Dodecanoic acid & palmitic acid disarms rifampicin resistance by putatively targeting mycobacterial efflux pump Rv1218c

Background & objectives: Drug-resistant tuberculosis (TB) jeopardizes the treatment process with poor outcomes. Efflux pumps (EPs) belonging to the ABC transporter family in Mycobacterium tuberculosis confer resistance to rifampicin (RMP) besides genetic mutations thus serving as a target for a potential adjunct therapeutic inhibitory molecule. Rv1218c is one such pump that was previously reported to be active in multidrug-resistant TB clinical isolates. Methods: In this study, the inhibition potential of Rv1218c-EP was tested on 8 molecules that were shortlisted by in silico methods. These molecules were subjected to the minimum inhibitory concentration (MIC) determination, checkerboard drug combination assay, ethidium bromide-DNA binding assay, and in vitro and ex vivo cytotoxicity assay. Results: Based on the outcome of the study, two molecules dodecanoic acid (DA) and palmitic acid (PA) were found to be potential enough to decrease the MIC of RMP by 8 to 1000 folds against multidrug-resistant clinical isolates and Rv1218c expressing recombinant Mycobacterium smegmatis. Interpretation & conclusions: These molecules were also found to reduce the time taken by RMP to kill these drug-resistant Mycobacteria to 48 h, unlike control isolates that survived more than 240 h of RMP exposure. The functional concentration of both molecules was non-toxic to the epithelial and blood mononuclear cells. With further comprehensive scientific validation, PA and DA could be recommended as adjunct therapeutic molecules with first-line anti-TB drugs to treat drug-resistant TB.

Effectiveness of chia (Salvia hispanica L.) as an adjuvant therapy for Type 2 diabetes mellitus: A systematic review and meta-analysis / The Health Sciences Journal

INTRODUCTION@#Salba-chia (Salvia hispanica L.) is a popular functional food containing high levels of protein, total dietary fiber, and is an excellent source of α-linolenic acid. Chia seeds significantly decreases weight, suppresses appetite, and has a potential benefit in the management of Type 2 diabetes mellitus (T2DM). This study aimed to determine the effectiveness of chia seeds as an adjuvant treatment for T2DM.@*METHODS@#Randomized controlled trials from 1990 onwards involving Type 2 diabetic patients given chia seed were included. PubMed, Cochrane, ClinicalKey, Google Scholar, and Hinari were searched systematically using MeSH terms “chia”, “Salvia hispanica”, “dietary supplement”, and “diabetes”. The quality of trials was assessed using the Cochrane Collaboration tool. Data on the study design, blinding status, characteristics of participants, medications taken by participants, chia seed intervention, comparator, duration of intake, and interval of assessment were extracted. The percent change of outcome from baseline was compared between the chia and control groups.@*RESULTS@#Four randomized trials with a total of 213 diabetic patients were enrolled in the treatment group using ground salba-chia or the control group using bran. The supplementation of chia resulted in a statistically significant decrease in fasting glucose (-2.90 mmol/L; 95% CI, -3.08, -2.72; p < 0.001), waist circumference (-2.49 cm; 95% CI -2.81, -2.17; p < 0.001), total cholesterol (-2.72 mmol/L; 95% CI -3.68, -1.74; p < 0.001), HDL (-3.69 mmol/L; 95% CI -3.95, -3.42; p < 0.001), LDL (-3.22 mmol/L; 95% CI -4.08, -2.36; p < 0.001); and an increase adiponectin levels (6.50 mg/L; 95% CI 6.25, 6.25; p < 0.001).@*CONCLUSION@#Intake of chia seeds resulted in a statistically significant decrease in fasting blood glucose, waist circumference, total cholesterol levels, HDL and LDL cholesterol levels, and increased adiponectin. Chia seeds are generally safer and have lesser side effects compared to the placebo. Chia is effective as adjunctive treatment for Type 2 diabetic patients.

