Homeopathic Formulations of Syzygium jambolanum Alleviate Glycation-Mediated Structural and Functional Modifications of Albumin: Evaluation through Multi-Spectroscopic and Microscopic Approaches.

BACKGROUND: The growing interest in identifying the mode of action of traditional medicines has strengthened its research. Syzygium jambolanum (Syzyg) is commonly prescribed in homeopathy and is a rich source of phytochemicals. OBJECTIVE: The present study aims to shed light on the anti-glycation molecular mechanism of Syzyg mother tincture (MT), 30c, and 200c on glycated human serum albumin (HSA) by multi-spectroscopic and microscopic approaches. METHODS: The phytochemicals and antioxidant potential of the Syzyg formulations were estimated by the high-performance liquid chromatography and spectroscopic technique, respectively. Glycation was initiated by incubating HSA with methylglyoxal, three Syzyg formulations, and the known inhibitor aminoguanidine in separate tubes at 37°C for 48 hours. The formation of glycation adducts was assessed by spectrofluorometer and affinity chromatography. The structural modifications were analyzed through circular dichroism, Fourier transform infrared spectroscopy, turbidity, 8-anilinonapthalene-1-sulfonic acid fluorescence, and nuclear magnetic resonance. Further, the formation of the aggregates was examined by thioflavin T, native-polyacrylamide gel electrophoresis, and transmission electron microscopy. Additionally, the functional modifications of glycated HSA were determined by esterase-like activity and antioxidant capacity. The binding analysis of Syzyg formulations with glycated HSA was evaluated by surface plasmon resonance (SPR). RESULTS: Syzyg formulations MT, 30c, and 200c contained gallic acid and ellagic acid as major phytochemicals, with concentrations of 16.02, 0.86, and 0.52 µg/mL, and 227.35, 1.35, and 0.84 µg/mL, respectively. Additionally, all three formulations had remarkable radical scavenging ability and could significantly inhibit glycation compared with aminoguanidine. Further, Syzyg formulations inhibited albumin's structural and functional modifications. SPR data showed that Syzyg formulations bind to glycated HSA with an equilibrium dissociation constant of 1.10 nM. CONCLUSION: Syzyg formulations inhibited the glycation process while maintaining the structural and functional integrity of HSA.

Protraction Headgear Compliance and Orthognathic Surgery in Patients With Cleft Lip and Palate.

Assess cephalometric parameters and the need for orthognathic surgery (OS) and its relationship with compliance in protraction headgear (PHG).Retrospective case series.Hospital cleft-craniofacial center.23 patients with nonsyndromic cleft lip and palate and history of lip and palate repair.Patients received PHG and orthodontic treatment. Compliant patients were compared to patients that were not. Protraction was applied with 170-gram elastics and patients were instructed to wear for at least 12 hours daily.Cephalometric measurements at initial (T1), post-PHG (T2), and pre-surgical or post-orthodontic treatment (T3) of at least age 15 for females and 17 for males and the presence of OS were compared.83% (19) of patients reported compliance with therapy. Of those compliant, 68% (13) had OS and 32% (6) did not (P = .99). Inter-group comparisons at T1 between compliant and noncompliant showed no significant differences and the non-OS patients started with larger nasolabial angles (P < .05). At T2, there were no significant cephalometric differences between groups. At T3, compliant patients showed significantly more upper incisor proclination than noncompliant patients. Between OS and non-OS, OS patients had significantly decreased ANB, Wits, convexity, overjet, and FMA and larger nasolabial angles (P < .05).Patients compliant with PHG showed no difference in the need for OS. However, after orthodontic treatment, compliant patients showed more upper incisor proclination and OS patients with decreased ANB, Wits, convexity, overjet, FMA, and larger nasolabial angles.

Digital intraoral imaging: analysis of retakes and reduction in radiation exposure using rectangular collimation.

