ORCID Profile
0000-0002-8912-6894
Current Organisations
INSERM U1034; Bordeaux university and hospital
,
James Cook University
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Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.NEUROSCIENCE.2009.04.063
Abstract: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are active at resting membrane potential and thus contribute to neuronal excitability. Their increased activity has recently been demonstrated in models of nerve injury-induced pain. The major aim of the current study was to investigate altered HCN channel protein expression in trigeminal sensory neurons following inflammation of the dura. HCN1 and HCN2 channel immunoreactivity was observed on the membranes of medium- to large-sized trigeminal ganglion neurons with 76% and 85% of HCN1 and HCN2 expressing neurons also containing the 200 kDa neurofilament protein (associated with myelinated fibers). Western immunoblots of lysates from rat trigeminal ganglia also showed bands with appropriate molecular weights for HCN1 and HCN2. Three days after application of complete Freund's adjuvant (CFA) to the dura mater, Western blot band densities were significantly increased compared to control, to 166% for HCN1 and 284% for HCN2 channel protein. The band densities were normalized against alpha-actin. In addition, the number of retrogradely labeled neurons from the dura expressing HCN1 and HCN2 was significantly increased to 247% (HCN1) and 171% (HCN2), three days after inflammation. When the opioid receptor partial agonist, buprenorphine, was given systemically, immediately after CFA, the inflammation-induced increase in HCN protein expression in both Western blot and immunohistochemical experiments was not observed. These results suggest that HCN1 and HCN2 are involved in inflammation-induced sensory neuron hyperexcitability, and indicate that an opioid receptor agonist can reverse the protein upregulation.
Publisher: Proceedings of the National Academy of Sciences
Date: 06-07-1999
Abstract: The mechanisms by which infants and children process pain should be viewed within the context of a developing sensory nervous system. The study of the neurophysiological properties and connectivity of sensory neurons in the developing spinal cord dorsal horn of the intact postnatal rat has shed light on the way in which the newborn central nervous system analyzes cutaneous innocuous and noxious stimuli. The receptive field properties and evoked activity of newborn dorsal horn cells to single repetitive and persistent innocuous and noxious inputs are developmentally regulated and reflect the maturation of excitatory transmission within the spinal cord. These changes will have an important influence on pain processing in the postnatal period.
Publisher: Georg Thieme Verlag KG
Date: 18-02-2016
Abstract: Worldwide statins are considered to be the first-line pharmacological treatment for dyslipidemia and reducing the risk of coronary heart disease. However, recently various studies have shown its adverse effect on glucose control among diabetic patients and the U.S. Food and Drug Administration have revised statin drug labels to include information that increases in fasting serum glucose and glycated hemoglobin levels have been reported. This systematic review objective is to evaluate the risks and benefits of statins in glucose control management of type 2 diabetes patients based on the 44 published journal articles included and obtained through MEDLINE full text, PubMed, Science Direct, Pro Quest, SAGE, Taylor and Francis Online, Google Scholar, High Wire, and Elsevier Clinical Key. Statins were found to affect glucose control through several ways, namely, by affecting insulin production and secretion by β-pancreatic cells, insulin resistance, insulin uptake by the muscles and adipocytes and production of adipokines. Current evidence available shows that most of the statins give unfavorable side effects with regards to glucose control among diabetic patients. A dose-dependent and time-dependent effect was also observed in some statins which may be present among other statins as well.
Publisher: American Diabetes Association
Date: 25-07-2016
DOI: 10.2337/DC16-0588
Abstract: Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis in type 2 diabetes, but the relationship between other vascular diseases and PAD has been poorly investigated. We examined the impact of previous microvascular and macrovascular disease on the risk of major PAD in patients with type 2 diabetes. We analyzed 10,624 patients with type 2 diabetes free from baseline major PAD in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) clinical trial. The primary composite outcome was major PAD defined as PAD-induced death, peripheral revascularization, lower-limb utation, or chronic ulceration. The secondary end points were the PAD components considered separately. Major PAD occurred in 620 (5.8%) participants during 5 years of follow-up. Baseline microvascular and macrovascular disease were both associated with subsequent risk of major PAD after adjustment for age, sex, region of origin, and randomized treatments. However, only microvascular disease remained significantly associated with PAD after further adjustment for established risk factors. The highest risk was observed in participants with a history of macroalbuminuria (hazard ratio 1.91 [95% CI 1.38–2.64], P & 0.0001) and retinal photocoagulation therapy (1.60 [1.11–2.32], P = 0.01). Baseline microvascular disease was also associated with a higher risk of chronic lower-limb ulceration (2.07 [1.56–2.75], P & 0.0001) and utation (1.59 [1.15–2.22], P = 0.006), whereas baseline macrovascular disease was associated with a higher rate of angioplasty procedures (1.75 [1.13–2.73], P = 0.01). Microvascular disease, particularly macroalbuminuria and retinal photocoagulation therapy, strongly predicts major PAD in patients with type 2 diabetes, but macrovascular disease does not.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-10-2006
Publisher: American Physiological Society
Date: 10-2011
Abstract: Hyperpolarization-activated inward currents ( I h ) contribute to neuronal excitability in sensory neurons. Four subtypes of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels generate I h , with different activation kinetics and cAMP sensitivities. The aim of the present study was to examine the postnatal development of I h and HCN channel subunits in trigeminal ganglion (TG) neurons. I h was investigated in acutely dissociated TG neurons from rats aged between postnatal day (P)1 and P35 with whole cell patch-cl electrophysiology. In voltage-cl studies, I h was activated by a series of hyperpolarizing voltage steps from −40 mV to −120 mV in −10-mV increments. Tail currents from a common voltage step (−100 mV) were used to determine I h voltage dependence. I h activation was faster in older rats and occurred at more depolarized potentials the half-maximal activation voltage ( V 1/2 ) changed from −89.4 mV (P1) to −81.6 mV (P35). In current-cl studies, blocking I h with ZD7288 caused membrane hyperpolarization and increases in action potential half-duration at all postnatal ages examined. ZD7288 also reduced the action potential firing frequency in multiple-firing neurons. Western blot analysis of the TG detected immunoreactive bands corresponding to all HCN subtypes. HCN1 and HCN2 band density increased with postnatal age, whereas the low-intensity HCN3 and moderate-intensity HCN4 bands were not changed. This study suggests that functional I h are activated in rat trigeminal sensory neurons from P1 during postnatal development, have an increasing role with age, and modify neuronal excitability.
