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1.
Cureus ; 14(11): e31889, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36579247

ABSTRACT

BACKGROUND: Bangladesh is anticipated to have the eighth-highest number of diabetic patients within the next 15 years. Approximately one-fifth of adult diabetes patients reside in Southeast Asian nations. This study aimed to find out the economic burden of extreme hypoglycemia on diabetic sufferers in Bangladesh. METHODS: A cross-sectional study was carried out amongst 164 Type 2 Diabetes sufferers admitted due to extreme hypoglycemia within 15 months at BIRDEM in Dhaka to decide if they have the impact of extreme hypoglycemia on the cost of illness. The cost was once expressed in BDT. RESULTS: Direct medical cost (37058) and direct non-medical cost (5261) was estimated during the study. Among the direct medical cost, hospital cost was 17735, physician cost was 5745, nonmedical transport cost was 1802, and attendant cost was 3459. The total cost was 48743 BDT (€617) for each severe hypoglycemic event leading to hospitalization, and 6.4244 BDT (€82.4) would be the indirect cost of reduced productivity from spending 5.8 days (46.4 hours) in the hospital. CONCLUSION: The analysis indicates that hypoglycemia has a significant negative influence on the cost and reduces the work output of diabetics.

2.
Biomed Pharmacother ; 153: 113510, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36076597

ABSTRACT

Balanites aeqyptiaca (BA) seeds were toasted at 70 °C, milled and the oil expelled to resolve to meal which were defatted to resolve to defatted balanites aeqyptiaca (BA) protein meal and (BA) protein concentrate respectively. These were subjected to analysis using standard methods. There exist marked trend between defatted balanites aeqyptiaca protein meal, protein concentrate and incidences of diabetes. This work investigated the anti- diabetic effects of balanites aeqyptiaca defatted protein meal and concentrate supplemented diets in streptozotocin (STZ)-induced diabetic rats. The rats were fattened for two weeks with high fat diet (HFD) to introduce Hyperglycemia and then made diabetic by intraperitoneal administration of STZ (35 mg/kg body weight) and fed diets containing 5 % defatted balanites aeqyptiaca protein meal (DAPM) and 5 % balanites aeqyptiaca protein concentrate (APC) for 14 days. The effect of the diet on blood glucose, serum glutathione peroxidase (GPx), glutathione transferase (GSH), thiobarbituric acid reactive species (TBARS), α-amylase and intestinal α-glucosidase activities were investigated. There was marked increase in the blood glucose, TBARS, pancreatic α-amylase and intestinal α-glycosidase with corresponding decrease in serum GPx and GSH contents in diabetic rats control groups. These trends were however, reversed in diabetic rats fed diet supplemented with the balanites aeqyptiaca protein meals for 14 days. The meals from defatted and protein concentrate inhibit α-amylase and α-glycosidase inhibitory activity in vivo. Thus, the anti-diabetes properties of the defatted meal and protein concentrate may be attributed to the influence of its constituent phytochemicals on starch digestion as well as endogenous enzymes activities. The study revealed that defatted aduwa meal and proteins concnentrate demonstrated potentials used as functional ingredients in food materials and could also increase income access of low resource populace.


Subject(s)
Balanites , Diabetes Mellitus, Experimental , Plant Proteins, Dietary , Animals , Balanites/chemistry , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/diet therapy , Diabetes Mellitus, Experimental/metabolism , Diet , Glutathione Peroxidase/metabolism , Hypoglycemic Agents/pharmacology , Plant Proteins, Dietary/pharmacology , Plant Proteins, Dietary/therapeutic use , Rats , Rats, Wistar , Streptozocin , Thiobarbituric Acid Reactive Substances/analysis , alpha-Amylases/metabolism
3.
J Cell Physiol ; 237(1): 128-148, 2022 01.
Article in English | MEDLINE | ID: mdl-34311499

ABSTRACT

Glucose metabolism is a mechanism by which energy is produced in form of adenosine triphosphate (ATP) by mitochondria and precursor metabolites are supplied to enable the ultimate enrichment of mature metabolites in the cell. Recently, glycolytic enzymes have been shown to have unconventional but important functions. Among these enzymes, pyruvate kinase M2 (PKM2) plays several roles including having conventional metabolic enzyme activity, and also being a transcriptional regulator and a protein kinase. Compared with the closely related PKM1, PKM2 is highly expressed in cancer cells and embryos, whereas PKM1 is dominant in mature, differentiated cells. Posttranslational modifications such as phosphorylation and acetylation of PKM2 change its cellular functions. In particular, PKM2 can translocate to the nucleus, where it regulates the transcription of many target genes. It is notable that PKM2 also acts as a protein kinase to phosphorylate several substrate proteins. Besides cancer cells and embryonic cells, astrocytes also highly express PKM2, which is crucial for lactate production via expression of lactate dehydrogenase A (LDHA), while mature neurons predominantly express PKM1. The lactate produced in cancer cells promotes tumor progress and that in astrocytes can be supplied to neurons and may act as a major source for neuronal ATP energy production. Thereby, we propose that PKM2 along with its different posttranslational modifications has specific purposes for a variety of cell types, performing unique functions.


