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1.
Indian J Occup Environ Med ; 28(1): 38-40, 2024.
Article in English | MEDLINE | ID: mdl-38783886

ABSTRACT

Background: Ocular health is significant as undetected and untreated eye conditions can lead to vision loss and blindness. Usually, dentists, dental assisting staff, and patients undergoing frequent dental corrections are likely affected by eye injuries. Methods: This survey aimed to evaluate eye safety protocols in the dental fraternity. A prevalidated questionnaire was given to practicing graduate and postgraduate dentists to obtain details of the eye safety protocol they adopted. Results: A total of 150 dentists approached; only 125 chose to participate in the survey and answered our questionnaire. Although most dentists used eye protection for themselves, primarily personal eyeglasses and face shields, eye injury was quite common in them. Conclusion: Data from this study revealed that the use of eye safety practices among the respondents could be improved. Clinicians should be aware that they are responsible for providing adequate eye protection for themselves and their assisting staff and patients.

2.
bioRxiv ; 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38464016

ABSTRACT

Adolescence involves significant reorganization within the medial prefrontal cortex (mPFC), including modifications to inhibitory neurotransmission mediated through parvalbumin (PV) interneurons and their surrounding perineuronal nets (PNNs). These developmental changes, which result in increased PV neuron activity in adulthood, may be disrupted by drug use resulting in lasting changes in mPFC function and behavior. Methamphetamine (METH), which is a readily available drug used by some adolescents, increases PV neuron activity and could influence the activity-dependent maturational process of these neurons. In the present study, we used male and female Sprague Dawley rats to test the hypothesis that METH exposure influences PV and PNN expression in a sex- and age-specific manner. Rats were injected daily with saline or 3.0 mg/kg METH from early adolescence (EA; 30-38 days old), late adolescence (LA; 40-48 days old), or young adulthood (60-68 days old). One day following exposure, effects of METH on PV cell and PNN expression were assessed using immunofluorescent labeling within the mPFC. METH exposure did not alter male PV neurons or PNNs. Females exposed in early adolescence or adulthood had more PV expressing neurons while those exposed in later adolescence had fewer, suggesting distinct windows of vulnerability to changes induced by METH exposure. In addition, females exposed to METH had more PNNs and more intense PV neuron staining, further suggesting that METH exposure in adolescence uniquely influences development of inhibitory circuits in the female mPFC. This study indicates that the timing of METH exposure, even within adolescence, influences its neural effects in females.

3.
Dev Neurosci ; 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38547851

ABSTRACT

INTRODUCTION: Adolescence involves significant reorganization within the medial prefrontal cortex (mPFC), including modifications to inhibitory neurotransmission that may be mediated through parvalbumin (PV) interneurons and their surrounding perineuronal nets (PNNs). These developmental changes, which can result in increased PV neuron activity in adulthood, may be disrupted by drug use resulting in lasting changes in mPFC function and behavior. Methamphetamine (METH), which is a readily available drug used by some adolescents, increases PV neuron activity and could influence the activity-dependent maturational process of these neurons. METHODS: In the present study, we used male and female Sprague Dawley rats to test the hypothesis that METH exposure influences PV and PNN expression in a sex- and age-specific manner. Rats were injected daily with saline or 3.0 mg/kg METH from early adolescence (EA; 30-38 days old), late adolescence (LA; 40-48 days old), or young adulthood (60-68 days old). One day following exposure, effects of METH on PV cell and PNN expression were assessed using immunofluorescent labeling within the mPFC. RESULTS: METH exposure did not alter male PV neurons or PNNs. Females exposed in early adolescence or adulthood had more PV expressing neurons while those exposed in later adolescence had fewer, suggesting distinct windows of vulnerability to changes induced by METH exposure. In addition, females exposed to METH had more PNNs and more intense PV neuron staining, further suggesting that METH exposure in adolescence uniquely influences development of inhibitory circuits in the female mPFC. CONCLUSIONS: This study indicates that the timing of METH exposure, even within adolescence, influences its neural effects in females.