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.DSX.2018.06.019
Abstract: To compare the clinical and glycemic profile as well as pregnancy complications and infant mortality among diabetic mothers in Indonesia. Data was obtained from medical records of Internal-Medicine Clinic in Hermina Podomoro General Hospital during the period January-December 2015. Subjects were grouped into good and poor outcome groups based on infant mortality. Forty-five subjects were obtained with an average age of 31 years, 41 had gestational diabetes mellitus while 4 had pregestational diabetes. Twenty-one patients had high-risk pregnancies (age >30 years or <20 years). No maternal mortalities were reported, only 6 pregnancies were complicated with infant death. Comorbidities mainly found were preecl sia, anemia and urinary tract infection. Most patients delivered through caesarian section. Almost all of them were treated with insulin. Comparison between both groups showed that those with poor outcomes have a significantly higher body mass index prior to pregnancy, higher body weight prior and after pregnancy as well as worse glycemic profile. Diabetes in pregnancy has been found to increase rates of infant mortality. This study showed that patients with poor glycemic control are at a greater risk of infant mortality. Therefore increased monitoring and prenatal care as well as optimal glycemic control for patients with diabetes in pregnancy is recommended. Optimal glycemic control will lead to diabetic mothers with pregnancies of equal risk and similar outcomes to those of normal patients.
Publisher: Unpublished
Date: 2014
Publisher: American Diabetes Association
Date: 27-09-2016
DOI: 10.2337/DC16-1594
Abstract: The burden of vascular diseases remains substantial in patients with type 2 diabetes, requiring identification of further risk markers. We tested the absence of dorsalis pedis and posterior tibial pulses as predictors of major macrovascular and microvascular events, death, and cognitive decline in this population. Data were derived from 11,120 patients with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) study. Absent peripheral pulses at baseline were defined as absence of at least one dorsalis pedis or posterior tibial pulse. Absent compared with present peripheral pulses (n = 2,218) were associated with increased 5-year risks for major macrovascular events (hazard ratio 1.47 [95% CI 1.28–1.69], P & 0.0001), myocardial infarction (1.45 [1.13–1.87], P = 0.003), stroke (1.57 [1.23–2.00], P = 0.0003), cardiovascular death (1.61 [1.33–1.95], P & 0.0001), heart failure (1.49 [1.21–1.84], P = 0.0002), all-cause mortality (1.48 [1.29–1.71], P & 0.0001), major microvascular events (1.17 [1.00–1.36], P = 0.04), nephropathy (1.24 [1.00–1.54], P = 0.04), end-stage renal disease or renal death (2.04 [1.12–3.70], P = 0.02), and peripheral neuropathy (1.13 [1.05–1.21], P = 0.0008) after multiple adjustment. Participants with absent dorsalis pedis or posterior tibial pulses had comparable hazard ratios. Risks increased proportionally with the number of absent peripheral pulses, with the highest risks observed in patients with three or four absent pulses. Every additional absent pulse increases the risk of all outcomes. Absent dorsalis pedis and/or posterior tibial pulses are independent predictors of major vascular outcomes in patients with type 2 diabetes. These simple clinical indicators should be used to improve risk stratification and treatment of these patients.
Publisher: Elsevier BV
Date: 09-2007
Publisher: Elsevier BV
Date: 03-2012
Publisher: American Scientific Publishers
Date: 08-2018
Abstract: According to WHO, 80 million pregnancies each year are unintended and 45 million undergo abortion. There remains a continuing need for effective long-term contraceptives with minimal side effects. Contraceptive Vaccines (CV) thus provides an attractive solution due to its periodic intake, high specificity, reversibility and minimal side effects. This review aims to evaluate the potential of contraceptive vaccines for pregnancy prevention based on journal articles obtained from PubMed, Elsevier Clinical Key and Google Scholar. CV works by using the body’s own immune system to target molecules which take part in the reproduction process but do not confer other pleiotropic effects other than infertility. Three main mechanisms of CV are currently studied, namely by affecting gamete production, gamete function and gamete differentiation (hCG). Of all these, hCG vaccines are of great interest as they are formed by early embryos, not the pregnant female hence providing the least side effects when inhibited. They are the first CV to pass Phase I and II trials successfully and found to remain effective as long as antibody titres stay above 50 ng/mL. Those vaccinated can also easily undergo pregnancy when titres go below 35 ng/mL. Normal reproductive functions also remain following vaccination. An immunological approach to contraception remains an innovative idea and has been proven effective in both experimental and clinical trials. If ongoing trials remain successful, CV will mark another progress in the field of mass contraception and its implementation would hopefully reduce the current prevalence of unintended pregnancies.
