The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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A Comparative Study between Thoracic Epidural Anesthesia and General Anesthesia for Patients Who Underwent Modified Radical Mastectomy with Axillary Lymph Node Dissection in De La Salle University Medical Center
BACKGROUND: To compare the recovery time and other related clinical outcomes among patients who underwent Modified Radical Mastectomy (MRM) with axillary lymph node dissection under Continuous Thoracic Epidural Anesthesia (CTEA) and General Endotracheal Tube Anesthesia (GETA).METHODS: A retrospective cross-sectional study with 70 patients who underwent MRM in De La Salle University Medical Centre (DLSUMC), categorized into GETA and CTEA group consisted of 35 patients each. Per oral premedications 15 mg midazolam, 40 mg omeprazole and 10 mg metoclopramide were given 1 hour prior to surgery. Intra-operative hypotension/hypertension, tachycardia/bradycardia status, length of Post-Anesthesia Care Unit (PACU) and hospital stay, and Post Operative Nausa and Vomiting (PONV) incidence were compared between 2 groups.RESULTS: Preoperatively, there were no significant differences between the groups in terms of subject characteristic. Intra-operatively, hypertension was more frequent in GETA group (28.6% vs. 0%), while hypotension was more frequent in the CTEA (80% vs. 57.1%). Tachycardia was more frequent in GETA group (46.6% vs. 0%), meanwhile bradycardia was more frequent in CTEA (40% vs. 17.1%). Postoperatively, the GETA group had shorter PACU stay than CTEA (230 mins vs. 267 mins), but CTEA group had a shorter time of hospital stay compared to GETA (58.1 hours vs. 67.7 hours). The incidence of PONV were comparable among the two groups (GETA 46.7% vs. CTEA 50%). Statistically there were no significant differences between the two groups in all of the above characteristics.CONCLUSION: CTEA technique has no effect on inducing hypertension and tachycardia, but hypotension and bradycardia may occur. Although GETA gives shorter PACU duration, CTEA gives shorter hospital stay. This gave impression that CTEA is an effective alternative technique to GETA in patients who underwent MRM with axillary dissection.KEYWORDS: modified radical mastectomy, general anesthesia, epidural anesthesi
Heterogeneous Stem Cells in Skin Homeostatis and Wound Repair
BACKGROUND: The skin protects mammals from insults, infection and dehydration and enables thermoregulation and sensory perception. Various skin-resident cells carry out these diverse functions. Constant turnover of cells and healing upon injury necessitate multiple reservoirs of stem cells. The skin is a complex organ harboring several distinct populations of stem cells and a rich array of cell types. Advances in genetic and imaging tools have brought new findings about the lineage relationships between skin stem cells and their progeny. Such knowledge may offer novel avenues for therapeutics and regenerative medicine.CONTENT: In the past years, our view of the mechanisms that govern skin homeostasis and regeneration have markedly changed. New populations of stem cells have been identified that behave spatio-temporally differently in healthy tissues and in situations of damage, indicating that a great level of stem cell heterogeneity is present in the skin. There are believed to be distinct populations of stem cells in different locations. The lineages that they feed are normally constrained by signals from their local environment, but they can give rise to all epidermal lineages in response to appropriate stimuli. Given the richness of structures such as blood vessels, subcutaneous fat, innervation and the accumulation of fibroblasts under the upper parts of the rete ridges (in the case of human skin), it is reasonable to speculate that the microenvironment might be essential for interfollicular epidermal homeostasis. The bloodstream is probably the main source of long-range signals reaching the skin, and cues provided by the vascular niche might be essential for skin homeostasis.SUMMARY: A key function of the interfollicular epidermis is to act as a protective interface between the body and the external environment, and it contains several architectural elements that enable it to fulfill this function. All elements of the epidermis play active roles in regulating skin function, which might not have been anticipated from their role in maintaining skin integrity. Skin cell research benefits from the integration of complementary technologies and disciplines. How skin function is regulated and how it may be possible to intervene to treat a variety of skin conditions. Ultimately also impairing the maintenance of self-renewing satellite cells. Therefore, only anti-aging strategies taking both factors, the stem cell niche and the stem cells per se, into consideration may ultimately be successful.KEYWORDS: epidermis, hair follicle, fibroblast, skin stem cells, homeostasis, regeneratio
Macerated-Pineapple Core Crude Extract-derived Bromelain Has Low Cytotoxic Effect in NIH-3T3 Fibroblast
