web of Science citation index, US clinical trials register and Google Scholar. The primary outcome was 24-hour opioid requirement, and secondary outcomes included pain scores, postoperative nausea and vomiting and other complications. RESULTS: Compared to systemic analgesia, PECs block was associated with reduced 24 hours opioid requirement [mean difference (MD) = -10.66 mg], lower pain score [9-12 hours postoperatively: MD = -1.18; 24 hours postoperatively: MD = -0.79] and less frequent PONV [risk ratio (RR) = 0.37, numbers needed to treat (NNT) = 5]. While the failure rate of PECs block was not well defined, several studies reported significant intraoperative opioid requirement despite PECs block. Lastly, trial sequential analysis indicated that no more clinical trials are needed to demonstrate the opioid sparing effect of PECs block. CONCLUSION: When compared to general anesthesia with systemic opioids, PECs block was associated with significantly better perioperative pain control. There are currently insufficient data on the complication and failure rate of PECs block in clinical practice.

Association of CD49d expression with clinicopathological features of chronic lymphocytic leukemia patients in the Iranian population.

Nematollahi P, Shakery M, Kefayat A … +1 more , Goli P

Int J Physiol Pathophysiol Pharmacol · 2020 · PMID 32211120

BACKGROUND: Identification of factors affecting prognosis in chronic lymphocytic leukemia (CLL) is important for risk stratification of patients. METHODS: In the present study, CD49d expression was analyzed by multi-colo... BACKGROUND: Identification of factors affecting prognosis in chronic lymphocytic leukemia (CLL) is important for risk stratification of patients. METHODS: In the present study, CD49d expression was analyzed by multi-color flow cytometry in 98 newly diagnosed and untreated CLL patients at the hematopathology ward. The patients were divided into two subgroups according to CD49d expression (30% cut off) and the association of this marker with the patients' clinicopathological properties were evaluated. RESULTS: In this study, CD49d expression exhibited significant association with the Rai stage of the disease (P<0.0001), CD38 status (P<0.0001), hemoglobin level (P=0.0006), and platelet count (P=0.0016). The CD49d-positive patients presented in higher stages in comparison with CD49d-negative patients. Although only 1% of the CD49d-negative patients were CD38-positive, this proportion for CD49d-positive group was 69%. However, no significant correlation was observed between CD49d expression and patients' age (P=0.2031), gender (P=0.8119), and absolute lymphocytes count (P=0.1073). CONCLUSION: Therefore, CD49d is a grateful biomarker with high association with clinicopathological parameters in CLL patients.

Gap junction connexin43 is a key element in mediating phagocytosis activity in human trabecular meshwork cells.

Li X, Nagy JI, Li D … +2 more , Acott TS, Kelley MJ

Int J Physiol Pathophysiol Pharmacol · 2020 · PMID 32211119

Human trabecular meshwork (TM) cells play pivotal roles in maintaining homeostasis of intraocular pressure via regulation of aqueous humor outflow. These cells are capable of phagocytosis, which is considered to be essen... Human trabecular meshwork (TM) cells play pivotal roles in maintaining homeostasis of intraocular pressure via regulation of aqueous humor outflow. These cells are capable of phagocytosis, which is considered to be essential for their regulatory function. In addition, there is a strong expression of the gap junction protein connexin43 (Cx43) in the TM. Here, we investigated functional relationships between phagocytosis activity of TM cells and their expression of Cx43. Phagocytosis was measured by showing the ability of TM cells to engulf inert fluorescent particles consisting of pHrodo. We found that internalized pHrodo was partially co-localized with Cx43 and that the phagocytic activity was dramatically reduced after knockdown of Cx43 using lentiviral Cx43 shRNA. These results suggest that Cx43 is involved in the regulation of phagocytosis by TM cells.

Amniotic mesenchymal stem cells derived hepatocyte-like cells attenuated liver fibrosis more efficiently by mixed-cell transplantation.

