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1.
Front Transplant ; 3: 1353124, 2024.
Article in English | MEDLINE | ID: mdl-38993754

ABSTRACT

Background: Donation after circulatory death (DCD) grafts are vital for increasing available donor organs. Gradual rewarming during machine perfusion has proven effective in mitigating reperfusion injury and enhancing graft quality. Limited data exist on artificial oxygen carriers as an effective solution to meet the increasing metabolic demand with temperature changes. The aim of the present study was to assess the efficacy and safety of utilizing a hemoglobin-based oxygen carrier (HBOC) during the gradual rewarming of DCD rat livers. Methods: Liver grafts were procured after 30 min of warm ischemia. The effect of 90 min of oxygenated rewarming perfusion from ice cold temperatures (4 °C) to 37 °C with HBOC after cold storage was evaluated and the results were compared with cold storage alone. Reperfusion at 37 °C was performed to assess the post-preservation recovery. Results: Gradual rewarming with HBOC significantly enhanced recovery, demonstrated by markedly lower lactate levels and reduced vascular resistance compared to cold-stored liver grafts. Increased bile production in the HBOC group was noted, indicating improved liver function and bile synthesis capacity. Histological examination showed reduced cellular damage and better tissue preservation in the HBOC-treated livers compared to those subjected to cold storage alone. Conclusion: This study suggests the safety of using HBOC during rewarming perfusion of rat livers as no harmful effect was detected. Furthermore, the viability assessment indicated improvement in graft function.

2.
J Burn Care Res ; 2024 May 24.
Article in English | MEDLINE | ID: mdl-38783715

ABSTRACT

The recovery of patients after severe burns is a long and complex process. Recently, genomic analysis of white blood cells from burn and trauma patients revealed excessive and prolonged innate immune activation in patients with complicated outcomes. However, translating this knowledge into practical biomarkers has not been possible yet. Although several biomarkers for monitoring burn patients have been proposed, their ability to accurately distinguish between inflammation stemming from initial tissue destruction, infections, and organ failure complications is limited. Here, we focused on monocytes, critical innate immune cells in the response to burn injured tissues. We measured the monocyte anisocytosis (quantified as monocyte distribution width, MDW, a recently emerged marker of sepsis) throughout the recovery of patients from the time of burn injury until the end of the hospital stay. We observed that MDW increases in patients during the first week after major burns. Among the patients with major burns who survive, MDW starts decreasing in the second week and normalizes by the end of the hospital stay. The duration of hospital stay appears to be proportional to how fast MDW decreases during the second week after the injury. We also found that MDW decreases significantly in most patients after excision and debridement surgeries but not after allo- and auto-graft surgeries. Moreover, high MDW values correlated with a higher rate of positive microbiology blood culture samples and respiratory infections. These findings underscore the importance of monitoring MDW as a potential biomarker for the risk of complications during burn patient recovery.

3.
Oper Dent ; 47(5): 514-526, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-36121737

ABSTRACT

OBJECTIVES: The initial shade of a resin-based restorative material should be the same as that after polymerization. In this study, the color changes of translucent and opaque composites from nine different brands were assessed after polymerization using a spectrophotometer and cross-polarization (CP) photography. METHODS AND MATERIALS: Thirteen nano-hybrid (Essentia LE, GC Corp; Ceram.x Duo SphereTEC A2E/A2D, Dentsply Sirona; Harmonize A2E/A2D, Kerr Dental; IPS Empress Direct A2E/A2D, Ivoclar Vivadent; Mosaic EN/A2, Ultradent Products; Clearfil Majesty Es-2 A2E/A2D, Kuraray Noritake; Charisma Topaz A2/OL, Kulzer), two supra nano-hybrid (Estelite Asteria NE/A2B; Tokuyama), two nano-filled (Filtek Ultimate A2E/A2D; 3M) light-curing resin composites, and one micro-hybrid (Essentia MD, GC Corp) light-curing resin composite were tested. Disc-shaped specimens (n=5) were prepared using silicone molds (12 × 5 mm) and polymerized from both sides using an LED curing light (Elipar Deepcure S, 3M) at a light intensity of 1470 mW/cm2. Measurements were performed before and 1 day after polymerization using a contact-type dental spectrophotometer (Easy Shade 5, VITA Zahnfabrik, Bad Säckingen, Germany) and a combination of CP photography and Photoshop CC software (Adobe Inc, San Jose, CA, USA). Spectrophotometry and CP photography ΔE* values were calculated; the perceptibility threshold was a ΔE* value of 1.2. VITA spectrophotometry color change scores were also calculated and evaluated. RESULTS: The overall ΔE* values ranged between 0.34 and 12.56. Two-way analysis of variance (ANOVA) showed that color change was associated most strongly with composite brand (p<0.001), followed by shade (p=0.002). Color change (p=0.002) and degree of darkening/lightening (p<0.001) were significantly greater for dentin compared to enamel shades. Clearfil Majesty Es-2 (Kuraray Noritake) showed significant lightening, whereas all other composites showed darkening after polymerization. All composite brands presented perceptible (ΔE*≥1.2) color changes. Estelite Asteria (Tokuyama), Ceram.x Duo SphereTEC (Dentsply Sirona), and Harmonize (Kerr Dental) were considered the most reliable brands regardless of the shade. The spectrophotometry and CP photography methods were positively correlated (p<0.001). Also, CIEDE2000 and CIELCH (also referred to as CIE L*c*h) color systems were positively correlated based on the ΔE* values (p<0.001). CONCLUSIONS: Despite improvements in the chemical composition of, and fillers for, contemporary resin-based composites (RBCs), all tested composite brands showed perceptible color change after polymerization, except for some shades. Under the conditions in this study, it is preferable to polymerize the composite during the trial phase, before identifying the most appropriate shade. CP photography in combination with Photoshop analysis appears to be a reliable and promising approach for color evaluation.