Subject(s)
Leukemia, Myeloid, Acute , Pyruvate Kinase , Adenosine Triphosphate/metabolism , Cell Line, Tumor , Glycolysis/physiology , Humans , Lactates , Protein Kinases/metabolism , Pyruvate Kinase/genetics
4.
Pharmacol Res Perspect ; 10(1): e00903, 2022 02.
Article in English | MEDLINE | ID: mdl-34918875

ABSTRACT

Metopimazine (MPZ) is a peripherally restricted, dopamine D2 receptor antagonist used for four decades to treat acute nausea and vomiting. MPZ is currently under clinical investigation for the treatment of gastroparesis (GP). MPZ undergoes high first-pass metabolism that produces metopimazine acid (MPZA), the major circulating metabolite in humans. Despite a long history of use, the enzymes involved in the metabolism of MPZ have not been identified. Here we report a series of studies designed to identify potential MPZ metabolites in vitro, determine their clinical relevance in humans, and elucidate the enzymes responsible for their formation. The findings demonstrated that the formation of MPZA was primarily catalyzed by human liver microsomal amidase. Additionally, human liver cytosolic aldehyde oxidase (AO) catalyzes the formation of MPZA, in vitro, although to a much lesser extent. Neither cytochrome P450 enzymes nor flavin-monooxygenases (FMO) were involved in the formation MPZA, although two minor oxidative pathways were catalyzed by CYP3A4 and CYP2D6 in vitro. Analysis of plasma samples from subjects dosed 60 mg of MPZ verified that these oxidative pathways are very minor and that CYP enzyme involvement was negligible compared to microsomal amidase/hydrolase in overall MPZ metabolism in humans. The metabolism by liver amidase, an enzyme family not well defined in small molecule drug metabolism, with minimal metabolism by CYPs, differentiates this drug from current D2 antagonists used or in development for the treatment of GP.


Subject(s)
Amidohydrolases/metabolism , Dopamine D2 Receptor Antagonists/metabolism , Isonipecotic Acids/metabolism , Microsomes, Liver/metabolism , Adolescent , Adult , Animals , Antiemetics/metabolism , Cohort Studies , Cytochrome P-450 Enzyme System/metabolism , Dogs , Double-Blind Method , Female , Humans , Male , Microsomes, Liver/enzymology , Middle Aged , Rats , Rats, Sprague-Dawley , Young Adult
5.
Article in English | MEDLINE | ID: mdl-34574379

ABSTRACT

Strategic Environmental Assessment (SEA) is a proactive and collaborative method for environmental management designed to integrate environmental considerations into decision-making; and it is good for Sierra Leone. To understand whether SEA would be useful in the context of Sierra Leone, the authors interviewed 64 out of 78 experts face to face from March to July 2019. In addition, government policies and regulatory documents on environmental management and sustainable development, published articles served as secondary sources of data. Data were analyzed using descriptive statistics. These Sierra Leonean experts agreed that SEA would be useful for integration and achievement of improved sustainable urban planning strategies. However, the barriers identified to integrating SEA include: not addressing environmental issues during the preparation of policies and programs, insufficient political will, the absence of clear objectives, targets, principles and approaches, overlapping mandates among environmental institutions, and inadequate institutional coordination and non-integrated development framework as barriers to integrating SEA into their work. The study shows that SEA has the potential to have a positive impact on environmental concerns in decision-making, but it would need to be supported by stronger political will, legal frameworks, and improved technical guidance from the policy perspective. Moreover, we propose a conceptual framework for the inclusion of SEA into the urban planning process in Sierra Leone.