4.
Arch Razi Inst ; 78(3): 823-829, 2023 06.
Article in English | MEDLINE | ID: mdl-38028834

ABSTRACT

One of the most important nosocomial organisms that cause urinary tract infections (UTIs) in cancer patients is Escherichia coli. A significant cause of concern in managing UTIs is the development of carbapenem-resistant bacteria. Escherichia coli with carbapenem resistance has become a more serious problem, particularly in Iraq. In this regard, the present study aimed to estimate the prevalence of carbapenem-resistant E. coli in Al-Basrah, Iraq. Conventional tests and the Vitek®2 system were used to identify the isolates and determine the susceptibility of E.coli isolates to antimicrobials. In addition, E.coli isolates were tested by mCIM and eCIM methods. Moreover, the major carbapenemase genes, including blaSPM, blaIMP, blaVIM, and blaKPC were detected by polymerase chain reaction. In total, 120 urine samples were collected from cancer patients who were suspected of having urinary tract infections at Basrah Center of Oncology Al-Sader Teaching Hospital, Basrah, Iraq. Identification of bacterial growth by using biochemical tests revealed different bacterial species. The most frequent bacteria were E. coli (n=22, 53.65%) isolates. The results showed that 13 (59.09%) and 11 (50%) out of 22 E. coli isolates were positive for the production of carbapenemase, based on the eCIM and sCIM, respectively. The majority of E.coli in this study possessed the blaVIM gene (n=13, 59.1%), followed by the blaKPC gene (n=5, 22.73%), blaIMP gene (n=5, 22.73%), and blaSPM gene (n=4, 18.18%). There is a spread of more than one type of carbapenemase among the E. coli isolates collected from UTI cancer patients in Basrah Hospital. The E. coli identified in the current study had a strong capacity to produce carbapenemase enzymes against the four generations of antibiotics, including imipenem and meropenem antibiotics.


Subject(s)
Neoplasms , Urinary Tract Infections , Humans , Escherichia coli/genetics , Genotype , Iraq/epidemiology , Anti-Bacterial Agents , Carbapenems , Urinary Tract Infections/epidemiology
5.
Neurotoxicol Teratol ; 99: 107288, 2023.
Article in English | MEDLINE | ID: mdl-37595675

ABSTRACT

Humans are exposed to phthalates, a class of endocrine-disrupting chemicals used in food packaging/processing, PVC plastics, and personal care products. Gestational exposure may lead to adverse neurodevelopmental outcomes. In a rat model, perinatal exposure to an environmentally relevant mixture and dose of phthalates leads to increased developmental apoptosis in the medial prefrontal cortex (mPFC) and a subsequent reduction in neurons and in cognitive flexibility measured in adults of both sexes (Sellinger et al., 2021b; Kougias et al., 2018b). However, whether these effects generalize to other cognitive regions, like the hippocampus, is less well understood as existing studies used single phthalates at large doses, unrepresentative of human exposure. In the current study, patterns of naturally occurring cell death were first established in the dorsal and ventral hippocampal subfields (CA3 and CA1). Both dorsal and ventral CA3 reached high levels of cell death on P2 while levels in dorsal and ventral CA1 peaked on P5 in both sexes. Exposure to a phthalate mixture (0.2 and 1 mg/kg/day) throughout gestation through postnatal day 10 resulted in subtle age- and region-specific decreases in developmental cell death, however there were no significant changes in adult neuron number or associated behaviors: the Morris water maze and social recognition. Therefore, perinatal exposure to a low dose mixture of phthalates does not result in the dramatic structural and behavioral changes seen with high doses of single phthalates. This study also adds to our understanding of the distinct neurodevelopmental effects of phthalates on different brain regions.


Subject(s)
Cognition , Hippocampus , Male , Pregnancy , Female , Rats , Adult , Humans , Animals , Hippocampus/physiology , Cell Death , Age Factors
6.
Eur Rev Med Pharmacol Sci ; 27(3): 836-844, 2023 02.
Article in English | MEDLINE | ID: mdl-36808328

