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Current Nutrition Reports Mar 2023The aim of this review is to provide an overview of the menopause-related changes in microbiota and their role in the pathogenesis of menopause-related diseases. In... (Review)
Review
PURPOSE OF REVIEW
The aim of this review is to provide an overview of the menopause-related changes in microbiota and their role in the pathogenesis of menopause-related diseases. In addition, evidence on probiotic supplementation as a therapeutic strategy is discussed.
RECENT FINDINGS
The human microbiota is a complex community that lives in a mutualism relationship with the host. Menopause is associated with dysbiosis, and these changes in the composition of microbiota in different sites (gut, vaginal, and oral microbiota) might play a role in the pathogenesis of menopause-related diseases (i.e., osteoporosis, breast cancer, endometrial hyperplasia, periodontitis, and cardiometabolic diseases). The present review highlights the pivotal role of microbiota in postmenopausal women health, in particular it (a) may increase intestinal calcium absorption thus preventing osteoporosis, (b) is associated with reduced risk of breast cancer and type 1 endometrial hyperplasia, (c) reduces gingival inflammation and menopausal periodontitis, and (d) beneficially affects multiple cardiometabolic risk factors (i.e., obesity, inflammation, and blood glucose and lipid metabolism). However, whether oral probiotic supplementation might be used for the treatment of menopause-related dysbiosis requires further clarification.
Topics: Female; Humans; Prebiotics; Endometrial Hyperplasia; Dysbiosis; Probiotics; Inflammation; Menopause; Breast Neoplasms; Osteoporosis
PubMed: 36746877
DOI: 10.1007/s13668-023-00462-3 -
Advances in Chronic Kidney Disease Jan 2020Calcineurin inhibitors (CNIs) are both the savior and Achilles' heel of kidney transplantation. Although CNIs have significantly reduced rates of acute rejection, their... (Review)
Review
Calcineurin inhibitors (CNIs) are both the savior and Achilles' heel of kidney transplantation. Although CNIs have significantly reduced rates of acute rejection, their numerous toxicities can plague kidney transplant recipients. By 10 years, virtually all allografts will have evidence of CNI nephrotoxicity. CNIs have been strongly associated with hypertension, dyslipidemia, and new onset of diabetes after transplantation-significantly contributing to cardiovascular risk in the kidney transplant recipient. Multiple electrolyte derangements including hyperkalemia, hypomagnesemia, hypercalciuria, metabolic acidosis, and hyperuricemia may be challenging to manage for the clinician. Finally, CNI-associated tremor, gingival hyperplasia, and defects in hair growth can have a significant impact on the transplant recipient's quality of life. In this review, the authors briefly discuss the pharmacokinetics of CNI and discuss the numerous clinically relevant toxicities of commonly used CNIs, cyclosporine and tacrolimus.
Topics: Calcineurin Inhibitors; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation
PubMed: 32147003
DOI: 10.1053/j.ackd.2019.08.006 -
International Journal of Molecular... Sep 2020Mucolipidosis II and III (ML II/III) are caused by a deficiency of uridine-diphosphate -acetylglucosamine: lysosomal-enzyme--acetylglucosamine-1-phosphotransferase... (Review)
Review
Mucolipidosis II and III (ML II/III) are caused by a deficiency of uridine-diphosphate -acetylglucosamine: lysosomal-enzyme--acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase, EC2.7.8.17), which tags lysosomal enzymes with a mannose 6-phosphate (M6P) marker for transport to the lysosome. The process is performed by a sequential two-step process: first, GlcNAc-1-phosphotransferase catalyzes the transfer of GlcNAc-1-phosphate to the selected mannose residues on lysosomal enzymes in the cis-Golgi network. The second step removes GlcNAc from lysosomal enzymes by -acetylglucosamine-1-phosphodiester α--acetylglucosaminidase (uncovering enzyme) and exposes the mannose 6-phosphate (M6P) residues in the trans-Golgi network, in which the enzymes are targeted to the lysosomes by M6Preceptors. A deficiency of GlcNAc-1-phosphotransferase causes the hypersecretion of lysosomal enzymes out of cells, resulting in a shortage of multiple lysosomal enzymes within lysosomes. Due to a lack of GlcNAc-1-phosphotransferase, the accumulation of cholesterol, phospholipids, glycosaminoglycans (GAGs), and other undegraded substrates occurs in the lysosomes. Clinically, ML II and ML III exhibit quite similar manifestations to mucopolysaccharidoses (MPSs), including specific skeletal deformities known as dysostosis multiplex and gingival hyperplasia. The life expectancy is less than 10 years in the severe type, and there is no definitive treatment for this disease. In this review, we have described the updated diagnosis and therapy on ML II/III.
