Cholecalciferol Exhibits no Antibacterial Effect on Staphylococcus aureus and Escherichia coli: An in vitro Study.

BACKGROUND: The pleiotropic effect of cholecalciferol (vitamin D3) has gained significant momentum and has been explored widely. OBJECTIVES: The study aimed to investigate the antimicrobial effect of cholecalciferol against S. aureus and E. coli. METHODS: An in vitro study was performed for the antimicrobial effect of cholecalciferol against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined following the broth microdilution method. RESULTS: The MIC value of cholecalciferol against both S. aureus and E. coli was 0.312 mg/ml, and the MBC for both organisms was 1.25 mg/ml. However, we also observed a significant antimicrobial effect in the dimethyl sulfoxide (DMSO) control at 12.5% (v/v). Therefore, the observed antimicrobial effect may be attributed to DMSO, indicating cholecalciferol does not directly inhibit S. aureus and E. coli. CONCLUSION: This study indicates that cholecalciferol does not directly inhibit S. aureus and E. coli. Hence, we suggest exploring the antibacterial properties of other vitamin D analogs, such as calcitriol or its synergetic effect with other antimicrobial agents.

KADAM topical warm oxygen therapy device for diabetic foot ulcer-a novel approach.

Purpose: Diabetic foot ulcer (DFU) is a significant healthcare burden demanding prompt attention. In the past decade, newer technologies such as topical oxygen therapy have grown increasingly popular. The purpose of the study was to determine effect of KADAM-a topical warm oxygen therapy (TWOT) medical device in healing of DFU. Methods: The KADAM medical device developed by Yostra Labs Pvt Ltd, delivered pure oxygen between 93 ± 3% concentration at an optimal temperature range of 39-42º Celsius to DFU wound site. Results: A total of 40 diabetic foot ulcer individuals, aged over 18 years were included in the study. Individuals with the Grade 1 DFU were 34 (85%), grade 2 were 5 (12.5%) and grade 3 were 1 (2.5%). The changes in initial area and final area for the various diabetic foot ulcer grades were as follows: 0.32 [0.12, 0.96] (< 0.001) for grade 1 ulcer, 0.76 [0.54, 1.17] (P = 0.013) for grade 2 ulcer and 1.26 for grade 3 ulcer. The percentage reduction in wound size achieved for the grade 1 & 2 DFU were 100%, and grade 3 was 75%. Conclusion: Topical warm oxygen therapy serves as an adjunctive modality to facilitate diabetic foot ulcer healing in the clinical practice.

The association between micronutrient levels and diabetic foot ulcer: A systematic review with meta-analysis.

Background: Diabetic foot ulcers (DFU) are a major complication of diabetes mellitus (DM). Nutrient deficiencies are among the major risk factors in DFU development and healing. In this context, we aimed to investigate the possible association between micronutrient status and risk of DFU. Methods: A systematic review (Prospero registration: CRD42021259817) of articles, published in PubMed, Web of Science, Scopus, CINAHL Complete, and Embase, that measured the status of micronutrients in DFU patients was performed. Results: Thirty-seven studies were considered, of which thirty were included for meta-analysis. These studies reported levels of 11 micronutrients: vitamins B9, B12, C, D, E, calcium, magnesium, iron, selenium, copper, and zinc. DFU, compared to healthy controls (HC) had significantly lower vitamin D (MD: -10.82 14 ng/ml, 95% CI: -20.47, -1.16), magnesium (MD: -0.45 mg/dL, 95% CI: -0.78, -0.12) and selenium (MD: -0.33 µmol/L, 95% CI: -0.34, -0.32) levels. DFU, compared to DM patients without DFU, had significantly lower vitamin D (MD: -5.41 ng/ml, 95% CI: -8.06, -2.76), and magnesium (MD: -0.20 mg/dL, 95% CI: -0.25, -0.15) levels. The overall analysis showed lower levels of vitamin D [15.55ng/ml (95% CI:13.44, 17.65)], vitamin C [4.99µmol/L (95% CI:3.16, 6.83)], magnesium [1.53mg/dL (95% CI:1.28, 1.78)] and selenium [0.54µmol/L (95% CI:0.45, 0.64)]. Conclusion: This review provides evidence that micronutrient levels significantly differ in DFU patients, suggesting an association between micronutrient status and risk of DFU. Therefore, routine monitoring and supplementations are warranted in DFU patients. We suggest that personalized nutrition therapy may be considered in the DFU management guidelines. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=259817, identifier CRD42021259817.