Subject(s)
Composite Resins , Dental Materials , Color , Composite Resins/chemistry , Dental Materials/chemistry , Materials Testing , Polymerization , Polymethyl Methacrylate , Silicones
4.
West Indian med. j ; 69(6): 395-398, 2021. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1515687

ABSTRACT

ABSTRACT Objective: The mean platelet volume (MPV) is a potential marker of platelet reactivity. Increased MPV levels are shown to be the predictors of inflammations. The aim of this study was to investigate whether MPV is an inflammatory indicator in children with allergic rhinitis. Methods: The study included 44 children with allergic rhinitis between the ages of 6 and 18 years (47.1% boys), and 45 healthy children between the ages of 6 and 18 years (52.9% boys), and the MPV, platelet (PLT), white blood cell (WBC), haemoglobin (Hb) values in their haemograms were compared. Results: No differences were found between the allergic rhinitis group and the healthy control group in terms of their age and their gender (p = 0.15 and 0.60, respectively). While the MPV value of the patient group was 6.9 fL (6-9), the MVP value of the control group was 7.0 fL (5.9-9.7). There was no statistically significant difference between the patient and the control groups in terms of their MPV data (p = 0.15). In addition, there were no differences between the patient and control groups in terms of PLT count, WBC count, or Hb data (p = 0.09, 0.22, and 0.22, respectively). Conclusion: To the best of our knowledge, this is the first study to analyse the role of MPV as an inflammatory indicator in children with allergic rhinitis. According to our results, MPV cannot be used as an indicator of inflammation in children with allergic rhinitis.

5.
Cell ; 178(1): 160-175.e27, 2019 06 27.
Article in English | MEDLINE | ID: mdl-31155233

ABSTRACT

Single-cell technologies have described heterogeneity across tissues, but the spatial distribution and forces that drive single-cell phenotypes have not been well defined. Combining single-cell RNA and protein analytics in studying the role of stromal cancer-associated fibroblasts (CAFs) in modulating heterogeneity in pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) model systems, we have identified significant single-cell population shifts toward invasive epithelial-to-mesenchymal transition (EMT) and proliferative (PRO) phenotypes linked with mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling. Using high-content digital imaging of RNA in situ hybridization in 195 PDAC tumors, we quantified these EMT and PRO subpopulations in 319,626 individual cancer cells that can be classified within the context of distinct tumor gland "units." Tumor gland typing provided an additional layer of intratumoral heterogeneity that was associated with differences in stromal abundance and clinical outcomes. This demonstrates the impact of the stroma in shaping tumor architecture by altering inherent patterns of tumor glands in human PDAC.


Subject(s)
Cancer-Associated Fibroblasts/metabolism , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/pathology , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Tumor Microenvironment , Animals , Cell Proliferation , Coculture Techniques , Epithelial-Mesenchymal Transition , Female , HEK293 Cells , Heterografts , Humans , Mice , Mice, Inbred NOD , Mice, SCID , Mitogen-Activated Protein Kinases/metabolism , RNA-Seq , STAT3 Transcription Factor/metabolism , Stromal Cells/metabolism , Transfection
6.
Cell ; 177(7): 1903-1914.e14, 2019 06 13.
Article in English | MEDLINE | ID: mdl-31031007