Subject(s)
City Planning , Sustainable Development , Sierra Leone
6.
Nigerian Medical Practitioner ; 78(1-2): 15-20, 2020.
Article in English | AIM (Africa) | ID: biblio-1267990

ABSTRACT

The concepts of social connectedness in the context of patient-providers relationships tends to focus on relationships from a healthcare provider's perspective; the patient's experience with the social relationship with their providers are inadequately described. This study examined patients' perspectives in terms of satisfaction with the perceived providers' attributes of social connectedness displayed during clinic encounter. This was a descriptive cross sectional study conducted between September and October 2019. A multistage sampling technique was used to select respondents and data was collected with the aid of a seven (7) items questionnaire on health care providers' social attributes of connectedness developed from the service quality (SERVIQUAL) questionnaire. The data was analyzed with the aid of SPSS 21.0 and statistical significance was set at a P value 0.05. Satisfaction was reported by 60.4% to 89.8% of patients with regard to the perceived health care providers' attributes of connectedness except for providers' support for which only 43.4% of the patients express satisfaction. Majority (89.8%) of patients were satisfied with the perceived providers' cooperation during clinical encounter. There was a significant association between patient satisfactions and all the perceived attributes.(p-value<0.001) The results of our study were encouraging, showing that the patients were generally satisfied with the perceived health care providers' social attributes. However, there is the need for improvement in social support given by the health care providers to their patients


Subject(s)
Nigeria , Outpatients , Patient Satisfaction , Sociological Factors
7.
J Cell Physiol ; 233(9): 6381-6392, 2018 09.
Article in English | MEDLINE | ID: mdl-29377108

ABSTRACT

RhoA GTPase plays a variety of functions in regulation of cytoskeletal proteins, cellular morphology, and migration along with various proliferation and transcriptional activity in cells. RhoA activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and the guanine nucleotide dissociation factor (GDI). The RhoA-RhoGDI complex exists in the cytosol and the active GTP-bound form of RhoA is located to the membrane. GDI displacement factors (GDFs) including IκB kinase γ (IKKγ) dissociate the RhoA-GDI complex, allowing activation of RhoA through GEFs. In addition, modifications of Tyr42 phosphorylation and Cys16/20 oxidation in RhoA and Tyr156 phosphorylation and oxidation of RhoGDI promote the dissociation of the RhoA-RhoGDI complex. The expression of RhoA is regulated through transcriptional factors such as c-Myc, HIF-1α/2α, Stat 6, and NF-κB along with several reported microRNAs. As the role of RhoA in regulating actin-filament formation and myosin-actin interaction has been well described, in this review we focus on the transcriptional activity of RhoA and also the regulation of RhoA message itself. Of interest, in the cytosol, activated RhoA induces transcriptional changes through filamentous actin (F-actin)-dependent ("actin switch") or-independent means. RhoA regulates the activity of several transcription regulators such as serum response factor (SRF)/MAL, AP-1, NF-κB, YAP/TAZ, ß-catenin, and hypoxia inducible factor (HIF)-1α. Interestingly, RhoA also itself is localized to the nucleus by an as-yet-undiscovered mechanism.


Subject(s)
Transcription Factors/metabolism , rhoA GTP-Binding Protein/metabolism , Actins/metabolism , Animals , Cytosol/metabolism , Humans , NF-kappa B/metabolism , Transcription, Genetic/physiology
8.
Drug Metab Dispos ; 44(4): 570-5, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26758853

ABSTRACT

Lorcaserin [(R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine] hydrochloride hemihydrate, a selective serotonin 5-hydroxytryptamine (5-HT) 5-HT(2C) receptor agonist, is approved by the U.S. Food and Drug Administration for chronic weight management. Lorcaserin is primarily cleared by metabolism, which involves multiple enzyme systems with various metabolic pathways in humans. The major circulating metabolite is lorcaserin N-sulfamate. Both human liver and renal cytosols catalyze the formation of lorcaserin N-sulfamate, where the liver cytosol showed a higher catalytic efficiency than renal cytosol. Human sulfotransferases (SULTs) SULT1A1, SULT1A2, SULT1E1, and SULT2A1 are involved in the formation of lorcaserin N-sulfamate. The catalytic efficiency of these SULTs for lorcaserin N-sulfamate formation is widely variable, and among the SULT isoforms SULT1A1 was the most efficient. The order of intrinsic clearance for lorcaserin N-sulfamate is SULT1A1 > SULT2A1 > SULT1A2 > SULT1E1. Inhibitory effects of lorcaserin N-sulfamate on major human cytochrome P450 (P450) enzymes were not observed or minimal. Lorcaserin N-sulfamate binds to human plasma protein with high affinity (i.e., >99%). Thus, despite being the major circulating metabolite, the level of free lorcaserin N-sulfamate would be minimal at a lorcaserin therapeutic dose and unlikely be sufficient to cause drug-drug interactions. Considering its formation kinetic parameters, high plasma protein binding affinity, minimal P450 inhibition or induction potential, and stability, the potential for metabolic drug-drug interaction or toxicological effects of lorcaserin N-sulfamate is remote in a normal patient population.


