Anti-glycating and anti-cytotoxic effect of silibinin on albumin at early glycation: A physiochemical study.

During persistent hyperglycaemia, albumin, one of the major blood proteins, can undergo fast glycation. It can be expected that timely inhibition of protein glycation might be add quality years to diabetic patients' life. Therefore, this study was designed to analyse the role of silibinin to reduced or delay amadori adduct formation at early glycation and its beneficial effect to improve the glycated albumin structure and conformation. We also analysed cytotoxic effect of amadori-albumin in the presence of silibinin on murine macrophage cell line RAW cells by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay. Formation of early glycated product (furosine) in all samples was confirmed by LCMS. Albumin incubated with glucose only showed presence of furosine like structure. Albumin treated with silibinin in the presence of glucose did not show such furosine like peak. This LCMS result showed the silibinin play a protective role in the formation of early glycated product. HMF contents were also reduced in the presence of silibinin, when albumin was incubated with increasing concentrations of silibinin (100 and 200 µM) in the presence of glucose. ANS binding fluorescence decrease by increasing silibinin concentrations with amadori-albumin. SDS-PAGE was also showed that no significant difference in the band mobility of albumin treated with silibinin as compared to native albumin. The secondary conformational alteration in amadori-albumin due to silibinin were confirmed by FTIR. This spectrum showed slight shift in amide I and Amide II band in albumin co-incubated with glucose and silibinin as compared to albumin incubated with glucose only. We further discussed about cytotoxic effect of amadori albumin and its prevention by silibinin. MTT assay results demonstrated that amadori-albumin showed cytotoxic effect on RAW cells but silibinin showed protective role and increased the cell viability. Moreover, the results showed that silibinin has anti-glycating potential and playing a role to prevent the formation of Amadori-albumin in-vitro. Silibinin possesses strong anti-glycating capacity and can improve albumin structure and function at early stage. It might be useful in delaying the progression of diabetes mellitus and its secondary complications at early stage.

A Study of the Friction Stir Lap Welding of AA5052 and Polypropylene.

Friction stir lap welding (FSLW) remains a pioneering technique for creating hybrid joints between AA5052 aluminium alloy and polypropylene (PP), particularly with the metal-on-top configuration. Building upon previous research, this study introduces a tapered fluted pin tool design and investigates its effectiveness in the welding process. Our results, supported by ANOVA, chemical, and microstructural analyses, reiterate that the optimal welding parameters stand at a rotational speed of 1400 RPM and a traverse speed of 20 mm/min. This combination produces a joint tensile strength of 3.8 MPa, signifying 16.54% of the weaker material's inherent strength. Microstructural evaluations revealed a unique composite of aluminium chips intermeshed with PP, strengthened further by aluminium hooks. Crucially, mechanical interlocking plays a predominant role over chemical bonding in achieving this joint strength. The study underscores the absence of significant C-O-Al bonds, hinting at the PP degradation without the thermo-oxidation process. Additionally, joint strength was found to inversely correlate with the interaction layer's thickness. The findings fortify the promise of FSLW with the novel fluted pin design for enhancing joints between AA5052 and PP, emphasising the potential of mechanical interlocking as a principal factor in achieving high-quality welds.

Attenuation of hyperglycemia and amadori products by aminoguanidine in alloxan-diabetic rabbits occurs via enhancement in antioxidant defenses and control of stress.

The micro- and macro-complications in diabetes mellitus (DM) mainly arise from the damage induced by Amadori and advanced glycation end products, as well as the released free radicals. The primary goal of DM treatment is to reduce the risk of micro- and macro-complications. In this study, we looked at the efficacy of aminoguanidine (AG) to prevent the production of early glycation products in alloxan-diabetic rabbits. Type1 DM was induced in rabbits by a single intravenous injection of alloxan (90 mg/kg body weight). Another group of rabbits was pre-treated with AG (100 mg/kg body weight) prior to alloxan injection; this was followed by weekly treatment with 100 mg/kg of AG for eight weeks. Glucose, insulin, and early glycation products (HbA1C and fructosamine) were measured in control, diabetic and AG treated diabetic rabbits. The effects of hyperglycemia on superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), reduced glutathione (rGSH), nitric oxide, lipid peroxides, and protein carbonyl were investigated. Alloxan-diabetic rabbits had lower levels of SOD, CAT, Gpx, and rGSH than control rabbits. Nitric oxide levels were considerably greater. AG administration restored the activities of SOD, CAT, Gpx enzymes up to 70-80% and ameliorated the nitric oxide production. HbA1c and fructosamine levels were considerably lower in AG-treated diabetic rabbits. The observed control of hyperglycemia and amadori adducts in alloxan-diabetic rabbits by AG may be attributed to decrease of stress and restoration of antioxidant defenses.