The purposes of this study were to examine the distribution and extent of retakes with digital intraoral imaging when operators transitioned from using round to rectangular collimators and to determine the effect of collimator shape on radiation exposure to patients. This study was conducted using digital intraoral radiographic data from 2018 to 2019 in a dental school radiology clinic. Digital intraoral radiography was performed with round collimators during 2018 and then with rectangular collimators in 2019 with the same cohort of students. Exposure values were obtained, and effective doses were calculated. Although the number of retakes increased with the transition from round to rectangular collimators, the transition also resulted in a statistically significant reduction in the overall effective dose for patients (P < 0.01; Pearson chi-square test), with an average difference of 60% between round and rectangular collimators. Even with the increase in the number of retakes, a decrease in effective dose was observed when rectangular collimation was used. Most retakes were due to placement errors, defined as missing contact points, missing apices of teeth, or a missing area of interest. As students gained more experience and practice with rectangular collimation, the number of retakes decreased. With proper clinical and didactic training and emphasis on the importance of rectangular collimation, a transition from round to rectangular collimation can be achieved with a minimal initial increase in retakes and subsequent normalization of rates, resulting in a significant reduction of the radiation dose to patients.

Cone-Beam Computed Tomography Incidental Findings in Individuals With Cleft Lip and Palate.

OBJECTIVES: The use of cone-beam computed tomography (CBCT) is well-established in clinical practice. This study seeks to categorize and quantify the incidental finding (IF) rate on CBCT in patients with cleft lip and palate (CLP) prior to orthodontic or surgical treatment. METHODS: This is systematic retrospective review of head and neck CBCTs in patients with nonsyndromic CLP taken between 2012 and 2019 at a single tertiary referral center. All assessments were performed independently by 4 observers (a head and neck radiologist and 3 orthodontists, including 2 fellowship-trained cleft-craniofacial orthodontists ). The images were divided into 9 anatomical areas and screened using serial axial slices and 3D reconstructions. The absolute number of IFs was reported for each area and statistical analysis was performed. RESULTS: Incidental findings were found in 106 (95.5%) of the 111 patients. The most common sites were the maxilla (87.4%, principally dental anomalies), paranasal sinuses (46.8%, principally inflammatory opacification), and inner ear cavities (18.9%, principally inflammatory opacification). Eleven patients had skull malformations. Thirty-three patients had IFs in 1 anatomical area, 49 patients in 2 anatomical areas, 19 patients in 3 areas, and 5 patients presented with IFs in 4 of the 9 anatomical areas. DISCUSSION: In patients with CLP, IFs on CBCT exam were present in the majority of cases. Most patients with IFs had them in multiple anatomical areas of the head and neck. The maxillary dental-alveolar complex was the most common area. Inflammatory changes in the inner ear cavities and paranasal sinuses were also common; however, cervical spine and skull abnormalities were also identified. Clinicians caring for patients with CLP should be aware of IFs, which may warrant further investigation and treatment.

Prescribing practices of Indian psychiatrists in the treatment of bipolar disorder.

OBJECTIVE: The treatment of bipolar disorder is challenging because of its clinical complexity and availability of multiple treatment options, none of which are ideal mood stabilizers. This survey studies prescription practices of psychiatrists in India and their adherence to guidelines. METHOD: In total, 500 psychiatrists randomly selected from the Indian Psychiatric Society membership directory were administered a face-to-face 22-item questionnaire pertaining to the management of bipolar disorder. RESULTS: For acute mania, most practitioners preferred a combination of a mood stabilizer and an atypical antipsychotic to monotherapy. For acute depression, there was a preference for a combination of an antidepressant and a mood stabilizer over other alternatives. Electroconvulsive therapy was preferred in the treatment of severe episodes and to hasten the process of recovery. Approximately, 50% of psychiatrists prescribe maintenance treatment after the first bipolar episode, but maintenance therapy was rarely offered lifelong. While the majority (85%) of psychiatrists acknowledged referring to various clinical guidelines, their ultimate choice of treatment was also significantly determined by personal experience and reference to textbooks. LIMITATIONS: The study did not study actual prescriptions. Hence, the responses to queries in the survey are indirect measures from which we have tried to understand the actual practices, and of course, these are susceptible to self-report and social-desirability biases. This was a cross-sectional study; therefore, temporal changes in responses could not be considered. CONCLUSION: Overall, Indian psychiatrists seemed to broadly adhere to recommendations of clinical practice guidelines, but with some notable exceptions. The preference for antidepressants in treating depression is contrary to general restraint recommended by most guidelines. Therefore, the efficacy of antidepressants in treating bipolar depression in the context of Indian psychiatrists' practice needs to be studied systematically. Not initiating maintenance treatment early in the course of illness may have serious implications on the long-term outcome of bipolar disorder.