Publisher: MDPI AG
Date: 16-04-2020
DOI: 10.3390/BIOM10040617
Abstract: Scorpion venoms are a rich source of bioactive molecules, but characterisation of toxin peptides affecting cytosolic Ca2+, central to cell signalling and cell death, is limited. We undertook a functional screening of the venom of the Australian scorpion Hormurus waigiensis to determine the breadth of Ca2+ mobilisation. A human embryonic kidney (HEK293) cell line stably expressing the genetically encoded Ca2+ reporter GCaMP5G and the rabbit type 1 ryanodine receptor (RyR1) was developed as a biosensor. Size-exclusion Fast Protein Liquid Chromatography separated the venom into 53 fractions, constituting 12 chromatographic peaks. Liquid chromatography mass spectroscopy identified 182 distinct molecules with 3 to 63 components per peak. The molecular weights varied from 258 Da—13.6 kDa, with 53% under 1 kDa. The majority of the venom chromatographic peaks (tested as six venom pools) were found to reversibly modulate cell monolayer bioimpedance, detected using the xCELLigence platform (ACEA Biosciences). Confocal Ca2+ imaging showed 9/14 peak s les, with molecules spanning the molecular size range, increased cytosolic Ca2+ mobilization. H. waigiensis venom Ca2+ activity was correlated with changes in bio-impedance, reflecting multi-modal toxin actions on cell physiology across the venom proteome.
Publisher: Public Library of Science (PLoS)
Date: 25-05-2021
DOI: 10.1371/JOURNAL.PONE.0251634
Abstract: The transition experience into university can be challenging for health profession students as they are required to rapidly learn erse and adaptable problem solving skills and advanced reflective thinking processes which are necessary to address complex patient-care problems, particularly in the face of uncertainty within a dynamic and rapidly evolving learning environment. A mixed-methods study was conducted to identify factors influencing this transition for first-year medical, dental, and pharmacy students at a regional Australian university. The Student Adaption to College Questionnaire (SACQ) examined participants’ levels of adjustment to university, while Schlossberg’s 4 S transition model was utilised in a framework analysis of the focus group and interview responses. Complete survey responses were obtained from 198 students, 17 of whom also participated in focus group discussions or interviews. Mean adjustment ratings obtained from the SACQ responses were academic (6.09 ± 1.3) personal-emotional (5.53 ± 1.55), social (6.30 ± 1.38), and institutional attachment (6.96 ± 1.6). These results indicate that the personal and emotional aspects of this transition were more challenging for the students. Analysis of the qualitative data revealed that generally, for these highly motivated health-professions students, dropping out of university was not an option and this had a positive influence on their ability to adjust to their new learning environment. Nonetheless, the transition involved role change school-leavers were excited about their newly found independence, while for mature-aged students, returning to university allowed them to pursue their lifelong dreams. Adjustment was more challenging for international, mature-aged and female students, with personal and social factors influencing the transition for each of these demographic groups. To facilitate smooth transition into university, tertiary education institutions must consider tailored on-going support strategies that promote social interaction among students with varied backgrounds and personal characteristics.
Publisher: Wiley
Date: 09-2007
DOI: 10.1002/DDR.20195
Publisher: Elsevier BV
Date: 06-2020
Publisher: Wiley
Date: 06-1998
DOI: 10.1111/J.1469-7793.1998.859BM.X
Abstract: 1. In vivo extracellular recordings were made of 171 dorsal horn cells in both superficial and deep laminae in urethane-anaesthetized newborn rats aged 3, 6, 10 and 21 days, and their response to single and repeated stimuli to primary afferent fibres investigated. 2. No long-latency spike responses were evoked in response to C fibre stimulation in pups at postnatal day 3 (P3) or P6, while by P10, 35 % of cells had a C fibre response. Latencies of response to A fibre skin stimulation were very long and varied widely in the youngest animals, particularly in superficial cells, but mean latencies decreased with postnatal age, from 33.1 +/- 2.78 ms at P3 to 7.3 +/- 0.3 ms at P21. The mean number of spikes evoked by a single A fibre skin stimulus was remarkably consistent between cells and not significantly different in superficial and deep laminae at each age. The mean value of 5.1 +/- 0.6 at P3 increased to 7.0 +/- 1.4 at P10. 3. Repeated stimulation of cutaneous A fibres at 0.5 Hz at twice the threshold level did not significantly alter the magnitude of the evoked response but led to shifts in latency, or 'latency jitter', which decreased with age. Deeper cells displayed more latency jitter than superficial cells. 4. Repeated stimulation of cutaneous A fibres at 0.5 Hz at twice the threshold level produced considerable sensitization in a population of dorsal horn cells in the neonate. This sensitization was unlike the classic C fibre-evoked 'wind-up' observed in adult dorsal horn. The direct A fibre-evoked activity did not increase, but the background activity increased during repetitive stimulation leading to a prolonged after-discharge beyond the stimulation period. At P6, 33 % of cells were sensitized, displaying a mean after-discharge of 70.6 +/- 18 s. At P10, only 6 % were sensitized, with a mean after-discharge of 63 s, and by P21, sensitization was no longer observed. 5. The present study demonstrates that the postsynaptic activity evoked in neonatal dorsal horn cells by cutaneous afferents differs considerably from that in adults. The results may account for the known behavioural reflex sensitization to low-intensity cutaneous stimulation observed in neonatal rats and man.