Topics: Animals; Biological Transport, Active; Disease Models, Animal; Enzyme Replacement Therapy; Genetic Therapy; Glycosaminoglycans; Hematopoietic Stem Cell Transplantation; Humans; Lysosomes; Mannosephosphates; Mucolipidoses
PubMed: 32957425
DOI: 10.3390/ijms21186812 -
Head and Neck Pathology Mar 2019Erythematous lesions of the oral mucosa are common and can reflect a variety of conditions, ranging from benign reactive or immunologically-mediated disorders to... (Review)
Review
Erythematous lesions of the oral mucosa are common and can reflect a variety of conditions, ranging from benign reactive or immunologically-mediated disorders to malignant disease. Together with vascular abnormalities, which can vary from reddish to bluish-purple in color, the differential diagnosis for erythematous oral mucosal change is quite diverse. This review focuses on salient clinical features and histopathologic findings of selected conditions which clinically present as red or vascular-like oral mucosal alterations, including oral vascular malformations and neoplasms, pyogenic granuloma, localized juvenile spongiotic gingival hyperplasia, denture stomatitis, benign migratory glossitis (geographic tongue), orofacial granulomatosis, granulomatosis with polyangiitis (Wegener granulomatosis), megaloblastic anemia, and erythroplakia. Recognition of the characteristic clinical features of these conditions, in conjunction with thorough patient history, will allow clinicians to narrow the differential diagnosis and guide appropriate clinical decision making, including the need for tissue biopsy, in order to complete the diagnostic process and initiate optimal patient care.
Topics: Erythema; Humans; Mouth Diseases; Mouth Mucosa; Vascular Diseases
PubMed: 30693460
DOI: 10.1007/s12105-019-01002-8 -
Internal Medicine (Tokyo, Japan) Feb 2024
PubMed: 38311423
DOI: 10.2169/internalmedicine.3106-23 -
Journal of Postgraduate Medicine 2022Levetiracetam is a new generation antiseizure medication which binds to synaptic vesicle protein SV2A and inhibits the release of neurotransmitters. Gingival hyperplasia...
Levetiracetam is a new generation antiseizure medication which binds to synaptic vesicle protein SV2A and inhibits the release of neurotransmitters. Gingival hyperplasia is a common side effect of conventional antiseizure medications like phenytoin, but very rare with the newer ones. A 14-year-old boy was started on levetiracetam 250 mg twice daily after a generalized seizure. Five days later he presented with gingival swelling and painful oral aphthae, without lymphadenopathy or systemic symptoms. Blood investigations were normal. After one-month of stopping the drug, the lesions cleared. This case highlights the importance of maintaining good oral hygiene and periodic dental review in patients on antiseizure medications.
Topics: Adolescent; Anticonvulsants; Gingival Hyperplasia; Humans; Levetiracetam; Male; Phenytoin; Seizures
PubMed: 35848684
DOI: 10.4103/jpgm.jpgm_1059_21 -
The Cochrane Database of Systematic... Sep 2021This is an updated version of the original Cochrane Review published in 2014. Epilepsy is a common neurological condition characterised by recurrent seizures.... (Review)
Review
BACKGROUND
This is an updated version of the original Cochrane Review published in 2014. Epilepsy is a common neurological condition characterised by recurrent seizures. Pharmacological treatment remains the first choice to control epilepsy. Sulthiame (STM) is widely used as an antiepileptic drug in Europe and Israel. In this review, we have presented a summary of evidence for the use of STM as monotherapy in epilepsy.
OBJECTIVES
To assess the efficacy and side effect profile of STM as monotherapy when compared with placebo or another antiepileptic drug for people with epilepsy.
SEARCH METHODS
We searched the following databases on 13 April 2020: the Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 10 April 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We imposed no language restrictions. We contacted the manufacturers of STM and researchers in the field to ask about ongoing and unpublished studies.
SELECTION CRITERIA
Randomised controlled monotherapy trials of STM in people of any age with epilepsy of any aetiology.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: treatment withdrawal; seizure-free at six months; adverse effects; and quality of life scoring. We conducted the primary analyses by intention-to-treat where possible, and presented a narrative analysis of the data.