ABSTRACT

OBJECTIVE: This study aims to analyze and compare the postural balance between two aquatic sports where vertical vs. horizontal body positions (i.e., windsurfing vs. swimming) are key techniques for both sports. SUBJECTS AND METHODS: Eight volunteer windsurfers and eight swimmers agreed to participate in this study. Each of the assessments was a 2D kinematic analysis of frontal and/or sagittal balance (i.e., in bipedal and/or unipedal stance) of the center of mass velocity on wobble board (Single Plane Balance Board) on hard and/or soft surface. Kinematic analysis was performed in 2D using two action-cams. Data were digitized using the video-based data analysis system SkillSpector. RESULTS: The results showed that the ANOVA, with repeated measures on 1 factor, showed a significant difference (p<0.001) between groups (i.e., swimmers and windsurfers) in all variables and in the interaction between ground (i.e., hard and foam) and group (p<0.01) in all tests in sagittal plane. Furthermore, for the ground*group interaction, a study (i.e., paired t-test) of the difference between balance (i.e., in frontal and/or sagittal plane) on hard and soft ground for each group showed that windsurfers had no difference in body sway in frontal and/or sagittal plane between hard and soft surface in bipedal stance. CONCLUSIONS: We concluded that the windsurfers showed better postural balance performances compared to swimmers in the bipedal posture on hard and soft ground. Also, the windsurfers presented a better stability level compared with the swimmers.


Subject(s)
Posture , Sports , Humans , Postural Balance , Biomechanical Phenomena
7.
Sports Biomech ; 22(2): 222-234, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35722746

ABSTRACT

This study focuses on certain characteristics of the jump take-offs in rhythmic gymnastics (RG). Rhythmic gymnasts always perform their jumps with the same preferred run-up technique, proceeded by a chassé-step in most of the cases. The overall idea was to analyse other step-techniques that could be performged on one-leg, which could prepare jumps. The aim of this study was to compare kinetic and kinematic variables between three-stag ring leaps with and without throwing-ball, performed using the glissade-step as a preparatory phase for take-off with one-leg these were as follows: glissade stag ring leap without-ball (GSWB), throw-ball glissade stag ring leap (TBGS) and glissade throw-ball stag ring leap (GTBS). Seven members of the Tunisian RG national team took part in this study. The technical elements were recorded in 2D using two-cameras on a specially designed floor carpet where a force-plate was integrated. The results showed that the three-leaps had significant impacts on the performance variables, especially on the force, the velocity and the flexibility. The GTBS was the most effective leap as the throw took place during the jump, which has increased its technicality and the applied physical variables, the vertical force, the rate of force development, the horizontal and vertical velocities and displacements.


Subject(s)
Gymnastics , Humans , Biomechanical Phenomena
8.
Neurotoxicology ; 94: 126-134, 2023 01.
Article in English | MEDLINE | ID: mdl-36442689

ABSTRACT

Bisphenol A (BPA) is an endocrine disruptor found in polycarbonate plastics and exposure in humans is nearly ubiquitous and it has widespread effects on cognitive, emotional, and reproductive behaviors in both humans and animal models. In our laboratory we previously found that perinatal BPA exposure results in a higher number of neurons in the adult male rat prefrontal cortex (PFC) and less play in adolescents of both sexes. Here we examine changes in the rate of postnatal apoptosis in the rat prefrontal cortex and its timing with brief BPA exposure. Because an increased number of neurons in the PFC is a characteristic of a subtype of autism spectrum disorder, we tested social preference following brief BPA exposure and also expression of a small group of genes. Males and females were exposed to BPA from postnatal days (P) 6 through 8 or from P10 through 12. Both exposures significantly decreased indicators of cell death in the developing medial prefrontal cortex in male subjects only. Additionally, males exposed to BPA from P6 - 8 showed decreased social preference and decreased cortical expression of Shank3 and Homer1, two synaptic scaffolding genes that have been implicated in social deficits. There were no significant effects of BPA in the female subjects. These results draw attention to the negative consequences following brief exposure to BPA during early development.


Subject(s)
Autism Spectrum Disorder , Endocrine Disruptors , Animals , Female , Male , Pregnancy , Rats , Apoptosis , Autism Spectrum Disorder/chemically induced , Autism Spectrum Disorder/metabolism , Benzhydryl Compounds/toxicity , Benzhydryl Compounds/metabolism , Endocrine Disruptors/toxicity , Gene Expression , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Social Behavior , Disease Models, Animal
9.
Neurotoxicology ; 87: 167-173, 2021 12.
Article in English | MEDLINE | ID: mdl-34599995