Wang H, Tian Y, Li X … +2 more , Yang M, Yan Y

Int J Physiol Pathophysiol Pharmacol · 2020 · PMID 32211118

BACKGROUND: Cell transplantation is a promising treatment for the patients with end-stage liver diseases. Stem cells derived hepatocyte-like cells (HLCs) attenuated liver injury upon transplantation in animal models for... BACKGROUND: Cell transplantation is a promising treatment for the patients with end-stage liver diseases. Stem cells derived hepatocyte-like cells (HLCs) attenuated liver injury upon transplantation in animal models for liver fibrosis. However, only a small portion of the transplanted cells propagated in the recipient liver. AIM: We hypothesized that the efficiency of cell therapy could be improved by transplanting amniotic mesenchymal stem cells (AMSCs) derived HLCs along with human umbilical vein endothelial cells (HUVECs) and undifferentiated AMSCs. METHODS: Briefly, we used a two-step protocol to generate induced HLCs. We confirmed organoids formation of HLCs in 3D collagen scaffolds with HUVECs and AMSCs. To determine whether the HLCs can migrate into the liver tissue and perform in vivo function, we transplanted the cells to mice with liver fibrosis. RESULTS: Co-culture of HLCs with HUVECs and AMSCs demonstrated improved function of HLCs within the organoids. Furthermore, transplantation using non-homogeneous cells, i.e. HLCs mixed with HUVECs and AMSCs, exhibited better graft survival in the host animals with liver fibrosis. Our experiment results suggested that compared to mock transplantation or HLCs transplantation groups, liver fibrosis was reduced significantly in mixed-cell groups. The AST levels in the plasma of transplanted mice were markedly decreased only in the mixed-cell transplantation group. The engraftment of HLCs in mice liver was better in mixed-cell transplantation group, compared with HLCs-only transplantation group. CONCLUSIONS: The HLCs attenuated liver fibrosis more efficiently when transplanted along with HUVECs and AMSCs, and this suggested that we could improve the efficiency of cell therapy by transplanting functional cells partially along with stromal cells.

ZO-1 associates with α3 integrin and connexin43 in trabecular meshwork and Schlemm's canal cells.

Li X, Acott TS, Nagy JI … +1 more , Kelley MJ

Int J Physiol Pathophysiol Pharmacol · 2020 · PMID 32211117

Cellular structures that perform essential homeostatic functions include tight junctions, gap junctions, desmosomes and adherens junctions. The aqueous humor, produced by the ciliary body, passes into the anterior chambe... Cellular structures that perform essential homeostatic functions include tight junctions, gap junctions, desmosomes and adherens junctions. The aqueous humor, produced by the ciliary body, passes into the anterior chamber of the eye and is filtered by the trabecular meshwork (TM), a tiny tissue found in the angle of the eye. This tissue, along with Schlemm's canal (SC) inner wall cells, is thought to control intraocular pressure (IOP) homeostasis for normal, optimal vision. The actin cytoskeleton of the tissue plays a regulatory role in maintaining IOP. One of the key risk factors for primary open angle glaucoma is persistent elevation of IOP, which compromises the optic nerve. The ZO-1 (Zonula Occludens-1), extracellular matrix protein integrins, and gap junction protein connexin43 (Cx43) are widely expressed in many different cell populations. Here, we investigated the localization and interactions of ZO-1, α3 integrin, β1 integrin, and Cx43 in cultured porcine TM and SC cells using RT-PCR, western immunoblotting and immunofluorescence labeling with confocal microscopy, along with co-immunoprecipitation. ZO-1 partially co-localized with α3 integrin, but not with β1 integrin, and co-immunoprecipitated with Cx43, as well as with α3 integrin. The association of ZO-1 with α3 integrin and Cx43 suggests that these proteins may form a multiple protein complex in porcine TM and SC cells. Since integrins interact with the actin cytoskeleton via scaffolding proteins, these results implicate junctional and scaffolding protein ZO-1 as a potential control point in regulation of IOP to normal levels for glaucoma therapy.