Mesenchymal Stem Cell-Derived Exosomes Exhibit Promising Potential for Treating SARS-CoV-2-Infected Patients.

The novel coronavirus severe acute respiratory syndrome-CoV-2 (SARS-CoV-2) is responsible for COVID-19 infection. The COVID-19 pandemic represents one of the worst global threats in the 21st century since World War II. This pandemic has led to a worldwide economic recession and crisis due to lockdown. Biomedical researchers, pharmaceutical companies, and premier institutes throughout the world are claiming that new clinical trials are in progress. During the severe phase of this disease, mechanical ventilators are used to assist in the management of outcomes; however, their use can lead to the development of pneumonia. In this context, mesenchymal stem cell (MSC)-derived exosomes can serve as an immunomodulation treatment for COVID-19 patients. Exosomes possess anti-inflammatory, pro-angiogenic, and immunomodulatory properties that can be explored in an effort to improve the outcomes of SARS-CoV-2-infected patients. Currently, only one ongoing clinical trial (NCT04276987) is specifically exploring the use of MSC-derived exosomes as a therapy to treat SARS-CoV-2-associated pneumonia. The purpose of this review is to provide insights of using exosomes derived from mesenchymal stem cells in management of the co-morbidities associated with SARS-CoV-2-infected persons in direction of improving their health outcome. There is limited knowledge of using exosomes in SARS-CoV-2; the clinicians and researchers should exploit exosomes as therapeutic regime.

Role of growth factors and cytokines in diabetic foot ulcer healing: A detailed review.

The aim of the review is to examine the role of growth factors and cytokines in the management of Diabetic Foot Ulcers, such as platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and Insulin like growth factor (IGF). Taking this a step further, the role of Hypoxia-inducible factors (HIFs), Transforming growth factor beta 1 (TGF-ß-1) and other growth factors have also been examined, with regard to the treatment of diabetic foot ulcers. The roles of these above-mentioned growth cytokines have been analyzed by studying various scholastic articles. The complete process of wound healing is implemented and regulated by numerous cytokines and human growth factors. The findings of the study indicate that wound healing of diabetic foot ulcers is a complex and extremely challenging biological and molecular process that involves coordinated efforts of multiple cell types. The therapeutic effects of various growth factors in the clinical management of wounds are chronic venous ulcers, pressure ulcers, and diabetic foot ulcers. It has been concluded that altercations of various cytokines are found in patients enduring diabetic foot ulcers. In a similar way, changes in the level of cytokines are also found in patients suffering from other diabetic complications such as diabetic nephropathy, retinopathy, and neuropathy. Subsequently, the diabetic wound healing process can be accelerated by regulating the levels of the cytokines.

A study on correlation between oxidative stress parameters and inflammatory markers in type 2 diabetic patients with kidney dysfunction in north Indian population.

BACKGROUND: Research reports support the statement that oxidative stress and inflammation are well-known risk factors for chronic kidney disease (CKD) in patients with diabetes. This study was designed to ascertain the associated role of oxidative stress parameters and inflammatory markers in diabetes and related CKD among the north Indian population. METHODS: The study was divided into three groups as healthy subjects (group 1), patients with diabetes without complication (group 2), and with CKD (group 3). Serum levels of malondialdehyde (MDA) and nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR) content were estimated in all individuals. Inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)-α were determined by enzyme-linked immuno-sorbent assay. RESULTS: MDA, protein carbonyl, and NO were significantly elevated in patients with type 2 diabetes as compared with healthy subjects (P ≤ 0.05). Total thiols content were found to be significantly decreased in patients with diabetes with CKD. The activity of antioxidant enzymes SOD, CAT, and GR showed a significant suppression in patients with type 2 diabetes with or without CKD as compared with healthy subjects. Nevertheless, the levels of proinflammatory cytokines IL-6 and TNF-α were significantly upregulated ( P ≤ 0.05) as compared with healthy subjects. CONCLUSION: Determination of antioxidant defense parameters and inflammatory markers contributes to understand the relationship between oxidative stress and inflammation on the development and prevention of chronic kidney disease in Indian patients with diabetes.