Publisher: Wiley
Date: 02-2011
Publisher: Unpublished
Date: 2016
Publisher: Wiley
Date: 23-02-2021
DOI: 10.1111/ADJ.12829
Abstract: Familiarity with cone beam computed tomography is a requisite for all dental practitioners involved in its use or referral. This scoping review examines the knowledge, attitudes, competence and confidence of dental practitioners and students towards cone beam computed tomography in the dental setting. A search of Medline, Scopus, Web of Science and Cumulative Index to Nursing and Allied Health Literature was conducted to identify and chart existing evidence. Relevant studies written in English and published after 1998 and up to July 2020 were included. Of 679 papers, 39 studies were included for analysis. Key findings include deficient knowledge despite a widespread recognition of its importance and willingness to increase proficiency in its use, as well as a largely positive and optimistic view of the technology. Future studies on practitioners’ knowledge and attitudes towards cone beam computed tomography are suggested to consider the contexts of an Australian setting.
Publisher: Elsevier BV
Date: 06-2012
Publisher: Springer Science and Business Media LLC
Date: 17-07-2021
DOI: 10.1038/S41405-021-00082-5
Abstract: To comprehensively review the existing studies of articaine in dentistry and conduct a systematic review and meta-analysis to answer the following Population, Intervention, Comparison and Outcome question: “Is articaine a safe and efficacious local anaesthetic for routine dental treatment compared to lidocaine?” Database searches were conducted in Medline Ovid, Medline Pubmed, Scopus, Emcare, Proquest and the Cochrane Central register of Controlled Trials. Inclusion criteria were all existing English, human, randomised controlled trials of interventions involving 4% articaine and 2% lidocaine in routine dental treatment. Twelve studies were included for meta-analysis using Cochrane Review Manager 5 software. Anaesthetic success odds ratios were calculated using a random-effects model. Articaine had a higher likelihood of achieving anaesthetic success than lidocaine overall and in all subgroup analyses with varying degrees of significance. Overall (OR: 2.17, 95% CI: 1.50, 3.15, I 2 = 62%) articaine had 2.17 times the likelihood of anaesthetic success of lidocaine ( P 0.0001). For mandibular blocks (OR: 1.50, 95% CI: 1.14, 1.98, I 2 = 0%) articaine had 1.5 times the likelihood of anaesthetic success of lidocaine ( P = 0.004). For all infiltrations, maxillary and mandibular (OR: 2.78, 95% CI: 1.61, 4.79, I 2 = 66%) articaine had 2.78 times the likelihood of anaesthetic success of lidocaine ( P = 0.0002). None of the studies reported any major local anaesthetic-related adverse effects as a result of the interventions. Articaine is a safe and efficacious local anaesthetic for all routine dental procedures in patients of all ages, and more likely to achieve successful anaesthesia than lidocaine in routine dental treatment. Neither anaesthetic has a higher association with anaesthetic-related adverse effects.
Publisher: American Scientific Publishers
Date: 08-2018
Abstract: Obesity has currently become a worldwide epidemic. Currently, lifestyle changes, pharmacotherapy and bariatric surgery remains the only available armamentarium. However, lifestyle changes and pharmacotherapy resulted in variable outcomes and are often unsustainable. On the other hand, advances in metagenomics and food biotechnology has reported the important role of gut microbiota in the complex pathophysiology of obesity and its possible role in treating it. This review aims to discuss the potential of manipulating gut microbiota to tackle obesity. Articles were obtained through Pubmed, Science Direct, Google Scholar, High Wire and Elsevier Clinical Key using the keywords “obesity AND gut microbiota or synonyms.” Various studies have shown the interactions between gut microbiota, gut permeability and the immune system as a mechanism that links diet, obesity and its comorbidities. There are currently several reported methods of manipulating gut microbiota namely, though probiotics, prebiotics, synbiotics and diet modification with varying outcomes based on the microbial strain affected and used. Studies have also proposed manipulating gut microbiota as a way to prevent and manage obesity en-mass. Conclusions : Gut microbiota plays a great role in maintaining body’s energy balance. Manipulating gut microbiota has great potential to become a low cost and effective treatment for obesity and its prevention with minimal side effects for long-term use. The various forms of prebiotics, probiotics and synbiotics currently available would be able to increase patient’s compliance and easiness in distribution. Better management of obesity would lead to a reduction in many comorbidities including heart disease, stroke and diabetes.