Phytotherapy in Diabetic Foot Ulcers: A Promising Strategy for Effective Wound Healing.

Despite the advancement in wound care, the effective therapy of chronic diabetic ulcers continues to be a challenge. Wound healing is a highly controlled process, which involves a sequence of complex overlapping steps. This healing pathway comprises of hemostasis, inflammation, proliferative, and remodeling phases. Recent evidence suggests that phytomedicines can prevent or repair different kinds of destructive cellular damage, including chronic wounds. Several phytochemicals such as polyphenols, alkaloids, flavonoids, terpenoids, and glycosides have pleiotropic effects, including stimulation of fibroblast proliferation, the main step in wound healing. Besides, the mechanism involves induction of collagen synthesis, migration, and reepithelization and their antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory actions. Similarly, the use of phytochemicals alone or as an adjuvant with standard therapy has demonstrated promising results in managing complications in the diabetic foot. For instance, the extract of Carica papaya has been shown antioxidant, antimicrobial, and anti-inflammatory, and immunomodulatory effects, which, together with proteolytic enzymatic activity, contributes to its wound healing property. It is generally believed that phytotherapy has no or minimal toxicity than synthetic therapeutic agents, favoring its use in diabetic foot ulcer management. The current review highlights the selected phytochemicals and their sources; and potential application in diabetic foot ulcer management.Key teaching points and nutritional relevanceCurrently, phytochemicals have been shown wide potential in disease. management including alleviating clinical manifestations, preventing degenerative disease, and curing illness.Increased evidence of phytochemical as anti-infective and anti-inflammatory suggests its role in the management of diabetic foot ulcer(DFU).Potential benefit along with minimal adverse effect favors its application as adjuvant therapy.Further research is needed to standardize its dose and formulation to enhance its clinical application in DFU management.

Vitamin D attenuates biofilm-associated infections via immunomodulation and cathelicidin expression: a narrative review.

INTRODUCTION: Infections are becoming more difficult to treat, at least partly on account of microbes that produce biofilms. Reports suggest that decreased levels of antimicrobial peptides like cathelicidin, elevated levels of inflammatory cytokines, and biofilm formation are all associated with vitamin D deficiency, making vitamin D - deficient individuals more susceptible to infection. Infections attributable to biofilm-producing microbes can be managed by adjuvant therapy with vitamin D because of its immunomodulatory role, particularly because of the ability of vitamin D-pathway to induce the antimicrobial peptides like cathelicidin and decrease proinflammatory cytokines. AREAS COVERED: This narrative review covers biofilm formation, infections associated with biofilm due to vitamin D deficiency, putative role of vitamin D in host protection and the effect of vitamin D supplementation in biofilm-associated infections. A comprehensive literature search in PubMed and Google Scholar utilizing suitable keywords at multiple time points extracted relevant articles. EXPERT OPINION: Although vitamin D deficiency has been associated with infections by biofilm producing microbes, comprehensive clinical trials in various ethnicities are required to understand the likely relationships between vitamin D receptor gene expression, cathelicidin levels, and infection outcome. Current evidence hypothesizes that maintaining normal vitamin D level can help prevent and treat these infections.

Effect of Vitamin D Supplementation in Type 2 Diabetes Patients with Tuberculosis: A Systematic Review.

BACKGROUND: Diabetes mellitus (DM) and tuberculosis (TB) have been recognized as reemerging epidemics, especially in developing countries. Among all the risk factors, diabetes causes immunosuppression, increasing the risk of active TB three times. Vitamin D has been found as a link between DM-TB co-morbidity. OBJECTIVE: Vitamin D affects the immune response, suppresses Mycobacterium tuberculosis (Mtb) growth, and affects insulin secretion. The present systematic review determines the effect of vitamin D supplementation on clinical and therapeutic outcomes of DM-TB patients. METHOD: A comprehensive literature search was carried out in PubMed, Cochrane, Web of Science, and Scopus database to determine eligible studies from inception to January 2021. Out of the 639 articles retrieved, three randomized controlled trials (RCTs) were included in the systematic review. RESULT: The effect of vitamin D3 or oral cholecalciferol supplementation was assessed on outcomes, such as duration to sputum smear conversion, TB scores improvement, change in glycemic parameters, including HbA1c, FBS, and PLBS, and laboratory parameters, such as Hb, ESR, and CRP. Duration of sputum smear conversion was decreased by two weeks in the vitamin D3 supplemented group in two studies. TB score improvement and changes in glycemic parameters were inclined towards supplemented group; however, they were not significant. CONCLUSION: The overall effect of vitamin D3 supplementation on TB patients with DM was not significant. Further studies are required in the future examining the effect of supplementation on outcomes in this population.