Comparison of Screws to Plate-and-Screw Constructs for Midfoot Arthrodesis.

BACKGROUND: We performed a prospective comparison of screws versus plate-and-screws for midfoot arthrodesis. MATERIALS: Between 2010 and 2015, a total of 50 patients with midfoot arthritis received screws or plate-and-screws for their midfoot arthrodesis. Function and pain were graded with the Foot and Ankle Ability Measures (FAAM) and visual analog scale (VAS), respectively. Data regarding arthrodesis healing and complications were recorded. RESULTS: Twenty-five patients received screws for fusion, where 21 achieved full arthrodesis healing by 6 months from surgery. Mean FAAM increased from 46.4 to 82.7 of 100 between initial and final visit. Mean pain decreased from 8.3 to 2.1 of 10 between initial and latest encounter. Twenty-five patients received plate-and-screws for their fusion, where 23 achieved full arthrodesis healing by 6 months from surgery. Mean FAAM increased from 48.2 to 86.3 of 100 between initial and final visit. Mean pain decreased from 8.0 to 1.8 of 10 between initial and latest encounter. These postoperative scores were not significantly different from patients with screws ( P > .05). Three and 6 patients with screws versus plate-and-screws, respectively, developed wound complications ( P = .03). Four and 2 patients with screws versus plate-and-screws, respectively, developed delayed or nonunion of their arthrodesis ( P = .15). DISCUSSION: A comparison of outcomes of midfoot arthrodesis with screws or plate-and-screws has not been previously reported. Both constructs provide improved function and pain. Using screws might generate less wound complications, but using plate-and-screws might produce higher rates of bony healing. LEVEL OF EVIDENCE: Level I, randomized, prospective, and comparative cohort study.

The Effect of Obesity on Surgical Treatment of Achilles Tendon Ruptures.

INTRODUCTION: We conducted a retrospective comparison of surgical treatment outcomes for acute Achilles tendon ruptures in nonobese and obese patients. METHODS: Between October 2006 and April 2014, we studied 76 patients with acute midsubstance Achilles tendon rupture: 44 nonobese and 32 obese (body mass index >30 kg/m). Preoperative and postoperative function and pain were graded with the Foot and Ankle Ability Measure (FAAM) Sports subscale and the visual analog scale for pain, respectively. RESULTS: All 76 patients presented for follow-up. On a scale of 100, the mean FAAM score for the nonobese patients increased from 38.1 preoperatively to 90.2 at final visit, and on a scale of 10, the mean pain score decreased from 7.1 preoperatively to 1.6 at latest follow-up. For obese patients, the mean FAAM score increased from 34.2 preoperatively to 83.3 at final visit, and the mean pain score decreased from 6.2 preoperatively to 1.9 at the latest follow-up. The postoperative scores of the two groups were not significantly different (P > 0.05). Postoperative wound complications developed in six nonobese patients and one obese patient (13.6% and 3.1%, respectively; P < 0.05). DISCUSSION: To our knowledge, comparing outcomes from surgically treated acute Achilles ruptures in nonobese and obese patients has not been previously reported. We found that both obese and nonobese patients can achieve improved Achilles tendon function and pain as a result of surgery. CONCLUSIONS: The findings of this study demonstrate that both nonobese and obese patients can achieve a high rate of improvement in ankle function and pain relief after surgical repair of the Achilles tendon.

Arthroscopic Treatment of Osteochondral Lesions of the Talus With Allograft Cartilage Matrix.