Acupuncture as an adjunct to standard therapy for Pruritus in patients with Atopic Dermatitis: A patient- and assessor-blinded, randomized, placebo-controlled trial

Background@#Pruritus can impair quality of life in patients with atopic dermatitis. There is evidence that acupuncture reduces pruritus and disease severity, and improves quality of life. @*Objectives@#This study aimed to determine the efficacy of acupuncture in reducing pruritus intensity, disease severity, and medication use, and improving quality of life. @*Methods@#This was a patient- and assessor-blinded, randomized, placebo-controlled trial. Patients diagnosed with atopic dermatitis underwent twice-weekly acupuncture for 12 weeks, with an 8-week follow-up period. Baseline and weekly assessment were done using standard data collection forms and validated assessment tools. @*Results@#Thirty patients were randomized and 28 patients were eligible for the efficacy analysis. There were no significant differences in the baseline demographic and clinical characteristics between the True Acupuncture group (TA) (n=16) and Sham Acupuncture group (SA) (n=12). Both groups showed reduction in mean itch intensity (visual analogue scale, VAS) (p=0.024) but TA showed greater reduction (p=0.009) that was sustained after end of treatment. There was also a reduction in medication use in both groups. The comparable efficacy of SA to TA is attributed to similar peripheral receptive fields and stimulation of cutaneous C-fibers which depletes the neurotransmitters mediating pruritus and results in tachyphylaxis. Mild adverse events, such as petechiae and erythema, were noted in both groups and resolved spontaneously. @*Conclusion@#Acupuncture is a promising adjunct treatment in atopic dermatitis with significant reduction in pruritus, disease severity and medication use and a trend towards improved quality of life. Studies with larger sample size and comparison to acupuncture points farther from the true acupuncture points are recommended. @*Trial Registration@#Food and Drug Administration Philippine Health Research Registry ID PHRR171012-001696

Evolution of specific RNA aptamers via SELEX targeting recombinant human CD36 protein: A candidate therapeutic target in severe malaria

Objective: To isolate and characterize RNA aptamers that are specific to human CD36 protein using systematic evolution of ligands by exponential enrichment (SELEX) technology to identify candidates for adjunct therapy to reverse the binding of Plasmodium-infected erythrocytes. Methods: RNA aptamers were isolated using nitrocellulose membrane-based SELEX and binding analysis was screened using an electrophoretic mobility shift assay and enzyme-linked oligonucleotide assay. Results: Thirteen cycles of nitrocellulose membrane-based SELEX yielded three aptamers (RC60, RC25, RC04) exhibiting high binding against CD36 protein as shown on electrophoretic mobility shift assay. The sequence analysis revealed a G-quadruplex sequence within all the isolated aptamers that might contribute to aptamer binding and thermodynamic stability. The specificity assay further showed that RC60 and RC25 were highly specific to CD36. The competitive inhibition assay demonstrated that RC60 and RC25 shared a similar binding epitope recognized by mAb FA6-152, a specific monoclonal antibody against CD36. Conclusions: RC60 and RC25 are promising candidates as anti-cytoadherence for severe malaria adjunct therapy.

Evolution of specific RNA aptamers via SELEX targeting recombinant human CD36 protein: A candidate therapeutic target in severe malaria

To isolate and characterize RNA aptamers that are specific to human CD36 protein using systematic evolution of ligands by exponential enrichment (SELEX) technology to identify candidates for adjunct therapy to reverse the binding of Plasmodiuminfected erythrocytes. Methods: RNA aptamers were isolated using nitrocellulose membrane-based SELEX and binding analysis was screened using an electrophoretic mobility shift assay and enzyme-linked oligonucleotide assay. Results: Thirteen cycles of nitrocellulose membrane-based SELEX yielded three aptamers (RC60, RC25, RC04) exhibiting high binding against CD36 protein as shown on electrophoretic mobility shift assay. The sequence analysis revealed a G-quadruplex sequence within all the isolated aptamers that might contribute to aptamer binding and thermodynamic stability. The specificity assay further showed that RC60 and RC25 were highly specific to CD36. The competitive inhibition assay demonstrated that RC60 and RC25 shared a similar binding epitope recognized by mAb FA6-152, a specific monoclonal antibody against CD36. Conclusions: RC60 and RC25 are promising candidates as anticytoadherence for severe malaria adjunct therapy.

Terapia complementaria a la insulina en el tratamiento de niños y adolescentes con diabetes mellitus tipo 1- (DM1) / Therapies complementaries to insulin in the treatment of children and adolescents with type 1 diabetes mellitus (T1DM)

La diabetes mellitus tipo 1 (DM1), es una enfermedad crónica caracterizada por la deficiencia de insulina debido a la pérdida de células ß pancreáticas, las alteraciones hormonales en la DM 1 no se limitan a la deficiencia de insulina; existiendo también secreción inadecuadada de glucagón en el período postprandial. Aunque el control glucémico con terapias intensivas con insulina ha reducido la incidencia de complicaciones microvascular y macrovasculares. La mayoría de las personas con DM1 tienen un control glucémico subóptimo; Por lo tanto, el uso de farmacoterapia adyuvante para mejorar el control ha sido de interés clínico. El uso de estos nuevos medicamentos brindaría la oportunidad de imitar más de cerca la fisiología pancreática normal, y contrarrestar otros mecanismos fisiopatológicos diferentes a Insulinopenia; contribuyendo a lograr un mejor control metabólico y expectativa de vida.