Publisher: Elsevier BV
Date: 02-2012
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.NEUROPHARM.2016.10.004
Abstract: This review categorizes functionally validated actions of defined scorpion toxin (SCTX) neuropeptides across ion channel subclasses, highlighting key trends in this rapidly evolving field. Scorpion envenomation is a common event in many tropical and subtropical countries, with neuropharmacological actions, particularly autonomic nervous system modulation, causing significant mortality. The primary active agents within scorpion venoms are a erse group of small neuropeptides that elicit specific potent actions across a wide range of ion channel classes. The identification and functional characterisation of these SCTX peptides has tremendous potential for development of novel pharmaceuticals that advance knowledge of ion channels and establish lead compounds for treatment of excitable tissue disorders. This review delineates the unique specificities of 320 in idual SCTX peptides that collectively act on 41 ion channel subclasses. Thus the SCTX research field has significant translational implications for pathophysiology spanning neurotransmission, neurohumoral signalling, sensori-motor systems and excitation-contraction coupling. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.'
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-1996
DOI: 10.1016/S0304-3959(96)03194-6
Abstract: The development of spinal cord nociceptive pathways has been investigated in neonatal rat pups using the expression of Fos immunoreactivity in laminae I and II cells produced by high and low intensity skin stimulation. Noxious pinch of the hindpaw evoked a clear response in the newborn rat pup, which was not significantly different from that seen at postnatal day (P) 21. Low intensity touch stimulation also produced a significant fos response in laminae I and II cells at P3 which was 60% that of the pinch response. This was reduced to 27% of the pinch response by P10 and was gone by P21. Electrical stimulation through percutaneous electrodes showed that A beta fibre stimulation also produced a fos response at P3 that was not significantly different from that produced by C fibre stimulation. By P21 and P30 the response to C fibre stimulation was much greater and the response to A fibre stimulation was not significantly above background. The results suggest that in the neonatal spinal cord, low threshold A fibres are able to activate pathways in lamina I and II of the dorsal horn that in the adult are predominantly nociceptive.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Springer Science and Business Media LLC
Date: 04-07-2022
DOI: 10.1038/S41405-022-00113-9
Abstract: Limited data exist on dental practitioner use and perceptions of articaine. This study is a cross-sectional survey of dental practitioners from January, 2021 to ascertain the extent of their use of the dental local anaesthetic, articaine, the basis of their perceptions about articaine and whether current practices are in line with recent evidence regarding articaine safety and efficacy. An anonymous survey was designed using the SAP Qualtrics Core XM software platform and a survey link was disseminated from December 2020 to January 2021 via social media. The survey was designed as a five minute, anonymous, online questionnaire including a plain language information sheet, request for participant consent and 14 questions. Data were entered onto a Microsoft™ Excel spreadsheet and analysed qualitatively, isolating the answers into recurrent themes. Sixty percent of the surveyed dental practitioner used articaine as their preferred dental anaesthetic. Twenty-three percent of the dental practitioner surveyed used articaine for all of their dental procedures including inferior alveolar nerve blocks, while 40% of respondents used articaine for all their dental procedures except inferior alveolar nerve blocks. The predominant basis of dental practitioner uses and perception of articaine were their countries dental guidelines. Despite the latest findings that articaine is as safe and more efficacious as lidocaine for all routine dental treatment, 40% of survey respondents avoided articaine use for inferior alveolar blocks. Our study recognises a discrepancy between reported clinical practice and current research evidence. Further research and clarifications are needed to achieve ubiquitous practice of evidence-based dentistry.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.DSX.2018.04.039
Abstract: To compare uric acid, lipid, and kidney profile along with management and complications of Indonesian diabetic patients with good and poor glycemic control based on glycated hemoglobin profile. Data was obtained from medical records of Internal Medicine Clinic in Hermina Podomoro General Hospital for the period January-December 2015. Subjects were grouped into good and poor glycemic control groups based on their glycated hemoglobin (HbA1c) levels. Fifty-five subjects were obtained with an average age of 54 years, 29 with good glycemic control and 26 with poor glycemic control. All glycemic parameters were worse in poor compared to good glycemic control group (p 0.05). Main comorbidities were dyslipidemia, hypertension, and nephropathy. Fatty liver disease, urinary tract infection and neuropathy was also reported. Most patients were prescribed with oral anti-diabetics. Diabetic patients regardless of glycemic control according to current guidelines have a greater average lipid and kidney profile than the optimum target. Therefore both are equally at greater risk for cardiovascular diseases, nephropathy, and other diabetic complications. Greater patient monitoring of these parameters is recommended to lower the risk of comorbidities and complications.