BACKGROUND: This prospective study evaluated the intermediate-term outcomes of operatively treating primary osteochondral lesions of the talus (OLT) of 1.5 cm2 or smaller with arthroscopic excision, microfracture, and allograft cartilage extracellular matrix (ECM). METHODS: Between 2012 and 2015, 30 consecutive patients received allograft cartilage ECM at their microfractured OLT of 1.5 cm2 or smaller after failing nonoperative treatment. Preoperative and postoperative function and pain were graded using the Foot and Ankle Ability Measure (FAAM) and a visual analog scale (VAS), respectively. Postoperative imaging was assessed for osteochondral healing and degenerative changes. This included computed tomography (CT) at 6 months from surgery. Data regarding postoperative complications were recorded. All 30 patients that received allograft cartilage ECM for their OLT were evaluated for final follow-up at a mean of 20.2 months. RESULTS: Mean FAAM increased from 51.4 preoperatively to 89.3 of 100 at final follow-up. Mean VAS decreased from 8.1 preoperatively to 1.7 of 10 at final follow-up. These differences between preoperative and postoperative function and pain were statistically significant ( P < .05). At 6 months from surgery, 2 patients (6.7%) received CT scans that revealed incomplete chondral formation at their OLT. At 19 months after surgery, a separate patient (3.3%) developed ankle arthritic changes. CONCLUSION: Treating OLTs with allograft cartilage ECM has not been previously reported. Using allograft cartilage ECM resulted in a high rate of improvement in ankle function and pain in patients with OLTs. These findings are important as allograft cartilage ECM could be of significant benefit for patients with OLTs. LEVEL OF EVIDENCE: Level III, prospective comparative series.

Incidence and Risk Factors of Venous Thromboembolism After Orthopaedic Foot and Ankle Surgery.

BACKGROUND: This study examines the incidence and risk of postoperative symptomatic venous thromboembolism (VTE) after orthopaedic foot/ankle surgery. MATERIALS: Patients that received foot/ankle surgery between 2006 and 2016 were reviewed. Inclusion criteria were surgical patients that were without coagulopathy, previous VTE, and/or using anticoagulation medications including aspirin. Age, sex, body mass index, medical comorbidities, and surgical diagnosis and procedure(s) were noted. Records were reviewed to see who developed a symptomatic VTE within 90 days from surgery. RESULTS: This study involved 2774 patients that received foot/ankle surgery between 2006 and 2016. Of them, 22 (0.79%) developed a VTE within 90 days from surgery. The mean age of these patients was 49.5 years. Twelve patients were male and 10 were female. Sixteen patients were obese and 6 were nonobese. Postoperative VTEs were 14 infrapopliteal deep vein thrombosis (DVT), 1 suprapopliteal DVT, and 7 pulmonary emboli. The most common surgeries involved were ankle fracture repair in 8 (0.29%), Achilles tendon repair in 2 (0.07%), ankle ligament reconstruction in 2, and hammer-toe correction in 2 patients. Obesity was predictive of a postoperative VTE to a statistically significant degree (P = .04). Age, sex, medical comorbidities, diagnosis, and type of surgery were not significantly prognostic for a postsurgical VTE (P ≥ .05). DISCUSSION: The incidence of VTE after foot/ankle surgery is low. However, obese patients are at significantly higher risk for VTE after such procedures. CLINICAL RELEVANCE: These findings are important when educating patients as to their risks of developing a VTE after orthopaedic foot/ankle surgery. LEVELS OF EVIDENCE: Level III: Retrospective cohort study.

Study of IL4-590C/T and IL6-174G/C Gene Polymorphisms in Type 2 Diabetic Patients With Chronic Kidney Disease in North Indian Population.

To explore the associations between potential functional promoter polymorphisms in pro-inflammatory and anti-inflammatory (IL-4(-590C/T) and IL-6(-174G/C) cytokine genes, and kidney dysfunction in North Indian type 2 diabetic subjects with chronic kidney disease. A total of 150 subjects aged 25-75 year were included in this study. The glomerular filtration rate (GFR) and serum creatinine were estimated. PCR was performed to analyse genotype distribution in IL-4 (-590T/C) and IL-6 (-174G/C) among healthy, type 2 diabetic patients with or without CKD. The genotype distributions were determined by Hardy-Weinberg equilibrium. CKD patients showed lower GFR (59.36 ± 1.33 ml/min/1.73 m2 ) and higher serum creatinine (1.93 ± 0.99% mg) level in comparison to diabetic patients without CKD and healthy subjects. Genotypic distribution of the different genotypes among the study groups in IL-4 gene was genotype CC = 30, TC = 12, and TT = 8 in CKD patients. In type 2 diabetic patients without CKD, genotype distribution was CC = 38, TC = 10, and TT = 2. In healthy subjects, distribution of genotype was CC = 35, TC = 14, and TT = 1. The distribution of different genotype among the study groups for IL-6 gene was GG = 27, GC = 20, and CC = 3 in healthy subjects; GG = 28, GC = 19, and CC = 3 in diabetic patients without CKD and GG = 38, GC = 11, and CC = 1 in diabetic patients with CKD. There was no significant difference in the distribution of genotype frequencies between healthy subjects and diabetic patients without CKD but a significant difference was found in diabetic patients with CKD. The functional promoter polymorphisms IL4-590C/T and IL6-174G/C, which affect the IL-4 and IL-6 levels in north Indian subjects, were associated with kidney dysfunction and CKD. J. Cell. Biochem. 118: 1803-1809, 2017. © 2016 Wiley Periodicals, Inc.