Probiotics in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects.

Saving lives and flattening the curve are the foremost priorities during the ongoing pandemic spread of SARS-CoV-2. Developing cutting-edge technology and collating available evidence would support frontline health teams. Nutritional adequacy improves general health and immunity to prevent and assuage infections. This review aims to outline the potential role of probiotics in fighting the COVID-19 by covering recent evidence on the association between microbiota, probiotics, and COVID-19, the role of probiotics as an immune-modulator and antiviral agent. The high basic reproduction number (R0) of SARS-CoV-2, absence of conclusive remedies, and the pleiotropic effect of probiotics in fighting influenza and other coronaviruses together favour probiotics supplements. However, further support from preclinical and clinical studies and reviews outlining the role of probiotics in COVID-19 are critical. Results are awaited from many ongoing clinical trials investigating the benefits of probiotics in COVID-19.

Vitamin D Supplementation in Diabetic Foot Ulcers: A Current Perspective.

INTRODUCTION: Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus, as it can physically and emotionally impact the person. Its management can be challenging and expensive, depending on the severity of the wound and the presence of infection. BACKGROUND: The fat-soluble molecule, vitamin D, has gained great importance ever since its pleiotropism has been recognized. Its efficacy could be attributed to the presence of vitamin D receptors in most of the body tissues. Vitamin D plays a significant role in cell proliferation, differentiation, and immune modulation. It modulates the T and B cells resulting in the suppression of the immunoglobulins, autoimmunity, and inflammation. METHODS: We performed a literature search with the objective to highlight the role of vitamin D in peripheral vascular disease and peripheral neuropathy, which are the major risk factors for DFU, as well as evidences of its role in wound healing and management of DFU. RESULTS: Preclinical and clinical studies have shown that vitamin D influences multiple phases of wound healing and thereby accelerates the process. It modulates various cells involved in proliferation and remodelling phases. Vitamin D also enhances the expression of antimicrobial peptides that help to eliminate the microbes, as well as suppress the proinflammatory responses while enhancing the anti-inflammatory responses. CONCLUSION: This review concludes vitamin D to have a protective role in the immune and vascular system, improve glycaemic outcomes, and wound healing. Therefore, vitamin D could be a preferred adjuvant in the management of DFU.

Microbial Community Distribution and Core Microbiome in Successive Wound Grades of Individuals with Diabetic Foot Ulcers.

Diabetic foot ulcer (DFU) is a major complication of diabetes with high morbidity and mortality rates. The pathogenesis of DFUs is governed by a complex milieu of environmental and host factors. The empirical treatment is initially based on wound severity since culturing and profiling the antibiotic sensitivity of wound-associated microbes is time-consuming. Hence, a thorough and rapid analysis of the microbial landscape is a major requirement toward devising evidence-based interventions. Toward this, 122 wound (100 diabetic and 22 nondiabetic) samples were sampled for their bacterial community structure using both culture-based and next-generation 16S rRNA-based metagenomics approach. Both the approaches showed that the Gram-negative microbes were more abundant in the wound microbiome. The core microbiome consisted of bacterial genera, including Alcaligenes, Pseudomonas, Burkholderia, and Corynebacterium in decreasing order of average relative abundance. Despite the heterogenous nature and extensive sharing of microbes, an inherent community structure was apparent, as revealed by a cluster analysis based on Euclidean distances. Facultative anaerobes (26.5%) were predominant in Wagner grade 5, while strict anaerobes were abundant in Wagner grade 1 (26%). A nonmetric dimensional scaling analysis could not clearly discriminate samples based on HbA1c levels. Sequencing approach revealed the presence of major culturable species even in samples with no bacterial growth in culture-based approach. Our study indicates that (i) the composition of core microbial community varies with wound severity, (ii) polymicrobial species distribution is individual specific, and (iii) antibiotic susceptibility varies with individuals. Our study suggests the need to evolve better-personalized care for better wound management therapies.IMPORTANCE Chronic nonhealing diabetic foot ulcers (DFUs) are a serious complication of diabetes and are further exacerbated by bacterial colonization. The microbial burden in the wound of each individual displays diverse morphological and physiological characteristics with unique patterns of host-pathogen interactions, antibiotic resistance, and virulence. Treatment involves empirical decisions until definitive results on the causative wound pathogens and their antibiotic susceptibility profiles are available. Hence, there is a need for rapid and accurate detection of these polymicrobial communities for effective wound management. Deciphering microbial communities will aid clinicians to tailor their treatment specifically to the microbes prevalent in the DFU at the time of assessment. This may reduce DFUs associated morbidity and mortality while impeding the rise of multidrug-resistant microbes.