ABSTRACT

Xenograft cell transplantation into immunodeficient mice has become the gold standard for assessing pre-clinical efficacy of cancer drugs, yet direct visualization of single-cell phenotypes is difficult. Here, we report an optically-clear prkdc-/-, il2rga-/- zebrafish that lacks adaptive and natural killer immune cells, can engraft a wide array of human cancers at 37°C, and permits the dynamic visualization of single engrafted cells. For example, photoconversion cell-lineage tracing identified migratory and proliferative cell states in human rhabdomyosarcoma, a pediatric cancer of muscle. Additional experiments identified the preclinical efficacy of combination olaparib PARP inhibitor and temozolomide DNA-damaging agent as an effective therapy for rhabdomyosarcoma and visualized therapeutic responses using a four-color FUCCI cell-cycle fluorescent reporter. These experiments identified that combination treatment arrested rhabdomyosarcoma cells in the G2 cell cycle prior to induction of apoptosis. Finally, patient-derived xenografts could be engrafted into our model, opening new avenues for developing personalized therapeutic approaches in the future.


Subject(s)
Animals, Genetically Modified/metabolism , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Muscle Neoplasms , Rhabdomyosarcoma , Zebrafish/metabolism , Animals , Animals, Genetically Modified/genetics , Animals, Genetically Modified/immunology , Female , Heterografts , Humans , K562 Cells , Male , Muscle Neoplasms/drug therapy , Muscle Neoplasms/immunology , Muscle Neoplasms/metabolism , Muscle Neoplasms/pathology , Neoplasm Transplantation , Phthalazines/pharmacology , Piperazines/pharmacology , Rhabdomyosarcoma/drug therapy , Rhabdomyosarcoma/immunology , Rhabdomyosarcoma/metabolism , Rhabdomyosarcoma/pathology , Temozolomide/pharmacology , Xenograft Model Antitumor Assays , Zebrafish/genetics , Zebrafish/immunology
7.
Eur J Trauma Emerg Surg ; 44(4): 597-605, 2018 Aug.
Article in English | MEDLINE | ID: mdl-28717983

ABSTRACT

PURPOSE: The aim of our study was to evaluate the effects of AKI development on mortality with four different classification systems (RIFLE, AKIN, CK, KDIGO) in critically ill trauma patients followed in the intensive care unit. METHODS: A retrospective review of 2034 patients in our intensive care unit was conducted between July 2010 and August 2013. A total of 198 patients with primary trauma were included in the study to evaluate the development of AKI. RESULTS: When the presence of AKI was investigated according to the four criteria (RIFLE, AKIN, CK, and KDIGO), the highest incidence of AKI was found according to the KDIGO classification (74.2%), followed by AKIN (72.2%), RIFLE (69.7%), and CK (59.1%). It was observed that more AKI developed according to KDIGO in patients with multiple trauma and thoracic trauma (p = 0.031, p = 0.029). Sixty-two (31%) of the 198 trauma patients monitored in the intensive care unit died; mortality was frequently found high in AKI stage 2 and 3 patients. According to the CK classification, there was a significant increase in mortality in patients with AKI on the first day (p = 0.045). AKI classifications by RIFLE, AKIN, CK, and KDIGO were independently associated with the risk of in-hospital death. CONCLUSION: In this study, the presence of AKI was found to be an independent risk factor in the development of in-hospital mortality according to all classification systems (RIFLE, AKIN, CK, and KDIGO) in critically traumatic patients followed in ICU, and the compatibility between RIFLE, AKIN, and KDIGO was the highest among the classification systems.


Subject(s)
Acute Kidney Injury/classification , Acute Kidney Injury/mortality , Critical Illness/classification , Critical Illness/mortality , Hospital Mortality/trends , Risk Assessment/methods , Adult , Aged , Female , Humans , Incidence , Intensive Care Units , Male , Middle Aged , Retrospective Studies , Risk Factors , Severity of Illness Index , Turkey/epidemiology
8.
Annals of Dentistry ; : 23-30, 2018.
Article in English | WPRIM (Western Pacific) | ID: wpr-750382

ABSTRACT

@#To assess the oral health behaviour and preventive dental care experiences of patients with special health care needs (SHCN) who attended the Special Care Dental (SCD) Clinic at University of Malaya. Data were collected from 31 patients using a self-administered questionnaire which consisted of questions pertaining to their oral health behaviours and experiences on receiving preventive dental care (PDC). For patients who were unable to answer due to existing health conditions, parents or primary caregivers were approached as proxy. Descriptive analysis was conducted and reported based on percentages to identify the oral health behaviour and PDC of the individuals. Majority brushed their teeth at least once a day (84%), used fluoridated toothpaste (87%) and oral hygiene aids (58%). However, almost half of them (48%) required assistance from parents or caregivers during tooth brushing and consumed sugary snacks in between meals (58%). About 80% had received PDC where the type of care received was mainly oral hygiene advice (77%). Slightly more than 80% preferred the one-to-one demonstration method during PDC. Most gave positive evaluation on their PDC experience especially on items pertaining to the dentist’s attitude. Whilst most of the SHCN patients in this study had positive perception on the PDC that they received and practised good brushing behaviour, their dietary habits need to be improved. Thus, regular preventive dental visit amongst SHCN patients is important for appropriate and comprehensive dental care in maintaining oral health..