Nicotinamide phosphoribosyltransferase contributes to cocaine addiction through sirtuin 1.

Singh S, William M, Chu XP

Int J Physiol Pathophysiol Pharmacol · 2019 · PMID 31993108

Drug addiction is a persistent mental illness and there is no effective treatment. The precise mechanisms underlying addictive responses have not been completely understood, although ion channels, neurotransmitters as we... Drug addiction is a persistent mental illness and there is no effective treatment. The precise mechanisms underlying addictive responses have not been completely understood, although ion channels, neurotransmitters as well as their receptors, and intracellular endogenous molecules in the brain have been shown to play important roles in cocaine addiction. Nicotinamide phosphoribosyltransferase (NAMPT) is an important rate-limiting enzyme found throughout the body that converts the intracellular pool of nicotinamide adenine dinucleotide (NAD) into nicotinamide mononucleotide (NMN). It reveals a critical role in physiological and pathophysiological conditions such as NAD biosynthesis, aging, inflammation, obesity, diabetes, stroke, motor dysfunction, and cancer. A recent study published in Experimental Neurology by Cen group demonstrated that NAMPT contributes to cocaine reward through sirtuin 1 (SIRT1) signaling in the brain ventral tegmental area. Thus, targeting NAMPT/SIRT1 signaling pathway may provide a promising therapeutic strategy against cocaine addiction.

Diabetes retinopathy and related health management in Asians versus whites using BRFSS 2005-2017 data.

Yan F, Guo J, Mayberry R … +3 more , Luo Q, Li Y, Qin G

Int J Physiol Pathophysiol Pharmacol · 2019 · PMID 31993107

PURPOSE: Asian Americans had high rate of type 2 diabetes and less risk for diabetes complications compared to white. The purpose of this study was to examine diabetic retinopathy and related healthcare management among... PURPOSE: Asian Americans had high rate of type 2 diabetes and less risk for diabetes complications compared to white. The purpose of this study was to examine diabetic retinopathy and related healthcare management among Asian American adults with diabetes. MATERIALS AND METHOD: Asian and white type 2 diabetes participants from 2005-2017 Behavioral Risk Factor Surveillance System (BRFSS) data were used to perform the analysis. SAS 9.4 survey procedures were used to conduct the statistical test. Health care management variables (self-blood sugar check, eye check and HbA1C check with doctors, health care professional visit) were analyzed and compared between Asian and white. RESULTS: During 2005-2017, diabetic retinopathy (DR) rate among Asian Americans was 10% higher than white, and Asian Americans was more than 100% more likely to develop DR compared to white. Asian Americans was less likely to check their blood sugar once a day (P<0.05 for all years except 2005 and 2007) and more likely to see the health care professional and perform eye and HbA1C check even the relationship was not statistically significant. After adjusting all the demo-social factors and health care management factors, Asian still had higher rate of DR compared to white. CONCLUSION: Asian Americans had higher rate of DR rate compared to white. Asian and white all had low rate of selfcare of blood sugar. Interventions for DR need to apply among Asian population.

CD200-CD200R signaling and diseases: a potential therapeutic target?

Ngwa C, Liu F

Int J Physiol Pathophysiol Pharmacol · 2019 · PMID 31993106

CD200 and its receptor, CD200R, constitutes an endogenous inhibitory signaling, and is being increasingly recognized in studies of various central nervous system (CNS) disorders. Emerging data have demonstrated that neur... CD200 and its receptor, CD200R, constitutes an endogenous inhibitory signaling, and is being increasingly recognized in studies of various central nervous system (CNS) disorders. Emerging data have demonstrated that neuronal CD200 binds to CD200R to modulate immune responses to pathogenic stimuli. However, on which component of the immune response that CD200-CD200R signaling acts is not well understood. In this review, we focused on cellular expression of the signaling, the effects on immune cell activation, and the function in pathological procedures of neurodegenerative diseases, in both clinical and experimental disease models. Essential functions of CD200-CD200R interaction and the treatment relevance have been elaborated. Immune responses to diseases under the control of CD200-CD200R axis were also discussed in the review.