Publisher: Springer Science and Business Media LLC
Date: 17-01-2018
DOI: 10.1038/S41387-017-0012-Y
Abstract: We aimed to evaluate the relationship between BMI and the risk of renal disease in patients with type 2 diabetes in the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) study. Participants were ided into six baseline BMI categories: .5 (underweight, n = 58) ≥18.5 to (normal, n = 2894) ≥25 to (overweight, n = 4340) ≥30 to (obesity grade 1, n = 2265) ≥35 to (obesity grade 2, n = 744) and ≥40 kg/m 2 (obesity grade 3, n = 294) those underweight were excluded. The composite outcome “major renal event” was defined as development of new macroalbuminuria, doubling of creatinine, end stage renal disease, or renal death. These outcomes and development of new microalbuminuria were considered in idually as secondary endpoints. During 5-years of follow-up, major renal events occurred in 487 (4.6%) patients. The risk increased with higher BMI. Multivariable-adjusted HRs (95% CIs), compared to normal weight, were: 0.91 (0.72–1.15) for overweight 1.03 (0.77–1.37) for obesity grade 1 1.42 (0.98–2.07) for grade 2 and 2.16 (1.34–3.48) for grade 3 ( p for trend = 0.006). These findings were similar across subgroups by randomised interventions (intensive versus standard glucose control and perindopril-indapamide versus placebo). Every additional unit of BMI over 25 kg/m 2 increased the risk of major renal events by 4 (1–6)%. Comparable results were observed with the risk of secondary endpoints. Higher BMI is an independent predictor of major renal events in patients with type 2 diabetes. Our findings encourage weight loss to improve nephroprotection in these patients.
Publisher: Elsevier BV
Date: 2007
Publisher: Elsevier BV
Date: 03-1996
DOI: 10.1016/0165-3806(95)00207-3
Abstract: Choleragenoid horseradish peroxidase (B-HRP) is a retrogradely transported marker that selectively labels large cutaneous myelinated primary afferent fibers. In adults, B-HRP labelled large afferent fibers are seen to enter laminae III-V, and to a lesser extent lamina I, whereas lamina II, which is the major termination site of unmyelinated primary afferents, remains unlabelled. In the neonate, however, there is extensive B-HRP label in lamina II. The present study shows that the B-HRP labelled fibers in the neonate make many synaptic contacts in lamina II. This supports the idea that large primary afferent fibers in neonatal animals make synaptic contact with post-synaptic targets that presumably process nociceptive information. Accordingly to ameliorate pain in neonates it may be more important to block low threshold sensory input whereas in adults it would be more important to block the high threshold inputs.
Publisher: Elsevier BV
Date: 07-2018
Publisher: Wiley
Date: 17-12-2012
DOI: 10.1002/J.1532-2149.2012.00261.X
Abstract: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels conduct an inward cation current (Ih ) that contributes to the maintenance of neuronal membrane potential and have been implicated in a number of animal models of neuropathic and inflammatory pain. In the current study, we investigated HCN channel involvement in inflammatory pain of the temporomandibular joint (TMJ). The contribution of HCN channels to inflammation (complete Freund's adjuvant CFA)-induced mechanical hypersensitivity of the rat TMJ was tested with injections of the HCN channel blocker ZD7288. Retrograde labelling and immunohistochemistry was used to explore HCN channel expression in sensory neurons that innervate the TMJ. Injection of CFA into the TMJ (n = 7) resulted in a significantly increased mechanical sensitivity relative to vehicle injection (n = 7) (p < 0.05). The mechanical hypersensitivity generated by CFA injection was blocked by co-injection of ZD7288 with the CFA (n = 7). Retrograde labelling and immunohistochemistry experiments revealed expression predominantly of HCN1 and HCN2 channel subunits in trigeminal ganglion neurons that innervate the TMJ (n = 3). No change in the proportion or intensity of HCN channel expression was found in inflamed (n = 6) versus control (n = 5) animals at the time point tested. Our findings suggest a role for peripheral HCN channels in inflammation-induced pain of the TMJ. Peripheral application of a HCN channel blocker could provide therapeutic benefit for inflammatory TMJ pain and avoid side effects associated with activation of HCN channels in the central nervous system.
Publisher: Wiley
Date: 08-2001
DOI: 10.1111/J.1469-7793.2001.00805.X
Abstract: 1. This study examined the cellular actions of cannabinoids on neurons in the substantia gelatinosa of the spinal trigeminal nucleus pars caudalis, using whole-cell and perforated patch recording in brain slices. 2. The cannabinoid agonist WIN55,212-2 (3 microM) decreased the litude of both GABAergic and glycinergic electrically evoked inhibitory postsynaptic currents (IPSCs) by 35 and 41 %, respectively. This inhibition was completely reversed by the CB(1) receptor-selective antagonist N-piperidino-5-(4-chlorophenyl)-l-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide) (SR141716A, 3 microM). WIN55,212-2 also produced relative facilitation of the second evoked IPSC to paired stimuli. 3. WIN55,212-2 decreased the rate of both GABAergic and glycinergic miniature IPSCs by 44 and 34 %, respectively, without changing their litude distributions or kinetics. 4. WIN55,212-2 did not affect the litude of electrically evoked non-NMDA glutamatergic excitatory postsynaptic currents (EPSCs). 5. WIN55,212-2 produced no postsynaptic membrane current and had no significant effect on membrane conductance over a range of membrane potentials (-60 to -130 mV). 6. These results suggest that, within the superficial medullary dorsal horn, cannabinoids presynaptically inhibit GABAergic and glycinergic neurotransmission. At the cellular level, the analgesic action of cannabinoids on these medullary dorsal horn neurons therefore differs from that of mu-opioids, which have both pre- and postsynaptic actions.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2004