ABSTRACT

Phthalates are a class of endocrine disruptors found in a variety of consumer goods, and offspring can be exposed to these compounds during gestation and lactation. Our laboratory has found that perinatal exposure to an environmentally relevant mixture of phthalates resulted in a decrease in cognitive flexibility and in neuron number in the adult rat medial prefrontal cortex (mPFC). Here, we examine effects of phthalate treatment on prenatal cellular proliferation and perinatal apoptosis in the mPFC. To examine the phthalate effects on cellular proliferation, dams consumed 0, 1, or 5 mg/kg of the phthalate mixture daily from embryonic day 2 (E2) through the day of birth (P0), and on E16 and E17, they were injected with BrdU. The mPFC of offspring was analyzed on P5 and showed a decrease in labelled cells in the phthalate exposed groups. To examine whether changes in BrdU density observed on P5 were due to altered cell survival, cell death was measured on E18, P0, and P5 using a TUNEL assay in a separate cohort of prenatally exposed offspring. There was an increase in TUNEL labelled cells at E18 in the phthalate exposed groups. In the final experiment, dams consumed the phthalate mixture from E2 through P10, at which time mPFC tissue was stained with TUNEL. Phthalate treated subjects showed a higher density of apoptotic cells at P10. These results indicate both pre- and postnatal phthalate exposure increases apoptosis in the male and female rat mPFC. While the impact of phthalates on proliferation cannot be ruled out, these data do not allow for definitive conclusions.


Subject(s)
Apoptosis/drug effects , Phthalic Acids/toxicity , Prefrontal Cortex/drug effects , Prenatal Exposure Delayed Effects/chemically induced , Animals , Animals, Newborn/growth & development , Cell Proliferation/drug effects , Female , In Situ Nick-End Labeling , Male , Prefrontal Cortex/embryology , Prefrontal Cortex/growth & development , Prefrontal Cortex/pathology , Pregnancy , Rats , Rats, Long-Evans
10.
Int Breastfeed J ; 16(1): 42, 2021 05 26.
Article in English | MEDLINE | ID: mdl-34039388

ABSTRACT

BACKGROUND: It is well established that exclusive breastfeeding can play a critical role in reducing child morbidity and mortality. Limited research has been done thus far on the practice and perceptions of breastfeeding in Sierra Leone, where more than 10 % of children die before the age of five. This study aimed to gain understanding into and explore both matters in order to develop recommendations for effective strategies to promote breastfeeding practice in Pujehun District, Southern Sierra Leone. METHODS: This exploratory mixed-method study included a cross-sectional survey of 194 mothers, semi-structured interviews and focus group discussions. Logistic regression analysis was used calculated odds ratios of factors associated with primarily breastfeeding practice, defined as 'Children under six months of age who are fed with breast milk only and children older than six months of age that were exclusively breastfed up to six months', based on recall from birth. Exclusive breastfeeding rate was based on breastfeeding practice 24 h prior to the survey. Qualitative data was analysed through a deductive approach, using a pre-determined framework on determinants of breastfeeding. RESULTS: This study revealed an exclusive breastfeeding rate of 62.8% (95% CI 53.9, 71.7); dropping from 74% in the 0-1-month age group to 33% in the 4-5 months group. Triangulation of qualitative and quantitative data revealed enabling factors for primarily breastfeeding practice included mothers receiving support during their first breastfeed, pregnant women being provided with information on the benefits of the practice, counselling by nurses, support from husbands, and women's awareness of how their friends and family members fed their own babies. The main barriers were a lack of encouragement by husbands, women's perception that their infants' stools were abnormal or that they were not producing enough breast milk. CONCLUSIONS: Although the exclusive breastfeeding may have risen over recent years, a gap remains compared to World Health Organization recommendations. According to the breastfeeding determinants identified in this study, promotion of counselling by a nurse, encouragement of husbands' support, and improve knowledge of mothers on breastfeeding are recommended to be incorporated in the design of future health programs.


Subject(s)
Breast Feeding , Health Knowledge, Attitudes, Practice , Child , Cross-Sectional Studies , Female , Humans , Infant , Mothers , Pregnancy , Sierra Leone/epidemiology
11.
Transl Psychiatry ; 9(1): 81, 2019 02 11.
Article in English | MEDLINE | ID: mdl-30745563