Disseminated cryptococcosis with multiple and mediastinal lymph node enlargement and lung involvement in an immunocompetent child.

Chen J, Zhang MJ, Ge XH … +6 more , Liu YH, Jiang T, Li J, Li Z, Miao HJ, Yang J

Int J Physiol Pathophysiol Pharmacol · 2019 · PMID 31993105

BACKGROUND: Disseminated cryptococcosis is less common in individuals with normal immune function. Most cases occur in HIV-infected people. Usually it affects the lungs, followed by the central nervous system (CNS), skin... BACKGROUND: Disseminated cryptococcosis is less common in individuals with normal immune function. Most cases occur in HIV-infected people. Usually it affects the lungs, followed by the central nervous system (CNS), skin and bone marrow, but rarely to the lymph nodes and chest wall. CASE PRESENTATION: This article reports a case of cryptococcal infection diagnosed as "lymphoma?" in a local hospital. It was characterized by chronic fever, weight loss, neck, axillary and inguinal lymph nodes enlargement, mediastinal and parabronchial lymphadenopathy, multiple nodular high-density images of both lungs, multi-serosal effusion, liver enlargement and other presentations. CONCLUSIONS: Disseminated cryptococcosis can occur in immunocompromised children without HIV infection. This case of multiple and mediastinal lymphadenopathy, easily misdiagnosed as "lymphoma", requires high clinical suspicion and early initiation of treatment to effectively identify and treat patients.

Comparing urine levels of BLCA-4 nuclear matrix protein in patients with bladder cancer and non-bladder cancer.

Alavi A, Izadpanahi MH, Haghshenas L … +3 more , Faridizad R, Eslami MJ, Ghadimi K

Int J Physiol Pathophysiol Pharmacol · 2019 · PMID 31993104

BACKGROUND: The molecular mechanism of bladder cancer is yet not fully understood. Aim of this study was to compare the levels of BLCA-4 nuclear matrix protein in the urine of patients with bladder cancer and non-affecte... BACKGROUND: The molecular mechanism of bladder cancer is yet not fully understood. Aim of this study was to compare the levels of BLCA-4 nuclear matrix protein in the urine of patients with bladder cancer and non-affected individuals. MATERIALS AND METHOD: The current cross sectional study was conducted on 45 patients with bladder cancer and 45 patients without bladder cancer who were referred to Alzahra Hospital of Isfahan, Iran in 2017. BCLA-4 Urinary Marker was measured in urine of the patients and individuals. Also correlation between the urine levels of BCLA-4 and other variables were evaluated. RESULTS: The urine levels of BLCA-4 in the patients with bladder cancer was significantly higher than non-bladder cancer group (P<0.001). There was no significant relationship between urine levels of BLCA-4 with tumor stage and size (P>0.05). CONCLUSION: The present study indicated that high urine levels of BLCA-4 was presented in patients with bladder cancer and this tumor marker has a high capability for early diagnosis of the disease, which can be used for screening and follow-up of bladder cancer.

How is the association between urinary prostate cancer antigen 3 (PCA3) levels and Gleason scores in patients suspicious of prostate cancer?

Gilani S, Shakery M, Shoureshi P … +4 more , Salimi H, Maleki H, Alavi A, Khodadadi F