Publisher: Wiley
Date: 08-2001
DOI: 10.1111/J.1469-7793.2001.00849.X
Abstract: 1. Whole-cell patch cl recordings were made from rat rostral ventromedial medulla (RVM) neurons in vitro to investigate the cellular actions of the opioid-like receptor ORL1 (NOP), ligand nociceptin/orphanin FQ and other putative prepronociceptin products. 2. Primary and secondary RVM neurons were identified as responding to the kappa-opioid receptor agonist U-69593 (300 nM to 1 microM) and the mu- and delta-opioid receptor agonist met-enkephalin (10 microM), respectively. Both primary and secondary RVM neurons responded to nociceptin (3 nM to 1 microM) with an outward current that reversed polarity at -115 mV in brain slices and with inhibition of Ca(2+) channel currents in acutely isolated cells. 3. The putative ORL1 antagonist J-113397 (1 microM) produced no change in membrane current and abolished the outward current produced by nociceptin (100 nM). In contrast, Phe(1)psi(CH(2)-NH)Gly(2)]-nociceptin-(1-13)NH(2) (300 nM to 1 microM) alone produced an outward current and partially reduced the outward current produced by nociceptin (300 nM) when co-applied. 4. In brain slices nociceptin (300 nM) reduced the litude of evoked GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) but not non-NMDA receptor-mediated excitatory postsynaptic currents (EPSCs). 5. Met-enkephalin (10 microM), but not nociceptin (300 nM), reduced the rate of spontaneous miniature IPSCs in normal external potassium solution (K(+) 2.5 mM). In high external potassium (K(+) 17.5 mM), nociceptin reduced the rate of miniature IPSCs in the presence (Ca(2+) 2.4 mM, Mg(2+) 1.2 mM) but not in the absence of external calcium (Ca(2+) 0 mM, Mg(2+) 10 mM, Cd(2+) 10 microM). Nociceptin and met-enkephalin had no effect on the litude of miniature IPSCs. 6. The putative nociceptin precursor products nocistatin (rat prepronociceptin(125-132)) and rat prepronociceptin(154-181) had no effect on membrane currents, evoked IPSCs and evoked EPSCs. 7. These results indicate that nociceptin acts via the ORL1 receptor to directly inhibit both primary and secondary RVM neurons by activating a potassium conductance and by inhibiting calcium conductances. In addition, nociceptin inhibits GABA release within the RVM via a presynaptic Ca(2+)-dependent mechanism. Thus, nociceptin has the potential to exert both disinhibitory and inhibitory effects on neuronal action potential firing within the RVM.
Publisher: Springer Science and Business Media LLC
Date: 10-10-2009
DOI: 10.1007/S00441-009-0869-8
Abstract: Hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels are active at resting membrane potential and thus are likely to contribute to neuronal excitability. Four HCN channel subunits (HCN1-4) have previously been cloned. The aim of the current study was to investigate the immunoreactivity of HCN4 channel protein in rat trigeminal (TG) and dorsal root ganglion (DRG) sensory neurons. HCN4 was present in 9% of TG neurons and 4.7% of DRG neurons, it was distributed in a discrete population of small-diameter neurons in the TG but was located in cells of all sizes in the DRG. Approximately two thirds of HCN4-containing neurons in each ganglia were labelled with antisera raised against the 200-kDa neurofilament (NF200). The remaining HCN4-containing neurons were NF200-negative, were not labelled with antisera raised against calcitonin-gene related peptide (CGRP), and did not bind the isolectin B4 (IB4). HCN4-containing neurons made up more than half of the population of small-diameter primary afferent neurons that did not contain either NF200 or CGRP or bind IB4 in both TG and DRG. This population was not insignificant, comprising 5% of TG neurons and 2% of DRG neurons.
Publisher: Springer Science and Business Media LLC
Date: 13-05-2014
Publisher: Elsevier BV
Date: 06-2020
Publisher: Cambridge University Press
Date: 07-01-2010
Publisher: Wiley
Date: 31-03-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2001
DOI: 10.1097/00001756-200103050-00043
Abstract: The actions of the endogenous ORL1 receptor (opioid receptor-like1) ligand nociceptin on the membrane properties of rat trigeminal nucleus caudalis neurons were examined by use of whole cell and perforated patch cl recording in brain slices. Nociceptin produced an outward current in all neurons tested (EC50 112 nM). The outward current produced by nociceptin was completely reversed with the addition of the non-peptide ORL1 antagonist J-113397. Outward currents reversed polarity at -99+/-2 mV, close to the potential for K+ of -102 mV, suggesting that they were mediated by an increased K+ conductance. These results suggest that the analgesic action of nociceptin might be mediated by direct postsynaptic inhibition within the dorsal horn.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2018
Publisher: Wiley
Date: 31-01-2003
Publisher: Wiley
Date: 25-02-2011
Publisher: Springer Science and Business Media LLC
Date: 27-07-2017
Publisher: Elsevier BV
Date: 11-1998
DOI: 10.1016/S0304-3940(98)00779-4
Abstract: The development of diffuse noxious inhibitory controls (DNIC) was studied in postnatal rats aged 12, 21 and 42-days-old, using immunoreactive localization of the c-fos protein products induced in the dorsal horn by noxious stimulation. The presence of DNIC was revealed by the reduction in the levels of Fos-like immunoreactivity that are normally induced by a standardized primary pinch stimulus when this stimulus was accompanied by a concurrent noxious stimulus (formalin) to a heterotopic body part. Significant reductions were seen at postnatal day 42 (P42 15% reduction) and P21 (17% reduction), but concurrent stimulation had no significant effect at P12. These results suggest that the system subserving DNIC is functionally mature by P21, but not effective at P12. This delayed maturation of an inhibitory system may underlie the extreme sensitivity to somatosensory stimulation seen in neonatal pups and premature infants.