ABSTRACT

Abnormal levels of dopamine (DA) are thought to contribute to several neurological and psychiatric disorders including drug addiction. Extracellular DA levels are regulated primarily via reuptake by the DA transporter (DAT). Amphetamine, a potent psychostimulant, increases extracellular DA by inducing efflux through DAT. Recently, we discovered that G protein ßγ subunits (Gßγ) interact with DAT, and that in vitro activation of Gßγ promotes DAT-mediated efflux. Here, we investigated the role of Gßγ in the actions of amphetamine in DA neurons in culture, ex vivo nucleus accumbens (NAc), and freely moving rats. Activation of Gßγ with the peptide myr-Ser-Ile-Arg-Lys-Ala-Leu-Asn-Ile-Leu-Gly-Tyr-Pro-Asp-Tyr-Asp (mSIRK) in the NAc potentiated amphetamine-induced hyperlocomotion, but not cocaine-induced hyperlocomotion, and systemic or intra-accumbal administration of the Gßγ inhibitor gallein attenuated amphetamine-induced, but not cocaine-induced hyperlocomotion. Infusion into the NAc of a TAT-fused peptide that targets the Gßγ-binding site on DAT (TAT-DATct1) also attenuated amphetamine-induced but not cocaine-induced hyperlocomotion. In DA neurons in culture, inhibition of Gßγ with gallein or blockade of the Gßγ-DAT interaction with the TAT-DATct1 peptide decreased amphetamine-induced DA efflux. Furthermore, activation of Gßγ with mSIRK potentiated and inhibition of Gßγ with gallein reduced amphetamine-induced increases of extracellular DA in the NAc in vitro and in freely moving rats. Finally, systemic or intra-accumbal inhibition of Gßγ with gallein blocked the development of amphetamine-induced, but not cocaine-induced place preference. Collectively, these results suggest that interaction between Gßγ and DAT plays a critical role in the actions of amphetamine and presents a novel target for modulating the actions of amphetamine in vivo.


Subject(s)
Amphetamine/pharmacology , Central Nervous System Stimulants/pharmacology , Dopamine Plasma Membrane Transport Proteins/metabolism , Dopamine/metabolism , GTP-Binding Protein beta Subunits/metabolism , GTP-Binding Protein gamma Subunits/metabolism , Amphetamine/adverse effects , Animals , Central Nervous System Stimulants/adverse effects , Cocaine/administration & dosage , Dopaminergic Neurons/metabolism , Male , Motor Activity/drug effects , Nucleus Accumbens/metabolism , Rats , Rats, Sprague-Dawley
12.
Orthop Traumatol Surg Res ; 104(1S): S107-S112, 2018 02.
Article in English | MEDLINE | ID: mdl-29155310

ABSTRACT

Current knowledge of the causes and risk factors of Legg-Calvé-Perthesdisease (LCPD) does not allow effective preventive strategies. The outcome in adulthood is usually good. Hip osteoarthritis rarely develops before 50 years of age. The risk of osteoarthrosis depends chiefly on the final degree of joint incongruence. Age at onset and the lateral pillar classification are the two main outcome predictors and serve to guide the surgical indications based on the studies by Herring's group. Non-operative treatment is not effective. In contrast, femoral varus osteotomy and Salter's innominate osteotomy provide good outcomes. In severe forms, however, combining these two techniques or performing a triple pelvic osteotomy seem preferable. Surgery is now performed considerably less often than in the past, as it is effective only in patients with lateral pillar group B or B/C disease with onset after eight years of age. In other situations, therapeutic abstention is recommended.


Subject(s)
Legg-Calve-Perthes Disease/surgery , Patient Selection , Femur/surgery , Humans , Legg-Calve-Perthes Disease/complications , Legg-Calve-Perthes Disease/diagnostic imaging , Legg-Calve-Perthes Disease/etiology , Osteoarthritis, Hip/etiology , Osteotomy , Pelvic Bones/surgery , Prognosis , Risk Factors , Treatment Outcome
13.
Mol Psychiatry ; 23(11): 2227-2237, 2018 11.
Article in English | MEDLINE | ID: mdl-28727685