Ileocecal Anastomosis Type Significantly Influences Long-Term Functional Status, Quality of Life, and Healthcare Utilization in Postoperative Crohn's Disease Patients Independent of Inflammation Recurrence.

OBJECTIVES: Anastomotic reconstruction following intestinal resection in Crohn's disease (CD) may employ side-to-side anastomosis (STSA; anti-peristaltic orientation) or end-to-end anastomosis (ETEA). Our aim was to determine the impact of these two anastomotic techniques on long-term clinical status in postoperative CD patients. METHODS: We performed a comparative effectiveness study of prospectively collected observational data from consented CD patients undergoing their first or second ileocolonic bowel resection and re-anastomosis between 2008 and 2012, in order to assess the association between anastomosis type and 2-year postoperative quality of life (QoL), healthcare utilization, disease clinical or endoscopic recurrence, use of medications, and need for repeat resection. RESULTS: One hundred and twenty eight postoperative CD patients (60 STSA and 68 ETEA) were evaluated. At 2 years postoperatively, STSA patients had higher rates of emergency department visits (33.3% vs. 14.7%; P=0.01), hospitalizations (30% vs. 11.8%; P=0.01), and abdominal computed tomography scans (50% vs. 13.2%; P<0.001) with lower QoL (mean short inflammatory bowel disease questionnaire 47.9 vs. 53.4; P=0.007). There was no difference among the two groups in the 30 day surgical complications and 2-year patterns of disease activity, CD medication requirement, endoscopic recurrence, and need for new surgical management (all P > 0.05). CONCLUSIONS: At 2 years postoperatively, CD patients with ETEA demonstrated better QoL and less healthcare utilization compared with STSA, despite having similar patterns of disease recurrence and CD treatment. These findings suggest that surgical reconstruction of the bowel as an intact tube (ETEA) contribute to improved functional and clinical status in patients with CD.

HLA-B27 testing: A journey from flow cytometry to molecular subtyping.

BACKGROUND: Determination of HLA-B27 status plays an important role as adjuvant in suspected cases for diagnosis of Ankylosing Spondilytis (AS). Objectives of this study were to evaluate (i) flow cytometry method in comparison with DNA microarray for HLA-B27 typing and (ii) EUROArray HLA-B27 Direct assay for HLA-B27 allele detection along with discrimination of AS/non-AS subtypes in Indian population. METHODS: A total of 7543 patients with a presumptive clinical diagnosis of AS were referred for screening of HLA-B27. All samples were initially tested by flow cytometry, and based on its findings, 1560 samples were analyzed for the presence of HLA-B27 allele by microarray technology. A subset of samples (n = 200) were further tested by DNA sequencing for identification of HLA-B27 subtypes. RESULTS: Screening of HLA-B27 by flow cytometry reported 1551 positive (20.56%) and 5556 negative (73.65%) cases. Remaining 436 (5.78%) samples were identified within equivocal zone. Of cases (n = 1560) analyzed by microarray method, 1333 (85.44%) and 227 (14.55%) were detected microarray positive and negative, respectively. DNA sequencing identified HLA-B*27:07 as the predominant subtype among cases showing ex2 positivity by microarray method. Of 200 cases, 20 cases (14 of HLA-B*07 and 6 of HLA-B*37) of HLA-B27 cross-reactive subtypes were also identified. CONCLUSION: We recommend DNA typing as a complementary tool along with flow cytometry to accomplish successful HLA-B27 phenotype determination. This is the first study among Indian population to evaluate efficacy of EUROArray to detect B27 allele and its potential to indicate the presence of nondisease-associated alleles in Indian population.

A Randomized, Nonblind, Naturalistic Comparison of Efficacy and Cognitive Outcomes With Right Unilateral, Bifrontal, and Bitemporal Electroconvulsive Therapy in Schizophrenia.