Corrigendum to "Role of UHRF1 in malignancy and its function as a therapeutic target for molecular docking towards the SRA domain" [Int. J. Biochem. Cell Biol. 114 (September 2019) 105558].

Cancer pathogenesis has been attributed to the minor and major disruptions in the cell cycle, with a key role being played by several of the recently discovered epigenetic factors. Lately, UHRF1 (Ubiquitin-like with containing PHD and RING Finger domains 1), an epigenetic regulator has been shown to be evidently over expressed in numerous malignancies through an in-depth review of literature. Molecular docking studies have found that existing drugs such as propranolol, naphthazarin and thymoquinone have favourable interactions with specific domains of UHRF1. However, these findings would need large scale clinical trials to confirm their potency and safety during chemotherapy. UHRF1 (Ubiquitin-like with containing PHD and RING Finger domains 1), an epigenetic factor, plays a crucial role as an important checkpoint in the cell machinery. Basic science continues to unravel multiple facets of this five domain protein which includes a detailed elucidation of its roles and mechanisms of interaction with various enzymes during DNA replication. The gene has recently begun to be also termed as the "Universal Oncogene" in response to the results of research conducted in heterogenous populations and in over 17 cancers displaying heightened mRNA and protein expression in breast, liver, lung, head and neck cancers and many more. This gene could therefore, be a potential biomarker for diagnosis and for the prediction of the prognosis and survival of the diseased. A scientifically established solution in the form of targeted treatment must follow such a discovery and therefore, several natural and synthetic compounds such as thymoquinone and the well-known antihypertensive, propranolol have been docked and reported to have favourable interactions with the SRA (Set and Ring Associated) domain of UHRF1 in this review. This comprehensive review is thus, a brief synopsis of details regarding the structure and heightened levels of UHRF1 in several malignancies. Furthermore, pharmacogenomic research revolving around this oncogene is a potential sphere for clinical studies to be conducted in much larger and heterogenous populations to not only validate these therapeutic docking results but to also to bring personalised medicine to the bedside for the benefit of the patients.

Role of UHRF1 in malignancy and its function as a therapeutic target for molecular docking towards the SRA domain.

The figure describes the location of UHRF1 (Ubiquitin-like with containing PHD and RING Finger domains 1) gene, mRNA and protein synthesis in the tumor cell and its structural domains with a focus on the docking of Naphthazarin on the SRA domain of UHRF1, resulting in reduction of tumor size.

Antimicrobial susceptibility pattern of aerobes in diabetic foot ulcers in a South-Indian tertiary care hospital.

PURPOSE: Diabetic foot infections (DFIs) are major public health concerns. In the view of the ever increasing burden of multidrug-resistant (MDR) organisms, improving the use of antimicrobial agents (AMAs) is a national priority. Objective of the study was to determine antimicrobial susceptibility (AMS) pattern of aerobes in DFIs. METHODS: A cross-sectional study was conducted for a period of 3 years at Department of Surgery, Kasturba hospital, Manipal, India during which, 260 diabetic foot ulcer (DFU) patients admitted in the general surgery wards were enrolled for the study. These patients' culture specimens were observed as Gram-stained smears and cultured aerobically on blood agar and MacConkey agar plates. AMS test was performed by disc diffusion technique according to Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: A total of 354 microbes were isolated from the ulcer wounds of 213 diabetic foot patients, with an average of 1.7 organisms per lesion. Monomicrobial infections were less common (n=81; 31.2%) than polymicrobial infections (n=132; 50.7%). Gram-negative bacteria were the most common among the isolates (n=192; 54.2%). Aerobic Gram-positive Cocci accounted for 162 (45.8%) of all isolates. On the other hand, Staphylococcus aureus was the most frequently isolated aerobe (n=106; 29.9%) followed by Pseudomonas aeruginosa (n=91; 25.7%). CONCLUSION: AMS data from our study recommends that doxycycline would be the appropriate choice as single drug for empirical coverage for Gram-positive organisms. The most appropriate antibiotic for Gram-negative organisms is meropenem. One of the critical observations is the presence of Acinetobacter, an MDR isolated from DFIs, which is either relatively or totally resistant to all the AMAs tested.