Treatment of Plantar Fasciitis With Botulinum Toxin.

BACKGROUND: This study examined the effect of botulinum toxin upon plantar fasciitis through a randomized, controlled, and blinded trial. MATERIALS: Between 2012 and 2015, 50 patients presented with plantar fasciitis. Twenty-five patients each randomly received an IncobotulinumtoxinA (IBTA) or saline injection of their affected foot. Pre- and postinjection function and pain were graded with the Foot and Ankle Ability Measures (FAAM) and visual analog scale (VAS), respectively. All 50 study patients who randomly received either placebo or IBTA presented at 6 and 12 months after injection. RESULTS: At 6 months, the mean FAAM increased from 35.9 to 40.9 of 100, and the mean pain score decreased from 8.4 to 7.9 of 10 within the placebo group. At 6 months, the mean FAAM increased from 36.3 to 73.8 of 100, and mean pain score decreased from 7.2 to 3.6 of 10 within the IBTA group. These postinjection scores were significantly better than the placebo group ( P = .01). At 12 months after injection, the IBTA group maintained significantly better function and pain than the placebo group ( P < .05). By that time, 0 (0%) and 3 (12%) patients who received IBTA and saline, respectively, underwent surgery for recalcitrant plantar fasciitis ( P < .005). CONCLUSION: Compared with placebo saline injection, using IBTA to treat plantar fasciitis resulted in significantly better improvement in foot function and pain. IBTA also lessened the need for operative treatment of plantar fasciitis. LEVEL OF EVIDENCE: I, Randomized, double-blinded, placebo-controlled study.

Randomized, Prospective Comparison of Bioabsorbable and Steel Screw Fixation of Lisfranc Injuries.

OBJECTIVE: This study's objective is to compare outcomes of bioabsorbable versus steel screws for treating Lisfranc injuries. DESIGN: This research was conducted in a prospective and randomized manner between September 2008 and December 2013. SETTING: This study was performed in the outpatient setting at a tertiary-level care center in a single surgeon's practice. PATIENTS/PARTICIPANTS: Forty patients with acute Lisfranc injuries, amenable to open reduction and screw fixation, enrolled and presented for final follow-up. INTERVENTION: Through randomization, 20 and 20 patients received bioabsorbable versus steel screws, respectively. OUTCOME MEASUREMENTS: Function and pain were graded using the Foot and Ankle Ability Measures (FAAM) and a visual analog scale of pain. Radiographs were assessed for joint stability and degeneration. RESULTS: For those with steel screws, the mean FAAM score increased from 24.9 to 89.6 of 100 and pain score decreased from 6.5 to 1.9 of 10 by latest follow-up. For those with absorbable screws, the mean FAAM score increased from 32.5 to 91.2 and pain score decreased from 4.7 to 1.3 by latest follow-up. These differences in final mean function (P = 0.4) and pain (P = 0.25) between the study groups were not statistically significant. Final radiographs showed no Lisfranc instability in any study patients, but rather midfoot arthritis in 4 and 2 patients with steel versus bioabsorbable screws, respectively. None of the patients who received steel screws had hardware-related problems, but 1 patient who received absorbable fixation developed an inflammatory reaction at a nonresorbed screw head at 2 years after surgery. CONCLUSIONS: Bioabsorbable screws provide short-term results that are comparable and not significantly different from steel screws for treating unstable Lisfranc injuries. Both methods are predictable in improving function and pain, but using absorbable screws eliminates the need for hardware removal after such trauma. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Treatment of Chronic Achilles Tendon Ruptures With Large Defects.