9.
Aust Dent J ; 62(2): 186-191, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27813093

ABSTRACT

BACKGROUND: Dentine hypersensitivity is a common problem attributed by patent dentinal tubules. Ingredients incorporated in toothpastes aim to occlude patent dentinal tubules to minimize the dentine hypersensitivity. However, frequent consumption of acidic soft drinks may reverse the dentinal tubules' occlusion. In this in vitro study, the efficacy of dentinal tubules occluded by commercially available toothpastes to withstand different durations of an acidic soft drink challenge was investigated. METHODS: One hundred and twenty dentine discs were divided into three groups. The discs from each group were brushed with toothpaste containing bioactive glass, arginine and control toothpaste. Each group was then divided into four subgroups and exposed to acidic soft drink over four different time durations. RESULTS: The scoring and the percentage of occluded dentinal tubules by Novamin-containing toothpaste was significantly better compared with arginine or the control toothpaste. Acidic soft drink challenge reduced the extent of dentinal tubules occlusion along with time. Dentinal tubules occluded by Novamin-containing toothpaste withstand the acidic challenge comparatively for a longer period. CONCLUSIONS: The findings demonstrated that occlusion of dentinal tubules is more efficient by the bioactive glass-containing toothpaste and thus may contribute to its better resistance to acidic soft drink challenge.


Subject(s)
Carbonated Beverages , Dentin Desensitizing Agents/pharmacology , Dentin Sensitivity/drug therapy , Tooth/ultrastructure , Toothpastes/pharmacology , Acids , Arginine/pharmacology , Dentin , Dentin Permeability/drug effects , Glass , Humans , Microscopy, Electron, Scanning , Time Factors , Tooth/drug effects
10.
Int J Impot Res ; 28(3): 110-3, 2016 May.
Article in English | MEDLINE | ID: mdl-27030054

ABSTRACT

Thiazolidinediones (TZDs) improve vascular endothelial dysfunction through non-genomic effects of peroxisomal proliferator-activated receptor γ. This study investigated the acute effect of one of the TZD, rosiglitazone, on endothelium-dependent relaxation response of corpus cavernosum (CC) in hypercholesterolemic rabbits. New Zealand rabbits were divided into two groups randomly as control and cholesterol groups. Hypercholesterolemia was induced by feeding rabbits with 2% cholesterol diet (w/w) for 6 weeks. Endothelium-dependent and -independent relaxation response of CC were evaluated in the presence of rosiglitazone by organ bath studies with cumulative doses of acetylcholine (Ach) and sodium nitroprusside (SNP). Maximal relaxation (Emax) response to Ach significantly decreased owing to hypercholesterolemia in CC tissues. However, in vitro incubation of rosiglitazone with different concentrations (0.1, 1 and 10 µm) did not improve the Ach-dependent Emax responses in hypercholesterolemic rabbit CC. Surprisingly, rosiglitazone caused a significant decrease in Ach-dependent relaxation in healthy CC. Emax responses to SNP did not differ in the presence of rosiglitazone in both the control and hypercholesterolemic groups. Rosiglitazone does not improve hypercholesterolemia-induced endothelial dysfunction in CC tissues while it dose-dependently impairs endothelium-dependent relaxation in healthy CC tissue.


Subject(s)
Hypercholesterolemia/physiopathology , Hypoglycemic Agents/pharmacology , Muscle Relaxation/drug effects , PPAR gamma/antagonists & inhibitors , Penis/drug effects , Thiazolidinediones/pharmacology , Acetylcholine/pharmacology , Animals , Body Weight/drug effects , Cholesterol, Dietary , Endothelium, Vascular/drug effects , Male , Muscle, Smooth, Vascular/drug effects , Rabbits , Rosiglitazone , Vasodilator Agents/pharmacology
11.
Bratisl Lek Listy ; 116(3): 177-83, 2015.
Article in English | MEDLINE | ID: mdl-25869567