BACKGROUND: There is little literature on the relative efficacy and cognitive safety of right unilateral (RUL), bifrontal (BF), and bitemporal (BT) electroconvulsive therapy (ECT) in schizophrenia. METHODS: We present a randomized, nonblind, naturalist comparison of a fixed course of 8 moderately high-dose RUL (n = 24), threshold BF (n = 27), and threshold BT (n = 31) ECT in patients with schizophrenia. Assessments included the Positive and Negative Syndrome Scale (PANSS), the Wechsler Memory Scale-Revised, and an autobiographical memory interview. A completer analysis was planned and conducted to capture the cognitive outcomes. RESULTS: The sample as a whole improved significantly on all efficacy outcomes and deteriorated significantly on all cognitive outcomes. The primary efficacy outcome, improvement in PANSS total scores, did not differ significantly across groups. The PANSS positive score (but no other subscale score) improved significantly less with RUL relative to BF and BT ECT. For autobiographical memory and for almost all Wechsler Memory Scale subtests, including memory quotient (the primary adverse effect outcome), BT ECT was associated with greater impairment than RUL or BF ECT. Importantly, all statistically significant differences between treatments were clinically small in magnitude. CONCLUSIONS: In patients with schizophrenia who receive a fixed course of 8 ECTs, threshold BT ECT is associated with greater cognitive impairment across a range of measures, and moderately high-dose RUL ECT is associated with poorer efficacy against positive symptoms. Threshold BF ECT exhibits the best efficacy-cum-neurocognitive safety profile. All differences between groups, however, are small and perhaps clinically insignificant.

Targetable Clinical Nanoparticles for Precision Cancer Therapy Based on Disease-Specific Molecular Inflection Points.

Novel translational approaches based on clinical modular nanoplatforms are needed in order to treat solid cancers according to their discrete molecular features. In the present study, we show that the clinical nanopharmaceutical Ferumoxytol, which consists of a glucose-based coat surrounding an iron oxide core, could identify molecular characteristics of prostate cancer, corresponding to unique phases of the disease continuum. By affixing a targeting probe for the prostate-specific membrane antigen on its surface, the nanopharmaceutical was able to assess the functional state of the androgen receptor pathway via MRI, guiding therapy and delivering it with the same clinical nanoparticle. In order to simultaneously inhibit signaling from key oncogenic pathways of more advanced forms of prostate cancer, a single-agent therapy for early stage disease to inhibit DNA replication, as well as combination therapy with two drugs co-retained within the nanopharmaceutical's polymeric coating, were tested and resulted in complete tumor ablation. Recalcitrant and terminal forms of the disease were effectively treated with a nanopharmaceutical delivering a combination that upregulates endoplasmic reticulum stress and inhibits metastasis, thereby showing that this multifunctional nanoplatform can be used in the clinic for patient stratification, as well as precision treatment based on the individual's unique disease features.

Barriers to sealant guideline implementation within a multi-site managed care dental practice.

BACKGROUND: The purpose of this study was to identify barriers frequently endorsed by dentists in a large, multi-site dental practice to implementing the American Dental Association's recommendation for sealing noncavitated occlusal carious lesions as established in their 2016 pit-and-fissure sealant clinical practice guideline. Although previous research has identified barriers to using sealants perceived by dentists in private practice, barriers frequently endorsed by dentists in large, multi-site dental practices have yet to be identified. Identifying barriers for these dentists is important, because it is expected that in the future, the multi-site group practice configuration will comprise more dental practices. METHODS: We anonymously surveyed the 110 general and pediatric dentists at a multi-site dental practice in the U.S. The survey assessed potential barriers in three domains: practice environment, prevailing opinion, and knowledge and attitudes. Results were summarized using descriptive statistics. RESULTS: The response rate to the survey was 62%. The principal barrier characterizing the practice environment was concern regarding liability; endorsed by 33% of the dentists. Many barriers of prevailing opinion were frequently endorsed. These included misunderstanding the standard of practice (59%), being unaware of the expectations of opinion leaders (56%) including being unaware of the guideline itself (67%), and being unaware of what is currently being taught in dental schools (58%). Finally, barriers of knowledge and attitudes were frequently endorsed. These included having suboptimal skill in applying sealants (23% - 47%) and lacking knowledge regarding the relative efficacy of the different ways to manage noncavitated occlusal carious lesions (50%). CONCLUSIONS: We identified barriers frequently endorsed by dentists in a large, multi-site dental practice relating to the practice environment, prevailing opinion, and knowledge and attitudes. All the barriers we identified have the potential to be addressed by implementation strategies. Future studies should devise and test implementation strategies to target these barriers.