Type 1 diabetes mellitus (T1DM), is a chronic disease characterized by insulin deficiency due to the loss of pancreatic ß cells, the hormonal alterations in T1DM are not limited to insulin deficiency; there is also a deregulated glucagon secretion in the postprandial period. Although glycemic control with intensive therapies with insulin has reduced the incidence of microvascular and macrovascular complications, most people with T1DM1 glycemic control; therefore, the use of adjuvant pharmacotherapy to improve control has been of clinical interest. The use of these new drugs would offer the opportunity to imitate more closely the normal pancreatic physiology, and to counteract other physiopathological mechanisms different from insulinopenia; contributing to achieve better metabolic control and life expectancy.

Adjunct role of nerve stimulator in ultrasound- guided axillary brachial plexus block / 实用医学杂志

Objective To evaluate the adjunct role of nerve stimulator in ultrasound- guided axillary bra-chial plexus block. Methods 50 patients undergoing lower elbow surgery in our hospital were selected from Sep-tember 2016 to November 2017. They were randomly divided into two groups with 25 cases each,which are guid-ance of ultrasound combined with nerve stimulator group(group US)and ultrasound alone group(group U). 32 mL of 0.4% ropivocaine were administered in both groups. The onset time and duration of sensory blockade in mus-culocutaneous,radial,median and ulnar nerve were recorded. The extent of sensory block of each in nervated re-gion and the anesthetic effect of surgical field(rated as excellent,good and failure)were both assessed. The anes-thetic complications were also observed and recorded. Results There were no significant differences in the onset time and duration of sensory blockade in both groups(P > 0.05). The anesthetic effects of surgical field were 92%in group US and 84% in group U(P > 0.05). No major anesthetic complications occurred in two groups. Conclu-sion Ideal anesthetic effects are achieved in both groups,and the successful rate of anesthesia in group US is not significantly increased. The role of nerve stimulator as an adjunct to ultrasound - guided axillary brachial plexus block may be very limited.

Application of Quality Control Circle in the Management of Drug Repercussion in Outpatient Pharmacy of Our Hospital / 中国药房

OBJECTIVE:To reduce drug repercussion of outpatient pharmacy,and to promote safe drug use.METHODS:By quality control circle (QCC),the data of drug repercussion were selected from outpatient pharmacy of our hospital in Sept.2016.The drug repercussion reason check list was designed to master the situation of drug repercussion in outpatient department,formulate improvement measures and confirm effect through field inspection.The case number of drug repercussion and the improvement of circle members' ability were compared one month before and after QCC (Mar.2017).Finally,the effects of QCC were evaluated.RESULTS:Referring to the reasons for the repercussion of adjunct drugs for inspection and the repercussion of unsuitable drug use in our hospital,those problems were improved by formulating manual for drug use examination project,optimizing and examining drug delivery process in the department,etc.The case number of drug repercussion in outpatient pharmacy decreased from 31 cases per month to 12 cases per month;the rate of goal achievement was 119％;the rate of improvement was 61％.The ability of QCC members to solve problems and the ability to use QCC skills were increased positively.CONCLUSIONS:The development of QCC activity in our hospital reduces case number of drug repercussion and optimizes drug delivery process in outpatient pharmacy,and promotes safe drug use.

Application of osmotic pump technology in Chinese materia medica preparation / 中草药

As a representative of controlled release preparations, osmotic pump has become a hot spot in the new preparation researches of Chinese materia medica (CMM). This paper reviewed CMM osmotic pump preparation from the following aspects: structure type of osmotic pump preparation, adjuncts of osmotic pump preparation of CMM, in vivo evaluation, and problems existing currently, which aimed to provide ideas and methods for the development of CMM osmotic pump preparation.