Development and Evaluation of Patient Information Leaflet for Diabetic Foot Ulcer Patients.

BACKGROUND: Patient education (PE) is as important as medical and surgical interventions in the management of diabetic foot ulcer (DFU). Patient information leaflets (PILs) are globally accepted patient counseling aids. OBJECTIVES: This study aimed at developing PILs for DFU patients and investigating its validation. METHODS: The PILs were prepared based on different model leaflets available from various online resources, including "Patient UK". The PILs readability was evaluated by Flesch/ Flesch-Kincaid readability (FRE/FK-GL) method before user-testing (n = 34 DFU patients) by quasi-experimental methods in patients with DFU. Additionally, user-opinion on legibility and content of the PIL was also determined. Baker Able Leaflet Design (BALD) method was employed to assess the layout and design characteristics of the PIL. RESULTS: The best FRE score achieved was 73.9 and the FK-GL score was 6.1. The mean BALD assessment score for English and Kannada versions of PIL were 27 and 26, respectively. The ICC of the test-retest reliability of user-testing and user-opinion questionnaires in both English and Kannada ranged from 0.91 to 0.96. The overall user-testing knowledge-based mean score significantly improved from 43.4 to 69.7 (P < 0.05). Overall, 82.4% of patients reported overall user-opinion on legibility and content of the PIL as good. CONCLUSIONS: The developed PILs met the criteria of fairly easy readability and good layout design. The user-opinion of the majority of patients reported the PIL content, legibility, and design as good. The Pictogram-based PILs (P-PILs) was found to be an effective PE tool in DFU patients.

Postoperative Pancreatic Fistula: A Surgeon's Nightmare! An Insight with a Detailed Literature Review.

CONTEXT: Postoperative fistula formation is an important complication following pancreatic resections. OBJECTIVE: A large volume of literature without uniform conclusions is available regarding various controversies about postoperative pancreatic fistulae. The term postoperative pancreatic fistula includes fistula resulting from any surgery involving pancreas, most commonly pancreaticoduodenectomy and distal pancreatectomy. In this review, we have tried to present a comprehensive account of postoperative pancreatic fistula with particular emphasis on important controversies clouding the subject. METHODS: We performed MEDLINE literature search for relevant articles using the key words pancreas, pancreatic cancer, pancreatectomy, pancreatoduodenectomy, Whipple's operation, postoperative, complications, fistula, management and treatment in various combinations with the Boolean operators AND, OR and NOT. CONCLUSIONS: Postoperative pancreatic fistula is a troublesome complication of pancreaticoduodenectomy. Although the risk factors for postoperative pancreatic fistula have been extensively described, none of the methods recommended for preventing postoperative pancreatic fistula have been conclusively proved to be effective. While endoscopic treatment and percutaneous treatment form important aspects of treatment of postoperative pancreatic fistula, surgery may be required for select cases.

Impact of diabetic foot ulcer on health-related quality of life: A cross-sectional study.

Studies have reported that health-related quality of life (HRQoL) is adversely affected by diabetic foot ulcer (DFU). There is a paucity of data on the effects of foot ulcers on HRQoL of diabetes patients in our population. Because South-Asians, especially Indians, have unique features related to diabetes and its complications, generalizing the data about their effect on HRQoL from any other part of the world is not a pragmatic approach. This study evaluated the impact of foot ulcers on HRQoL of diabetes patients. This cross-sectional study, conducted in Kasturba Hospital, Manipal (coastal South India), included 200 DFU patients in a study group (SG) and 200 diabetes patients in a control group (CG). The RAND-36 questionnaire was employed for evaluating HRQoL scores for the patients in both groups. DFU patients also completed the Diabetic Foot Ulcer Scale-Short Form questionnaire. Independent t-test was used to test the differences in mean scores. Results found that both CG and SG have "poor" HRQoL (mean score <50) on all the subscales except for two in CG. There is a statistically significant difference between groups (P < 0.05) on all eight of the subscales of HRQoL. For both CG and SG, the Physical Component Summary domain score (44.9 ± 6.3 v 28.4 ± 3.4) and Mental Component Summary domain score (42.5 ± 3.8 v 29.5 ± 7.1) were poor. There were significant differences between CG and SG for both mean Physical Component Summary score and Mental Component Summary score of HRQoL (p < 0.05). The Diabetic Foot Ulcer Scale-Short Form found that HRQoL is very poor for DFU patients on all six domains. The study concludes that DFU patients have very poor HRQoL compared with diabetic patients. Likewise, the diabetic foot is associated with severely impaired HRQoL in both physical and mental health aspects. This study will help to develop a patient education model for DFU patients by looking at the various HRQoL domains that are adversely affected by the presence of foot ulcer.