Subject(s)
Benzazepines/metabolism , Microsomes, Liver/metabolism , Sulfonic Acids/metabolism , Sulfotransferases/metabolism , Dose-Response Relationship, Drug , Female , Humans , Male , Protein Binding/physiology
9.
Ann Med Health Sci Res ; 5(4): 321-2, 2015.
Article in English | MEDLINE | ID: mdl-26229725

ABSTRACT

Cerebral malaria is a severe manifestation of a parasitic infection caused by Plasmodium falciparum. The sequelae of this disease such as blindness, deafness, loss of motor function could be emotionally traumatic and physically disabling. We, therefore, present this case of an 8-year-old boy who presented with high-grade intermittent fever associated with multiple convulsions and prolonged coma. He regained consciousness after 12 days of treatment with intravenous quinine but was found to have blindness, sensory-neural deafness and extrapyramidal sign. This extrapyramidal sign regressed following treatment with chlorpromazine. He also regained his sight and auditory function before he was discharged though not completely. This report is aimed at emphasizing these rare complications of cerebral malaria as well as reminding clinicians working in malaria endemic areas of the world on the need for early diagnosis and prompt treatment.

10.
Mol Pharm ; 10(12): 4739-45, 2013 Dec 02.
Article in English | MEDLINE | ID: mdl-24102111

ABSTRACT

The objectives of the study were (1) to demonstrate that a Caco-2 cell-based permeability assay, developed in our laboratory, is suitable to identify the permeability classification according to the US Food and Drug Administration Biopharmaceutics Classification System guidance, and (2) to use the validated Caco-2 method to determine permeability class membership of lorcaserin. Lorcaserin, marketed in United States as Belviq, is a selective human 5-hydroxytryptamine 2C agonist used for weight management. First, the permeability of twenty commercially available drugs was determined in the apical-to-basolateral direction at a final concentration of 10 µM, with the pH of transporter buffer in the apical and basolateral compartments being 6.8 and 7.4, respectively. A rank-order relationship between in vitro permeability results and the extent of human intestinal absorption for the drugs tested was observed. Second, the apparent permeability coefficient values of lorcaserin at 2, 20, and 200 µM and apical pH values of 6.8 and 7.4 in the apical-to-basolateral direction were determined using the validated method and found to be comparable to those of the high-permeability internal standard metoprolol. Lorcaserin permeability across Caco-2 cell monolayers was not dependent on the variation of apical pH. Furthermore, lorcaserin was not a substrate for efflux transporters such as P-glycoprotein. In conclusion, using the validated Caco-2 permeability assay, it was shown that lorcaserin is a highly permeable compound.


Subject(s)
Benzazepines/pharmacology , Serotonin Antagonists/pharmacology , Serotonin/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Biopharmaceutics/methods , Caco-2 Cells , Humans , Hydrogen-Ion Concentration , Intestinal Absorption , Permeability , Solubility , United States , United States Food and Drug Administration
11.
J Pharmacol Exp Ther ; 347(3): 645-59, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24049061

ABSTRACT

The kinetics of drug-receptor interactions can profoundly influence in vivo and in vitro pharmacology. In vitro, the potencies of slowly associating agonists may be underestimated in assays capturing transient signaling events. When divergent receptor-mediated signaling pathways are evaluated using combinations of equilibrium and transient assays, potency differences driven by kinetics may be erroneously interpreted as biased signaling. In vivo, drugs with slow dissociation rates may display prolonged physiologic effects inconsistent with their pharmacokinetic profiles. We evaluated a panel of 5-hydroxytryptamine2B (5-HT2B) receptor agonists in kinetic radioligand binding assays and in transient, calcium flux assays, and inositol phosphate accumulation assays; two functional readouts emanating from Gαq-mediated activation of phospholipase C. In binding studies, ergot derivatives demonstrated slow receptor association and dissociation rates, resulting in significantly reduced potency in calcium assays relative to inositol phosphate accumulation assays. Ergot potencies for activation of extracellular signal-regulated kinases 1 and 2 were also highly time-dependent. A number of ergots produced wash-resistant 5-HT2B signaling that persisted for many hours without appreciable loss of potency, which was not explained simply by slow receptor-dissociation kinetics. Mechanistic studies indicated that persistent signaling originated from internalized or sequestered receptors. This study provides a mechanistic basis for the long durations of action in vivo and wash-resistant effects in ex vivo tissue models often observed for ergots. The 5-HT2B agonist activity of a number of ergot-derived therapeutics has been implicated in development of cardiac valvulopathy in man. The novel, sustained nature of ergot signaling reported here may represent an additional mechanism contributing to the valvulopathic potential of these compounds.