BACKGROUND: Bromelain is a sulfhydryl proteolytic enzyme that can hydrolyze protein, protease or peptide. Bromelain can be found in pineapple stem, fruit and core. Bromelain is composed of 212 amino acid residues with cysteine-25 forming a polypeptide chain that can hydrolyze peptide bonds by H2O. In medicine, bromelain has been developed as antibiotic, cancer drug, anti-inflammatory agent and immunomodulator. In dentistry, bromelain has potential to reduce plaque formation on the teeth and to irrigate root canal.METHODS: Pineapple core was dried for 3 days to get simplicia. Then simplicia was extracted with water solvent for 24 hours. After that, the macerated-pineapple core crude extract-derived bromelain (PCB) was separated by Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) followed by Coomassie Brilliant Blue (CBB) staining to ensure the presence of bromelain. In cytotoxic test, NIH-3T3 fibroblast cultures were treated with extracts in various concentrations to for 24 or 48 hours. Number of fibroblasts was calculated using 3-(4,5-dimethylthiazol-2- yl)-2,5-Diphenyltetrazolium bromide (MTT) assay.RESULTS: Pineapple core extraction using maceration method produced relative high yield (concentration: 1.5424 g/mL) of bromelain, which was confirmed by CBB staining results with the molecular weight of 33 kDa. Based on cytotoxic test results of PCB on NIH-3T3 fibroblasts, 24-hours-incubation LD50 was 95.7 g/L, while 48-hours-incubation LD50 was 51.1 g/L.CONCLUSION: PCB has low cytotoxic effect in NIH-3T3 fibroblasts.KEYWORDS: bromelain, pineapple, extract, cytotoxic, MT
Free Radical Scavenging and Alpha/Beta-glucosidases Inhibitory Activities of Rambutan (Nephelium lappaceum L.) Peel Extract
BACKGROUND: Diabetes mellitus (DM) is associated with oxidative reaction and hyperglycemic condition. Human body has an antioxidant defense system toward free radical, but overproduction of free radical causing imbalance condition between the free radical and the antioxidant defense in the body that lead to several diseases, including DM. Glucosidase is an enzyme that hydrolize carbohydrates causing increase of blood glucose level, so by inhibiting this enzyme blood glucose level in plasma could be effectively decreased. Rambutan (Nephelium lappaceum L.) peel has been reported to have many potential roles, such as antioxidant and anti-glycemia. Therefore our current study was conducted to evaluate possible effectivity of Rambutan peel to scavenge free radical and to inhibit α- and β-glucosidases. METHODS:Rambutan peel extraction (RPE) was performed based on maceration method. Geraniin was used as control. For antioxidant study, 2,2-diphenyl-1- picrylhydrazyl (DPPH) free radical scavenging test was performed. For glucosidase inhibitory activity study, α- and β-glucosidases inhibitory activity tests were performed. Results were analyzed for median of Inhibitory Concentration (IC50).RESULTS: The scavenging activity of RPE was comparable with Geraniin. Meanwhile, the α-glucosidase inhibitory activity of RPE was higher than the one of Geraniin. The α-glucosidase-inhibitory-activity IC50 of RPE and Geraniin were 0.106±0.080 μg/ml and 16.12±0.29 μg/ml, respectively. The β-glucosidase inhibitory activity of RPE was also higher than the one of Geraniin. The β-glucosidase-inhibitory-activity IC50 of RPE and Geraniin were 7.02±0.99 μg/ml and 19.81±0.66 μg/ml, respectively.CONCLUSION: Since RPE showed comparable free radical scavenging activity with Geraniin and higher α- and β-glucosidases inhibitory activities than Geraniin, RPE could be suggested as a promising antioxidant and antiglycemic agent. KEYWORDS: Nephelium lappaceum L., rambutan, hypoglycemic, antioxidant, free radical, diabetes mellitus, glucosidase, DPP
Dynamics of Interleukin-10 Levels in Chronic Rhinosinusitis with/without Allergy
BACKGROUND: Rhinosinusitis occurs when the lining of the nasal and sinuses gets inflamed, infected or irritated, become swollen, and create extra mucus, the swollen lining may also interfere with drainage of mucus. Chronic rhinosinusitis (CRS) is a more persistent problem that requires a specific treatment approach. Aim of this study was to determine changes in interleukin (IL)-10 as an anti-inflammatory cytokines in allergic and non-allergic CRS at Makassar. METHODS: A prospective cohort study was designed to assess the level of IL-10 for three times during two weeks of therapy. Medication of Cefadroxil 500 mg 2x1, Pseudoephedrine 30 mg 2x1, Terfenadine 40 mg 2x1 and Methylprednisolone 4 mg 3x1, was conducted during two weeks for 13 subjects in allergic CRS group and 12 subjects in non-allergic CRS group. Results were statistically analyzed with student t-test and paired t-test.RESULTS: The changes in levels of IL-10 in allergic CRS group were increased, but not significant (5.293 to 5.769, p=0.058), and in non-allergic CRS group were decreased, but not significant (6.125 to 5.475, p=0.103). CONCLUSION: The serum levels of IL-10 were not significant increased in allergic CRS group and not significant decreased in non-allergic CRS group. KEYWORDS: interleukin-10, chronic rhinosinusitis, allergy, cefadroxil, pseudoephedrine, terfenadine, methylprednisolon