A comparison of crown preparation grading via PrepCheck versus grading by dental school instructors.

Recent reports in the literature demonstrate the influence that digital dentistry is having on the preclinical training of dental students. However, none of these articles have discussed the use of PrepCheck (Sirona Dental Systems) in the evaluation of preparation taper in a preclinical environment. The present study compared the subjective grading of student tooth preparations by experienced, well-calibrated faculty with objective digital grading of the same preparations by means of the PrepCheck software. Sixty-nine sophomore dental student preparations were first subjectively graded by their dental instructors, and then the preparations were evaluated by the PrepCheck software. Neither the students nor the instructors were aware that the second PrepCheck evaluation was going to occur. The statistically significant results of this study conclude that the subjective instructor grades were inflated compared with the digital PrepCheck grades. The inflated grading by the instructors may give students a sense that their progress is better than it actually is. The objective, exact nature of the PrepCheck evaluation gives students immediate feedback regarding their preclinical preparations. Although taper was the only parameter examined in this study, PrepCheck allows the operator to examine many other features of a student's preparation. Also made evident in this study is the fact that the present standard for preparation taper is unattainable in a preclinical environment and needs to be readjusted to a wider, attainable range.

Psychiatric Co-morbidities in Women with Epilepsy.

Background: The co-existence of psychiatric co-morbidities with Epilepsy in women is multifactorial and complex, being closely related to hormonal status, medication side effects, and psychosocial factors. Aims: We aimed to study associated Psychiatric co-morbidities in women with Epilepsy (WWE), and correlate the same with seizure subtype and medication , compliance with treatment and seizure control. Material and Methods: This was a prospective, interview based study in OPD over 18 months, evaluating WWE over 13 years of age with at least 1 seizure in the last 1 year. The primary outcome evaluated was the psychiatric diagnosis. Covariables assessed included sociodemographic data, details of seizures and treatment taken. Study population included 143 WWE. Thirty women with a chronic disease, viz., Diabetes and with no h/o seizures, and another group of 25 healthy women from the community with no seizures ever and no Diabetes, were evaluated as 2 sets of controls. Results and Conclusions: One hundred and forty three women with Epilepsy (WWE) were recruited into the study. Psychiatric co-morbidity prevalence was 28.6 % (41/143) in WWE, 13.7 % in women with Diabetes and 8.3 % in women with no Epilepsy or Diabetes (normal controls). Overall, Depression was the commonest psychiatric co-morbidity. Psychiatric co-morbidity was significantly more in WWE as compared to normal controls. Seizure duration over 2 years, complex partial seizures and Polypharmacy were significantly linked to Psychiatric co-morbidities.

Association of Vitamin D Level With Clinical Status in Inflammatory Bowel Disease: A 5-Year Longitudinal Study.

OBJECTIVES: Emerging data suggest that vitamin D has a significant role in inflammatory bowel disease (IBD). Prospective data evaluating the association of vitamin D serum status and disease course are lacking. We sought to determine the relationship between vitamin D status and clinical course of IBD over a multiyear time period. METHODS: IBD patients with up to 5-year follow-up from a longitudinal IBD natural history registry were included. Patients were categorized according to their mean serum 25-OH vitamin D level. IBD clinical status was approximated with patterns of medication use, health-care utilization, biochemical markers of inflammation (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), pain and clinical disease activity scores, and health-related quality of life. RESULTS: A total of 965 IBD patients (61.9% Crohn's disease, 38.1% ulcerative colitis) formed the study population (mean age 44 years, 52.3% female). Among them, 29.9% had low mean vitamin D levels. Over the 5-year study period, subjects with low mean vitamin D required significantly more steroids, biologics, narcotics, computed tomography scans, emergency department visits, hospital admissions, and surgery compared with subjects with normal mean vitamin D levels (P<0.05). Moreover, subjects with low vitamin D levels had worse pain, disease activity scores, and quality of life (P<0.05). Finally, subjects who received vitamin D supplements had a significant reduction in their health-care utilization. CONCLUSIONS: Low vitamin D levels are common in IBD patients and are associated with higher morbidity and disease severity, signifying the potential importance of vitamin D monitoring and treatment.

Prescription pattern of antidepressants in five tertiary care psychiatric centres of India.