Subject(s)
Receptor, Serotonin, 5-HT2B/drug effects , Serotonin Receptor Agonists/pharmacology , Signal Transduction/drug effects , Adrenergic alpha-Antagonists/pharmacology , Amphetamines/pharmacokinetics , Arrestins/metabolism , Calcium/metabolism , Dose-Response Relationship, Drug , Ergot Alkaloids/pharmacology , Extracellular Signal-Regulated MAP Kinases/metabolism , HEK293 Cells , Humans , Phenoxybenzamine/pharmacology , Phosphorylation , Radioligand Assay , beta-Arrestins
12.
Environ Monit Assess ; 185(1): 241-51, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22350346

ABSTRACT

Human health depends on reliable access to safe drinking water, but in many developing countries only a limited number of wells and boreholes are available. Many of these water resources are contaminated with biological or chemical pollutants. The goal of this study was to examine water access and quality in urban Bo, Sierra Leone. A health census and community mapping project in one neighborhood in Bo identified the 36 water sources used by the community. A water sample was taken from each water source and tested for a variety of microbiological and physicochemical substances. Only 38.9% of the water sources met World Health Organization (WHO) microbial safety requirements based on fecal coliform levels. Physiochemical analysis indicated that the majority (91.7%) of the water sources met the requirements set by the WHO. In combination, 25% of these water resources met safe drinking water criteria. No variables associated with wells were statistically significant predictors of contamination. This study indicated that fecal contamination is the greatest health risk associated with drinking water. There is a need to raise hygiene awareness and implement inexpensive methods to reduce fecal contamination and improve drinking water safety in Bo, Sierra Leone.


Subject(s)
Health Status , Water Pollution/analysis , Water Supply/statistics & numerical data , Drinking Water/chemistry , Environmental Monitoring , Humans , Risk Assessment , Sierra Leone , Water Pollutants/analysis , Water Pollution/statistics & numerical data
13.
Health Res Policy Syst ; 10: 22, 2012 Jul 04.
Article in English | MEDLINE | ID: mdl-22759725

ABSTRACT

BACKGROUND: Resource-limited tropical countries are home to numerous infectious pathogens of both human and zoonotic origin. A capability for early detection to allow rapid outbreak containment and prevent spread to non-endemic regions is severely impaired by inadequate diagnostic laboratory capacity, the absence of a "cold chain" and the lack of highly trained personnel. Building up detection capacity in these countries by direct replication of the systems existing in developed countries is not a feasible approach and instead requires "leapfrogging" to the deployment of the newest diagnostic systems that do not have the infrastructure requirements of systems used in developed countries. METHODS: A laboratory for molecular diagnostics of infectious agents was established in Bo, Sierra Leone with a hybrid solar/diesel/battery system to ensure stable power supply and a satellite modem to enable efficient communication. An array of room temperature stabilization and refrigeration technologies for reliable transport and storage of reagents and biological samples were also tested to ensure sustainable laboratory supplies for diagnostic assays. RESULTS: The laboratory demonstrated its operational proficiency by conducting an investigation of a suspected avian influenza outbreak at a commercial poultry farm at Bo using broad range resequencing microarrays and real time RT-PCR. The results of the investigation excluded influenza viruses as a possible cause of the outbreak and indicated a link between the outbreak and the presence of Klebsiella pneumoniae. CONCLUSIONS: This study demonstrated that by application of a carefully selected set of technologies and sufficient personnel training, it is feasible to deploy and effectively use a broad-range infectious pathogen detection technology in a severely resource-limited setting.