Lactobacilli isolated from Algerian goat's milk as adjunct culture in dairy products

In this study, nineteen Lactobacillus isolated from Algerian goat's milk, 13 belonging to L. plantarum, three to L. pentosus, two to L. rhamnosus and one to L. fermentum, were examined in vitro in order to be used as adjunct culture in dairy products. The strains were tested for their proteolytic activity, sensory and safety properties. Strains LbMS16 and LbMS21 L. plantarum and LbMF25 L. rhamnosus presented the highest proteolytic activity. All the tested lactobacilli were able to grow on MRS agar containing 0.5 and 1% (W/V) of oxgall, whereas none produced biogenic amine (BA) from the four tested amino acids and were resistant to pH 2.0 and 3.0, but some strains were able to grow at pH 3.5. None of examined strains were β-haemolytic when grown in hors blood agar. Result of antibiotic resistance showed that all the strains were susceptible to penicillin, erythromycin and resistant to vancomycin. Diacetyl production was observed for two strains of L. plantarum and one of L. rhamnosus. Most of strains were able to produce pleasant flavours in fermented milk and gave a good acceptance. According to these results, the strains LbMS16, LbMS21and LbMF25 could be good candidates to be used as adjunct culture, playing a probiotic role in dairy products manufacture in Algeria.

Effects of Acupuncture Therapy on Triglyceride of Quadriceps Femoris in High Fat Diet Feeding-induced Insulin Resistance Rats / 中国中医药信息杂志

Objective To observe the effects of acupuncture therapy on triglyceride (TG) content of quadriceps femoris in the high fat diet feeding-induced insulin resistance rats; To discuss acupuncture mechanisms to improve the insulin sensitivity. Methods Thirty-two Wistar rats at the age of eight weeks were randomly divided into normal group, model group, electro-acupuncture group, and sham electro-acupuncture group. The normal group was given basic diet, and model group, electro-acupuncture group and sham electro-acupuncture group were given high fat diet for 8 weeks, after which, the model of insulin resistance was successfully obtained. Electro-acupuncture group was given acupuncture therapy with “Guanyuan (GV4)”, “Zhognwan (GV12)”, “Zusanli (ST36)”, and “Fenglong (ST40)” for 8 weeks. Sham electro-acupuncture group was given stimulation at non-acupuncture points which were not on the meridians and near the acupoints but not at the area of the acupoints. In addition, food intake and body weight of each group were recorded, blood glucose was tested, TG content of quadriceps femoris was measured by enzymatic method after the treatment. Results The weight of the rats and TG levels of quadriceps femoris in electro-acupuncture group and sham electro-acupuncture group were significantly lower than those in model group, with significant statistical difference (P<0.05), especially in electro-acupuncture group. Conclusion Acupuncture therapy could improve insulin sensitivity to prevent and its related diseases.

Adjunct therapy of Ayurvedic medicine with anti tubercular drugs on the therapeutic management of pulmonary tuberculosis.

Background: Pulmonary tuberculosis (PTB) is an age old disease described in Vedic Medicine as ‘Yakshma’. Later on, in Ayurveda it earned a prefi x and found way into mythology as ‘Rajayakshma’. After the discovery of streptomycin, the therapeutic management of PTB received a major breakthrough. The treatment module changed remarkably with the formulation of newer anti-tubercular drugs (ATD) with appreciable success. Recent resurgence of PTB in developed countries like United States posed a threat to the medical community due to resistant strains. Consequently, WHO looked toward traditional medicine. Literature reveals that Ayurvedic treatment of PTB was in vogue in India before the introduction of ATD with limited success. Records show that 2766 patients of PTB were treated with Ayurvedic drugs in a tertiary care hospital in Kolkata in the year 1933-1947. Objectives: To evaluate the toxicity reduction and early restoration by adjunct therapy of Ayurvedic drugs by increasing the bio-availability of ATDs. Materials and Methods: In the present study, treatment response of 99 patients treated with ATD as an adjunct with Aswagandha (Withania somnifera) and a multiherbal formulation described in Chikitsa-sthana of Charaka samhita i.e. Chyawanprash were investigated. Hematological profi le, sputum bacterial load count, immunoglobulin IgA and IgM, blood sugar, liver function test, serum creatinine were the assessed parameters besides blood isoniazid and pyrazinamide, repeated after 28 days of treatment. Results: The symptoms abated, body weight showed improvement, ESR values were normal, there was appreciable change in IgA and IgM patterns and signifi cantly increased bioavailability of isoniazid and pyrazinamide were recorded. Conclusion: This innovative clinical study coupled with empowered research may turn out to be promising in fi nding a solution for the treatment of PTB.

African Breadfruit (Treculia africana) Seed as Adjunct in Ethanol Production.

African breadfruit seeds have the potentials as carbon source for ethanol production with a carbohydrate value of 72.19%. On malting the seeds at 28±2oC for 9 days it yielded a 96% germination capacity and total malting loss of 25.70%. Grain dormancy was broken by the second day of malting. Malted breadfruit seeds were ground and defatted to 0.78% fat content. Full fat breadfruit and defatted breadfruit flours were used as adjuncts in the ratio of 3:5 (adjuncts: barley). Fermentation parameters such as wort fermentable sugar, specific gravity, extract yield and ethanol were measured over the 9 days of fermentation. Extract yields were 12.59, 9.66 and 11.23% while ethanol production was 5.79, 6.39 and 6.10% for wort from defatted breadfruit, full fat breadfruit and maize, respectively.