ABSTRACT

Genetic variants of Neuregulin 1 (NRG1) and its neuronal tyrosine kinase receptor ErbB4 are associated with risk for schizophrenia, a neurodevelopmental disorder characterized by excitatory/inhibitory imbalance and dopamine (DA) dysfunction. To date, most ErbB4 studies have focused on GABAergic interneurons in the hippocampus and neocortex, particularly fast-spiking parvalbumin-positive (PV+) basket cells. However, NRG has also been shown to modulate DA levels, suggesting a role for ErbB4 signaling in dopaminergic neuron function. Here we report that ErbB4 in midbrain DAergic axonal projections regulates extracellular DA levels and relevant behaviors. Mice lacking ErbB4 in tyrosine hydroxylase-positive (TH+) neurons, but not in PV+ GABAergic interneurons, exhibit different regional imbalances of basal DA levels and fail to increase DA in response to local NRG1 infusion into the dorsal hippocampus, medial prefrontal cortex and dorsal striatum measured by reverse microdialysis. Using Lund Human Mesencephalic (LUHMES) cells, we show that NRG/ErbB signaling increases extracellular DA levels, at least in part, by reducing DA transporter (DAT)-dependent uptake. Interestingly, TH-Cre;ErbB4f/f mice manifest deficits in learning, spatial and working memory-related behaviors, but not in numerous other behaviors altered in PV-Cre;ErbB4f/f mice. Importantly, microinjection of a Cre-inducible ErbB4 virus (AAV-ErbB4.DIO) into the mesencephalon of TH-Cre;ErbB4f/f mice, which selectively restores ErbB4 expression in DAergic neurons, rescues DA dysfunction and ameliorates behavioral deficits. Our results indicate that direct NRG/ErbB4 signaling in DAergic axonal projections modulates DA homeostasis, and that NRG/ErbB4 signaling in both GABAergic interneurons and DA neurons contribute to the modulation of behaviors relevant to psychiatric disorders.


Subject(s)
Memory, Short-Term/physiology , Receptor, ErbB-4/physiology , Spatial Memory/physiology , Animals , Axons/metabolism , Behavior, Animal/physiology , Dopamine/metabolism , Dopaminergic Neurons/metabolism , ErbB Receptors/metabolism , Gene Expression Regulation/genetics , Hippocampus/metabolism , Interneurons/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Neuregulin-1/metabolism , Parvalbumins/metabolism , Prefrontal Cortex/metabolism , Receptor, ErbB-4/genetics , Receptor, ErbB-4/metabolism , Signal Transduction/physiology , Spatial Behavior/physiology , Synapses/metabolism , gamma-Aminobutyric Acid/metabolism
14.
Mol Psychiatry ; 22(12): 1673-1679, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28894302

ABSTRACT

The dopamine transporter (DAT) is an important regulator of brain dopamine (DA) homeostasis, controlling the intensity and duration of DA signaling. DAT is the target for psychostimulants-like cocaine and amphetamine-and plays an important role in neuropsychiatric disorders, including attention-deficit hyperactivity disorder and drug addiction. Thus, a thorough understanding of the mechanisms that regulate DAT function is necessary for the development of clinical interventions to treat DA-related brain disorders. Previous studies have revealed a plethora of protein-protein interactions influencing DAT cellular localization and activity, suggesting that the fine-tuning of DA homeostasis involves multiple mechanisms. We recently reported that G-protein beta-gamma (Gßγ) subunits bind directly to DAT and decrease DA clearance. Here we show that Gßγ induces the release of DA through DAT. Specifically, a Gßγ-binding/activating peptide, mSIRK, increases DA efflux through DAT in heterologous cells and primary dopaminergic neurons in culture. Addition of the Gßγ inhibitor gallein or DAT inhibitors prevents this effect. Residues 582 to 596 in the DAT carboxy terminus were identified as the primary binding site of Gßγ. A TAT peptide containing the Gßγ-interacting domain of DAT blocked the ability of mSIRK to induce DA efflux, consistent with a direct interaction of Gßγ with the transporter. Finally, activation of a G-protein-coupled receptor, the muscarinic M5R, results in DAT-mediated DA efflux through a Gßγ-dependent mechanism. Collectively, our data show that Gßγ interacts with DAT to promote DA efflux. This novel mechanism may have important implications in the regulation of brain DA homeostasis.


Subject(s)
Dopamine Plasma Membrane Transport Proteins/metabolism , Dopamine/metabolism , GTP-Binding Protein beta Subunits/metabolism , GTP-Binding Protein gamma Subunits/metabolism , Animals , Binding, Competitive , Brain/metabolism , Cells, Cultured , Cricetulus , Dopamine Plasma Membrane Transport Proteins/genetics , Dopaminergic Neurons/metabolism , Female , Humans , Membrane Potentials/drug effects , Membrane Potentials/physiology , Rats, Sprague-Dawley , Receptor, Muscarinic M5/metabolism
15.
Methods Enzymol ; 583: 279-307, 2017.
Article in English | MEDLINE | ID: mdl-28063495