Utility of serum pancreatic enzyme levels in diagnosing blunt trauma to the pancreas: a prospective study with systematic review.

INTRODUCTION: Reliability of serum pancreatic enzyme levels in predicting pancreatic injuries has been a parameter of interest and the present recommendations on its utility are based primarily on anecdotal observations. The aim of this study was to evaluate the utility of serum pancreatic enzyme assessment in predicting blunt pancreatic injury with imaging and surgical correlation and compare our results with a systematic review of literature till date. METHODS: A prospective cohort study conducted over 4 years in a tertiary care referral centre with 164 consecutive patients who presented to the emergency department with a history of blunt abdominal trauma and had serum pancreatic enzyme assessment, USG and subsequent diagnostic CECT were analyzed. The CT findings and AAST grade of pancreatic injury, various intra-abdominal injuries and time elapsed since injury and other associated factors were correlated with serum pancreatic enzyme levels. For systematic review of literature MEDLINE database was searched between 1940 and 2012, also the related citations and bibliographies of relevant articles were analyzed and 40 articles were included for review. We compared our results with the systematic critique of literature till date to formulate recommendations. RESULTS: 33(21%) patients had pancreatic injury documented on CT and were graded according to AAST. Statistically significant elevated serum amylase levels were observed in patients with pancreatic and bowel injuries. However, elevated serum lipase was observed specifically in patients with pancreatic injury with or without bowel injury. Combined serum amylase and lipase showed 100% specificity, 85% sensitivity in predicting pancreatic injury. Elevated (n=28, 85%) vs. normal (n=5, 15%) serum amylase and lipase levels showed sole statistically significant association with time elapse since injury to admission, with a cutoff of 3h. CONCLUSIONS: Based on our results and the systematic review of the literature till date we conclude, persistently elevated or rising combined estimation of serum amylase and lipase levels are reliable indicators of pancreatic injury and is time dependent, nondiagnostic within 6h or less after trauma. In resource constrained countries where CT is not available everywhere it may support a clinical suspicion of pancreatic injury and can be reliable and cost-effective as a screening tool.

Topical application/formulation of probiotics: will it be a novel treatment approach for diabetic foot ulcer?

Treatment of chronic conditions like diabetic foot ulcer (DFU) is challenging due to increased susceptibility for infection and delayed wound healing. Complexity of existing therapy, adverse effects and microbial resistance emphasizes the need of an alternative approach for the management of DFU. The increasing body of evidence associated with probiotic application in diverse disease states merits its use in wound healing and infection too. Different probiotic strains have shown their efficacy in various infections like gut infections, oral infections and urogenital infections. Experimental studies have demonstrated probiotics' ability for gastric ulcer healing. Underlying mechanism of the above therapeutic effects of probiotics involves modulation of local and systemic immunity. The hypothesis is based on the concept that mechanism of anti-infective and ulcer healing action of probiotics will be similar in peripheral wounds and ulcers as on any other part of the body. This paper focuses on the hypothesis that topical applications/formulation of probiotics may be effective for the treatment of diabetic foot ulcers.

Synbiotic formulation of probiotic and lactulose combination for hepatic encephalopathy treatment: a realistic hope?

Gut-produced ammonia plays a vital role in the pathogenesis of hepatic encephalopathy because cirrhotic liver fails to clear toxic metabolites. Small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhosis add to the pathogenesis. Lactulose is a mainstay in the treatment of hepatic encephalopathy. Another benefit of lactulose is its prebiotic effect on probiotics that reduce the activity of bacterial urease, resulting in decreased hyperammoneamia and increased elimination of ammonia and other nitrogenous waste through enteric toxin reduction technology. Synbiotic formulation of probiotic and lactulose can synergistically/additively reduce ammonia production, increase utilization and excretion of ammonia and other nitrogenous wastes, thereby improving the well-being of patients with hepatic encephalopathy. We hypothesize that oral administration of a synbiotic formulation prepared from a combination of selected microbial strains of probiotics and lactulose will offer additional protection against hepatic encephalopathy via intra-intestinal extraction of toxic solutes in patients with cirrhosis.