Subject(s)
Disease Outbreaks/prevention & control , Influenza in Birds/diagnosis , Laboratories/organization & administration , Microarray Analysis/methods , Reverse Transcriptase Polymerase Chain Reaction/methods , Animals , Communication , Developing Countries , Disease Outbreaks/veterinary , Drug Stability , Early Diagnosis , Electric Power Supplies , Indicators and Reagents , Influenza in Birds/epidemiology , Klebsiella Infections/diagnosis , Klebsiella Infections/epidemiology , Klebsiella Infections/veterinary , Laboratory Personnel/education , Microarray Analysis/veterinary , Molecular Diagnostic Techniques/methods , Molecular Diagnostic Techniques/veterinary , Poultry , Pseudomonas Infections/diagnosis , Pseudomonas Infections/epidemiology , Pseudomonas Infections/veterinary , Reverse Transcriptase Polymerase Chain Reaction/veterinary , Sierra Leone/epidemiology , Specimen Handling
14.
Drug Metab Dispos ; 40(4): 772-8, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22259019

ABSTRACT

Lorcaserin, a selective serotonin 5-HT(2C) receptor agonist, is a weight management agent in clinical development. Lorcaserin N-carbamoyl glucuronidation governs the predominant excretory pathway of lorcaserin in humans. Human UDP-glucuronosyltransferases (UGTs) responsible for lorcaserin N-carbamoyl glucuronidation are identified herein. Lorcaserin N-carbamoyl glucuronide formation was characterized by the following approaches: metabolic screening using human tissues (liver, kidney, intestine, and lung) and recombinant enzymes, kinetic analyses, and inhibition studies. Whereas microsomes from all human tissues studied herein were found to be catalytically active for lorcaserin N-carbamoyl glucuronidation, liver microsomes were the most efficient. With recombinant UGT enzymes, lorcaserin N-carbamoyl glucuronidation was predominantly catalyzed by three UGT2Bs (UGT2B7, UGT2B15, and UGT2B17), whereas two UGT1As (UGT1A6 and UGT1A9) played a minor role. UGT2B15 was most efficient, with an apparent K(m) value of 51.6 ± 1.9 µM and V(max) value of 237.4 ± 2.8 pmol/mg protein/min. The rank order of catalytic efficiency of human UGT enzymes for lorcaserin N-carbamoyl glucuronidation was UGT2B15 > UGT2B7 > UGT2B17 > UGT1A9 > UGT1A6. Inhibition of lorcaserin N-carbamoyl glucuronidation activities of UGT2B7, UGT2B15, and UGT2B17 in human liver microsomes by mefenamic acid, bisphenol A, and eugenol further substantiated the involvement of these UGT2B isoforms. In conclusion, multiple human UGT enzymes catalyze N-carbamoyl glucuronidation of lorcaserin; therefore, it is unlikely that inhibition of any one of these UGT activities will lead to significant inhibition of the lorcaserin N-carbamoyl glucuronidation pathway. Thus, the potential for drug-drug interaction by concomitant administration of a drug(s) that is metabolized by any of these UGTs is remote.


Subject(s)
Benzazepines/metabolism , Glucuronides/metabolism , Glucuronosyltransferase/metabolism , Microsomes/metabolism , Receptor, Serotonin, 5-HT2C/metabolism , Serotonin 5-HT2 Receptor Agonists/metabolism , Benzazepines/chemistry , Benzazepines/pharmacology , Enzyme Inhibitors/pharmacology , Glucuronides/chemistry , Glucuronosyltransferase/antagonists & inhibitors , Glucuronosyltransferase/genetics , Humans , In Vitro Techniques , Intestinal Mucosa/metabolism , Intestines/enzymology , Kidney/enzymology , Kidney/metabolism , Kinetics , Liver/enzymology , Liver/metabolism , Microsomes/enzymology , Molecular Structure , Serotonin 5-HT2 Receptor Agonists/pharmacology
15.
Drug Metab Dispos ; 40(4): 761-71, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22266842