MAIN RESULTS
We included four studies involving a total of 355 participants: three studies (209 participants) with a diagnosis of benign epilepsy of childhood with centrotemporal spikes (BECTS), and one study (146 participants) with a diagnosis of generalised tonic-clonic seizures (GTCS). STM was given as monotherapy compared with placebo and with levetiracetam in the BECTS studies, and compared with phenytoin in the GTCS study. An English translation of the full text of one of the BECTS studies could not be found, and analysis of this study was based solely on the English translation of the abstract. For the primary outcome, the total number of dropouts caused either by seizure recurrence or adverse reaction was significantly higher in the levetiracetam treatment arm compared to the STM treatment arm (RR 0.32, 95% Cl 0.10 to 1.03; 1 study, 43 participants; low-certainty evidence). For the secondary outcomes for this comparison, results for seizure freedom were inconclusive (RR 1.12, 95% Cl 0.88 to 1.44; 1 study, 43 participants; low-certainty evidence). Reporting of adverse effects was incomplete. Participants receiving STM were significantly less likely to develop gingival hyperplasia than participants receiving phenytoin in the GTCS study (RR 0.03, 95% CI 0.00 to 0.58; 1 study, 146 participants; low-certainty evidence). No further statistically significant adverse events were noted when STM was compared with phenytoin or placebo. The most common adverse events were related to behavioural disturbances when STM was compared with levetiracetam (RR 0.95, 95% Cl 0.59 to 1.55; 1 study, 43 participants; low-certainty evidence), with the same incidence in both groups. No data were reported for quality of life. Overall, we assessed one study at high risk of bias and one study at unclear bias across the seven domains, mainly due to lack of information regarding study design. Only one trial reported effective methods for blinding. The risk of bias assessments for the other two studies ranged from low to high. We rated the overall certainty of the evidence for the outcomes as low using the GRADE approach.
AUTHORS' CONCLUSIONS
This review provides insufficient information to inform clinical practice. Small sample sizes, poor methodological quality, and lack of data on important outcome measures precluded any meaningful conclusions regarding the efficacy and tolerability of sulthiame as monotherapy in epilepsy. More trials, recruiting larger populations, over longer periods, are needed to determine whether sulthiame has a clinical use.
Topics: Anticonvulsants; Epilepsy; Humans; Quality of Life; Randomized Controlled Trials as Topic; Thiazines
PubMed: 34554571
DOI: 10.1002/14651858.CD010062.pub3 -
The Cochrane Database of Systematic... Mar 2014Epilepsy is a common neurological condition characterised by recurrent seizures. Sulthiame (STM) is widely used as an antiepileptic drug in Europe and Israel. In this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epilepsy is a common neurological condition characterised by recurrent seizures. Sulthiame (STM) is widely used as an antiepileptic drug in Europe and Israel. In this review, we present a summary of evidence for the use of STM as monotherapy in epilepsy.
OBJECTIVES
To examine the efficacy and side effect profile of STM as monotherapy when compared with placebo or another antiepileptic drug.
SEARCH METHODS
We searched the Cochrane Epilepsy Group Specialised Register (24 October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), MEDLINE Ovid (1946 to 24 October 2013), SCOPUS (1823 to 24 October 2013), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal (28 October 2013) and ClinicalTrials.gov (28 October 2013). We imposed no language restrictions. We contacted the manufacturers of STM and researchers in the field to ask about ongoing and unpublished studies.
SELECTION CRITERIA
Randomised controlled monotherapy trials of STM in people of any age with epilepsy of any aetiology.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion and extracted the relevant data.The following outcomes were assessed: (1) time to treatment failure; (2) time to 12-month remission; (3) proportion seizure free at 12 months; (4) adverse effects; and (5) quality of life scoring. Primary analyses were intention-to-treat when possible. A narrative analysis of the data was presented.
MAIN RESULTS
Two studies representing 100 participants with a diagnosis of benign epilepsy of childhood with centrotemporal spikes (BECTS) and one study representing 146 participants with a diagnosis of generalised tonic-clonic seizures (GTCS) were included. STM was given as monotherapy compared with placebo in the BECTS studies and compared with phenytoin in the GTCS study. An English translation of the full text of one of the BECTS studies could not be found, and analysis of this study was based solely on the English translation of the abstract. No data were reported for outcome (1), (2), (3) or (5). Reporting of adverse effects was incomplete. Participants receiving STM were significantly less likely to develop gingival hyperplasia than were participants receiving phenytoin in the GTCS study (risk ratio (RR) 0.03, 95% confidence interval (CI) 0.00 to 0.58). No further statistically significant adverse events were noted when STM was compared with phenytoin or placebo. Two ongoing studies comparing STM monotherapy versus placebo or levetiracetam in BECTS were identified.
AUTHORS' CONCLUSIONS
Small sample size, poor methodological quality and lack of data on important outcome measures prevent any meaningful conclusions regarding the efficacy and safety of sulthiame as monotherapy in epilepsy.
Topics: Adult; Anticonvulsants; Child; Child, Preschool; Early Termination of Clinical Trials; Epilepsy; Epilepsy, Tonic-Clonic; Female; Humans; Male; Phenytoin; Randomized Controlled Trials as Topic; Thiazines
PubMed: 24609897
DOI: 10.1002/14651858.CD010062.pub2