UNLABELLED: Background When Achilles tendon ruptures become chronic, a defect often forms at the rupture site. There is scant literature regarding the treatment of chronic Achilles ruptures with defects of 6 cm or larger. We examined outcomes from combining a turndown of the proximal, central Achilles with a flexor hallucis longus (FHL) tendon transfer to treat this condition. Materials Between September 2002 and December 2013, 32 patients presented with a chronic Achilles rupture and a defect of 6 cm or more. Twenty patients were male and 12 were female. Patient age was between 20 and 74 years, with a mean of 53.3 years. Eighteen and 14 patients had their right and left Achilles tendon affected, respectively. The number of days between injury and surgery ranged from 30 to 315 days, with a mean of 102 days. Reconstruction of the Achilles involved a turndown of the proximal, central tendon and FHL augmentation. Final patient follow-up ranged from 18 to 150 months, with a mean of 62.3 months. RESULTS: At surgery, the gap between the ruptured ends of the Achilles ranged from 6 to 12 cm, with a mean gap of 7.5 cm. Full healing was achieved in all 32 patients (100%) by 5 months postoperatively. Mean Foot and Ankle Ability Measures scores increased from 36.3% to 90.2% between initial and latest follow-up (P < .05). Mean visual analogue scales of pain decreased from 6.6 to 1.8 of 10 between first and last encounter (P < .05). Postoperative complications occurred in 5 patients (15.6%), including 3 (9.4%) superficial wound problems, 1 (3.1%) deep wound infection, and 1 (3.1%) deep vein thrombosis. Discussion Outcomes from treating chronic Achilles ruptures with large defects are scant within the orthopaedic literature. Our method of Achilles reconstruction results in a high rate of improved function and pain relief. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case series.

Comparison of Osteochondral Autografts and Allografts for Treatment of Recurrent or Large Talar Osteochondral Lesions.

BACKGROUND: The purpose of this study was to prospectively evaluate and compare the long-term clinical and radiographic outcomes of using osteochondral autograft and allograft to manage either recurrent or large osteochondral lesions of the talar dome (OLT) in a single surgeon's practice. METHODS: Between January 2008 and January 2014, a total of 40 patients presented with either a recurrent OLT that failed initial arthroscopic treatment (ie, excision, curettage, debridement, and micro-fracture) or a primary OLT greater than 1.5 cm2 that had undergone no prior surgery. Before surgery, 20 patients were randomized to receive osteochondral autograft plugs (Arthrex, Naples, FL) from the ipsilateral superolateral distal femoral condyle whereas the remaining 20 were randomized to receive osteochondral allograft plugs from a fresh size-matched donor talus (Joint Restoration Foundation, Centennial, CO, and Arthrex, Naples, FL), but 4 of these were excluded that received a hemi-talus allograft with internal fixation. Preoperative and postoperative function and pain was graded using the Foot and Ankle Ability Measures (FAAM) scoring system and a Visual Analog Scale (VAS) of pain, respectively. Radiographs were assessed for osteochondral graft healing, joint congruency, and degenerative changes. Data regarding postoperative complications and revision surgeries were also recorded. RESULTS: Of the 20 patients who received osteochondral autograft, the mean FAAM score increased from 54.4 preoperatively to 85.5 at the time of final follow-up. The mean VAS pain score decreased from 7.9 of 10 preoperatively to 2.2 of 10 at final follow-up. Two patients (10%) that received osteochondral autograft, 1 for a recurrent OLT of 1.3 cm2 and 1 for a primary OLT of 2.0 cm2, developed a symptomatic nonunion at the entire graft site. Both of these patients had their autograft converted to talar allograft plugs and achieved full osteochondral healing. At the time of final follow-up, no patients who received osteochondral autograft developed ankle degenerative changes or knee complications. The mean FAAM score of the 16 patients who received osteochondral allograft plugs increased from 55.2 preoperatively to 80.7 at the time of final follow-up. This postoperative score was lower than that of the osteochondral autograft group, but not to a statistically significant degree (P = .25). The mean VAS pain score decreased from 7.8 of 10 preoperatively to 2.7 of 10 at final follow-up. This postoperative score was higher than that of the osteochondral autograft group but not to a statistically significant degree (P = .15). Three patients (18.8%) that received osteochondral talar allograft, 2 for recurrent OLTs less than 1.5 cm2 and 1 for a primary OLT of 2.2 cm2, developed a symptomatic nonunion at the entire graft site. Two of these 3 patients had their allograft converted to osteochondral autograft plugs harvested from the ipsilateral superolateral distal femoral condyle and achieved full osteochondral healing. At the time of final follow-up, 1 of these 16 (6.3%) patients who received talar allograft as OLT treatment had developed asymptomatic anterior ankle arthritis upon radiographs. CONCLUSION: Using fresh talar osteochondral allograft provided results that were comparable to the use of distal femoral osteochondral autograft for treating recurrent or large OLTs. Although the use of allograft avoided the risk of knee complications when harvesting autograft from the distal femur, fresh talar allograft may have lower healing rates than osteochondral autograft. LEVEL OF EVIDENCE: Level II, comparative case series.