ABSTRACT

Lorcaserin, a selective serotonin 5-hydroxytryptamine 2C receptor agonist, is being developed for weight management. The oxidative metabolism of lorcaserin, mediated by recombinant human cytochrome P450 (P450) and flavin-containing monooxygenase (FMO) enzymes, was examined in vitro to identify the enzymes involved in the generation of its primary oxidative metabolites, N-hydroxylorcaserin, 7-hydroxylorcaserin, 5-hydroxylorcaserin, and 1-hydroxylorcaserin. Human CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4, and FMO1 are major enzymes involved in N-hydroxylorcaserin; CYP2D6 and CYP3A4 are enzymes involved in 7-hydroxylorcaserin; CYP1A1, CYP1A2, CYP2D6, and CYP3A4 are enzymes involved in 5-hydroxylorcaserin; and CYP3A4 is an enzyme involved in 1-hydroxylorcaserin formation. In 16 individual human liver microsomal preparations (HLM), formation of N-hydroxylorcaserin was correlated with CYP2B6, 7-hydroxylorcaserin was correlated with CYP2D6, 5-hydroxylorcaserin was correlated with CYP1A2 and CYP3A4, and 1-hydroxylorcaserin was correlated with CYP3A4 activity at 10.0 µM lorcaserin. No correlation was observed for N-hydroxylorcaserin with any P450 marker substrate activity at 1.0 µM lorcaserin. N-Hydroxylorcaserin formation was not inhibited by CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2D6, and CYP3A4 inhibitors at the highest concentration tested. Furafylline, quinidine, and ketoconazole, selective inhibitors of CYP1A2, CYP2D6, and CYP3A4, respectively, inhibited 5-hydroxylorcaserin (IC(50) = 1.914 µM), 7-hydroxylorcaserin (IC(50) = 0.213 µM), and 1-hydroxylorcaserin formation (IC(50) = 0.281 µM), respectively. N-Hydroxylorcaserin showed low and high K(m) components in HLM and 7-hydroxylorcaserin showed lower K(m) than 5-hydroxylorcaserin and 1-hydroxylorcaserin in HLM. The highest intrinsic clearance was observed for N-hydroxylorcaserin, followed by 7-hydroxylorcaserin, 5-hydroxylorcaserin, and 1-hydroxylorcaserin in HLM. Multiple human P450 and FMO enzymes catalyze the formation of four primary oxidative metabolites of lorcaserin, suggesting that lorcaserin has a low probability of drug-drug interactions by concomitant medications.


Subject(s)
Benzazepines/metabolism , Cytochrome P-450 Enzyme System/metabolism , Microsomes, Liver/enzymology , Oxygenases/metabolism , Receptor, Serotonin, 5-HT2C/metabolism , Serotonin 5-HT2 Receptor Agonists/metabolism , Benzazepines/pharmacology , Biotransformation , Catalysis , Humans , In Vitro Techniques , Metabolic Detoxication, Phase I , Serotonin 5-HT2 Receptor Agonists/pharmacology
16.
Int Health ; 4(4): 307-13, 2012 Dec.
Article in English | MEDLINE | ID: mdl-24029678

ABSTRACT

The factors that influence the selection of a healthcare provider once the decision to seek care has been made can be summarized using a triad of cost, location and reputation. The goal of this study was to identify which of these factors is the primary consideration when women in urban Bo, Sierra Leone, select a healthcare provider for themselves or their children. We interviewed 1091 mothers during a household census of two neighbourhoods of Bo in April 2010. Reputation was the top consideration for about half of the women, cost was the second most common priority, and the location of the healthcare facility was the primary consideration for less than 7% of the participants. The majority of women said they would select a new provider if cost was not a barrier. Socioeconomic characteristics were not significant predictors of whether cost, location or reputation was selected as the highest-ranked consideration. This evidence for the importance of reputation in healthcare decision-making even in low-resource areas highlights the need for health systems to address issues of quality and responsiveness, and not just cost, in order to increase access to and utilization of health services.

17.
Health Care Women Int ; 32(3): 177-89, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21337241

ABSTRACT

The Breast Health Global Initiative 2007 emphasized education and cultural values for promoting breast cancer screening in developing countries. This cross-sectional study investigated if educational level and cultural beliefs affect breast cancer screening practices in 152 women 40 years or older in Dhaka, Bangladesh. Women with a higher (>12 years) educational level were more likely to know about breast self-examination (BSE; OR(adj), 95%CI = 22, 6.39-76.76), to know about mammograms (6, 2.49-15.70), and to practice BSE (3, 1.27-6.83) compared with those with a lower educational level. Breast cancer screening practices or knowledge was not affected by perceiving barriers to having mammograms.


Subject(s)
Breast Neoplasms/diagnosis , Breast Self-Examination , Culture , Educational Status , Health Knowledge, Attitudes, Practice , Mammography/statistics & numerical data , Adult , Aged , Asian People/statistics & numerical data , Bangladesh , Breast Neoplasms/ethnology , Breast Neoplasms/prevention & control , Cross-Sectional Studies , Early Detection of Cancer/statistics & numerical data , Female , Humans , Mass Screening/statistics & numerical data , Middle Aged , Surveys and Questionnaires
18.
West Afr J Med ; 29(4): 267-70, 2010.
Article in English | MEDLINE | ID: mdl-20931516