Int J Physiol Pathophysiol Pharmacol · 2019 · PMID 31993103

INTRODUCTION: Prostate cancer is one of the most common cancers in men which is mostly slow growing and responses well to treatments if early diagnosed. Urinary prostate cancer antigen 3 (PCA3) assay is a new method with... INTRODUCTION: Prostate cancer is one of the most common cancers in men which is mostly slow growing and responses well to treatments if early diagnosed. Urinary prostate cancer antigen 3 (PCA3) assay is a new method with effective results in diagnosing prostate cancer. The aim of this present study was evaluate the correlation between urinary PCA3 and Gleason scores in patients who are suspicious of prostate cancer and undergo tissue biopsies. METHODS: This is a cross-sectional study which was performed in 2017-2018. The patients included this study complain of prostate problems and were selected from Nour hospital, Ali-Asghar hospital and Ordibehesht clinic in Tehran, Iran. Urinary PCA3 levels were checked in all patients and then they went under prostate biopsies. Amounts of PCA3 and Gleason scores were collected and analyzed using SPSS software. FINDINGS: We evaluated a total number of 80 patients. 40 patients had prostate cancer and 40 had no cancer. We indicated that no significant relation was reported between Gleason scores and urinary PCA3 levels. Levels of urinary PCA3 were higher in patients with prostate cancer than in patients with no cancer (P=0.007). DISCUSSION: Generally, urinary PCA3 test is indicated as a non-invasive method to improve the specificity of prostate cancer diagnosis and its potential predictive value was studied in numerous clinical researches, but here we found higher PCA3 levels in patients with prostate cancer than in patients with and other prostate problems. We conclude that PCA3 functions as a diagnostic test and its changes in prostate cancer need to be further studied in different populations and races.

Comparison of cognitive auditory event related potentials and executive functions in adolescent athletes and non-athletes - A cross sectional study.

Sharma VK, Subramanian SK, Rajendran R

Int J Physiol Pathophysiol Pharmacol · 2019 · PMID 31993102

There is strong evidence for the positive physical health outcomes of physical conditioning (athletic training. But there is a dearth of data on the impact of exercise on cognition, particularly in the adolescent age gro... There is strong evidence for the positive physical health outcomes of physical conditioning (athletic training. But there is a dearth of data on the impact of exercise on cognition, particularly in the adolescent age group. Further, most of the studies done on this topic are mainly acute in nature, and few that have seen long term effect of exercise have very rarely used objective measures such as event-related potentials. Hence, the present study was conceived to compare cognition in athletes (individual who have undergone long term physical activity) and non-athletes. We designed a cross-sectional comparative study involving apparently healthy volunteer boys in the age group of 10-19 years-non-athletes (n = 30) and athletes (n = 30). Paper pencil tests such as letter cancellation test, auditory and visual recognition reaction time, trail making test (A and B) were recorded along with auditory event-related potentials (N100, P200, N200, and P300). Data were analyzed using an unpaired t-test and Mann-Whitney U test according to the data distribution. Athletes completed letter cancellation task and trail making test faster than non-athletes. Athletes visual and auditory reaction time were lesser. Athletes had reduced latency and higher amplitude of auditory event-related potentials (N100, P200, N200, and P300) as compared to non-athletes. Hence, we conclude that athletic level physical training has a beneficial role in the executive cognitive domain among adolescents.

Serum levels of IL-6 and IL-17 in multiple sclerosis, neuromyelitis optica patients and healthy subjects.

Ashtari F, Madanian R, Shaygannejad V … +2 more , Zarkesh SH, Ghadimi K

Int J Physiol Pathophysiol Pharmacol · 2019 · PMID 31993101

BACKGROUND: Studies reported that evaluating the interleukin serum level of MS and NMO patients is helpful for differentiating these two diseases from each other. This study aimed to compare the level of IL-6 and IL-17 i... BACKGROUND: Studies reported that evaluating the interleukin serum level of MS and NMO patients is helpful for differentiating these two diseases from each other. This study aimed to compare the level of IL-6 and IL-17 in MS and NMO patients and healthy subjects. METHODS: This study is a case control study that evaluated the serum level of IL-6 and IL-17 in MS and NMO patients in comparison to controls in patients who referred to Kashani hospital clinics. The level of serum IL-6 and IL-17 were measured by ELISA test in all patients. Participants were divided in to three groups include MS patients, NMO patients and controls and the level of IL-6 and IL-17 were compared in this three groups. RESULTS: Mean of serum level of IL-6 in the NMO group was significantly lower than MS and healthy subject (P=0.02 for NMO and MS, P=0.001 for NMO and healthy subjects) but there was no significant difference between MS and healthy subjects (P=0.09). The mean of serum level of IL-17 in the MS and NMO were significantly higher than healthy subjects (P<0.001 for both). Also the mean of serum level of IL-17 in the MS was significantly higher than NMO (P=0.01). A positive significant correlation between age and serum level of IL-6 in all subjects (r=0.23, P=0.01). There was a positive significant correlation between age and serum level of IL-17 in MS and NMO patients (r=0.28, P=0.012). CONCLUSION: Using IL-17 and IL-6 were inflammatory markers to diagnosis of NMO, MS and healthy subjects.