Management of diabetic nephropathy: Recent progress and future perspective.

Diabetic nephropathy (DN), a leading cause of end-stage renal disease (ESRD) affecting ∼20-30% diabetics, is associated with increased cardiovascular mortality. The progression of kidney disease in patients with diabetes can take many years. It occurs as a result of interaction between both genetic and environmental factors in individuals with both type 1 and type 2 diabetes. Hyperglycaemia, hypertension, and genetic pre-disposition are the main risk factors besides elevated serum lipids, smoking habits, and the amount of dietary proteins. Interventions such as glycaemic control, blood pressure control and inhibition of the renin-angiotensin-aldosterone system have been shown to slow this progression. Despite the implementation of these strategies, the number of patients with diabetes that ultimately develop end-stage renal disease remains high. The treatment of DN, therefore, has posed a formidable challenge besides optimization of renin-angiotensin-aldosterone system blockade in patients with DN; additional investigation has focused on the potential of novel therapies that target various pathways upregulated by hyperglycaemia or other targets believed to promote the progression of DN such as oxidative stress, inflammation, endothelin system and vitamin D receptors. This review article addresses the pathogenesis and some of the well established principles regarding the progression and accepted management of DN, and also includes the perspectives of novel anti-DN agents and the future directions for the prevention of DN.

Plasma Heat Shock Proteins (HSPs) 70 and 47 levels in diabetic foot and its possible correlation with clinical variables in a North Indian Tertiary care hospital.

OBJECTIVE: HSPs have been proposed to have a role in the wound healing process, supported by finding that its expression is rapidly induced after skin is wounded in animal models. Because of this phenomenon, we have made a hypothesis that circulating HSPs will have any relationship with DFU. METHODS: The circulating levels of HSP 70 and HSP 47 were measured in diabetic patients with an ulcer (Group A: n=30), without ulcer (Group B: n=30) and healthy subjects (Group C: n=30). RESULTS: Diabetic foot ulcer showed higher median plasma level of HSP 70 [3229.01 (1984.5-4137.1) vs 1625.7 (1435.1-2253.5) vs 1025.7 (835.1-1653.5)] ng/ml and HSP 47 [2.33 (2.118-2.58) vs 0.98 (0.83-1.07) vs 0.58 (0.42-0.68) pg/ml] of the diabetic foot, diabetic control and healthy subjects. Odds ratio and risk ratio for DFU after age adjusted were BMI (>25 kg/m(2)) [OR 1.78, RR 1.35], HbA1c>7% [OR 3.37), RR 1.76], neuropathy [OR 5.79, RR 3.13], retinopathy [OR 3.44, RR 1.82], hypertension [OR 1.54, RR 1.18], and smoking cessation [OR 4.53, RR 2.09]. CONCLUSION: In the near future, it would be interesting to find out whether this high plasma HSPs precedes in early would healing mechanism and will have a relationship with type of infections and/or nature of therapy for infection in such patients.

Production of polypeptide antibiotic from Streptomyces parvulus and its antibacterial activity.