BACKGROUND & OBJECTIVES: Limited data are available on prescription patterns of the antidepressants from India. We studied antidepressants' prescription pattern from five geographically distant tertiary psychiatric care centers of the India. METHOD: In this cross-sectional study, all patients who attended outpatients department or were admitted in the psychiatry wards at Lucknow, Chandigarh, Tiruvalla, Mumbai and Guwahati on a fixed day, who were using or had been prescribed antidepressant medications, were included. The data were collected on a unified research protocol. RESULTS: A total of 312 patients were included. Mean age was 39±14.28 yr and 149 (47.76%) were females, 277 (87.5%) were outpatients. Among the patients receiving antidepressants, 150 (48.1%) were of diagnoses other than depression. Diabetes mellitus 18 (5.78%) was the most common co-morbid medical illness. A total of 194 (62.2%) patients were using selective serotonin reuptake inhibitors (SSRIs) with escitalopram 114 (36.53%) being the most common antidepressant used. Overall, 272 (87.18%) patients were using newer antidepressants. Thirty (9.62%) were prescribed more than one antidepressant; 159 (50.96%) patients were prescribed hypnotic or sedative medications with clonazepam being the most common (n=116; 37.18%). INTERPRETATION & CONCLUSIONS: About half of the patients with diagnoses other than depression were prescribed antidepressants. SSRIs were the most common group and escitalopram was the most common medication used. Concomitant use of two antidepressants was infrequent. Hypnotic and sedatives were frequently prescribed along with antidepressants.

Evaluating the anticancer activity and nanoparticulate nature of homeopathic preparations of Terminalia chebula.

BACKGROUND: Breast cancer is the most common cancer diagnosed among women and is the second leading cause of cancer death. Homeopathic medicines are part of the alternative medicines that are given as a supportive therapy in breast cancer. The objective of this study was to investigate the anticancer activity of commercially available homeopathic preparations of Terminalia chebula (TC) and evaluate their nanoparticulate nature. METHODS: Mother tincture (MT) and other homeopathic preparations (3X, 6C and 30C) of TC were tested for their effect on the viability of breast cancer (MDAMB231 and MCF7) and non-cancerous (HEK 293) cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell growth assay was performed to analyze the effect of the different potencies on the growth kinetics of breast cancer cells. MT and 6C were evaluated for the presence of nanoparticles by using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: MT decreased the viability of breast cancer (MDAMB231 and MCF7) and non-cancerous (HEK 293) cells. However, the other potencies (3X, 6C and 30C) decreased the viability of only breast cancer cells without affecting the viability of the non-cancerous cells. All the potencies, MT, 3X, 6C and 30C, reduced growth kinetics of breast cancer cells, more specifically at 1:10 dilution at 24, 48 and 72 h. Under SEM, MT appeared as a mesh-like structure whereas under TEM, it showed presence of nanoclusters. On the other hand, 6C potency contained 20 nm sized nanoparticles. CONCLUSION: The current study reports the anticancer activity of homeopathic preparations of TC against breast cancer and reveals their nanoparticulate nature. These preliminary results warrant further mechanistic studies at both in vitro and in vivo levels to evaluate the potential of TC as nanomedicine in breast cancer.

Nonsteroidal anti-inflammatory drug sensitizes Mycobacterium tuberculosis to endogenous and exogenous antimicrobials.

Existing drugs are slow to eradicate Mycobacterium tuberculosis (Mtb) in patients and have failed to control tuberculosis globally. One reason may be that host conditions impair Mtb's replication, reducing its sensitivity to most antiinfectives. We devised a high-throughput screen for compounds that kill Mtb when its replication has been halted by reactive nitrogen intermediates (RNIs), acid, hypoxia, and a fatty acid carbon source. At concentrations routinely achieved in human blood, oxyphenbutazone (OPB), an inexpensive anti-inflammatory drug, was selectively mycobactericidal to nonreplicating (NR) Mtb. Its cidal activity depended on mild acid and was augmented by RNIs and fatty acid. Acid and RNIs fostered OPB's 4-hydroxylation. The resultant 4-butyl-4-hydroxy-1-(4-hydroxyphenyl)-2-phenylpyrazolidine-3,5-dione (4-OH-OPB) killed both replicating and NR Mtb, including Mtb resistant to standard drugs. 4-OH-OPB depleted flavins and formed covalent adducts with N-acetyl-cysteine and mycothiol. 4-OH-OPB killed Mtb synergistically with oxidants and several antituberculosis drugs. Thus, conditions that block Mtb's replication modify OPB and enhance its cidal action. Modified OPB kills both replicating and NR Mtb and sensitizes both to host-derived and medicinal antimycobacterial agents.