Early consumption of high-fat diet worsens renal damage in spontaneously hypertensive rats in adulthood.

Pereira RO, Muller CR, de Nascimento NRF … +4 more , Fonteles MC, Evangelista FS, Fiorino P, Farah V

Int J Physiol Pathophysiol Pharmacol · 2019 · PMID 31993100

The association between hypertension and obesity has been shown to be an important cause of kidney disease. We aimed to investigate the impact of a high-fat diet (HFD) administered in spontaneously hypertensive rats (SHR... The association between hypertension and obesity has been shown to be an important cause of kidney disease. We aimed to investigate the impact of a high-fat diet (HFD) administered in spontaneously hypertensive rats (SHR) after weaning in renal morphology and functional parameters. Male post-weaned SHR were divided into two groups: standard control diet (CD) (3% lipids; n = 8) or HFD (30% lipids; n = 8) during 8 weeks. The group HFD showed an increase in serum triglycerides (HFD: 96 ± 7 vs. CD: 33 ± 2 mg/dL) and glucose intolerance (HFD: 185 ± 7 vs. CD: 149 ± 4 mg/dL/min). Moreover, the HFD also showed an increase in almost 90% of the periepididymal and retroperitoneal adiposity. There was no difference in arterial blood pressure between groups. Renal morphofunctional parameters were decreased in HFD group for glomerular tuft area and diameter (4733 ± 65 µm and 82 ± 1 µm, respectively) when compared with CD group (5289 ± 171 µm and 88 ± 2 µm, respectively). HFD also showed a decrease of 50% of the renal function, which was associated with higher renal extracellular matrix and lipid deposition. Therefore, our data suggest that HFD since early period of life may contribute to renal damage in adults with hypertension, and this impairment can be associated with increased renal lipid accumulation.

Mechanism of membrane fusion: protein-protein interaction and beyond.

Wang H, Zhang C, Xiao H

Int J Physiol Pathophysiol Pharmacol · 2019 · PMID 31993099

Membrane fusion is a universal event in all living organism. It is at the heart of intracellular organelle biogenesis and membrane traffic processes such as endocytosis and exocytosis, and is also used by enveloped virus... Membrane fusion is a universal event in all living organism. It is at the heart of intracellular organelle biogenesis and membrane traffic processes such as endocytosis and exocytosis, and is also used by enveloped viruses to enter hosting cells. Regarding the cellular mechanisms underlying membrane fusion, pioneering studies by Randy Schekman, James Rothman, Thomas C. Südhof and their colleagues have demonstrated the function of specific proteins and protein-protein interactions as essential fusogenic factor to initiate membrane fusion. Since then, function of lipids and protein-lipid interaction has also been identified as important players in membrane fusion. Based on that NSF (NEM-sensitive factor where NEM stands for -ethyl-maleimide) and acyl-CoA are required for the membrane fusion of transporting vesicles with Golgi cisternae, it is further suggested that the transfer of the acyl chain to a molecule(s) is essential for membrane fusion. Among the previously identified fusogens, phosphatidic acid (PA) is found as an acyl chain recipient. Functionally, acylation of PA is required for tethering the membranes of Rab5a vesicles and early endosomes together during membrane fusion. As certain threshold of proximity between the donor and acceptor membrane is required to initiate membrane fusion, fusogenic factors beyond protein-protein and protein-lipid interaction need to be identified.

How does the brain remove its waste metabolites from within?