ABSTRACT

BACKGROUND: We aimed to investigate the therapeutic effectiveness of leflunomide (LEF) in lung injury after an aspiration of unknown pathophysiology. MATERIAL AND METHODS: Forty-two healthy Sprague Dawley rats were anesthetized and allocated to six experimental groups: saline (S) aspirated, S+LEF, hydrochloric acid (HCl) aspirated, HCl+LEF, formula aspirated (FOR), and FOR+LEF. The treatment groups (S+LEF, HCl+LEF, and FOR+LEF) received 20 mg/kg/day intraperitoneal (i.p.) injection of LEF for seven days. At the end of the seven days, blood and tissue samples were taken from the rats for histopathological, biochemical, and immunohistochemical examination. RESULTS: There was a significant increase in serum levels of YKL-40, a chitinase-like protein, in the HCl group after the aspiration (p<0.01). The increase in serum YKL-40 levels decreased significantly with LEF treatment (p<0.01). There was no significant difference in serum YKL-40 levels in the FOR group compared to the control group at pretreatment and in the FOR+LEF group at post-treatment. There was a significant increase in serum thiobarbituric acid-reactive species (TBARS) values in the HCl and FOR groups compared to the control group (p=0.001 and p<0.01, respectively). In both treatment groups, the serum TBARS values significantly decreased after treatment with LEF (p=0.001 and p<0.05, respectively). There was a significant improvement in the histopathological scores, which deteriorated after the aspiration, and in the number of inducible nitric oxide synthase (iNOS)-positive cells after treatment with LEF.


Subject(s)
Acute Lung Injury/prevention & control , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antioxidants/pharmacology , Isoxazoles/pharmacology , Respiratory Aspiration/complications , Acute Lung Injury/etiology , Animals , Leflunomide , Lung/pathology , Nitric Oxide Synthase Type II/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley
12.
Bratisl Lek Listy ; 116(3): 196-202, 2015.
Article in English | MEDLINE | ID: mdl-25869570

ABSTRACT

BACKGROUND AND OBJECTIVES: Despite advances in treatment modalities, the discovery of optimal medical therapies still remains a necessity in the management of pulmonary fibrosis. MATERIAL AND METHODS: The experiments were performed in 35 adult Sprague Dawley rats, randomly allotted into one of five groups (n=7). The control group was treated with 1 ml/kg, 0.9 % saline; the BLM group was given a single dose of BLM (2.5 U/kg); the BLM+ER group was treated with ER (10 mg/kg/day po) for 14 days after BLM administration; the BLM+SMT group was treated with i.p injections of SMT (20 mg/kg/ day) for 14 days after BLM administration; the BLM+ER+SMT group was treated with ER and SMT for 14 days after BLM administration. At the end of day 14, the results of histopathological, biochemical, and immunohistochemical investigations were analyzed. RESULTS: Serum TNF-α, nitrate/nitrite, and TBARS levels significantly increased in BLM group compared to control group (p < 0.001, p < 0.001 and p < 0.05 respectively). Lung tissue content of IL-6 was found to be lower in BLM+ER, BLM+SMT and BLM+ER+SMT groups compared to BLM group by immunhistochemical examinations (p < 0.01, p < 0.01 and p < 0.001, respectively). Similarly, the TNF-α reactions (p < 0.01 for each group) and NF-kB expressions were shown to be significantly different among the study groups (p < 0.05, p < 0.05 and p < 0.001, respectively). CONCLUSION: Based on our study, ER and SMT attenuate BLM-induced pulmonary fibrosis; the combination of two agents has a greater protective efficacy against fibrosis than one alone, reducing the inflammatory markers (Tab. 2, Fig. 2, Ref. 31).


Subject(s)
Acute Lung Injury/drug therapy , Enzyme Inhibitors/administration & dosage , Expectorants/administration & dosage , Isothiuronium/analogs & derivatives , Nitric Oxide Synthase Type II/antagonists & inhibitors , Pulmonary Fibrosis/drug therapy , Thioglycolates/administration & dosage , Thiophenes/administration & dosage , Acute Lung Injury/chemically induced , Acute Lung Injury/pathology , Animals , Bleomycin , Drug Therapy, Combination , Injections, Intraperitoneal , Isothiuronium/administration & dosage , Lung/pathology , Male , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/pathology , Random Allocation , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/metabolism
13.
Int J Dent Hyg ; 13(3): 199-205, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25040653

ABSTRACT

OBJECTIVE: To assess Malaysian dental therapists' perceptions of their job satisfaction and future roles. METHODS: A nationwide postal survey involving all Malaysian dental therapists who met the inclusion criteria (n = 1726). RESULTS: The response rate was 76.8%. All respondents were females; mean age 35.4 years (SD = 8.4). Majority were married (85.5%) and more than one-half had a working experience of <10 years (56.1%). Majority worked in community dental service (94.3%) and in urban areas (61.7%). Overall, they were highly satisfied with most aspects of their career. However, they were least satisfied with administrative workload (58.1%), career advancement opportunities (51.9%) and remuneration package; specifically income (45.2%), allowances (45.2%) and non-commensurate between pay and performance (44.0%). Majority perceived their role as very important in routine clinical tasks such as examination and diagnosis, preventive treatment, extraction of deciduous teeth and oral health promotion. However, fewer than one-half consider complex treatment such as placement of preformed crowns on deciduous teeth (37.1%) and extraction of permanent teeth (37.2%) as very important tasks. CONCLUSION: Majority expressed high career satisfaction with most aspects of their employment but expressed low satisfaction in remuneration, lack of career advancement opportunities and administrative tasks. We conclude that most Malaysian dental therapists have positive perceptions of their current roles but do not favour wider expansion of their roles. These findings imply that there was a need to develop a more attractive career pathway for therapists to ensure sustainability of effective primary oral healthcare delivery system for Malaysia's children.