The Efficacy, Safety and Tolerability of Retapamulin as a Treatment Option for Impetigo and Other Uncomplicated Superficial Skin Infections: A Meta-analysis
BACKGROUND: The treatment of impetigo, secondarily infected dermatitis and infected traumatic lesions continue to develop as new generations of drugs are being formulated. Bacteria causing impetigo show growing resistance rates for commonly used antibiotics. Retapamulin being a new drug has been recently approved as topical antibiotic in children and adult. This study aimed to ascertain the efficacy, safety and tolerability of retapamulin as the treatment option for impetigo and other uncomplicated superficial skin infections.METHODS: A search for studies published from 2006-2014 was done in Pubmed, EBSCO, OVID, Science Direct, and Cochrane using the search strategy. The search was limited to studies conducted in human subjects and published in the English language. Randomized controlled trials evaluating the efficacy, safety and tolerability of retapamulin as treatment for impetigo and other uncomplicated superficial skin infections in children and adult were included and extracted independently and the qualities of the studies were appraised using critical appraisal tools. Data analysis was conducted by using RevMan 5.RESULTS: This study has high heterogeneity and found Retapamulin has no statistically significant difference in the clinical success after seven days and follow up among per-protocol-patients, bacteriogical confirmed patients and intention-to-treat patients with impetigo and other secondary infected traumatic lesions compared to other regimens. However, Retapamulin has beneficial effect in the clinical success, well tolerated and safe for children and adults.CONCLUSION: Retapamulin is comparably effective and safe as a treatment option for impetigo and other uncomplicated superficial skin infections.KEYWORDS: efficacy, safety, tolerability, retapamulin, impetigo, meta-analysi
Brucea javanica Leaf Extract Induced Apoptosis in Human Oral Squamous Cell Carcinoma (HSC2) Cells by Attenuation of Mitochondrial Membrane Permeability
BACKGROUND: Brucea javanica extract has been reported to have anti-proliferative and cell death induction activities. B. javanica extract was reported to induce apoptosis through caspase cascade. Most of investigated B. javanica extracts were derived from seeds and fruits, or commercially available oil emulsion. Therefore we conducted a study on B. javanica leaf extract (BJLE) in oral cancer cells.METHODS: B. javanica leaves were collected, identified, minced, dried, extracted with distilled ethanol at room temperature for 24 hours, filtered and evaporated. Resulted BJLE was stored at 4°C. Human oral squamous cell carcinoma (HSC)-2 cells were fasted for 12 hours and treated with BJLE in various concentrations for 24 hours. Cells were then quantified with 3-(4,5-dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium bromide (MTT) assay, demonstrated with 4',6'-diamidino-2-phenylindole (DAPI) staining. To find out mitochondrial membrane permeability (MMP), mitochondrial membrane potential (ΔΨM) was analyzed.RESULTS: BJLE reduced percentage of viable HSC-2 cells in a concentration dependent manner. BJLE induced apoptosis in HSC-2 cells. With treatment of 50 μg/ml BJLE, fragmented nuclei were seen. ΔΨM of HSC-2 cells treated with 50 μg/ml BJLE were shifted to the left, meaning that BJLE induced reduction of ΔΨM and attenuation of MMP.CONCLUSION: Our results suggested that BJLE could induce apoptosis by attenuating MMP.KEYWORDS: Brucea javanica, leaf, apoptosis, HSC-2, MTT, DAPI, mitochondria, permeabilit
The Pharmacogenetics of Cytochrome P450 2C19 Enzymes - Effects on Clopidogrel and Proton Pump Inhibitors
BACKGROUND: Cytochrome P450 (CYP) enzymes play important roles in human, including drug metabolism. CYP2 is the largest family of human CYP, with its sequence comprising almost one third of all CYP sequences, and responsible for the metabolism of approximately 2% of clinically administrated drugs. One of the most important enzymes in this family is the CYP2C19 enzyme. The CYP2C19 gene is polymorphic, and the variation is common especially in the Asian population.CONTENT: CYP2C19 is responsible for the metabolism of various drugs, including proton pump inhibitors (PPIs) such as omeprazole and lansoprazole, psychotropic drugs including diazepam and imipramine, anticonvulsants such as phenobarbital and mephenytoin. and the recently most studied the anti-platelet drug, clopidogrel, and many others. Drugs metabolized predominantly by this enzyme like clopidogrel and PPIs might be much affected by the genotype status of CYP2C19. Clopidogrel is a pro-drug requiring a group of enzymes to convert to its active form, particularly the CYP2C19. PPIs are metabolized to its inactive metabolites mainly by CYP2C19 in the liver. Some PPIs are inhibitor of CYP2C19 enzymes, and interaction of PPIs and clopidogrel has been widely studied.SUMMARY: The association of CYP2C19 genotypes with the plasma level of active clopidogrel and platelet reactivity in individual taking this drug is well-established. Although conflicting results still exist for the association of CYP2C19 genotypes to the clinical outcomes of clopidogrel therapy, this effect seems to be consistent in patients receiving clopidogrel for coronary stents. Due to the interaction of certain PPIs and clopidogrel, the use of PPIs other than omeprazole is recommended, especially for patients taking dual anti platelet therapy of clopidogrel and aspirin.KEYWORDS: pharmacogenetics, CYP2C19, proton pump inhibitors, clopidogre