ABSTRACT

Structural studies on lipases by X-ray crystallography have revealed conformational changes occurring in the presence of surfactants/inhibitors and the pivotal role played by a molecular "lid" of variable size and structure depending on the enzyme. Besides controlling the access to the enzyme active site, the lid is involved in lipase activation, formation of the interfacial recognition site (IRS), and substrate docking within the active site. The combined use of surfactants and inhibitors has been critical for a better understanding of lipase structure-function relationships. An overview of crystal structures of lipases in complex with surfactants and inhibitors reveals common structural features and shows how surfactants monomers interact with the lid in its open conformation. The location of surfactants, inhibitors, and hydrophobic residues exposed upon lid opening provides insights into the IRS of lipases. The mechanism by which surfactants promote the lid opening can be further investigated in solution by site-directed spin labeling of lipase coupled to electron paramagnetic resonance spectroscopy. These experimental approaches are illustrated here by results obtained with mammalian digestive lipases, fungal lipases, and cutinases.


Subject(s)
Carboxylic Ester Hydrolases/chemistry , Enzyme Inhibitors/chemistry , Fungal Proteins/chemistry , Lipase/chemistry , Surface-Active Agents/chemistry , Animals , Carboxylic Ester Hydrolases/antagonists & inhibitors , Catalytic Domain , Crystallography, X-Ray , Electron Spin Resonance Spectroscopy , Fungal Proteins/antagonists & inhibitors , Fusarium/chemistry , Fusarium/enzymology , Hydrophobic and Hydrophilic Interactions , Lipase/antagonists & inhibitors , Mammals , Models, Molecular , Protein Binding , Protein Structure, Secondary , Substrate Specificity
16.
Geburtshilfe Frauenheilkd ; 76(9): 964-971, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27681521

ABSTRACT

Background: Peripartum anesthesia may consist of parenteral opioids and/or regional analgesia. There is only limited data in the literature comparing both methods in daily obstetric practice. This observational study investigated the opioids pethidine and meptazinol as well as regional analgesics with regard to their administration, efficacy, side effects and subjective maternal satisfaction with therapy. The rates of secondary regional analgesia administration after administration of the respective opioid served as a means of evaluating treatment. Methods: This study collected data on pain management during vaginal delivery in a German university hospital over a twelve month period. Severity of pain was measured intrapartum using a numerical rating scale. Maternal, neonatal and delivery-related data were obtained postpartum from the clinical records and from the mothers using a questionnaire. Results: The study is based on data obtained from 449 deliveries. Pain relief achieved by the administration of pethidine and meptazinol was similarly low; maternal satisfaction with the respective therapy was high. Meptazinol was usually administered intravenously (83 % vs. 6 %; p < 0.001), repeatedly (27 % vs. 6 %; p < 0.001) and closer to the birth (1.9 ± 2.7 h vs. 2.6 ± 2.8 h; p < 0.05) compared to pethidine. Secondary regional analgesia was more common after the administration of pethidine (16 % vs. 8 %; p < 0.05). Regional analgesia resulted in greater pain relief compared to opioid therapy (78 % vs. 24 % after 30 min; p < 0.001) and was associated with longer times to delivery (7.6 ± 2.5 h vs. 5.7 ± 2.5 h; p < 0.001) and higher levels of maternal satisfaction with therapy (6.1 ± 1.2 vs. 4.8 ± 1.6 on a 7-point scale; p < 0.001). Conclusion: In daily clinical practice, meptazinol can be adapted more readily to changes during birth and requires less secondary analgesia. Regional neuraxial analgesia was found to be an efficacious and safe way of managing labor pain.