Subject(s)
Attitude of Health Personnel , Dental Auxiliaries/psychology , Job Satisfaction , Adult , Career Mobility , Community Health Services , Cross-Sectional Studies , Delegation, Professional , Dental Auxiliaries/trends , Dental Care , Female , Health Promotion , Humans , Income , Interprofessional Relations , Malaysia , Marital Status , Middle Aged , Oral Health , Primary Health Care , Professional-Patient Relations , Salaries and Fringe Benefits , Urban Health Services , Workload , Workplace
14.
Br J Pharmacol ; 172(6): 1434-54, 2015 Mar.
Article in English | MEDLINE | ID: mdl-24661203

ABSTRACT

The ability to get and keep an erection is important to men for several reasons and the inability is known as erectile dysfunction (ED). ED has started to be accepted as an early indicator of systemic endothelial dysfunction and subsequently of cardiovascular diseases. The role of NO in endothelial relaxation and erectile function is well accepted. The discovery of NO as a small signalling gasotransmitter led to the investigation of the role of other endogenously derived gases, carbon monoxide (CO) and hydrogen sulphide (H2 S) in physiological and pathophysiological conditions. The role of NO and CO in sexual function and dysfunction has been investigated more extensively and, recently, the involvement of H2 S in erectile function has also been confirmed. In this review, we focus on the role of these three sister gasotransmitters in the physiology, pharmacology and pathophysiology of sexual function in man, specifically erectile function. We have also reviewed the role of soluble guanylyl cyclase/cGMP pathway as a common target of these gasotransmitters. Several studies have proposed alternative therapies targeting different mechanisms in addition to PDE-5 inhibition for ED treatment, since some patients do not respond to these drugs. This review highlights complementary and possible coordinated roles for these mediators and treatments targeting these gasotransmitters in erectile function/ED.


Subject(s)
Carbon Monoxide/metabolism , Erectile Dysfunction/physiopathology , Hydrogen Sulfide/metabolism , Nitric Oxide/metabolism , Animals , Cyclic GMP/metabolism , Drug Design , Erectile Dysfunction/drug therapy , Guanylate Cyclase/metabolism , Humans , Male , Molecular Targeted Therapy , Penile Erection/drug effects , Penile Erection/physiology , Receptors, Cytoplasmic and Nuclear/metabolism , Signal Transduction/physiology , Soluble Guanylyl Cyclase
15.
Bratisl Lek Listy ; 115(9): 538-43, 2014.
Article in English | MEDLINE | ID: mdl-25318911

ABSTRACT

BACKGROUND: Cardiac contusion is an important cause of mortality after blunt chest trauma (BCT). The aim of this study was to investigate the therapeutic efficacy of the usage of aminoguanidine (AG), in myocardial damage occurring after BCT, alone and in combination with methylprednisolone (MP). METHODS: Thirty-five female Wistar albino rats were randomly assigned to five groups (n = 7) including: sham controls (S); only cardiac contusion (CONT); cardiac contusion treated with methylprednisolone (CONT+MP); cardiac contusion treated with aminoguanidine (CONT+AG); and cardiac contusion treated with methylprednisolone and aminoguanidine (CONT+MP+AG). Seven days following the treatments, heart and serum specimens were evaluated histopathologically, immunohistochemically, and biochemically in all groups. RESULTS: Serum AOPP and Tn-I levels increased significantly after cardiac contusions. Haemorrhage, tissue degeneration, and necrosis development was evident following contusions. Increased iNOS expression in myocardial tissue was significantly decreased in the CONT+AG+MP group compared to CONT+AG and CONT+MP groups (p = 0.001 and p = 0.011, respectively). The combined treatment of AG and MP increased Bcl-2 expression significantly after contusions compared to the other treatment groups. CONCLUSIONS: Combined usage of AG, a selective iNOS inhibitor, with MP, in cardiac contusions, showed a more powerful cardioprotective effect by increasing Bcl-2 expression and reducing iNOS expression (Tab. 3, Fig. 4, Ref. 33).