ABSTRACT

BACKGROUND: Superficial fungal infections are common in the tropics, partly due to the climate, relatively poor hygiene, and lifestyle of the people. OBJECTIVE: To determine the clinical forms and aetiological agents of superficial fungal infections as seen among skin cases in the north- central part of Nigeria. METHODS: All consecutive new patients seen at the skin clinic of the General Out-patient Department of the Federal Medical Centre, Bida from July 2006 to December 2007 were included in this prospective study. Participants were examined for superficial fungal lesions. Samples of skin scrapings for microbiological investigations were obtained from suspicious lesions. RESULTS: A total of 381 patients attended the Skin Clinic during the period of study. Superficial fungal infections constituted 89(23.4%) of all skin cases seen. The commonest clinical type of fungal infection was Tinea corporis, followed by Tinea unguium. Male to female ratio of clinical lesions was 1: 1.5. A total of 41 samples grew fungal organisms on Sabouraud Dextrose Agar culture, of which dermatophytes were the isolates in 22(53.7%), while non-dermatophytes accounted for the rest. Seven species of dermatophytes, dominated by Trichophyton spp. 15 (68.2%), followed by Microsporum gypseum 4(18.2%), and Epidermophyton floccosum 3(13.6%) were the main isolates. The most commonly recovered species were T. mentagrophytes (36.4%). CONCLUSION: These data show the continued predominance of dermatophytes as the principal pathogen in superficial fungal infection. Trichophyton spp. is the predominant class of which T. mentagrophyte is the most prevalent.


Subject(s)
Dermatomycoses/epidemiology , Dermatomycoses/etiology , Mitosporic Fungi/isolation & purification , Skin/microbiology , Adolescent , Adult , Age Distribution , Child , Dermatomycoses/diagnosis , Female , Humans , Male , Middle Aged , Mitosporic Fungi/classification , Nigeria/epidemiology , Prevalence , Prospective Studies , Sex Distribution , Tropical Climate , Young Adult
19.
Hematol Oncol Stem Cell Ther ; 2(3): 399-402, 2009.
Article in English | MEDLINE | ID: mdl-20139053

ABSTRACT

Acute lymphoblastic leukemia (ALL) is a relatively rare disease during pregnancy, accounting for about 15% of all cases of pregnancy-associated leukemia. Although mixed lineage leukemia gene (MLL) rearrangement is the dominant genetic aberration in infantile acute leukemia, the occurrence of MLL gene rearrangement in maternal ALL occurring during pregnancy has not been reported. Out of 31 cases of maternal leukemia diagnosed during pregnancy at our institution, 5 were ALL cases. Three of the 5 patients had MLL gene rearrangement. The data for these 5 patients are presented in this report. We believe that the association of MLL gene rearrangement with maternal leukemia is biologically plausible and this observation needs to be validated in a larger cohort of pregnancy-associated maternal leukemia cases.


Subject(s)
Gene Rearrangement , Myeloid-Lymphoid Leukemia Protein/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Pregnancy Complications, Neoplastic , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell Lineage , Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 4/genetics , Combined Modality Therapy , Female , Gestational Age , Histone-Lysine N-Methyltransferase , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Pregnancy , Prognosis , Stem Cell Transplantation , Translocation, Genetic , Young Adult
20.
An Sist Sanit Navar ; 30 Suppl 2: 99-115, 2007.
Article in Spanish | MEDLINE | ID: mdl-17898831

ABSTRACT

The treatment of tuberculosis is important both to preserve the health of the patient and to prevent the spread of the disease amongst the population. Its bacteriological bases are found in the high number of bacillae existing in the majority of human TB lesions and the capacity to mutate of Mycobacterium tuberculosis when it achieves a high number of divisions; this makes it essential to associate drugs that avoid the selection of resistant mutants. In our setting the pharmacological therapy that has shown greatest efficacy consists in the association during two months of isoniacide, rifampicine and pyrazinamide followed by four additional months with the first two drugs. In general the first choice tuberculostatic drugs are well tolerated, but they can produce potentially serious secondary effects that it is necessary to understand and know how to manage. This article also describes how to act from the therapeutic point of view facing certain special situations and when the initial treatments have been abandoned or have failed. In the last five years in Navarre, there has been a significant increase in the presence of immigrants proceeding from developing countries with high rates of tuberculosis and primary resistances. Because of its specific socio-economic conditions and its cultural idiosyncrasy, this group frequently generates difficulties with respect to complying with the treatment, as well in follow-up and control. The treatment of tuberculosis must always be carried out by expert doctors.


Subject(s)
Antitubercular Agents/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Algorithms , Antitubercular Agents/adverse effects , Humans , Recurrence , Risk Factors , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/microbiology
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