Correlations Among the Stroke Patient Family's Health Status, Burden and of Life / 간호학회지

PURPOSE: This study is used to investigate the correlation among a stroke patient family's health, burden and quality of life. METHOD: Data was collected from one hundred twenty family care-givers registered at K and H Hospital in Seoul. Questionnaire data was drawn up by personal interviews aided by the staff nurses. The analyses of collected data are based on the rate of 100 percentage to the average, t-test, ANOVA, DMR, Pearson Correlation. Result: (1) The influential factors on physical health proved to be age, sex, academic career, matrimonial status, present occupation, economic situation, the relationship with the patient, the patient-caring term, and the family-formation. The psychological health issues were age, final academic career, matrimonial status, the relation with patient and the family-formation. Burdens were shown to be age, matrimonial status, the relation with patient, and the patient-caring term. The quality of life was determined by age, final academic career, matrimonial status, and the relationship with the patient, the patient- caring term, and the family-formation. (2) The rate of the physical condition was 2.87, the psychological condition 2.43, the sense of burden 3.08, and the quality of life was 2.42. (3) The rate of correlation between the burden and the quality of life was (r= -.547), the psychological health and the burden was (r= -.531), the physical health and the burden was (r= -.263), physical health and quality of life was (r= .301), psychological health, and quality of life was (r= .413). CONCLUSION: It follows from this study that there is a very close correlation among the stroke patient family's health, the burden, and quality of life. Therefore it is necessary that we should find various nursing intervention ways in order to mitigate the burden of family when caring for the stroke patients.

Effects of Topical Mitomycin C on Glaucoma Filtration Surgery

We studied the efficacy and safety of using topical mitomycin C(MMC) as an adjunct to glaucoma filtration surgery. Trabeculectomy was performed in 23 eyes of 19 patients with poor surgical prognosis. After the preparation of a scleral flap. 0.2mg or 0.4 mg/ml MMC was applied to the exposed tissue for 5 minutes. The wound was then irrigated with 250ml of normal saline. The follow-up period was from 2 to 12 months(mean 7.8 +/- 4.3 months). Preoperative mean intraocular pressure(IOP) was 33.8 +/- 7.1 mmHg, ranged from 25 to 51 mmHg. The mean IOPs after 1, 3, 6 and 12 months were 10.3 +/- 4.4, 12.5 +/- 6.9, 12.4 +/- 6.6 and 12.3 +/- 6.7 mmHg, respectively. Nineteen(82.6%) among 23 eyes were successfully controlled with the IOP below 20 mmHg without any antiglaucomatous therapies, and success rate was 0.747 by Kaplan-Meier method at Postoperative 12 months. There were early postoperative complications of aqueous leaking from conjunctival wound in 3 eyes(13.0%), shallow anterior chamber in 2 eyes, and hyphema in one eye and one eye had long-term hypotony lasting more than 3 months. Although MMC is simple to use and a potent adjunct to glaucoma filtration surgery, more work will be needed to determine the mechanism of action, indications, dosage and optimal exposure time of MMC.

Effects of topical mitomycin C on glaucoma filtration surgery

We studied the efficacy and safety of using topical mitomycin C (MMC) as an adjunct to glaucoma filtration surgery. Trabeculectomy was performed in 23 eyes of 19 patients with poor surgical prognosis. After the preparation of a scleral flap, 0.2 mg or 0.4 mg/ml MMC was applied to the exposed tissue for 5 minutes. The wound was then irrigated with 250ml of normal saline. The mean follow-up period was 7.8 months. Preoperative mean intraocular pressure (IOP) was 33.8mmHg, and the mean IOPs on 1, 3, 6, and 12 months after operation were 10.3, 12.5, 12.4 and 12.3mmHg, respectively. At postoperative 12 months, 74.7% achieved an IOP of less than or equal to 20mmHg without any antiglaucoma medication. There were early postoperative complications of aqueous leaking from conjunctival wounds in 3 eyes (13.0%), shallow anterior chamber in 2 eyes, and hyphema in one eye and one eye had long-term hypotony lasting more than 3 months. Although MMC is simple to use, it is a potent adjunct to glaucoma filtration surgery, more work should follow to determine the mechanism of action, indications, dosage and optimal exposure time of MMC.