Syzygium jambolanum and Cephalandra indica homeopathic preparations inhibit albumin glycation and protect erythrocytes: an in vitro study.

BACKGROUND: Diabetes mellitus is a common endocrine disorder characterized by hyperglycemia eventually resulting in long-term complications. Increased glycation of proteins is implicated in the pathogenesis of complications. For treatment of diabetes, Syzygium jambolanum and Cephalandra indica are frequently prescribed in homeopathy. However their role in glycation is not well elucidated. The present study aimed to evaluate the role of these homeopathic preparations in glycation induced structural modifications and further to examine their cellular protection ability. METHODS: In human erythrocytes, in vitro mother tincture and dilutions of S. jambolanum (Sj ф, 30c, 200c), C. indica (Ci ф, 30c, 200c) and standard antiglycator (AG) were compared and their antiglycation potential assessed by the estimating different markers of glycation (frcutosamines, carbonyls, bound sugar), structural modifications (free amino and thiol group). Phytochemical characterization (total phenolic, flavonoids and glycosides contents) was performed. RESULTS: The homeopathic preparations have different mode of action on albumin glycation modifications. Sj ф preparation demonstrated effective inhibition of all glycation, structural modifications except amino group protection. When dilutions were compared, Sj preparations showed reduction of glycation, structural modifications. All preparations showed significant erythrocyte protection. Sj ф preparation exhibited noteworthy antiglycation and cell protection ability as compared to AG. CONCLUSION: These homeopathic preparations especially Sj ф prevented glycation induced albumin modifications and subsequent toxicity in human eryrthrocytre in vitro. Further investigation of their potential as antiglycators is justified.

Plasma inflammatory and apoptosis markers are associated with dialysis dependence and death among critically ill patients receiving renal replacement therapy.

BACKGROUND: Survivors of critical illness complicated by acute kidney injury requiring renal replacement therapy (RRT) are at an increased risk of dialysis dependence and death but the mechanisms are unknown. METHODS: In a multicenter, prospective, cohort study of 817 critically ill patients receiving RRT, we examined association between Day 1 plasma inflammatory [interleukin (IL)-1ß, IL-6, IL-8, IL-10 and IL-18; macrophage migration inhibitory factor (MIF) and tumor necrosis factor]; apoptosis [tumor necrosis factor receptor (TNFR)-I and TNFR-II and death receptor (DR)-5]; and growth factor (granulocyte macrophage colony stimulating factor) biomarkers and renal recovery and mortality at Day 60. Renal recovery was defined as alive and RRT independent. RESULTS: Of 817 participants, 36.5% were RRT independent and 50.8% died. After adjusting for differences in demographics, comorbid conditions; premorbid creatinine; nephrotoxins; sepsis; oliguria; mechanical ventilation; RRT dosing; and severity of illness, increased concentrations of plasma IL-8 and IL-18 and TNFR-I were independently associated with slower renal recovery [adjusted hazard ratio (AHR) range for all markers, 0.70-0.87]. Higher concentrations of IL-6, IL-8, IL-10 and IL-18; MIF; TNFR-I and DR-5 were associated with mortality (AHR range, 1.16-1.47). In an analysis of multiple markers simultaneously, increased IL-8 [AHR, 0.80, 95% confidence interval (95% CI) 0.70-0.91, P < 0.001] and TNFR-I (AHR, 0.63, 95% CI 0.50-0.79, P < 0.001) were associated with slower recovery, and increased IL-8 (AHR, 1.26, 95% CI 1.14-1.39, P < 0.001); MIF (AHR, 1.18, 95% CI 1.08-1.28, P < 0.001) and TNFR-I (AHR, 1.26, 95% CI 1.02-1.56, P < 0.03) were associated with mortality. CONCLUSIONS: Elevated plasma concentrations of inflammatory and apoptosis biomarkers are associated with RRT dependence and death. Our data suggest that future interventions should investigate broad-spectrum immune-modulation to improve outcomes.