Subject(s)
Contusions/drug therapy , Enzyme Inhibitors/therapeutic use , Glucocorticoids/therapeutic use , Guanidines/therapeutic use , Heart Injuries/drug therapy , Methylprednisolone/therapeutic use , Animals , Drug Therapy, Combination , Female , Nitric Oxide Synthase Type II/antagonists & inhibitors , Rats, Wistar
16.
Hum Exp Toxicol ; 33(9): 980-90, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24505046

ABSTRACT

OBJECTIVE: The purpose of this study was to evaluate the patients with acute amitriptyline poisoning and investigate predictive factors for the development of life-threatening complications. METHODS: Demographics, clinical, laboratory, and electrocardiographic (ECG) findings of 250 patients were evaluated retrospectively. Predictive parameters for the development of serious complications were studied. RESULTS: Median age of patients was 14.6 years, of which, 70% of patients were female and 66% were in pediatric age group. The most common pathological clinical finding and laboratory abnormality were alteration of consciousness and hyponatremia. The rate of convulsive seizure, arrhythmia, and respiratory depression were 17 (6.8%), 16 (6.4%), and 11 (4.4%), respectively. These complications were more seen in pediatric patients than adults (15.8% and 1.2%). The incidence of hyponatremia was more in pediatric patients and severe poisoning groups (38.8 and 53.4%, respectively). The levels of amitriptyline and nortriptyline were significantly higher in the group with complications than the group without complications (p < 0.05). All adult patients were discharged with good prognosis. In pediatric age group, one patient was discharged with severe neurological sequelae and one patient died. QRS duration >100 ms, long corrected QT duration interval, and low Glasgow Coma Score (GCS) at admission were identified as independent risk factors for the development of life-threatening complications (odds ratio: 69.4, 1.9, and 1383, respectively; p < 0.05). CONCLUSION: Amitriptyline poisoning may be associated with life-threatening complications, especially in pediatric age group and in patients with hyponatremia. Low GCS, presence of hyponatremia, high serum drug levels, and pathological ECG findings on admission may be helpful in predicting the development of complications and poor prognosis.


Subject(s)
Amitriptyline/poisoning , Antidepressive Agents, Tricyclic/poisoning , Drug Overdose/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Amitriptyline/administration & dosage , Amitriptyline/blood , Amitriptyline/pharmacokinetics , Antidepressive Agents, Tricyclic/administration & dosage , Antidepressive Agents, Tricyclic/blood , Antidepressive Agents, Tricyclic/pharmacokinetics , Area Under Curve , Child , Child, Preschool , Drug Overdose/mortality , Female , Humans , Infant , Male , Middle Aged , Retrospective Studies , Young Adult
17.
Int J Dent Hyg ; 11(4): 280-6, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23802751

ABSTRACT

UNLABELLED: To describe the perceptions of senior dental officers (SDOs) on the roles of dental therapists (DTs) and their education needs in Malaysia. METHODS: A cross-sectional survey was conducted using a self-administered postal questionnaire targeting all 112 SDOs in the Malaysian Ministry of Health. The SDOs were asked about their perceptions of DT's roles in relation to clinical tasks, oral health promotion, administration and the dental team and their perceptions of DT's future education needs. Data were analysed using spss software, version 17 (SPSS Inc., Chicago, IL, USA). RESULTS: The response rate was 60%. A majority of SDOs were women (68%) with a mean age of 44.9 (SD: 8.04). Generally, the majority of SDOs perceived the current roles of DT in non-complex clinical tasks such as examination and diagnosis, preventive treatment, extraction of deciduous teeth and oral health promotion as very important. Fewer than half of SDOs perceived DT's role in the extraction of permanent teeth as important. Most SDOs perceived the need to train DT in 'scaling and polishing for adults' (80.5%), 'delivering inferior alveolar nerve block' (57.3%) and 'pulp therapy' (59.2%). They also had positive perceptions of providing education for DT up to degree level (70.8%). CONCLUSION: This study suggests that Malaysian SDOs have positive perceptions of the current roles of DT and of the expansion of some of their clinical tasks to include broader client groups through further training and education. These findings indicate a need to revise the current curriculum and legislation pertaining to DT's education and scope of practice in Malaysia.