Publisher: American Scientific Publishers
Date: 09-2018
Publisher: MDPI AG
Date: 22-12-2020
DOI: 10.3390/DJ9010002
Abstract: This review sheds light on the recent published scientific evidence relating to the use of professionally delivered local antimicrobial agents (LA’s). The review also analyses drug delivery systems available to date and provides an update on the latest scientific evidence about the benefits, limitations, and clinical results obtained by use of local drugs in the treatment of periodontal disease. The search strategy revealed randomized controlled trials (RCTs) that compared the efficacy of adjunctive LA’s to mechanical therapy alone. Based on the available evidence gathered from this review, we can infer that the use of local antimicrobial agents in conjunction to scaling and root debridement (SRD) delivers significant benefits in periodontal therapy and it is a useful aid, avoiding many of the side effects that systemic antibiotic therapy may involve. Local drug delivery (LDD) is an efficient and effective means of delivering drugs based on the evidence presented in the review. The authors of this review would suggest the use of local antimicrobials in cases of localized periodontitis or in idual areas that do not respond to the usual mechanical therapy alone. This review summarizes the current use of local drug delivery in periodontal management ensuring that the general practitioners are able to choose an appropriate local antimicrobial.
Publisher: Springer Science and Business Media LLC
Date: 12-11-2021
DOI: 10.1186/S12889-021-12016-9
Abstract: The prevalence of the oral-systemic relationship has accounted for potentially preventable chronic conditions and morbidity worldwide. Health literacy is a large contributing factor. This systematic review investigates the knowledge and awareness of patients with major systemic conditions, regarding the oral associations to their condition. Electronic databases including Medline (Ovid), CINAHL, The Cochrane Library, Web of Science, Informit Health Databases and Scopus were searched. All articles from 2011 to 2020, investigating knowledge of the oral-systemic link, of adult patients with the following major system conditions were searched: diabetes mellitus (DM), respiratory disease, cardiovascular disease (CVD), pregnancy and bone disease. Two independent reviewers completed screening, data extraction and quality assessment. A synthesis without meta-analysis was conducted. Twenty-four studies, from 14 different countries, were included in the systematic review. Analysis showed that globally, patients with major systemic conditions have poor knowledge and awareness ( 50%) of the oral health associations to their condition. Improvements in health education are particularly necessary for patients with heart disease, bone disease and diabetes. Dentists and the media were the most common source of information. There were no relevant studies investigating the knowledge of patients with respiratory disease. To improve the global burden of preventable chronic conditions, it is essential to address inequalities in the dissemination of health education to at-risk populations. Improvements in patient education rely on an increase in patient-practitioner communication on the oral-systemic link, implementation of oral health educational programs and greater interdisciplinary collaboration.
Publisher: Springer Science and Business Media LLC
Date: 02-09-2016
Publisher: Springer Science and Business Media LLC
Date: 04-01-2021
DOI: 10.1186/S12933-020-01198-Y
Abstract: In iduals with diabetes and lower-limb complications are at high risk for cardiovascular and all-cause mortality, but uncertainties remain in terms of cancer-related death in this population. We investigated this relationship in a large cohort of people with type 2 diabetes. We used data from the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) study. The primary outcome was adjudicated cancer death secondary outcomes were overall and site-specific incident cancers, determined according to the International Classification of Diseases Code (ICD-10). We compared outcomes in in iduals with ( versus without) a baseline history of lower-limb complications (peripheral artery disease (PAD) or sensory peripheral neuropathy) using Cox regression models. Among 11,140 participants (women 42%, mean age 66 years), lower-limb complications were reported at baseline in 4293 (38%) in iduals: 2439 (22%) with PAD and 2973 (27%) with peripheral neuropathy. Cancer death occurred in 316 (2.8%) participants during a median of 5.0 (25th–75th percentile, 4.7–5.1) years of follow-up corresponding to 53,550 person-years and an incidence rate of 5.9 (95% CI 5.3–6.6) per 1000 person-years. The risk of cancer death was higher in in iduals with ( versus without) lower-limb complication [hazard ratio 1.53 (95% CI, 1.21–1.94), p = 0.0004], PAD [1.32 (1.02–1.70), p = 0.03] or neuropathy (1.41 (1.11–1.79), p = 0.004], adjusting for potential confounders and study allocations. PAD, but not neuropathy, was associated with excess risk of incident cancers. PAD and peripheral neuropathy were independently associated with increased 5-year risk of cancer death in in iduals with type 2 diabetes. PAD was also associated with increased risk of incident cancers. Our findings provide new evidence on the non-cardiovascular prognostic burden of lower-limb complications in people with type 2 diabetes.
No related grants have been discovered for Ernest Jennings.