A highly potent secondary metabolite producing actinomycetes strain is isolated from marine soil sediments of Visakhapatnam sea coast, Bay of Bengal. Over all ten strains are isolated from the collected soil sediments. Among the ten actinomycetes strains the broad spectrum strain RSPSN2 was selected for molecular characterization, antibiotic production and its purification. The nucleotide sequence of the 1 rRNA gene (1261 base pairs) of the most potent strain evidenced a 96% similarity with Streptomyces parvulus 1044 strain, Streptomyces parvulus NBRC 13193 and Streptomyces parvulus BY-F. From the taxonomic features, the actinomycetes isolate RSPSN2 matches with Streptomyces parvulus in the morphological, physiological and biochemical characters. Thus, it was given the suggested name Streptomyces parvulus RSPSN2. The active metabolite was extracted using ethyl acetate (1:3, v/v) at pH 7.0. The separation of active ingredient and its purification was performed by using both thin layer chromatography (TLC) and column chromatography (CC) techniques. Spectrometric studies such as UV-visible, FTIR, and NMR and mass were performed. The antibacterial activity of pure compound was performed by cup plate method against some pathogenic bacteria including of streptomycin resistant bacteria like (Pseudomonas mirabilis, Pseudomonas putida and Bacillus cereus). In conclusion, the collected data emphasized the fact that a polypeptide antibiotic (Actinomycin D) was produced by Streptomyces parvulus RSPSN2.

Production of polypeptide antibiotic from Streptomyces parvulus and its antibacterial activity

A highly potent secondary metabolite producing actinomycetes strain is isolated from marine soil sediments of Visakhapatnam sea coast, Bay of Bengal. Over all ten strains are isolated from the collected soil sediments. Among the ten actinomycetes strains the broad spectrum strain RSPSN2 was selected for molecular characterization, antibiotic production and its purification. The nucleotide sequence of the 1 rRNA gene (1261 base pairs) of the most potent strain evidenced a 96% similarity with Streptomyces parvulus 1044 strain, Streptomyces parvulus NBRC 13193 and Streptomyces parvulus BY-F. From the taxonomic features, the actinomycetes isolate RSPSN2 matches with Streptomyces parvulus in the morphological, physiological and biochemical characters. Thus, it was given the suggested name Streptomyces parvulus RSPSN2. The active metabolite was extracted using ethyl acetate (1:3, v/v) at pH 7.0. The separation of active ingredient and its purification was performed by using both thin layer chromatography (TLC) and column chromatography (CC) techniques. Spectrometric studies such as UV-visible, FTIR, and NMR and mass were performed. The antibacterial activity of pure compound was performed by cup plate method against some pathogenic bacteria including of streptomycin resistant bacteria like (Pseudomonas mirabilis. Pseudomonas putida and Bacillus cereus). In conclusion, the collected data emphasized the fact that a polypeptide antibiotic (Actinomycin D) was produced by Streptomyces parvulus RSPSN2.

Serum levels of TNF-α in peripheral neuropathy patients and its correlation with nerve conduction velocity in type 2 diabetes mellitus.

OBJECTIVE: To compare serum levels of TNF-α in patients of peripheral neuropathy and patients without neuropathy in type 2 diabetes mellitus. MATERIAL AND METHODS: This cross sectional study was conducted in diagnosed type 2 diabetes mellitus patients. They were divided in groups, Group I (n=37) with clinically detectable diabetic peripheral neuropathy of shorter duration and Group II (n=27) with clinically detectable diabetic peripheral neuropathy of longer duration. They were compared with patients without clinical neuropathy (n=22), clinical diagnosis was based on neuropathy symptom score (NSS) and neuropathy disability score (NDS) for signs. Blood samples were collected for baseline investigations and estimation of serum TNF-α. Nerve conduction velocity was measured in both upper and lower limbs. Median, Ulnar, Common Peroneal and Posterior Tibial nerves were selected for motor nerve conduction study and Median and Sural nerves were selected for sensory nerve conduction study. RESULTS: The comparisons were done between various clinical and biochemical parameters in clinically detectable and undetectable peripheral neuropathy groups of type 2 diabetes mellitus. The study showed raised serum levels of TNF-α in peripheral neuropathy patients and significant correlation with nerve conduction velocity. CONCLUSION: High level of TNF-α in serum of T2DM patients with neuropathy shows possible contribution in development of neuropathy. Due to its independent association this cytokine might be used as biomarker for diabetic peripheral neuropathy.