18.
Orthop Traumatol Surg Res ; 101(6 Suppl): S275-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26215089

ABSTRACT

INTRODUCTION: The treatment of severe slipped capital femoral epiphysis (SCFE) remains controversial. Despite numerous treatments being available, the outcome of published studies has been variable. Recent studies emphasize that poor reduction of the severe SCFE is responsible for the appearance of joint cartilage lesions and progression towards early osteoarthritis. But surgical reduction of severe SCFE also results in a significant rate of necrosis. OBJECTIVE: Evaluate the results of various treatment strategies for severe SCFE and identify the optimal course of action. MATERIAL AND METHODS: This was a French multicenter retrospective study of severe SCFE cases (>45° displacement) evaluated a minimum of 12 months after treatment. The stability of the slipped epiphysis, type of the treatment, delay before treatment, early and short-term complications, Harris and WOMAC functional scores and radiological signs of femoroacetabular impingement (FAI) at the last review were evaluated. A total of 186 cases of severe SCFE in 182 patients were included. One hundred and seven (58.7%) of these were male. The average age was 13 years. The average follow-up was 23 months. The average displacement was 60°. The SCFE was considered stable in 94 cases (50.5%) and unstable in 92 cases (49.5%). The main surgical treatments used by the various centers were in situ fixation (ISF), lateral Dunn, anterior Dunn and reduction using traction or under anesthesia (for unstable forms). RESULTS: In the stable SCFE cases, there were 6 cases of necrosis (6.4%), all of which occurred after reduction by osteotomy; there were 32 cases of radiological FAI (34%), 30 of which occurred after ISF. The necrosis rate in the unstable SCFE cases was 21.7%: one (11%) after ISF, seven (19%) after anterior Dunn, eight (21%) after preoperative reduction and three (43%) after lateral Dunn. CONCLUSIONS: The results of this study confirm the diverse nature of SCFE treatments available and the variability of their results. When selecting a treatment for severe SCFE, the goal is to stop the slip and also to prevent osteoarthritis by correcting the hip deformities. The "anterior" Dunn procedure was able to achieve these two goals, while having a lower complication rate than the other reduction techniques.


Subject(s)
Osteotomy/methods , Slipped Capital Femoral Epiphyses/surgery , Adolescent , Child , Disease Progression , Female , Follow-Up Studies , France , Humans , Male , Orthopedics , Retrospective Studies , Societies, Medical
19.
Arch Pediatr ; 22(6): 621-5, 2015 Jun.
Article in French | MEDLINE | ID: mdl-25934605

ABSTRACT

We report the case of a 13-year-old boy presenting with stiffness and pain in the elbow, which had appeared a few years before consultation. He reported a history of a closed, nondisplaced supracondylar fracture of the humerus 7 years before. Progression was good after orthopedic treatment. X-rays and CT showed a distinctive deformation, called a fishtail deformity, associated with severe arthritic injuries. We recall here that supracondylar fractures of the humerus are common in children and that early reduction decreases the complication rate. However, this case shows that fishtail deformity is a late and serious complication, which may occur after a nondisplaced supracondylar fracture of the humerus, with no severity factors and with good early progression.


Subject(s)
Humeral Fractures/complications , Humerus/abnormalities , Adolescent , Humans , Male , Time Factors
20.
Food Funct ; 6(5): 1726-35, 2015 May.
Article in English | MEDLINE | ID: mdl-25923344

ABSTRACT

Formulating healthy food rich in omega 3 fatty acids requires prior knowledge of the parameters influencing their bioavailability and their metabolic fate. In this context, we studied the effects of various emulsifiers widely used in the food industry, on the gastrointestinal lipolysis of flaxseed oil emulsions in an in vitro model and on the intestinal absorption and lymphatic secretion of alpha-linolenic acid (ALA) in rats. In vitro data showed that the emulsification of flaxseed oil with soya lecithin improved the gastric lipolysis of the oil (+30%), while the presence of Tween 80 or of sodium caseinate decreased it (-80% and -40%, respectively). The in vivo data demonstrated that the intestinal absorption and the lymphatic secretion of ALA were improved with soya lecithin (Cmax = 24 mg mL(-1)) and reduced in the presence of sodium caseinate (Cmax = 7 mg mL(-1)) compared to unemulsified flaxseed oil (Cmax = 16 mg mL(-1)); Tween 80 had no effect. In addition, the synthesized chylomicrons were notably larger and more numerous with soya lecithin whereas they were smaller in the presence of sodium caseinate (p < 0.05). This study shows that the intestinal bioavailability of ALA was increased by the emulsification of flaxseed oil with soya lecithin via an improved lipolysis, favouring the intestinal absorption of ALA and the secretion of many large chylomicrons in lymph.


Subject(s)
Chylomicrons/biosynthesis , Gastrointestinal Tract/metabolism , Lipolysis/drug effects , alpha-Linolenic Acid/chemistry , alpha-Linolenic Acid/pharmacokinetics , Animals , Biological Availability , Chemistry, Pharmaceutical , Emulsifying Agents/chemistry , Lecithins/chemistry , Linseed Oil/chemistry , Linseed Oil/pharmacokinetics , Male , Rats , Rats, Wistar , Glycine max/chemistry
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