Potential Biomarkers for Diagnosis and Screening of Autism Spectrum Disorders
BACKGROUND: Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental condition, which is typically characterized by a triad of symptoms: impaired social communication, social reciprocity and repetitive stereotypic behavior. While the behavioral phenotype of ASD is well described, the search for reliable ‘autism biomarkers’ continues.CONTENT: Insulin growth factor (IGF) is essential for the myelination of developing fetal neurons; this is in addition to the well-known links between IGF, maternal inflammation, infection and autism supporting IGF as a potential marker. Combining IGF data with data regarding levels of the known markers, serotonin and anti-myelin basic protein, in order to calculate an autism index, could provide a new diagnostic method for at-risk neonates. Disruptions to multiple pathophysiological systems, including redox, folate, methylation, tryptophan metabolism, and mitochondrial metabolism, have been well documented in autistic patients. Maternal infection and inflammation have known links with autism. Autoimmunity has therefore been a well-studied area of autism research. The potential of using autoantibodies as novel biomarkers for autism, in addition to providing insights into the neurodevelopmental processes that lead to autism.SUMMARY: The six proposed causes of autism involve both metabolic and immunologic dysfunctions and include: increased oxidative stress; decreased methionine metabolism and trans-sulfuration: aberrant free and bound metal burden; gastrointestinal (GI) disturbances; immune/inflammation dysregulation; and autoimmune targeting. A newborn screening program for early-onset ASD should be capable of utilizing a combination of ASD-associated biomarkers representative of the six proposed causes of autism in order to identify newborns at risk. The biomarkers discussed in this article are useful to guide the selection, efficacy and sufficiency of biomedical interventions, which would likely include nutritional supplementation, dietary changes and specific medications for treating GI pathogens and reducing inflammation.KEYWORDS: ASD, autism, biomarkers, newborn screening, diagnosi
A Closer Look at Cardioprotective Function of HDL: Revise the HDL – Cholesterol Hypothesis?
BACKGROUND: The strong inverse association of plasma levels of high-density lipoprotein (HDL) cholesterol with coronary heart disease (CHD) found in human epidemiological studies led to the development of the ‘HDL cholesterol hypothesis’, which posits that intervention to raise HDL cholesterol will result in reduced risk of CHD. A number of recent developments have brought the potential protective role of HDL into question. Several clinical trials of agents that substantially raise HDL-C have been demonstrated to not reduce CHD event rates.CONTENT: For decades, HDL and HDL-cholesterol (HDL-C) levels were viewed as synonymous, and modulation of HDL-C levels by drug therapy held great promise for the prevention and treatment of cardiovascular disease. Nevertheless, recent failures of drugs that raise HDL-C to reduce cardiovascular risk and the now greater understanding of the complexity of HDL composition and biology have prompted researchers in the field to redefine HDL. As such, the focus of HDL has now started to shift away from a cholesterol-centric view toward HDL particle number, subclasses, and other alternative metrics of HDL. Many of the recently discovered functions of HDL are, in fact, not strictly conferred by its ability to promote cholesterol flux but by the other molecules it transports, including a diverse set of proteins, small RNAs, hormones, carotenoids, vitamins, and bioactive lipids. Based on HDL’s ability to interact with almost all cells and deliver fat-soluble cargo, HDL has the remarkable capacity to affect a wide variety of endocrine-like systems.SUMMARY: There is a significant need to redefine HDL and its benefit. HDL transports a diverse set of functional proteins, including many binding proteins. HDL transports and deliver vitamins, carotenoids, and other small molecules. Moreover, HDL transports hormones, steroids and bile acids, and can modulate multiple endocrine pathways. HDLs also transport and deliver microRNAs to recipient cells and control gene expression. Likewise, HDLs carry bioactive lipids and can activate signaling cascades and receptors that control endothelial apoptosis, migration, survival and activation. Many of HDL’s alternative noncholesterol cargo likely confer many of HDL’s alternative functions.KEYWORDS: HDL, ApoA1, RCT, ABCA1, ABCG1, miRNA, HDL lipidome, HDL proteom