Subject(s)
Attitude of Health Personnel , Dental Auxiliaries/education , Dentists/psychology , Health Services Needs and Demand , Adult , Child , Child, Preschool , Clinical Competence , Cross-Sectional Studies , Delegation, Professional , Dental Auxiliaries/organization & administration , Dental Care/organization & administration , Dental Prophylaxis , Dental Restoration, Permanent , Dental Scaling , Female , Health Promotion , Humans , Malaysia , Male , Mandibular Nerve , Nerve Block , Oral Health , Patient Care Team/organization & administration , Physical Examination , Preventive Dentistry , Root Canal Therapy , Tooth Extraction
18.
Bratisl Lek Listy ; 114(5): 258-61, 2013.
Article in English | MEDLINE | ID: mdl-23611047

ABSTRACT

This study was performed to clarify the role of extracellular and intracellular Ca2+ on rho-kinase enzyme inhibition-induced relaxation in rabbit renal arteries. The response to rho-kinase inhibitor (Y-27632) was studied in isolated renal artery segments precontracted with phenylephrine in the presence of voltage-gated calcium channel blocker nifedipine and in the absence of intracellular or extracellular Ca2+. Cumulative addition of rho-kinase inhibitor Y-27632 (10-8-10-5 M) produced a concentration-dependent relaxation in renal artery rings precontracted with phenylephrine. Preincubation with nifedipine (1µM) resulted in a significant increase in relaxation response to rho-kinase inhibitor Y-27632 compared with preincubation with DMSO; the solvent of nifedipine. The maximal relaxation to Y-27632 in renal arteries precontracted with phenylephrine was significantly increased in the Ca-free Krebs containing 100 µmol/l ethylene glycol tetraacetic acid (EGTA) but after depletion of intracellular stores with 20 mmol/l caffeine and 1mmol/l EGTA in Ca2+ free Krebs there was no significant difference between the relaxation to Y-27632 from control response in 2.5 mmol/l Ca2+ Krebs in the renal artery. These results suggest the involvement of extracellular Ca and L-type voltage-operated Ca2+ channels in phenylephrine-induced rho-kinase activation (Fig. 3, Ref. 20).


Subject(s)
Amides/pharmacology , Calcium/physiology , Enzyme Inhibitors/pharmacology , Pyridines/pharmacology , Renal Artery/drug effects , Renal Artery/physiology , rho-Associated Kinases/antagonists & inhibitors , Animals , Male , Muscle Relaxation/drug effects , Muscle, Smooth, Vascular/drug effects , Rabbits
19.
Hum Exp Toxicol ; 32(1): 53-61, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23023024

ABSTRACT

Our aim in this study is to examine the effects of α-tocopherol (AT) on rats with aspiration pneumonitis induced with bile acids (BAs). The animals were divided in to four groups, namely saline group (n = 7), saline + AT group (n = 7), BA group (n = 7), and BA + AT group (n = 7). Saline and BA groups aspirated intratracheally with 1 ml/kg saline and 1 ml/kg bile acids, respectively. AT was given at 20 mg/kg/day dosage for 7 days to the groups. AT group was given 20 mg/kg/day AT for 7 days. Malondialdehyde (MDA), Clara cell protein 16 (CC-16), catalase (CAT), superoxide dismutase (SOD), as well as peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar histiocytes, and necrosis were evaluated. The CAT activity of the BA group was significantly lower than the saline group. In the BA + AT group, there was a significant increase in SOD and CAT activities when compared with that of the BA group. The CC-16 and MDA contents in the BA group were significantly higher than in the saline group. The CC-16 and MDA levels of the BA + AT group were significantly lower than BA group. Histopathologic changes were seen in BA group, and there was a significant decrease in the BA + AT group. In conclusion, AT might be beneficial in the treatment of aspiration pneumonitis induced by BAs because AT decreased oxidative damage and resulted in a decrease in CC-16 levels.


Subject(s)
Antioxidants/therapeutic use , Pneumonia, Aspiration/drug therapy , alpha-Tocopherol/therapeutic use , Animals , Antioxidants/pharmacology , Bile Acids and Salts , Female , Malondialdehyde/blood , Oxidative Stress/drug effects , Pneumonia, Aspiration/blood , Pneumonia, Aspiration/chemically induced , Pneumonia, Aspiration/pathology , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/blood , Uteroglobin/blood , alpha-Tocopherol/pharmacology
20.
Adv Exp Med Biol ; 696: 581-8, 2011.
Article in English | MEDLINE | ID: mdl-21431599

ABSTRACT

Even with today's advances in technology, the processes involved in medical research continue to be both time consuming and labor intensive. We have built an experimental integrated tool to convert the textual information available to the researchers into a concept map using the Web Ontology Language as an intermediate source of information. This tool is based on building semantic models using concept maps. The labor-intensive sequence of processes involved in medical research is suitably replaced by using this tool built by a suitable integration of concept maps and Web Ontology Language. We analyzed this tool by considering the example of linking vitamin D deficiency with prostate cancer. This tool is intended to provide a faster solution in building relations and concepts based on the existing facts.


Subject(s)
Biomedical Research/statistics & numerical data , Efficiency , Humans , Information Storage and Retrieval , Internet , Male , Medical Informatics , Natural Language Processing , Prostatic Neoplasms/etiology , Vitamin D Deficiency/complications
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