Cheng Y, Haorah J

Int J Physiol Pathophysiol Pharmacol · 2019 · PMID 31993098

The brain is the command center of the body that regulates the vital functions of circulation, respiration, motor function, metabolic activities, or autonomic nervous system outcomes. The brain coordinates these continuo... The brain is the command center of the body that regulates the vital functions of circulation, respiration, motor function, metabolic activities, or autonomic nervous system outcomes. The brain coordinates these continuous activities at the expense of huge energy utilization. This energy demand is achieved by active transport of nutrients across the endothelial blood-brain barrier (BBB). This review discusses the barrier interfaces in the CNS that include the BBB, blood-spinal cord barrier, the epithelial choroid plexus, and the epithelial arachnoid. While transporting of nutrients across the BBB is a normal physiological function, the trafficking of xenobiotics and inflammatory cells/agents across these interfaces is harmful to brain cells. This leads to production of waste metabolites in the brain. Clearance of these waste metabolites maintains the normal brain homeostasis, while aggregation is detrimental to neurological complications. Since the CNS lacks lymphatic system, the CSF serves as the clearance path for water-soluble peptides/solutes, but not large size waste metabolites like Aβ protein. In particular, this review will focus on the mechanisms of waste metabolites clearance paths in the CNS. This will include the recently discovered waste metabolites movement from interstitial space (IS) directly into perivascular clearance (PVC), or via IS-CSF-PVC, and its exchange from PVC to circulation. Concluding remarks will discuss the therapeutic approach to improve the clearance mechanisms for ameliorating neurological diseases.

Hypoglycaemic and anti-diabetic activity of selected African medicinal plants.

Oguntibeju OO

Int J Physiol Pathophysiol Pharmacol · 2019 · PMID 31993097

The use of medicinal plants in the treatment and management of diabetes mellitus is not very popular in Europe and USA as it is in Africa due to adequate availability of synthetic drugs and insulin for the effective mana... The use of medicinal plants in the treatment and management of diabetes mellitus is not very popular in Europe and USA as it is in Africa due to adequate availability of synthetic drugs and insulin for the effective management of diabetes in the western countries. In Africa, over 80% of the population live in poor resource settings and depend on medicinal plants for the treatment of various diseases including diabetes mellitus. Africa is very rich in medicinal plants and many of these plants are used in the treatment of diabetes mellitus. These plants play important role as alternative medicine due to their low cost, perception of their minimal side-effects, availability and knowledge about their use in the treatment of diseases. Many African medicinal plants have been reported to possess pancreatic beta cells regenerating insulin potential, hypoglycaemic effects, increase insulin secretion, enhance glucose uptake by adipose tissue or muscles and inhibit glucose absorption from the intestine and glucose production from the liver. Medicinal plants may potentially provide useful source of new oral hypoglycaemic agents for drug development in pharmaceutical application or as adjuncts for existing therapies in the management of diabetes. This review therefore focuses on selected African medicinal plants with hypoglycaemic and anti-diabetic activities that are used in traditional medicine in the treatment and management of diabetes mellitus. There is an urgent need to document the knowledge of medicinal plants that are used mainly in the treatment and management of diabetes mellitus in various parts of Africa.

Intraoperative methadone for postoperative pain management - systematic review protocol.

Jin Z, Lin EJ, He Y … +1 more , Lin J

Int J Physiol Pathophysiol Pharmacol · 2019 · PMID 31777646

Methadone is a long acting opioid initially used to treat opioid withdrawal symptoms. It has been suggested that methadone, when given as a single bolus while under anesthesia, provides good postoperative analgesia and i... Methadone is a long acting opioid initially used to treat opioid withdrawal symptoms. It has been suggested that methadone, when given as a single bolus while under anesthesia, provides good postoperative analgesia and is associated with minimal risk of opioid adverse events. Several small studies have investigated the use of methadone for postoperative analgesia with some promising results. Here we describe our protocol for a meta-analysis to investigate the postoperative analgesic effect of methadone.
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